| Dokumendiregister | Riigikogu |
| Viit | 1-2/26-340/1 |
| Registreeritud | 29.05.2026 |
| Sünkroonitud | 29.05.2026 |
| Liik | EL dokument |
| Funktsioon | |
| Sari | |
| Toimik | Töödokument - SWD(2026) 450, COM(2025) 1022, COM(2025) 1031 |
| Juurdepääsupiirang | Avalik |
| Adressaat | |
| Saabumis/saatmisviis | |
| Vastutaja | |
| Originaal | Ava uues aknas |
EN EN
EUROPEAN COMMISSION
Brussels, 26.5.2026
SWD(2026) 450 final
PART 1/2
Addendum to
COM(2025) 1022 and COM(2025) 1031 adopted on 16.12.2025
COMMISSION STAFF WORKING DOCUMENT
European Biotech Act
Accompanying the documents
Proposal for a Regulation of the European Parliament and of the Council on
establishing a framework of measures for strengthening Union's biotechnology and
biomanufacturing sectors particularly in the area of health and amending Regulations
(EC) No 178/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795
and (EU) 2024/1938 (European Biotech Act)
and
Proposal for a Directive of the European Parliament and of the Council amending
Directives 2001/18/EC and 2010/53/EU as regards the placing on the market of
genetically modified micro-organisms and the processing of organs
{COM(2025) 1022 final} - {COM(2025) 1031 final}
Table of contents
1 INTRODUCTION .................................................................................................................. 5
2 BACKGROUND .................................................................................................................... 6
2.1 Political and legal context ........................................................................................... 6
2.2 Related EU legislation ................................................................................................ 7
2.3 Background on the sector .......................................................................................... 11
3 PROBLEM DEFINITION .................................................................................................... 13
3.1 Problem: biotech companies struggle to innovate, raise capital, bring innovations to
market, produce and grow in the EU, while maintaining high level of protection and
safety ......................................................................................................................... 13
3.2 What are the problem drivers? .................................................................................. 14
3.3 Consequences ............................................................................................................ 22
3.4 What is the baseline from which measures are assessed? ......................................... 29
4 APPROACH TO THE BIOTECH ACT ............................................................................... 38
4.1 Objectives of the proposal ......................................................................................... 38
4.2 Choice of the legal instruments and legal basis ......................................................... 38
4.3 Subsidiarity: necessity for EU action and EU added value ....................................... 39
4.4 Intervention logic of the proposal.............................................................................. 40
5 DESCRIPTION OF THE PROPOSED MEASURES AND ANALYSIS OF THEIR MAIN
IMPACTS ............................................................................................................................. 41
5.1 Interventions for regulatory simplification: measures and expected impacts ............ 41
5.2 Interventions on industrial enablers: measures and expected impacts ....................... 73
6 CUMULATIVE ECONOMIC, SOCIAL, ENVIRONMENTAL AND OTHER IMPACTS
OF THE PROPOSAL ......................................................................................................... 107
6.1 Regulatory simplification and administrative burden .............................................. 108
6.2 Competitiveness and investment attractiveness....................................................... 111
6.3 Innovation and research........................................................................................... 113
6.4 Public health and safety ........................................................................................... 115
6.5 Environmental impacts ............................................................................................ 116
6.6 Digital by default principle ...................................................................................... 117
7 MONITORING AND EVALUATION ............................................................................... 117
ANNEXES:
ANNEX 1: PROCEDURAL INFORMATION
ANNEX 2: STAKEHOLDER CONSULTATION
ANNEX 3: WHO IS AFFECTED AND HOW?
ANNEX 4: ANALYTICAL METHODS
ANNEX 5: ADDITIONAL INFORMATION ON BACKGROUND ON THE SECTOR AND PROBLEM
DEFINITION
ANNEX 6: OVERVIEW OF THE PROPOSED MEASURES AND ARTICLES OF THE PROPOSED
REGULATION AND DIRECTIVE
ANNEX 7: ADDITIONAL INFORMATION ON MEASURES AND EXPECTED IMPACTS
ANNEX 8: COMPETITIVENESS CHECK
ANNEX 9: SME CHECK
2
Glossary
Term or acronym Meaning or definition
AI Artificial Intelligence
ATMP Advanced Therapy Medicinal Product
BMWP Biosimilar Medicinal Products Working Party
CAGR Compound Annual Growth Rate
CAPEX Capital Expenditure
CES Comparative efficacy study
CfE Call for Evidence
CHMP Committee for Medicinal Products for Human Use
CMA Critical Medicines Act
CRO Contract Research Organization
CT Clinical Trial
CTR Clinical Trials Regulation
DNA Deoxyribonucleic acid
EEA European Economic Area
EFSA European Food Safety Authority
EIB European Investment Bank
EMA European Medicines Agency
3
ERA Environmental Risk Assessment
EU European Union
FTE Full-Time Equivalent
GDP Gross Domestic Product
GDPR General Data Protection Regulation
GMM Genetically Modified Micro-organism
GMO Genetically Modified Organism
GMP Good Manufacturing Practices
GVA Gross Value Added
HTA Health Technology Assessment
IMP Investigational Medicinal Product
IP Intellectual Property
IVDR Regulation (EU) 2017/746 on in vitro diagnostic medical devices
MAA Marketing Authorisation Application
mAB Monoclonal antibody
MDR Regulation (EU) 2017/745 on medical devices
MFF Multiannual Financial Framework
MSC Member State Concerned
NGOs Non-Governmental Organisations
4
OPEX Operating Expenses
R&D Research and Development
R&I Research and Innovation
RMS Reporting Member State
SDG Sustainable Development Goal
SMEs Small and Medium-sized Enterprises
SoHO Substances of Human Origin
SPC Supplementary Protection Certificate
STEP Strategic Technologies for Europe Platform
TEP Tissue Engineered Product
TFEU Treaty on the Functioning of the European Union
VMP Veterinary Medicinal Product
VNRAs Variations Not Requiring Assessment
5
1 INTRODUCTION
This staff working document summarises the analysis supporting the proposal for a
Regulation1 (the ‘proposed Regulation’) and the proposal for a Directive2 (the ‘proposed
Directive’) which were adopted by the Commission on 16 December 2025. These two
proposals (collectively referred to as the ‘Biotech Act’) aim to strengthen the EU’s
biotechnology and biomanufacturing sectors, particularly in the area of health. They amend
key legislation relevant to these sectors.
Biotechnology and biomanufacturing, supported by artificial intelligence (AI) and digital
tools, could help modernise entire parts of the EU economy. They hold huge potential to
boost competitiveness and innovation, while delivering for patients, public health, food
safety, security and other areas. Despite its world-class scientific base, the EU is trailing
its competitors when it comes to translating biotechnology research into development,
market deployment and manufacturing at scale. Fragmented ecosystems, financing
constraints, complex regulatory pathways, and a lag in adapting regulatory frameworks to
technological advances, hinder EU biotechnology companies’ potential to innovate, bring
innovation to market, produce and grow in the EU. As a result, the EU’s biotechnology
sector does not meet its full potential to tackle major societal challenges and faces a
widening global competitiveness gap.
The proposed Regulation and Directive present a series of measures primarily for the
health biotechnology sector, with targeted actions addressing other biotechnology areas
(food and feed, industrial and agricultural biotechnologies). The two proposals aim to
accelerate the way biotechnology innovations, products and services are developed and
placed on the single market, while maintaining the highest safety standards. The proposed
Biotech Act is one of the flagship initiatives of the Competitiveness Compass3, designed
to unleash the EU’s innovation potential. It also contributes to regulatory simplification
and administrative burden reduction goals.
The Biotech Act is in line with the United Nations’ Sustainable Development Goals
(SDGs), in particular SDG 3 ‘Good health and well-being: Ensure healthy lives and
promote well-being for all at all ages’; SDG 9 ‘Industry, innovation and infrastructure:
Build resilient infrastructure, promote inclusive and sustainable industrialisation and foster
innovation’; and SDG 12 ‘Responsible consumption and production: Ensure sustainable
consumption and production patterns’. More details on the relevant SDG targets and
indicators are available in Annex 3. Regarding specialisation in terms of scientific output,
the EU leads inter alia in SDGs 9 and 12.4
1 COM(2025) 1022 final. 2 COM(2025) 1031 final. 3 COM(2025) 30 final. 4 European Commission: Directorate-General for Research and Innovation, Science, research and innovation
performance of the EU, 2024 – A competitive Europe for a sustainable future, Publications Office of the European Union,
2024, https://data.europa.eu/doi/10.2777/965670 (see Chapter 3: Scientific knowledge production).
6
2 BACKGROUND
2.1 Political and legal context
A ‘European Biotech Act’ was announced by the President of the Commission in the 2024
- 2029 Political Guidelines of the European Commission5, to make it easier to bring
biotechnology products from the laboratory to the factory and then onto the market, while
maintaining high safety standards. It was further reflected in the mission letter of
Commissioner Várhelyi6.
In the Commission Recommendation on critical technology areas for the EU’s
economic security7, biotechnology was recognised as having “an enabling and
transformative nature in areas such as agriculture, environment, healthcare, life sciences,
food chains or biomanufacturing”. The Commission Communication on Biotechnology
and Biomanufacturing8 highlighted the high growth potential and labour productivity
of biotechnology and biomanufacturing. This makes the sector pivotal to the
competitiveness and modernisation of the EU’s economy, as well as conducive to its
strategic autonomy and resilience. While the EU’s strengths were recognised (i.e.
research and innovation base and capacities), the Commission stressed the need to address
the challenges faced by companies, users and consumers. It called for both a supportive
regulatory environment and a coordinated approach, particularly for developing
infrastructures, fostering the use of AI, and encouraging private and public investments.
Additionally, the EU’s Economic Security Strategy9 identified biotechnology as one of
the 10 technology areas most likely to present sensitive and immediate risks related to
technology security and technology leakage. This strategy launched an EU joint risk
assessment with Member States on biotechnology, which identified relevant biosecurity
risks that require mitigation measures.
The seminal reports by Enrico Letta10 and Mario Draghi11 also underscored the need to
take action in the biotechnology and biomanufacturing sectors. They identified the need
for a stronger, more dynamic European industrial policy, including measures for the
biotechnology and biomanufacturing sectors to scale up and get products on the market
faster. The report by Sauli Niinistö12 also pointed to the need to strengthen biological
defence capabilities and preparedness against emerging biological threats, including
synthetic pathogens.
5 See footnote 1, page 5. 6 Ursula von der Leyen, Mission Letter – OlivérVárhelyi – Commissioner-designate for Health and Animal Welfare, 17
September 2024. 7 Commission Recommendation (EU) 2023/2113 of 3 October 2023, OJ L, 2023/2113, 11.10.2023,
ELI: http://data.europa.eu/eli/reco/2023/2113/oj. 8 COM(2024) 137 final/2. 9 JOIN(2023) 20 final 10 Enrico Letta, Much more than a Market. April 2024. 11 Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe, European
Commission, 9 September 2024. 12 Niinistö, Sauli Safer Together – Strengthening Europe’s Civilian and Military Preparedness and Readiness, 30 October
2024.
7
In line with this growing political impetus, reducing the EU’s strategic dependencies in
sensitive sectors has become a priority of the European Council13, including in health
and food, as identified in the Versailles Declaration of 202214. The Council15 has urged
the Commission to unlock the potential of biotechnologies for the EU’s competitiveness
through the European Biotech Act, while maintaining environmental and safety standards.
In particular, the Council has encouraged actions to advance the use of regulatory
sandboxes, promote research and development (R&D) in advanced therapy medicinal
products (ATMPs) and address the falling global share of EU clinical trials (CTs). It also
supports the greater use of AI and the development of appropriate skills.In parallel, three
Important Projects of Common European Interest (IPCEI) in the biotechnology domain are
currently under design16, reflecting Member States’ interest in coordinated, large-scale
investment approaches.
The European Parliament’s recommendations in its resolution ‘Future of the EU
biotechnology and biomanufacturing sector’ are in line with these priorities, asking to
facilitate “a fast and efficient uptake of biotechnology and biomanufacturing through clear
regulatory frameworks”17. Recommendations include facilitating the uptake of
biotechnology and biomanufacturing; enabling more efficient scale-up and
commercialisation of innovations; streamlining and simplifying the time-to-market for
biotechnology throughout their life-cycles; streamlining the clinical trials framework by
minimising administrative burden and delays; and using regulatory sandboxes. It also
recognises the need for a skilled workforce, dedicated support for SMEs to access funding,
and biosecurity screening standards. The European Parliament has also prepared an own-
initiative report on the ‘Public health aspects of biotechnology and life sciences’18,
where it puts forward similar recommendations. It has called for the Biotech Act to review,
simplify and optimise the regulatory framework for biotechnology in healthcare to foster
innovation, as well as for structured EU support to help excellent biotechnology innovation
districts in the EU grow and ensure that they have sufficient capacity, resources and the
scientific edge to promote new groundbreaking biotechnology discoveries, innovation and
commercialisation.
2.2 Related EU legislation
2.2.1 Existing EU legislation
Health biotechnology products are subject to several EU legislative frameworks, in
particular Regulation (EU) No 536/2014 on clinical trials on medicinal products for
human use 19, Regulation (EC) No 1394/2007 on ATMPs20, Regulation (EU) 2024/1938
on standards of quality and safety for substances of human origin intended for human
13 European Council, Special meeting of the European Council (17 and 18 April 2024) – Conclusions, EUCO 12/24. 14 European Council, The Versailles declaration, 10 and 11 March 2022. 15 Council of the European Union, A call for action on life sciences for the EU’s competitiveness - Council conclusions,
13323/25, approved on 30 September 2025. 16https://competition-policy.ec.europa.eu/state-aid/ipcei/design-support-hub_en#ipcei-candidates-in-the-design-
support-hub. 17 European Parliament, 2025/2008(INI), 10 July 2025. 18 European Parliament: 2025/2087(INI). 19 Regulation (EU) No 536/2014, OJ L 158, 27.5.2014, pp. 1–76. ELI: http://data.europa.eu/eli/reg/2014/536/oj. 20 Regulation (EC) No 1394/2007, OJ L 324, 10.12.2007, pp. 121–137. ELI: http://data.europa.eu/eli/reg/2007/1394/oj.
8
application (SoHO)21, Directive 2010/53/EU on quality and safety of human organs
intended for transplantation22, and Regulation (EU) 2019/6 on veterinary medicinal
products (VMPs)23. These legislative frameworks govern different stages of the product’s
lifecycle, including research, clinical development, authorisation and the placing on the
market of biotechnology products and therapies. Accordingly, the EU biotechnology sector
can only flourish if they are efficient, coherent and innovation-friendly.
For food and feed safety, the placing on the market of biotechnology products must comply
with requirements set out in the General Food Law24 and with specific legal frameworks,
where applicable25. Placing products on the market that contain or consist of genetically
modified organisms (GMOs), other than food and feed, falls within the scope of the
legislation on the deliberate release of GMOs26. These legislative frameworks ensure
high levels of human and animal health, and environmental protection. To foster
biotechnology innovation, it is important to keep these objectives front and centre and
maximise procedural efficiency and speed, because risk-assessment and authorisation
procedures directly affect the time and cost for biotechnology products to reach the market.
The proposed Biotech Act reviews and seeks synergies with other legislation to ensure
coherence with the overall EU regulatory system. It complements the Critical Medicines
Act (CMA)27 in strengthening EU-based biotechnology research and manufacturing. It is
in line with the pharmaceutical strategy for Europe28 and complements the recent
revision of the EU pharmaceutical legislation29. It is also complementary to the
Commission’s proposal to revise the EU medical device legislation30, sharing the same
overall objectives and including common measures such as the single authorisation process
for combined device-medicine clinical studies. It also aims to improve coordination and
consultation between relevant competent authority groups established under other
frameworks, such as medical devices31, medicines, SoHO, health technology assessment32,
etc.
2.2.2 Aligning with the broader priorities of the Commission
As a flagship initiative under the Competitiveness Compass33, the Biotech Act aligns with
the EU’s broader innovation and competitiveness agenda, turning its priorities into actions
in the strategic sector of biotechnology. In particular, the Biotech Act aims to reduce the
administrative burden, improve coordination, simplify rules and streamline procedures, in
line with both the Competitiveness Compass and the Commission’s Communication on
21 Regulation (EU) 2024/1938, OJ L, 2024/1938, 17.7.2024. ELI: http://data.europa.eu/eli/reg/2024/1938/oj. 22 Directive 2010/53/EU, OJ L 207, 6.8.2010, p. 14, ELI: http://data.europa.eu/eli/dir/2010/53/oj. 23 Regulation (EU) 2019/6, OJ L 4, 7.1.2019, pp. 43–167. ELI: http://data.europa.eu/eli/reg/2019/6/oj. 24 Regulation (EC) No 178/2002, OJ L 31, 1.2.2002, pp. 1–24. ELI: http://data.europa.eu/eli/reg/2002/178/oj. 25 E.g. genetically modified food and feed is subject to Regulation (EC) No 1829/2003, OJ L 268, 18.10.2003, pp. 1–23.
ELI: http://data.europa.eu/eli/reg/2003/1829/oj. 26 Directive 2001/18/EC, OJ L 106, 17.4.2001, pp. 1–39. ELI: http://data.europa.eu/eli/dir/2001/18/oj. 27 European Commission website, Critical medicines Act. 28 COM(2020) 761 final. 29 European Commission website, Reform of the EU pharmaceutical legislation. 30 European Commission website, Simpler and more effective rules for medical devices. 31 Regulations (EU) 2017/745, OJ L 117, 5.5.2017, pp. 1–175. ELI: http://data.europa.eu/eli/reg/2017/745/oj and (EU)
2017/746, OJ L 117, 5.5.2017, pp. 176–332. ELI: http://data.europa.eu/eli/reg/2017/746/oj. 32 Regulation (EU) 2021/2282, OJ L 458, 22.12.2021, pp. 1–32. ELI: http://data.europa.eu/eli/reg/2021/2282/oj 33 see footnote 4, page 5.
9
implementation and simplification34. The Biotech Act forms part of the Commission’s
Life Sciences Strategy35 which recognises biotechnology as a strategic cross-sectoral
technology and seeks to strengthen the EU’s biotechnology ecosystem, streamline
regulatory pathways and boost the EU’s competitiveness more broadly in life sciences.
The Biotech Act complements other policy initiatives announced in the Competitiveness
Compass. For example, it aims to improve access to risk-tolerant capital for biotechnology
firms, aligning with the Savings and Investments Union36 and the Start-up and Scale-
up Strategy37, which establishes the Scaleup Europe Fund38. Its biosecurity provisions
reflect the link between competitiveness and security by strengthening safeguards for
biotechnology products of concern. They address the risks identified by the biotechnology
joint risk assessment launched under the EU’s Economic Security Strategy39 and
complement Regulation (EU) 2022/2371 on serious cross-border threats to health40.
The provisions aim at helping to prevent and prepare for such threats and to ensure a
coordinated EU-level response, also for arising public health emergencies (including any
arising from the misuse of emerging biotechnologies). They also complement the Medical
Countermeasures Strategy41for preparing and responding to health threats, including
human-made biosecurity threats.
The Biotech Act reflects the emphasis on talent and contributes to the Union of Skills42. It
aligns with actions under the European Strategy on Research and Technology
Infrastructures43. It aligns with EU funding and investment initiatives that support
biotechnology research, innovation and industrial scale-up. It takes into account EU
financial support available, including cohesion policy programmes, InvestEU, the
European Investment Bank (EIB) Group’s TechEU programme44,45 and the European
Innovation Council. The strategic importance of biotechnology is also acknowledged in
preparations for the next Multiannual Financial Framework (MFF), namely the next
iteration of the Horizon Europe programme (2028-2034).It is acknowledged in the
section on collaborative research activities in the Competitiveness component, as well as
the proposed European Competitiveness Fund, which includes a dedicated ‘Health,
Biotech, Agriculture and Bioeconomy’ policy window.
The Biotech Act is designed to be coherent with related digital policies and pursue digital
transformation objectives. It aims to support secure, data-driven biotechnology
ecosystems and contribute to the EU’s technological sovereignty by promoting greater data
34 COM/2025/47 final. 35 COM(2025) 525 final. 36 COM(2025) 124 final. 37 COM(2025) 270 final. 38 Scaleup Europe Fund - European Innovation Council - European Commission. 39 JOIN(2023) 20 final. 40 Regulation (EU) 2022/2371, OJ L 314, 6.12.2022, pp. 26–63. ELI: http://data.europa.eu/eli/reg/2022/2371/oj. 41 COM/2025/529 final. 42 COM(2025) 90 final. 43 COM(2025) 497 final. 44 European Investment Bank. ”Tech EU. The EU's largest ever financing programme to support Europe's innovators
from idea to IPO and from lab to leadership.” European Investment Bank website accessed 12 March 2026,
https://www.eif.org/flagship-initiatives/techeuhttps://www.eif.org/flagship-initiatives/techeu. 45 European Investment Bank. ”European Tech Champions Initiative. Overview.” European Investment Bank website
accessed 12 March 2026, https://www.eif.org/flagship-initiatives/european-tech-champions-initiative/overview.
10
use and AI integration in the biotechnology sector. Its emphasis on AI is consistent with
the AI in Science Strategy46, the Apply AI strategy47, the AI continent action plan48,
the European AI Act49, the Data Union strategy50, as well as the EU Cybersecurity
framework 51. The Biotech Act is also consistent with the objectives of the European
Health Data Space Regulation (EU) 2025/32752 and of the Data Union Strategy 53, in
particular with regard to data and metadata semantic interoperability and quality
accelerators, data labs, and AI factories. It should also be read in coherence with ongoing
interoperability and standardisation work for common European data spaces under Article
33 of Regulation (EU) 2023/285454, including the European Trusted Data Framework,
insofar as these initiatives are relevant to metadata, discoverability, semantic
interoperability and the cross-border re-use of data.
The Biotech Act is consistent with the Vision for Agriculture and Food55, in particular
because it amends the General Food Law to make the regulatory environment more
supportive of innovation and competitiveness in the agri-food sector. The Biotech Act is
also consistent with the Commission proposal on plants developed by certain new genomic
techniques 56 as it continues to adapt the GMO framework to ensure that innovative
products are regulated proportionately. The Biotech Act is also designed to build synergies
with initiatives such as the recently-adopted Bioeconomy Strategy 57.
Climate change has highlighted the need to prioritise the EU’s resilience, so the Biotech
Act reflects this priority too. It is in line with the Commission’s climate neutrality
objectives set out in the EU Climate Law58 and the EU’s Strategy on Adaptation to
Climate Change59. It also ensures alignment with the ‘do no significant harm’ principle.
Biotechnology products have the potential to support adaptation to climate change,
contribute to health and food security through sustainable biomanufacturing, and protect
biodiversity. They may also replace products potentially more harmful for the environment
and provide benefits for consumers and users.
The Biotech Act will not affect EU legislation on the Registration, Evaluation,
Authorisation and Restriction of Chemicals (REACH)60, Regulation (EU) 2024/1735
on sustainable biogas and biomethane technologies and biotechnology climate and
energy solutions61 or the Directive 2010/63/EU on the protection of animals used for
scientific purposes.
46 COM(2025) 724 final 47 COM(2025) 723 final. 48 COM(2025) 165 final. 49 Regulation (EU) 2024/1689, OJ L, 2024/1689, 12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj. 50 COM(2025) 835 final. 51 Regulation (EU) 2019/881, OJ L 151, 7.6.2019, pp. 15–69. ELI: http://data.europa.eu/eli/reg/2019/881/oj. 52 Regulation (EU) 2025/327, OJ L, 2025/327, 5.3.2025. ELI: http://data.europa.eu/eli/reg/2025/327/oj. 53 COM/2025/835 final. 54 Regulation (EU) 2023/2854, OJ L, 2023/2854, 22.12.2023, ELI: http://data.europa.eu/eli/reg/2023/2854/oj. 55 COM/2025/75 final. 56 COM/2023/411 final. 57 COM/2025/960 final. 58 Regulation (EU) 2021/1119, OJ L 243, 9.7.2021, pp. 1–17. ELI: http://data.europa.eu/eli/reg/2021/1119/oj. 59 COM/2021/82 final. 60 Consolidated text: Regulation (EC) No 1907/2006, ELI: http://data.europa.eu/eli/reg/2006/1907/2025-09-01. 61 Consolidated text: Regulation (EU) 2024/1735, ELI: http://data.europa.eu/eli/reg/2024/1735/2025-08-17.
11
2.3 Background on the sector
For the purposes of this document, and as per the proposed Regulation, biotechnology62
means “the application of science and technology to living organisms, as well as parts,
products and models thereof, to alter living or non-living materials for the production of
knowledge, products and services”. On this bases, health, food and feed are the main scope
of the proposals.
Biotechnology and biomanufacturing are major contributors to the EU’s economy. In
2022, the overall biotechnology sector accounted for EUR 38.1 billion of EU GDP (ca.
1.58% of the European industrial sector), with health biotechnology being the dominant
contributor. Additionally, it contributed to 913,160 jobs, with around 77%63 of those jobs
coming from the health biotechnology sector. The sector in the EU is characterised by a
large base of small and medium-sized enterprises (SMEs) (47%) and micro
enterprises (35%), complemented by a smaller number of large companies (18%)64. The
sector’s dynamism is illustrated by the 5,000 R&D-active biotechnology companies in
the EU65. Furthermore, there were 3,232 unique biotechnology startups founded since
2015 that are still operative in 2025, largely in health66(See Annex 5, Figure 1).
The sector’s strategic importance is underscored by its rapid expansion. Over the last
decade, the EU biotechnology industry has almost doubled to the share of GDP it
generates, growing by around 7% per year on average between 2015 and 202467 (See
Annex 5, Figure 2 for details on the sector GVA comparison).
From a global perspective, the EU has significant strengths in biotechnology, but its
overall competitiveness position is under increasing pressure (see section 3 on problem
definition). The EU is the largest global exporter of biotechnology products,
demonstrating the sector’s strong industrial base and integration into global value chains
(see Annex 5, Figures 3 and 4)68. It is also a leader in biotechnology science, reflected by
a publication record comparable to that of the US and China, with all three regions having
between 20 – 25% of the top 10% most cited publications across biology, biomedical
research and clinical science69. The EU also represents 15% of global patent families in
the biotech field (see Annex 5, Figure 5 for details on the distribution across the EU)70. At
the same time, other major jurisdictions are accelerating policy and investment efforts to
strengthen their biotechnology ecosystems, as shown by recent initiatives in the US at both
62 COM(2025) 1022 final, Article 2 (1). 63 Andreas Haaf and Vera Sale, Measuring the Economic Footprint of the Biotechnology Industry in the European Union,
Research Report March 2025, WiFOR (Prepared for EuropaBio – The European Association for Bioindustries). 64 Landscape analysis study. 65 Landscape analysis study; Biotech R&D firms are firms that perform biotechnology R&D. 66 Landscape analysis study. 67 Landscape analysis study. 68 Landscape analysis study. 69 European Commission: Directorate-General for Research and Innovation, Science, research and innovation
performance of the EU, 2024 – A competitive Europe for a sustainable future, Publications Office of the European Union,
2024, pp. 151-229 https://data.europa.eu/doi/10.2777/965670. https://ec.europa.eu/assets/rtd/srip/2024/ec_rtd_srip-
report-2024-chap-03.pdf. 70 Landscape analysis study.
12
congressional and federal level, which frame biotechnology as a core economic and
national security priority requiring coordinated action to sustain global leadership71.
In terms of projections, biotechnology and gene technologies are some of the most
impactful technology trends expected to influence business models over the next five
years72 (i.e. the second most impactful technology in the medical and healthcare devices
industry, with similar trends expected in agriculture, forestry, and fishing). In terms of job
creation, a strong positive trend has been observed73. In the public consultation on the
European Biotech Act stakeholders agreed that biotechnology and biomanufacturing
products could positively impact the EU’s economy74.
Finally, biotechnology applications have a significant potential to generate positive
societal and environmental outcomes, making this sector a pillar of the EU’s societal
wellbeing in key areas in particular in health and food. This potential is positively
perceived by stakeholders, recognising in the public consultation the contribution of
biotechnology and biomanufacturing products to society (90%) and to the environment
(79%) and considered that biotechnology and biomanufacturing products that reach the
single market are safe and secure (77%)75. Moreover, around a third of respondents
(38%) agreed or strongly agreed that the EU regulatory environment ensures a higher
level of safety and security than in some other countries76.
Health biotechnologyencompasses a wide range of applications, from the development of
innovative medicines and new medical devices addressing unmet medical needs, to
combating epidemics and transforming the treatment of rare diseases. Gene and cell
therapies, for example, hold great promise for treating genetic disorders77 and restoring
biological functions. Although the timeline for developing conventional vaccines is
lengthy, current biotechnology tools allow scientists to develop new vaccines or adapt
existing vaccines much faster than before78.
Agri-food biotechnology innovations support farmers and food producers.
Environmental and industrial biotechnology solutions contribute to the sustainable
transformation of our economy. Genetically modified micro-organisms (GMMs) play a
decisive role in the development of industrial, environmental and agricultural
biotechnology, both as a tool for manufacturing and in products. Products containing
71 U.S. House of Representatives (2025), Congressional Biotechnology Caucus announcement, June 2025; National
Security Commission on Emerging Biotechnology (NSCEB) (2025), Report to Congress, April 2025; The White House
(2022), Executive Order on Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and
Secure American Bioeconomy (establishing the National Biotechnology and Biomanufacturing Initiative). 72 Landscape analysis study. Based on World Economic Forum. (2025, January 7). The Future of Jobs Report 2025.
https://www.weforum.org/publications/the-future-of-jobs-report-2025/digest/. 73 Andreas Haaf and Vera Sale, Measuring the Economic Footprint of the Biotechnology Industry in the European Union,
Research Report March 2025, WiFOR (Prepared for EuropaBio – The European Association for Bioindustries). 74 European Commission, Open Public Consultation on a European Biotech Act, 2025, available at:
https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/14627-Biotech-Act/public-consultation_en. 75 Public consultation, see footnote 74. 76 Public consultation, see footnote 74. 77 Qie B, Tuo J, Chen F, Ding H, Lyu L. Gene therapy for genetic diseases: challenges and future directions. MedComm.
2025;6:e70091. https://doi.org/10.1002/mco2.70091. 78 Aida V, Pliasas VC, Neasham PJ, North JF, McWhorter KL, Glover SR and Kyriakis CS (2021) Novel Vaccine
Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines. Front. Vet. Sci. 8:654289. doi:
10.3389/fvets.2021.654289.
13
GMMs often yield innovative and beneficial product characteristics that other products
cannot achieve or can achieve but with a higher cost or environmental impact. Examples
of products containing GMMs already on the market outside the EU or in development
include novel biofertilisers, biopesticides, and bioremediation products (i.e. to remove
hazardous and toxic substances from the soil or wastewater).
3 PROBLEM DEFINITION
Figure 1. Problem tree
The Commission has refined and clarified the problem tree and intervention logic (see
Section 4.4) from the version presented in the Explanatory Memorandum of the Biotech
Act. These adjustments do not alter the underlying problem definition or policy rationale
but provide a more structured and detailed explanation of the issues and causal pathways.
3.1 Problem: biotech companies struggle to innovate, raise capital, bring
innovations to market, produce and grow in the EU, while maintaining high
level of protection and safety
Although the EU benefits from a sizeable biotechnology sector and strong scientific
capabilities (see section 2.3), it does not meet its full potential for innovation in
biotechnology and biomanufacturing. The EU lags behind other regions when it comes to
translating its world-class science and innovation into commercially viable products
in the EU, and even more so in manufacturing such products at scale. As a result,
biotech companies often end up investing, growing, employing, creating value and
placing their products on markets abroad. This pattern weakens the EU’s ability to
retain value creation and industrial capacity from its research base79.
79 See also Landscape analysis study, forthcoming, for further details on the aspects summarised here.
14
The EU faces a substantial gap in venture capital with limited investment by pension
funds and other institutional investors. Biotech is especially affected by this market failure
due to the particular risk profile of biotech start-ups. Long delays between the initial
innovation and first revenue generation due to lengthy regulatory process, massive upfront
investments needed for CTs, and a high risk of failure of individual projects deter venture
capital investors.
In addition to the fact that the EU accounts for 22% of biotech start-ups, against 49% in
the US, the EU’s scale-up capacity also remains limited. Only a small share of EU
biotech firms reaches significant funding levels (12% of agricultural biotechnology start-
ups, 10% of health biotechnology start-ups, and 8% of industrial biotechnology start-ups
secure over EUR 10 million80). Very few exceed EUR 200 million81. As many companies
struggle to scale in the EU, they increasingly rely on mergers and acquisitions as a common
exit route. Around 40% of acquisitions of EU biotech start-ups are executed by US
acquirers, highlighting how EU biotech innovation is frequently integrated into global
pharmaceutical and life-science value chains instead of growing into large firms in the EU.
AI and data are now foundational to competitiveness in biotechnology, driving rapid
advancements in discovery, development and manufacturing. While 20% of EU
enterprises with 10 or more employees adopted AI by 2025 - up from 13.5% in 2024 -
adoption in EU pharma and biotech manufacturing has surged even further, with large
companies integrating AI at scale and shifting from pilot projects to system-level
transformation82. However, in-house AI development and scaling remain constrained
by data and compute bottlenecks - particularly for SMEs. AI biotech platforms are
inherently capital-intensive, relying on costly model training and large-scale data
generation, and depend on access to high-quality data and advanced compute
infrastructure. As the industry matures, the gap between large pharma industry and smaller
players is widening, underscoring the need for equitable access to technology and robust
regulatory frameworks.
3.2 What are the problem drivers?
The problem is caused by three main related factors. Firstly, the regulatory and
administrative operating environment for biotechnology in the EU is complex which in
turn impacts speed.
Secondly, the EU’s biotechnology ecosystem operates in a fragmented manner, failing to
tap the full scaleof the EU research or testing infrastructure, markets, access to capital or
production capacities, thus limiting companies’ ability to grow and compete
internationally.
Thirdly, technological advances in biotech can result in obsolete frameworks to govern
this fast-moving sector.
80 Landscape analysis study. 81 Landscape analysis study: 12 health biotech firms, 5 industrial biotech firms, one in agricultural biotechnology and
none in marine biotechnology have raised more than EUR 200 million. 82 https://ec.europa.eu/eurostat/web/products-eurostat-news/w/ddn-20251211-2.
15
3.2.1 Driver 1: the complexity of the EU regulatory framework, leading to slow
time-to-market
A first set of challenges relates to the regulatory environment, which stakeholders
consistently perceive as complex, time-consuming and difficult to navigate. In the EU,
60% of companies see regulatory burden as a key obstacle to long-term investment83. This
finding applies to the biotechnology and biomanufacturing sector, as reflected in responses
to the public consultation. Complex regulatory pathways and divergent
implementation of EU legislation were identified as barriers to the expansion of EU
companies, particularly start-ups, spin-offs and other SMEs84. Respondents largely agreed
that EU rules create regulatory barriers, particularly when products move closer to
market entry and formal approval processes85.
In addition, the perception of the EU regulatory environment compared to other countries
showed a limited agreement about the level of predictability of the EU regulatory
environment86. Also, a small number of respondents agreed or strongly agreed that the
EU regulatory environment accelerates access to the market, is less complex and clearer,
or leads to lower compliance costs than in some other countries87.
Such issues linked to the regulatory environment are confirmed across a variety of
biotechnology areas. Detailed descriptions are presented in Annex 5.
With regards to the authorisation of clinical trials, the EU faces growing challenges in
maintaining its competitive edge due to (i) lengthy regulatory timelines (particularly for
the authorisation of multinational trials), and (ii) higher administrative requirements and
costs in the EU/EEA associated with the authorisation and conduct of clinical trials,
compared to other regions. As a result, sponsors88 increasingly favour jurisdictions that
offer faster regulatory timelines, simpler and more streamlined approval processes, and
improved access for the recruitment of patient populations. This contributes to widening
the competitiveness gap. On ATMPs, delays and increased costs are caused by
administrative complexity and overly stringent requirements for GMO-based gene
therapies. This stems from dual regulatory compliance requirements i.e. under the Clinical
Trials Regulation and with the fragmented implementation of GMO legislation by Member
States, further complicated by a blanket requirement for environmental risk assessment
that does not take into account the specificities of low-risk gene therapies.
83 See footnote 10. 84 Public consultation, see footnote 74. 85 Public consultation: Three-quarter of the respondents indicated regulatory barriers in the assessment and market
authorisation (77%). About 70% indicated pre-commercial testing or clinical trials, 68% noted impediments in
commercialising products and 67% in scaling-up production or manufacturing, while 64% signalled regulatory barriers
in product development matters. 86 Public consultation: 21% agreed or strongly agreed and 43% disagreed or strongly disagreed that the EU regulatory
environment is more predictable in comparison with some countries outside of the EU. 87 Public consultation: About 9-10% agreed or strongly agreed and between 64% and 68% disagreed or strongly disagreed
that EU regulatory environment enables products to reach the market faster, is less complex and clearer, or leads to lower
compliance costs in comparison with some countries outside of the EU. 88 Sponsor as defined in the CTR, Article (2) `means an individual, company, institution or organisation which takes
responsibility for the initiation, for the management and for setting up the financing of the clinical trial’.
16
In the EU framework for VMPs, two main challenges are observed: (i) duplicative, not-
fit-for purpose regulatory framework applicable to VMPs that contain or consists of GMOs
and (ii) disproportionate administrative burden in the handling of variations not requiring
assessment.
There is an increasing focus in the EU and globally on the authorisation of biosimilar
medicines, where approval is increasingly based on analytical and functional
characterisation to demonstrate similarity to the reference product89. However, the EU’s
regulatory framework can still lead to the conduct of lengthy and costly multi-country
comparative efficacy studies, even when robust analytical methods may demonstrate
comparability and where a more tailored, risk-proportionate approach could therefore be
justified. In the food area, EU law requires pre-market authorisations/approvals for several
categories of food and feed products and related food chain inputs, the so-called
‘regulated products’90. In those cases, the European Food Safety Authority (EFSA) must
conduct a scientific risk assessment under the applicable sectoral legislation before risk
managers at EU and/or national level decide to grant a pre-market authorisation/approval.
Delays have been observed in both validation and risk assessment phases as also confirmed
by the findings of the ongoing evaluation of the Commission on EFSA’s Performance
covering the period 2017-2024. These have been linked to: (i) dossier deficiencies and
limited effectiveness of pre-submission advice, (ii) procedural consequences linked to non-
compliance with study notification requirements; and (iii) governance constraints relating
to EFSA’s Scientific Committee/Scientific Panels.
As a cross-cutting element of complexity, developers of AI applications in biotechnology
face a rapidly evolving regulatory landscape due to sectoral legislation and AI-specific
requirements, including validation, documentation, explainability and risk-management
obligations. The increasing integration of AI across the biotechnology lifecycle requires
clarity on how existing EU frameworks apply across different development stages. Limited
capacity, especially among SMEs and start-ups, to navigate applicable regulatory
frameworks, further constrain the uptake of AI-enabled solutions in biotechnology. Public
consultation responses91 confirm that stakeholders see a need for greater clarity in the
practical application of AI-related requirements across the biotechnology lifecycle (58%
agreement). Stakeholders report uncertainty regarding how AI-related requirements
interact with existing medicinal product and clinical research frameworks, particularly in
areas such as model validation, documentation and lifecycle monitoring92 and highlight
the importance of guidance. Taken together, these patterns show that the EU biotech
companies’ difficulty to thrive is not a science deficit, but rather a lack of translation and
89 Reflection paper on a tailored clinical approach in biosimilar development: ”Based on the advancements in analytical
technology and the regulatory experience gained, a tailored approach for clinical development of biosimilar candidates
is possible. CES are no longer expected to be required for approval of biosimilars that can be thoroughly characterised
using state-of-the-art analytical methods and have demonstrated similarity in physicochemical and functional properties.
Comparative clinical PK studies are still essential elements in the biosimilar development and can provide supportive
safety and immunogenicity data. This tailored clinical approach is expected to be applicable for the majority of biosimilar
candidates. A regulatory option that, under certain conditions, allows authorisation of biosimilars based on demonstrated
comparability at the analytical level with a limited clinical data package streamlines the development process without
compromising efficacy and safety”. 90 E.g. substances used in food and feed (such as additives, enzymes, flavourings, and nutrient sources), novel foods,
food contact materials, genetically modified organisms, plant protection products etc. 91 Public consultation, see footnote 74. 92 Based on Landscape analysis study.
17
a scale-up deficit shaped by long, complex and capital-intensive pathways from
research to market.
3.2.2 Driver 2: Fragmentation of enabling ecosystems and suboptimal
incentives for private investment constraining the scale-up of EU
biotechnology and biomanufacturing
The EU’s ambition to scale and industrialise biotechnology is currently limited by
challenges in key enabling factors, in particular fragmented thus insufficient access to
finance, development of infrastructures (e.g. clusters), availability of specialised talent and
the deployment of AI and use of data.
First, with regards to access to finance, the EIB estimates the sector investment gap at
EUR 40 billion annually.93 US biopharma start-ups received around nine times more late-
stage funding than EU biopharma start-ups, with around EUR 219 billion of venture capital
focused on health biotechnology invested in the US compared to EUR 25 billion in the
EU, between 2015 and June 2025.94 Even larger gaps in access to late-stage capital have
pushed biotech companies to find funding abroad, notably in the US. Between 2015 and
2021, 67 EU biotech companies going for a public listing have targeted the US NASDAQ
rather than the European stock markets, with 60% of them only listing on NASDAQ
without any listing on an EU exchange.95
Similarly, in earlier stages of capital, although the EU biotech venture ecosystem has
expanded materially in recent years, it remains a second-tier venture capital market
in global biotechnology. Annual investment increased from EUR 0.84 billion (2015) to a
peak of EUR 5.47 billion (2021) during a rapid expansion phase, before partially
normalising to EUR 3.89 billion (2025) (around 29% below the 2021 peak) consistent with
post-pandemic slower deployment (see Annex 5, Figure 7). As a comparison, the US
operates at a different order of magnitude across the cycle (peaking at around EUR 45
billion in 2021)96. In the public consultation97, stakeholders reported difficult access to
private and some public investment instruments in the EU in equity, debt, and
commercialisation support (for more information, see synopsis report in Annex 2). In their
answers, companies also noted that public funding mechanisms, while supportive for early
R&D stages are also insufficiently tailored to the needs of biotech scale-ups. Specific
challenges of start-ups and SMEs were also underlined from both representatives of
business associations and public authorities. Respondents from academic and research
also pointed the fragmentation in funding rules and tax incentives across Member States,
limited availability of large venture capital funds, and a lack of banking expertise in
biotechnology. Non-Governmental Organisations (NGOs) also reported challenges
related to fragmented and insufficient public funding and a lack of significant grant-making
institutions. This shows a need to reinforce de-risking financial instruments and budgetary
guarantees in the EU.
93 The EIB Group uses industry data of EUR 69.7 billion investment for the US vs EUR 26.5 billion in the EU in 2021,
resulting in a gap of ca. EUR 40 billion. 94 Landscape analysis study. 95 Kempen & Co analysis, Liquidity slides for dual listed companies, 2021. 96 Landscape analysis study. 97 Public consultation, see footnote 74.
18
Biological VMPs benefit from two protection mechanisms: regulatory data protection
(Articles 39-40 of Regulation 2019/6) and intellectual property (IP) protection (patents and
SPCs) under Regulation (EC) No 469/200998. Nevertheless, the veterinary pharmaceutical
market presents specific challenges for innovation, such as fragmented species-specific
markets, low price levels, and a small overall market size. In this context, there is a need
for enhanced incentives to support the development of biotechnological VMPs to diagnose,
treat or prevent zoonotic diseases.
Second, with regards to biotechnology clusters, their outreach in the EU remains
fragmented, with significant disparities in scope and resources. Biotechnology clusters
foster collaboration across entities at different stages of the biotechnology value chain and
across biotech sectors. They enable the transformation and evolution of, for example,
university spin-offs into companies ready for the commercialisation of their product99.
While clusters compete for investment, talent and projects, there is substantial scope for
collaboration, exchange of best practices allowing the realisation of scale effects that
cannot be achieved at regional level. The few clusters that have an EU-wide relevance
provide networking and coordination support, yet the landscape remains fragmented,
risking duplication of efforts and limiting impacts. As a result, EU biotechnology clusters
cannot fully leverage their collective potential to compete with clusters in other regions,
and the EU as a whole underperforms in the field of biotechnology.
Respondents to the public consultation100 identified five main barriers to clusters:
insufficient financial support (58%), insufficient public support (54%), incapacity to
reach a critical mass of stakeholders (46%), insufficient collaboration among existing
clusters (46%) and insufficient start-up incubators or business support infrastructure
(45%). Other barriers were identified, with representatives of companies pointing to the
limited involvement of end-users (patients, healthcare providers) and public authorities
underlining the insufficient support for product development. In the area of ATMPs, the
lack of innovation hubs that combine emerging ATMP specialisation with infrastructure
capabilities, regulatory expertise and collaboration among clinical centres, research bodies,
industrial participants and commercialisation services, obstructs development in the EU.
Third, productivity gains, acceleration of innovation and efficiency improvements
associated with the use of AI and big data remain below their potential in the EU’s
biotechnology ecosystem101. Fragmented, heterogeneous, and high-dimensional data is
one of the challenges, as datasets generated in healthcare or research contexts are often not
readily usable for the training, testing and validation of AI systems without significant
curation and standardisation efforts. For health data, ongoing EU initiatives, such as the
European Health Data Space, are expected in the coming years to facilitate access and
cross-border use; at the same time ensuring that such data are sufficiently curated,
annotated and interoperable to support AI development remains a key challenge. Data
access challenges affect non-health data relevant to biotech, such as datasets on chemical
98 Regulation (EC) No 469/2009 OJ L 152, pp. 1–10 ELI: http://data.europa.eu/eli/reg/2009/469/oj. 99 Landscape analysis study. 100 Public consultation, see footnote 74. 101 Submissions to the Call for Evidence and Public Consultation, as well as stakeholder workshop insights, as analysed
in the study supporting the rapid assessment of policy scenarios to strengthen innovation and competitiveness in the field
of biotechnology in the EU (Rapid Assessment Scenario Study forthcoming); Landscape analysis study - Annex 2 – Case
Studies (forthcoming).
19
reactions used in drug discovery and biomanufacturing processes102. Public consultation103
results confirm these challenges. Companies, business associations and academic or
research institutions report the highest levels of difficulty. Around two-thirds of companies
and research institutions rely on data sourced from outside the EU/EEA, primarily due to
higher reliability and quality of available datasets, as well as clearer legal frameworks for
data access and lower perceived access costs. This suggests that improving the quality,
usability and interoperability of datasets available within the EU could significantly
strengthen the competitiveness of the European biotechnology ecosystem.
Fourth, the EU’s ambition to scale and industrialise biotechnology also depends on the
availability of specialised talent. While the EU maintains a strong scientific base,
stakeholder evidence points to persistent gaps in the workforce segments critical for scale-
up and deployment.
In the EU’s biotechnology sector, stakeholders have identified gaps in the workforce
segments needed for scale-up, progression to commercial scale and manufacturing104.
There is a significant shortage in the total number of higher education and vocational
education and training graduates entering the biotechnology sector105, with shortages
particularly observed in the following competences: biomanufacturing and bioprocessing,
regulatory and compliance (e.g. ATMPs and pharmacovigilance), and digital skills106 (e.g.
bioinformatics, AI-enabled processes, data governance). Furthermore, for some profiles,
stakeholder consultations indicated that technical skills would need to be complemented
by additional competencies107. This challenge can be explained by several factors108, such
as constrained hands-on training capacity due to the scarcity and high cost of specialised
facilities, the fragmentation of qualification systems across Member States, limiting skills
portability and talent mobility and the lack of entrepreneurial skills in the EU (less
than 50% of EU students have access to entrepreneurial education in secondary and higher
education109). Barriers to the upskilling of workers are also relevant.
3.2.3 Driver 3: Rapid technological developments & regulatory adaptation lag
EU biotechnology companies also face barriers to manufacture, place products on the
market and grow due to EU regulatory frameworks not always keeping up with rapid
technological advances. This perception was confirmed in stakeholder consultations, as
regulatory frameworks that insufficiently account for the innovative and rapidly
developing nature of the biotechnology sector were also identified as a barrier to the
expansion of EU companies110.
102 Landscape analysis study - Annex 2 – Case Studies. 103 Public consultation, see footnote 74. 104 Landscape analysis study. 105 Landscape analysis study. 106 In 2023, only 55.6% of the EU adult population had at least basic digital skills. Digital Decade DESI visualisation
tool DESI 2025, DESI indicators, Indicator: At least basic digital skills. https://digital-decade-desi.digital-
strategy.ec.europa.eu/datasets/desi/charts/desi-indicators.107 Landscape analysis study based on Biotechnology Jobs. (2025, February 12). Building the Ultimate Biotech Skill Set:
Technical and Soft Skills Employers Want in 2025. 108 Landscape analysis study. 109 EU Startup and Scaleup Strategy, based on European Commission’s Entrepreneurship 2020 Action Plan. 110 Public consultation, see footnote 74.
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One major reason brought forward by stakeholders and some Member States is the
complex, not innovation friendly and in part ill-fitting EU legislation on GMOs, in
particular as regards GMMs. The EU’s legal framework for GMOs (including GMMs111)
originates from the 1990s and was primarily tailored to genetically modified plants. The
framework as it currently stands is less suitable to handle GMMs given the biological
differences compared to plants and the variety of micro-organisms and their
applications112.In a recent scientific opinion, EFSA concluded that the potential risk of a
microbial product relates to the changes introduced in the micro-organism itself regardless
of the method used to introduce them, supporting a more holistic approach to the
assessment of micro-organisms based on the characteristics of the final product.113 It
further concluded that for certain GMMs less assessment requirements would be sufficient
to ensure safety. In this respect, considering the risks of typical GMMs and derived
products and the variety of risk profiles, the current GMO regulatory procedures are
considered by many stakeholders and some Member States as disproportionate, overly
rigid and time consuming, rendering the EU unattractive for investing and bringing such
GMMs to the market as products. In addition, the particularly short development cycles of
GMMs, with one product frequently being based on a previous product, mean that a quick,
efficient authorisation path is very important.
There is also a regulatory gap between the existing EU legal framework on the quality
and safety of human organs intended for transplantation and current medical practice on
organ preservations, leading to diverging interpretations across Member States and
hence legal uncertainty. The current EU framework was designed for preservation rather
than processing and does not provide a clear, harmonised approach for these activities. It
does not include a particular framework for authorising processing operations, nor a
mechanism for benefit-risk assessment of these interventions, and no provisions for
oversight of transplantation centres that seek to apply a specific processing technique.
Furthermore, the current framework does not contain a mechanism for coordination
between the organ transplant competent authority and the competent authorities operating
under other legislative frameworks (e.g. on medical devices, medicinal products, or on
SoHO). In 2024, although over 32,000 organ transplants were performed across the EU,
the gap between the supply of transplantable organs and clinical demand remained, with
over 52,000 patients registered on transplant waiting lists across the EU (as of 31
December 2024)114.
Similarly, in the ATMP area, outdated definitions and technological lag in the regulatory
framework are leading to discrepancies between the legal framework (classification
111 In line with the definitions provided in Directive 2001/18/EC, GMO means an organism, except for human beings, in
which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination.
In line with the definition provided in Directive 2009/41/EC (OJ L 125, 21.5.2009, p. 75-97. ELI:
http://data.europa.eu/eli/dir/2009/41/oj), a GMM means a microorganism in which the genetic material has been altered
in a way that does not occur naturally by mating and/or natural recombination. 112 Regulatory Framework Study (forthcoming, see Annex 1). 113 EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), Mullins, E., Bresson, J.-L., Dewhurst, I. C.,
Epstein, M. M., Firbank, L. G., Guerche, P., Hejatko, J., Moreno, F. J., Naegeli, H., Nogué, F., Rostoks, N., Sánchez
Serrano, J. J., Savoini, G., Veromann, E., Veronesi, F., Cocconcelli, P. S., Glandorf, D., Herman, L., Jimenez Saiz, R.,
Ruiz Garcia, L., Aguilera Entrena, J., Schoonjans, R., Kagkli, D. M., Dalmay, T. (2024). New developments in
biotechnology applied to microorganisms. EFSA Journal, 22(7), e8895. https://doi.org/10.2903/j.efsa.2024.8895. 114 SANTE-SoHO/D2 - European Commission. (2026). Introducing “organ processing” into directive 2010/53/EU
[Unpublished slideshow]. See Annex 5 for more details.
21
uncertainty) and progressing science, hampering market access for these products (e.g.
affecting in vivo tissue generation, acellular therapies, and bio-synthetic hybrids).
The rapid technological advances characterising the biotechnology sector challenge
existing regulatory frameworks. While these frameworks ensure high safety standards,
they offer limited regulatory flexibility in a context of rapid technological advances. As a
result, innovative biotechnology applications may struggle to progress efficiently from
development to market deployment across these sectors when regulatory frameworks are
not sufficiently adapted to emerging technologies. In the health area, existing regulatory
frameworks are not fully adapted or adaptable to complex and hybrid emerging health
biotechnology products, leading to barriers such as a lack of legal certainty on products
classification and evaluation. In the VMPs sector, regulatory uncertainty also represents
a serious hurdle to the marketing or use of novel technologies, methods or products. In
the food chain sector, EU legislation requires pre-market authorisations for several
categories of food, feed and related food chain inputs but also provide for limited
regulatory flexibility.
Biotechnologies are critical for the Union's defence and security. And while rapid
advances in biotechnology over the last decades have brought considerable benefits for
healthcare, research and the economy, such advances also make biological agents more
widely accessible, increasing risk of their misuse. For example, the price of synthetic
nucleic acids (such as DNA or RNA) has decreased more than 100-fold over the past 20
years115, making it increasingly feasible to synthesise potentially dangerous genomic
sequences, such as the DNA or RNA of viruses, at limited cost.
While some commercial nucleic acid synthesis providers screen orders to identify
potentially dangerous sequences and verify the legitimacy of their customers, there are
currently no EU-level rules on this. National rules diverge116, failing to offer a level playing
field, fragmenting the single market and undermining the EU’s prevention and biosecurity
efforts.117 In stakeholder consultations, several industry actors, including SMEs, have
therefore called for harmonised EU biosecurity rules.
Finally, the potential of data and AI remains largely untapped in the EU. Despite new
regulatory frameworks (European Open Science Cloud, AI regulatory sandboxes
mandated in the AI Act, EuroHPC/AI factories/gigafactories), some challenges remain. AI
biotech platforms are inherently capital-intensive, relying on costly model training and
large-scale data generation, and depend on access to high-quality data and advanced
computing infrastructure, which remain comparatively limited in the EU118. Furthermore,
the scaling of AI119 in biotechnology requires sophisticated experimentation environments
capable of integrating high-performance computing, biological laboratories and advanced
115 DNA Synthesis and Sequencing Costs and Productivity for 2025, Rob Carlson, 2025
https://www.synthesis.cc/synthesis/2025/5/dna-synthesis-and-sequencing-costs-and-productivity-for-2025. 116 https://ibbis.bio/policy-spotlight-french-leadership-defining-and-regulating-genetic-fragments/ 117 See IBBIS mapping of explicit and implicit rules on NA synthesis screening across countries:
https://globalsynthesismap.bio/policy?country=FRA. 118 Landscape analysis study - Annex 2 – Case Studies. 119 COM(2025) 30 final based on Eurostat data: EU survey on ICT usage and e-commerce in enterprises (January 2025).
22
data infrastructures.120 However, the availability of such integrated environments remains
limited in the EU. Stakeholders underlined the importance of collaborative environments
that facilitate the responsible testing, validation and deployment of AI-enabled
biotechnology solutions while ensuring compliance with EU legislation121.
3.3 Consequences
3.3.1 EU is facing a major competitiveness gap in biotech, despite being a
leader in science
The problem presented in section 3.1. results in a gap between the EU and the US in
terms of entrepreneurial dynamism. The EU only represents 22% of the global biotech
start-up activity (i.e. start-ups founded since 2015) while the US accounts for nearly half
(49%) of them (see Annex 5, Figure 6)122.
This competitiveness gap is observed across the health and agri-food biotechnology
sectors:
The EU is becoming less attractive to sponsors for conducting clinical trials in global
comparison, affecting the economy, public health, and skill capacity building. The number
of clinical trials conducted worldwide has increased substantially over the past decade,
rising from approximately 13,000 in 2013 to 22,000 in 2023. Over the same period, the
geographical distribution of clinical trials has shifted markedly. While the EEA’s share of
global clinical trials declined from 18% in 2013 to 9% in 2023, China’s share increased
from less than 10% to nearly 30%123. A similar trend is observed in cell and gene therapy
trials: between 2013 and 2023, Europe’s global share steadily declined, whereas China
experienced a dramatic rise over the same period, emerging as the leading region.124 This
growth also reflects a different portfolio structure, with China placing stronger emphasis
on early-stage and post-marketing development, particularly mononational Phase I and
Part IV trials, compared to the EEA’s stronger focus on multinational Phase II and Phase
III trials125. Despite the strong growth in global clinical trial activity, the level of activity
in terms of number of clinical trials submissions in the EU remained broadly stable
between 2013 and 2025126. Consequently, the EU did not capture a proportional share of
this growth, leading to a widening competitiveness gap relative to other regions with
120 Breakthroughs in in silico, AI-driven and digital-twin approaches can transform biomedical research, diagnostics, and
personalised medicine. In silico modelling leverages computer simulations increasingly integrated with AI and can
potentially replace some traditional animal testing and clinical trials. AI-driven analytics can enable precise,
individualised therapies and accelerating tissue repair (Healing the Future - Horizon scanning for emerging technologies
and breakthrough innovations in the field of cell and gene therapies
https://publications.jrc.ec.europa.eu/repository/handle/JRC141934). 121 See Annex 2, Synopsis report for more details. 122 Landscape analysis study. 123 EFPIA report: assessing-the-clinical-trial-ecosystem-in-europe.pdf. 124 EFPIA report: assessing-the-clinical-trial-ecosystem-in-europe.pdf. 125 Fast-track landscape analyses to assess the regulatory clinical trial eco-system in the EU/EEA and in other relevant
regions (forthcoming) 126 The annual number of clinical trial applications submitted in the EU, as well as the shares of mononational,
commercially sponsored, and pediatric trials, exhibited little variation over this period, aside from temporary changes
during the COVID-19 pandemic. Between 2013 and 2025, the annual average number of clinical trials application is
2,895 with a standard deviation of 303.
23
potential implications for economic performance and timely access by patients to
innovative treatments127.
Figure 2. Clinical trial activity in the EU128
Note: Figure 2 describes the trend in the submission of clinical trial applications in the
EU between 2013 and 2025. The bars illustrate the total number of applications per year,
while the remaining lines show the share of the applications for mononational,
commercial, paediatric and rare-disease trials.
The gap in clinical trial activity between the EU and other markets, particularly China, is
also reflected in changes in annual pharmaceutical R&D expenditure of which
approximately 60% can be on average allocated to clinical trials129. Using overall
pharmaceutical R&D expenditure as a proxy, China experienced a significantly larger
increase in R&D expenditure compared to the other regions130.
127 The decline in the EEA share of global clinical trials stems from multiple, interlinked factors, with enhanced
regulatory complexity being one of the driving factors. 128 Calculations done by the European Commission based on data from EudraCT and CTIS. 129 EFPIA report (2024) The Pharmaceutical Industry in Figures. Key Data. According to the report, 48.4% of the
pharmaceutical R&D expenditures are allocated to Phase I to III trials and additional 11.5 % to Phase IV trials. The data
is based on a survey with Members of PhRMA and collected in 2022. See further information here: PhRMA_membership
survey_single page_70523_es_digital.pdf. 130 China experienced an increase by a factor of 8.55 compared to a factor of 1.68 increase in Europe.
24
Figure 3.Pharmaceutical R&D expenditure in selected regions in 2010 and 2022131.
Note: Figure 3 illustrates annual pharmaceutical R&D expenditures in 2010 and 2022 for
China, Europe, Japan and the USA.
These trends show that Europe’s position in global pharmaceutical R&D, including its
clinical trial activity, is facing increasing challenges in maintaining its competitive edge132.
The relative decline in clinical trial activity is likely to come along with adverse effects on
the public healthcare systems, the economy and the development of skills, and capacity
within the Union. Although estimating the economic impact of clinical trial activity is
inherently complex and dependent on multiple model assumptions, recent studies based on
national and EU-wide data indicate that each euro invested in clinical trials generates
between EUR 1.60 and 2.50 of added value for the economy, along positive effects on
employment133. A recent report estimates that commercial trials, which account for 53.1%
of the trials authorised in the Union134, create annually about EUR 35.7 billion in gross
value added to the economy in the EEA and support the creation of over 165,000 jobs135.
In addition, clinical trial activities are estimated to reduce costs for national healthcare
systems. For example, two studies conducted in Italy indicate a leverage effect of avoided
costs between 2.2 and 3.5; that is, for every euro invested in clinical trials or disbursed by
131 EFPIA report (2024) The Pharmaceutical Industry in Figures. Key Data. 132 Tan et al. (2024) Current landscape of innovative drug development and regulatory support in China | Signal
Transduction and Targeted Therapy. 133 Walter et al. (2020) Economic impact of industry-sponsored clinical trials of pharmaceutical products in Austria -
PubMed; Battelle Technology Partnership Practice (2015) Biopharmaceutical Industry-Sponsored Clinical Trials: Impact
on State Economies (battelle-2015-study.pdf); Fast-track landscape analyses to assess the regulatory clinical trial eco-
system in the EEU/EEA and in other relevant regions (forthcoming). 134See EU clinical trials during the 3-year CTR transition period
135EFPIA report (2026) the-economic-impact-of-industry-clinical-trials-across-europe.pdf.
25
sponsoring companies to health facilities, the Italian national health system saved more
than two euros136. Finally, clinical trial activities also affect the health of European citizens.
For example, patients participating in clinical trials can access innovative medicines up to
5 to 10 years before commercial launch in the EU.137
The innovation and competitiveness gap in the EU’s ATMP sector is also becoming
increasingly evident. Although Europe currently holds a 22.1% share of the global gene
therapy market (2025) and the sector is projected to grow at a compound annual growth
rate of 14,6% (2026–2033), the region risks falling behind North America and the
Asia-Pacific region. Forecasts indicate that North America will generate the highest
revenue in the sector by 2033, while the Asia-Pacific market is expected to reach USD
4,193.1 million in the same year138. This trend, also highlighted in the Draghi Report139,
underscores the EU‘s struggle to strengthen its R&D capabilities and address the
innovation and competitiveness gap in the region’s ATMP market. Slow progress in
ATMP development threatens the EU's position in the global healthcare and biotechnology
sectors, as innovators may increasingly choose to operate in jurisdictions with more agile
regulatory frameworks.
When it comes to biosimilars, the EU’s biomanufacturing capacity can be further utilised.
The EU has significant untapped potential in biosimilar manufacturing. The EU retains the
largest cumulative authorisations of biosimilars (151 products vs. 72 in the US and 66 in
Canada) and leads the global market in revenue valued at approximately EUR 25.6 billion
in 2024, representing around 6% of the total pharmaceutical industry's contribution to
GDP. Sales grew at 15% annually between 2020 and 2024 across five core therapeutic
areas, and the sector supports around 81,000 jobs in Europe: 16,000 direct (20%), with the
remainder split between indirect roles such as clinical research (30%) and induced
employment (50%). The sector depends on a highly skilled workforce, with 40% of direct
employees (~7,000) in technical roles and 70% holding university degrees.140However,
manufacturing activity is increasingly migrating to Asia, particularly South Korea and
India141. While the EU remains a key innovation hub — supplying over 75% of active
ingredients for innovative biologics — it must develop more dedicated and cost-efficient
manufacturing infrastructure to keep pace with international competitors.142
Similarly, challenges to bring novel health biotechnology products to the market have
been observed143, and are generally expected to increase given the increasing complexity
and hybrid nature of novel products. These challenges further weaken the EU’s position in
136 Cicchetti et al. (2020) Valorization of clinical trials from the Italian National Health Service perspective: definition
and first application of a model to estimate avoided costs - PubMed; Polignano et al. (2022) Economic impact of industry-
sponsored clinical trials in inflammatory bowel diseases: Results from the national institute of gastroenterology “Saverio
de Bellis” - PMC. 137 EFPIA report (2024) Assessing the clinical trial ecosystem in Europe: Final report, p.37 138 https://www.grandviewresearch.com/horizon/outlook/gene-editing-market/europe. 139 See footnote 11, page 6. 140 Medicines for Europe, European Biosimilar Medicines Sector: Delivering Impact Beyond Health – Economic,
Scientific & Strategic Contribution, Biotech Act Factsheet Series, March 2026, Pillar 1-2-3-4-FOOTPRINT-SPC-
Biotech-Act-facsheets-ppt.cdr. 141 Cohen, H. P., Turner, M., McCabe, D., & Woollett, G. R. (2023). Future evolution of biosimilar development by
application of current science and available evidence: The developer’s perspective. BioDrugs, 37(5), 583–593. 142 BioPlan Associates (2024). Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production 143 Maxwell, A. (2025, August 20). Why EU innovators face growing barriers with EU combination product regulation.
Medtech Insight.
26
the global innovation race, delaying the availability of these products to patients across the
EU.
Regulatory uncertainty also has practical implications for cross-border exchange of
processed organs and for the scaling of machine perfusion technologies, contributing to
uneven uptake and fragmentation within the EU144, and eventually reducing the potential
for optimal matching of organs and recipients. Over the last three years, the cross-border
exchange rate of allocated organs fluctuated between 20-23%145.
In the field of GMMs, recent evidence shows that there is significant activity in the
development of innovative GMMs by both private and public/academic entities. However,
the majority of the identified GMMs originates from the US or China, while only a limited
number were developed within the EU146. Notably, there are currently no products on
the single market that contain or consist of GMMs, except for medicinal products which
are, however, not authorised under the GMO legal framework but under the EU framework
on pharmaceuticals. This is particularly affecting the competitiveness of SMEs in the
GMM field, since they are typically among the most innovative companies in the
biotechnology sector but may lack the regulatory expertise and financial resources to
navigate complex legal frameworks that may not adequately fit their innovative products.
At the same time, this lack of products on the markets, or prospect to bring products
efficiently to the market, is discouraging investments in R&D, thus negatively
impacting the wider science community in the EU. EU economic sectors, foremost the
agricultural, industrial and environmental sectors, are negatively impacted as they cannot
easily make use of novel tools available in third countries that make operations more
efficient.
As a consequence of the issues outlined under drivers 1 and 3, a competitiveness gap is
also observable for biotechnology products in the food chain (food and feed products),
including substances (e.g. additives, enzymes etc), and other food chain inputs (e.g. food
contact materials).
Finally, as AI continues to expand across the biotechnology lifecycle in the health and food
sectors, the bottlenecks innovators face when attempting to develop, validate and deploy
AI-enabled biotechnology solutions in the EU slow the transition from scientific discovery
to real-world deployment. As a result, the Union risks failing to fully capture the
productivity gains, efficiency improvements and innovation opportunities associated with
the large-scale use of AI in biotechnology. This under-utilisation of AI may therefore
translate into a growing competitiveness gap, as other jurisdictions more effectively
integrate AI into biotechnology research, development and production across multiple
biotech sectors.
144 See Annex 5 for more details. 145 See Rapid Assessment Scenario Study 146 Ballester, A.R., Roqué, M., Ricci-Cabello, I., Rotger, A., Malih, N. 2023. Horizon scanning on microorganisms and
their products obtained by new developments in biotechnology. EFSA supporting publication 2023:EN-8503, 65 pp.
doi:10.2903/sp.efsa.2023.EN-8503.
27
3.3.2 Biotech’s potential to help address major societal challenges is
underexploited
Despite its innovation and growth potential, and expected benefits for patients and society
at large, the potential of biotechnology remains largely underexploited in the EU, across
the different biotechnology areas.
In the health sector, ATMPs – such as gene therapies – offer a transformative potential for
treating a broad spectrum of diseases, from rare genetic disorders to common chronic
conditions. Despite this promise and the innovative potential in the EU, patient access in
the EU remains severely limited.
Organ transplantation also increasingly involves ex-vivo organ processing, such as
machine perfusion to assess and recondition donor organs prior to transplantation. These
techniques can expand the pool of transplantable organs, improve matching of organs and
recipients, improve clinical outcomes and strengthen health-system resilience. However,
there is limited cross-border exchange and slow EU-wide uptake of innovative processing
technologies147.
In the VMP sector, the potential of biotechnology to improve animal health and strengthen
food supply chain resilience remains underdeveloped. Favourable regulatory conditions
for the use of biotechnology in animal health will not only benefit the biotech
pharmaceutical industry, but also farmers, animal health, the food supply chain and human
health (zoonotic diseases). When disease spreads in food-producing animals, the impact
on farmers can be dire and food security can be put at risk. Vaccination is a powerful tool
to prevent and control animal diseases and contributes to reducing the use of
antimicrobials. As a large share of emerging infectious diseases in humans has a zoonotic
origin, preventing animal diseases also has positive effects on human health. Novel
biotechnology tools enable the development of safer and more effective vaccines, as well
as the distinction of vaccinated animals from those infected, and allow vaccines to be
developed or adapted much faster than with conventional approaches, which is critical to
prevent and control animal diseases.
When it comes to innovative GMMs148, their non-deployment in the EU market, in
addition to the loss of competitiveness opportunities outlined under the driver 3, result in
an unfulfilled potential for GMMs to contribute to other social and environmental
objectives. For example, GMMs can now be used as or in biofertilisers, biostimulants,
biopesticides, biocides, bioremediation, wastewater treatment, biomining and bioleaching,
offering benefits in the wider agri-food, industrial, marine and environmental sectors. As
GMM-based products that would be more efficient or environmentally friendly than the
alternatives are not being used, EU society and consumers are negatively impacted as they
are being deprived of innovative solutions to important challenges linked to climate
change, environmental pollution and food and feed security.
Moreover, in the food and feed sector, the potential of biotechnology remains
underexploited and experimentation in real conditions (e.g. real-world food production and
147 See Rapid Assessment Scenario Study. 148 See Annex 7, Section 5.2. for examples.
28
processing environments) is constrained. Biotechnology tools can support more efficient
production processes across the food chain. These technologies can improve the safety and
quality of food products, for example by reducing pathogens and toxins and enhancing
nutritional properties149. Enzymes and biocatalysts can reduce environmental impacts by
replacing chemical processes and improving process efficiency150. As regulatory drivers
constrain the deployment of innovations in such areas, the single market as well as the
contribution of biotechnology to food safety and security, resource efficiency,
environmental sustainability and the EU’s strategic autonomy, are not fully realised.
Furthermore, the rapid advancement of technology, including AI, alongside increased
data collection and use are cross-cutting enablers with huge potential across the different
areas of the biotech sector, yet to be fully utilised. AI and advanced data use act as key
enablers of biotechnology innovation across health and agri-food applications. AI-driven
tools support target identification, molecular design, optimisation of biological processes,
CT design and manufacturing efficiency, while in the agri-food sector they enable
advanced fermentation, strain optimisation and resource-efficient production. These
applications can accelerate innovation cycles, reduce development costs and strengthen
resilience in areas such as medical countermeasures, disease detection and sustainable food
systems. However, the full potential of AI-enabled biotechnology remains underexploited
in the EU. The effective deployment of these technologies requires clear lifecycle
guidance, as well as access to integrated environments combining experimental and
computational capabilities for testing and validation, and high-quality, well-curated
datasets that allow AI systems to be trained and deployed reliably. The absence of these
enabling conditions limits the EU’s ability to fully harness biotechnology to address major
societal challenges and strengthen its strategic autonomy in health and food systems.
Regarding the application of biotechnology to defence and security, the primary challenges
identified by stakeholders in the public consultation were the risks to strategic autonomy
in biomanufacturing and availability of countermeasures (50%), cybersecurity risks (e.g.
biotechnology infrastructure, AI tools used) (45%), vulnerabilities in the resilience of
biotechnology supply chains (44%), and threats related to biosecurity and biosafety
including misuse of biotechnology (40%). Finally, opportunities in biosecurity were also
particularly underlined in the public consultation151: the development of new innovative
medical countermeasures (45%), detection of biological threats (45%), as well as increased
food security (43%).
3.3.3 Potential for misuse of biotechnology poses growing biosecurity risks
In addition, the rapid progress in and increasing accessibility of biotech innovations also
increase the likelihood and impact of biosecurity incidents, as certain applications of
149 Siddiqui SA, Erol Z, Rugji J, Taşçı F, Kahraman HA, Toppi V, Musa L, Di Giacinto G, Bahmid NA, Mehdizadeh M,
Castro-Muñoz R. An overview of fermentation in the food industry - looking back from a new perspective. Bioresour
Bioprocess. 2023 Nov 28;10(1):85. doi: 10.1186/s40643-023-00702-y. PMID: 38647968; PMCID: PMC10991178. 150 Palanisamy Vasudhevan, Zhang Ruoyu, Hui Ma, Subhav Singh, Deekshant Varshney, Shengyan Pu,
Biocatalytic enzymes in food packaging, biomedical, and biotechnological applications: A comprehensive review,
International Journal of Biological Macromolecules, https://doi.org/10.1016/j.ijbiomac.2025.140069. 151 Public consultation, see footnote 74.
29
technologies and products may have the potential for misuse, posing threats to public
health and safety.
The exponential decrease in the cost of synthesising DNA and RNA has made the physical
material needed to create biological agents, including dangerous pathogens, increasingly
accessible. Studies by RAND Europe152 and CLTR153, two independent non-profits,
estimate the current annual probability of a large-scale biological attack using synthetic
nucleic acid at 1%, and accidents from their use at 1.5%, with expected economic harm to
the EU of almost EUR 20 trillion for a large-scale event.
The EU joint biotechnology risk assessment carried out under the EU’s Economic Security
Strategy argues that the likelihood and impact of such incidents is further amplified by
advancements in AI and computational tools in biological applications, which can lower
the technical barriers to the design, optimisation and misuse application of biological
agents.
These advances could significantly expand the pool of individuals capable of conducting
technical tasks with biotechnology products that could be misused for malicious purposes,
such as synthesising dangerous pathogens. Modelling published in 2025 suggests that,
under a set of assumptions about near-term AI capabilities, could increase the annual
probability of an epidemic from biological misuse by a non-state actor roughly sixfold,
from 0.15% to 1%154. This reflects broader concerns that AI tools developed for beneficial
applications in life sciences may also present dual-use risks if misapplied.155
3.4 What is the baseline from which measures are assessed?
The baseline trajectory through 2038156 is expected to show a widening of the
competitiveness gap between the EU and its main competitors. This is driven by the
compounding interaction of the identified drivers. Regulatory complexity deters
investment; market fragmentation, in particular capital scarcity, constrained innovation;
and the expanding pipeline of frontier technologies amplifies administrative burdens and
regulatory barriers, within an ecosystem that is not positioned to absorb them. The thematic
sections that follow detail these dynamics across five interconnected dimensions157.
Regulatory landscape and administrative burdens
Under the baseline, biotechnology developers will be confronted with an EU regulatory
landscape characterised by three mutually reinforcing deficiencies: the proliferation of
overlapping and partially incompatible regulatory frameworks, the persistent national
152 Zakaria, S. et al. (2026). Cost–benefit analysis for synthetic nucleic acid screening in the European Union. Santa
Monica, CA: RAND Corporation, 2026. https://www.rand.org/pubs/research_reports/RRA4805-1.html. 153 Fady, P. et al. (2025). Cost-Benefit Analysis of Synthetic Nucleic Acid Screening for the UK. The Centre for Long-
Term Resilience. doi.org/10.71172/kyey-h0ya, p.18. 154 Righetti, 2025 (https://www.governance.ai/research-paper/dual-use-ai-capabilities-and-the-risk-of-bioterrorism-
converting-capability-evaluations-to-risk-assessments). 155 Urbina, F., Lentzos, F., Invernizzi, C. et al. Dual use of artificial-intelligence-powered drug discovery. Nat Mach
Intell 4, 189–191 (2022). https://doi.org/10.1038/s42256-022-00465-9 156 Some interventions have been assessed over a different baseline. See Annex 4 for more information on the timeline
and baseline. 157 See Rapid Assessment Scenario Study for more information including on assumptions used.
30
heterogeneity in the implementation of procedures, and the absence of structured pathways
for innovations that do not fit neatly within existing legislative frameworks.
The most pervasive source of regulatory burden is procedural duplication across
intersecting frameworks. Under the baseline, developers of GMO-containing ATMPs
will continue to incur in up to 50 additional days in CT authorisation timelines beyond
conventional medicines, with further extensions for substantial modifications. For VMPs,
GMO-containing products will continue to face approval timelines two to three times
longer than non-GMO equivalents despite the fact that no GMO-containing VMP has ever
received a negative opinion on the basis of its GMO component, triggering an 'innovation
tax', estimated at EUR 269,000-840,000 per year in FTE burden. Such a burden is set to
compound, reaching EUR 403,000-1,119,000 by 2040, as the pipeline is projected to
encompass approximately 100 GMO-containing VMPs in various stages of development
at any point through 2040. In addition, CT applications subject to dual-track requirements
will increase from 8-15 to 12-20 per year and annual GMO-containing marketing
authorisation applications are expected to rise from the current 3-5 to approximately 5-8
per year by 2040. Meanwhile, the administrative burden from variations not requiring
assessment (VNRA) is projected to scale proportionally with the expanding marketing
authorisation base: the number of active veterinary Marketing Authorisations is expected
to grow to approximately 55,000-60,000 by 2040, with annual VNRA volumes scaling
accordingly. The aggregate annual VNRA fee burden is projected to grow in proportion.
In the biosimilar domain, the disproportionality of certain regulatory requirements
will also persist. Between 2012 and 2022, 100% of all 36 monoclonal antibody and fusion
protein marketing authorisation applications included a Phase III comparative efficacy
study, yet in no case did the clinical data determine the regulatory decision. Thus, the most
costly component of biosimilar development (EUR 19-26 million per study, representing
20-50% of total expenditure and adding 12-24 months to timelines), is likely to function
as a de facto procedural requirement rather than a scientifically decisive evidentiary
input. Indeed, there is increasing experience with tailored clinical efficacy and safety
approaches for biosimilars at the Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency (EMA). Based on EMA data, in 2025 more
than 70% of adopted scientific advice procedures for biosimilars incorporated a tailored
clinical efficacy and safety approach. In addition, among all biosimilar marketing
authorisation applications submitted last year under Article 10(4) of Directive 2001/83/EC,
approximately 8% proposed a tailored clinical efficacy and safety approach. While there
is a gradual shift toward more tailored approaches by EMA158, a slow uptake of these
changes risks putting Europe at a competitive disadvantage compared with other regions
that operate under more agile frameworks.
The EU’s regulatory framework will be marked by persistent fragmentation in the
implementation of clinical trials across Member States. The EU’s share of global clinical
trial initiations has halved, declining from 18% in 2013 to 9% in 2023. Without
fundamental reforms, particularly in streamlining authorisation procedures and simplifying
regulatory requirements, the EU risks a further decline in its clinical research
158 EMA, 2026 (https://www.ema.europa.eu/en/documents/other/reflection-paper-tailored-clinical-approach-biosimilar-
development_en.pdf-0).
31
competitiveness. Meanwhile, the more centralised markets of the US and China continue
to outperform the EU, further consolidating their dominance. China’s share of global
clinical trials, for instance, has surged from 8% to 29% over the last decade, while the US
maintains its strong position. Current projections suggest that the EU’s growth in
clinical trial activity will remain sluggish compared to these faster-expanding regions,
risking a further relative decline in its standing as a key hub for clinical research.
However, this does not imply a decline in the absolute number of EEA trials as the Clinical
Trial Regulation (fully applicable to all clinical trials since January 2025) is expected to
generate a ‘learning effect’ as sponsors and national authorities gain experience with the
Clinical Trials Information System (CTIS). This will lead to moderate improvements in
median authorisation times and greater procedural stability over 2025-2030. Between 2025
and 2030, AI tools are projected to achieve 60-70% routine adoption, e.g. in trial design
and conduct, and digital trial components are expected to become increasingly integrated
into standard protocol design. However, national heterogeneity in ethics review,
contracting, insurance, and site activation will persist. Clinical trial activity concentrates
further in a few Member States, large firms widen their advantage over SMEs, and clinical
translation of the EU's strong scientific output stagnates. SMEs and academic innovators
increasingly rely on partnerships with larger companies, slowing EU-based evidence
generation and eroding Europe's leadership in emerging technologies. In absolute terms,
the number of EU clinical trials has remained broadly stable over the past decade at
approximately ~2,400–2,500 trials per year, with no structural upward trend expected
under the baseline159.
For SoHO, 50 national competent authorities will continue to oversee blood and tissue
establishments (currently at 1,400 and 3,258, respectively), with recurring administrative
costs to businesses estimated at EUR 4.14 million over ten years under the incoming risk-
based authorisation model. While Regulation (EU) 2024/1938 introduces a more unified
SoHO Preparation Authorisation (SPA) model, regulatory uncertainty will persist for
novel, complex, and cross-framework SoHO innovations. Meanwhile, permitting for
strategic health biotechnology projects is projected to remain fragmented and slow under
the lack of EU-level priority-project recognition or fast-track governance mechanisms.
These burdens are further aggravated by the absence of structured innovation support.
In the food and feed domain, over 90% of application dossiers assessed by EFSA in 2021-
2023 contained administrative or scientific errors leading to the suspension of the legal
deadlines for risk assessment (the so-called stop-the-clock procedure) resulting in delays
in the overall authorisation process, which are likely to persist under the baseline scenario.
For AI-enabled methodologies, EMA's Qualification Procedure for Novel Methodologies
costs EUR 89,000 per request, takes 160-250 days, and produces confidential, non-
reusable outcomes, meaning each new entrant faces identical navigation costs with no
cumulative learning. The scale of regulatory demand on the EMA is itself accelerating. It
received 635 scientific advice requests in 2024, a figure that grew 16% year-on-year in the
first half of 2024 alone, this mismatch between the pace of technological innovation and
159 Rapid Assessment Scenarios study, forthcoming
32
the capacity of existing regulatory infrastructure to absorb it is expected to grow under the
dynamic baseline.
Competitiveness and investment attractiveness
The capital base underpinning the biotech sector shows a pronounced investment gap.
As presented under section 3.2.2, EU biotech venture capital stood at approximately EUR
4.8 billion across 243 rounds in 2024, roughly six times below US levels. The average EU
late-stage financing round (approximately USD 49 million) is around half of the US
equivalent, and the EIB estimates the structural annual investment gap at approximately
EUR 40 billion. This capital shortfall is not merely quantitative; it is structurally embedded
(see sections 3.1 and 3.2.2). Despite the existence of significant public financial
engagement, this gap shows no prospect of autonomous closure under the baseline.
The deep dependence on external capital, which weakens strategic autonomy over the
direction and location of value creation, is expected to grow. The median time gap between
funding rounds has increased from 17 to 20 months, with higher incidence of down rounds
at Series C stage (growth stage), signalling that investor confidence in the EU’s late-stage
pipeline remains fragile. Without sufficient public investment to bridge the late-stage
capital gap and catalyse private co-investment, the structural investment deficit is projected
to persist through 2038.
The exit asymmetry is equally stark and is expected to continue. Only 138 EU biotech
healthcare companies completed an IPO compared to 451 in the US (over the period 2013-
2023). In 2024, no European biotech raised more than EUR 58.1 million in IPO proceeds.
The commercial viability of biotechnology investments is further conditioned by the
existing IP protection framework. Health biotech innovators reinvest a large portion of
their revenue back into R&D. By ensuring a viable commercial timeframe, the SPC is one
of the measures that enables innovative companies to re-invest their revenue in additional
research and development, improving patient access to innovative therapies, and
generating broader economic benefits. However, intellectual property, including SPC, is
just one part of innovators’ investment decisions. Without policy change, innovators’
decisions on investment location continue to reflect expected lifecycle revenues under
protection, alongside market size, access conditions, regulatory predictability and
operational considerations. In the immediate baseline period to 2030, effective protection
durations are expected to remain broadly stable, with the revised general pharmaceutical
legislation not expected to produce observable effects within this period. In the longer term
to 2038, effective regulatory protection outcomes are expected to become more
heterogeneous across medical products, reflecting the continued shift towards biologics
and advanced therapies with longer and more variable development timelines. The EU
share of earliest biotech patent filings is projected to remain stable at low single-digit levels
(around 3-5%), while global biotech patenting activity continues to expand.
This capital deficit compounds a broader erosion of the EU's global competitive position
across several dimensions that collectively determine where biotechnology innovation is
located, financed, and commercialised. The global clinical trials market is expected to
grow at approximately 5.7% annually, compared with approximately 4.8% in Europe,
indicating a gradual but persistent loss of relative competitiveness for the EU as a location
for clinical research in the absence of improvements to the clinical trial ecosystem. In
33
biosimilars, the EU’s first-mover advantage has declined. While 71% of biosimilars are
approved in the EU before the US, there has been a rising share of biosimilars that get
approved in the US first, or only received US approval, which indicates the growth of the
US market. At the same time, the European biosimilar medicines sector makes a significant
contribution to European gross domestic product, contributing EUR 25.6 billion in 2024
and representing approximately 6% of the total pharmaceutical industry contribution.160
The number of the CHMP of EMA scientific opinions on biosimilars has itself increased
markedly, from 8 in 2023 to 25 in 2024 and 40 in 2025, reflecting a growing pipeline that
amplifies the stakes of regulatory competitiveness. Cumulative biosimilar
authorisations are also projected to rise from 151 in 2025 to 250-350 by 2030 and 450-
650 by 2038, with new reference product classes entering biosimilar development
expanding from approximately 27 to 35-45 by 2030 and 55-75 by 2038. However, 79% of
the approximately 100 biologics losing exclusivity by 2032 have no biosimilars in
development, representing a ‘biosimilar void’ valued at approximately EUR 122 billion in
global forecast sales at loss of exclusivity. This indicates that a substantial proportion of
the projected market value will not materialise without a reduction in per-product
development costs.
The competitive erosion is reinforced by the fact that no single-entry point exists for
health biotechnology innovators to navigate the regulatory and funding landscape.
Investor-innovator connections will likely remain ad hoc and geographically
concentrated in a few leading ecosystems. Disparities in innovation capacity and
ecosystem maturity across Member States are expected to persist, with Central and Eastern
European Member States lacking the cluster foundations that sustain leading ecosystems
in some Member States. These fragmentation effects are compounding: without a
coordinated ecosystem support mechanism, the navigational burden for SMEs is expected
to increase further as new regulatory frameworks layer additional complexity and the
pipeline of frontier biotechnologies expands. Meanwhile, other major jurisdictions are
actively accelerating policy and investment efforts to strengthen their biotechnology
ecosystems161, suggesting that, in the absence of intervention, the EU’s relative
competitive position is likely to continue to deteriorate over time.
Innovation and research
The baseline reveals a structural and persistent translation deficit at the centre of the
EU biotechnology innovation system. Under the baseline, the EU innovation system’s
upstream scientific base will remain internationally competitive, while the downstream
deficiency in infrastructure for converting that science into products, trials, and market-
ready applications will grow.
One of the key innovation-side deficits is the absence of structured pathways for
technologies that do not fit neatly within existing regulatory categories. Developers of
novel health biotechnology products will continue to operate simultaneously across two
160 Medicines For Europe factsheet: Pillar 1-2-3-4-FOOTPRINT-SPC-Biotech-Act-facsheets-ppt.cdr. 161 See for example US initiatives which frame biotechnology as a core economic and national security priority requiring
coordinated action to sustain global leadership: U.S. House of Representatives. (2025). Congressional Biotechnology
Caucus announcement, June 2025; National Security Commission on Emerging Biotechnology (NSCEB). (2025).
Report to Congress, April 2025.
34
to three regulatory frameworks, with no structured cross-framework anticipatory dialogue
in place. Forecast analyses project that up to 30% of such products could be stalled by
regulatory uncertainty between 2030 and 2038, even as the volume of novel, hybrid health
technologies is expected to increase by approximately 20% between 2025 and 2030. In
ATMPs, as the current definitions fail to capture emerging modalities, this is projected to
widen progressively as in vivo genome editing and cell-device combinations advance over
2030-2038. Without clarification of tissue-engineered product and related definitions,
more products are likely to require case-by-case classification by EMA and bespoke
scientific advice from 2030 onwards, increasing regulatory workload and amplifying
unpredictability for the SME dominated ATMP developer base (over 60% of ATMP
developers are SMEs). For GMMs used outside food and feed, the EU's process-based
framework has resulted in no market authorisations for deliberate release under Directive
2001/18/EC, effectively excluding the EU from the specific parts of global markets in
biofertilisation, biocontrol, bioremediation, and bioleaching using GMMs. Taking into
account GM and conventional products, these markets have a combined value exceeding
EUR 29 billion and growth rates of 9-14% annually. These global GMM-relevant markets
are projected to grow significantly under the baseline: biofertilisers from EUR 1.18 billion
(2024) to EUR 2.42 billion by 2030; microbial biocontrol from EUR 5.55 billion (2025)
to EUR 14.2 billion by 2032; bioremediation from EUR 14.1 billion (2024) to EUR 32.9
billion by 2033; and bioleaching from EUR 8.66 billion (2024) to EUR 18.2 billion by
2033. Under the baseline scenario, the EU's partial exclusion from these markets persists
indefinitely, and European companies developing GMM products will increasingly serve
non-EU markets or relocate R&D and commercialisation activities to jurisdictions such as
the US, where a product-based regulatory approach has already enabled commercial
deployment. Similarly, under the baseline, organ processing practices would be driven
by local institutional arrangements rather than a coherent EU standard. Under the baseline,
the share of EU transplantation programmes with active processing capability is projected
to rise from an estimated 27% to approximately 35-38% by 2030 and 42-48% by 2035,
before plateauing at approximately 48-55% by 2040. This plateau reflects the absence of
an EU-level framework.
Regulatory sandboxes, which could provide structured testing environments for such
innovations, are either absent or fragmented and underused across the relevant domains.
No EU-level sandbox exists for veterinary innovation. Similarly, the EU food acquis does
not provide for the operation of regulatory sandboxes; any existing food and feed
sandboxes remain weakly connected to food law and unevenly available across Member
States. The incoming SoHO risk-based authorisation model does not incorporate a sandbox
mechanism under the baseline. In the SoHO domain specifically, expert estimates indicate
that sandbox-eligible cases represent 5-10% of overall SoHO activities, translating to 90-
250 eligible cases per annum; based on comparable sandbox acceptance rates observed in
other regulatory domains (7-16%), between 6 and 40 sandboxes could be established per
annum, illustrating both the latent demand for structured innovation pathways and the scale
of innovation potential that remains unexploited under the current baseline.
The innovation investment consequences of these constraints are illustrated in the
biosimilars domain. Under the current framework, the sector’s contribution to European
CTs for biosimilar medicine candidates amounts to EUR 4.9 billion. Under the baseline,
the near-term biosimilar MAA volume is projected at 25-45 per year, with the lower bound
reflecting persistence of the biosimilar void and the upper bound assuming gradual
35
spontaneous adaptation; the medium-term range rises to 35-55 per year. However, without
formalised regulatory streamlining, per-product development costs remain at EUR 90-280
million over 6-9 years, with the CES representing the single largest component (EUR 19-
26 million per product, approximately 57% of total clinical development costs being
clinical), constraining the commercial viability of biosimilar development for lower-value
reference biologics
Public health and safety
Under the baseline, while the EU maintains among the highest regulatory safety standards
globally, aspects of the current regulatory architecture - particularly complexity,
fragmentation and procedural duplication - can constrain the pace at which patients,
consumers, and citizens benefit from biotechnological innovation. This tension will
continue to manifest across the following interconnected dimensions:
First, delayed and uneven patient access to biotechnology-derived treatments will
continue. The most consequential public health gap in the baseline concerns the widening
distance between the availability of advanced biotechnology therapies and the speed at
which EU patients can access them. The EU’s share of global clinical trial initiations has
halved from 18% in 2013 to 9% in 2023, with trial authorisation taking 100-120 days
compared to approximately 30-60 days in the United States and China. For ATMPs, the
current provisions of the CTR will continue to add up to 50 additional assessment days. In
addition, foresight analyses projecting that up to 30% of novel health biotechnology
products could be stalled by 2030-2038.
• Under the baseline, annual healthcare system savings from biosimilars are
projected to rise from approximately EUR 13 billion in 2024 to EUR 16-22 billion
per year by 2030 and EUR 22-35 billion per year by 2035-2038, but the upper
bounds of these projections are constrained by the biosimilar void, meaning that
the full savings potential depends on whether per-product development costs can
be reduced sufficiently to make lower-value biologics commercially viable targets
for biosimilar competition.
• In organ transplantation, the absence of a harmonised EU-level authorisation
framework for organ processing means that advanced ex-vivo machine perfusion
techniques diffuse unevenly, with no systematic mechanism for capturing
processing-related safety data. Under the baseline, with a transplant growth
trajectory of 1.54% CAGR annual transplant volumes are projected to rise to
approximately 35,350 by 2030, 38,200 by 2035, and 41,200 by 2040. However,
demand-side growth will outpace supply-side gains: waiting lists are expected to
grow at approximately 0.5% per year to approximately 55,000-56,500 active
patients by 2035 and 57,000-58,000 by 2040, meaning waiting-list mortality is
projected to decline only marginally from approximately 3,366 deaths per year to
approximately 3,100-3,200 by 2035 and 2,900-3,100 by 2040. The EU's dialysis-
dependent population is projected to rise from approximately 310,000 to 330,000-
340,000 by 2035 and 350,000-365,000 by 2040, with demand-side growth driven
by population ageing, rising diabetes and hypertension prevalence, and widening
dialysis initiation criteria outpacing the supply-side gains from transplant volume
increases. The organ discard rate is projected to decline from approximately 12-
13% to 10–11% by 2035 and 9-10.5% by 2040 under organic, centre-led adoption,
36
but these gains will be concentrated in liver and lung organs in a small number of
advanced Member States and will remain below the levels achievable with wider
processing adoption.
Second, in the food and feed area, although safety standards will be maintained,
innovation will remain constrained. EFSA's rigorous risk assessment framework
continues to underpin world-leading food safety standards. In the area of nutrition,
biotechnology can enhance nutritional properties. However, the current legislation faces
limitations in addressing the scientific aspects given the limited mandate of EFSA to
deliver scientific advice in relation to nutrition matters. This may become even more
relevant in the future considering the expected increase in the prevalence of diet-related
health issues in the coming years. Similarly,regarding the One Health risks from
veterinary regulatory design, the dual-track system for GMO-containing VMPs
generates an 'innovation tax' of 2-3 times longer approval periods without commensurate
safety benefit: no GMO-containing VMP has ever received a negative opinion on its GMO
component. The absence of a legal 'firewall' clarifying that animals treated with GMO-
derived VMPs are not themselves classified as GMOs will continue to create commercial
risk. It could deter farmer uptake of next-generation biotech vaccines, sustaining reliance
on antimicrobials and impeding progress towards the EU's target of halving antimicrobial
sales by 2030.
Third, the baseline presents a structural gap in the EU's capacity to detect and
prevent biological threats. Wastewater-based surveillance beyond SARS-CoV-2 and
influenza remains limited (only 11 Member States monitor antimicrobial resistance, six
monitor emerging pathogens), with no agnostic detection layer for novel or engineered
threats. Concurrently, synthetic nucleic acid screening remains voluntary and fragmented:
only 69 of over 700 global custom synthesis providers are confirmed to screen. The RAND
analysis estimates that the expected monetised annual loss due to biological threats across
all event categories amounts to approximately EUR 184 billion for large-scale events (1%
annual probability; EUR 19.6 trillion expected harm), supplemented by small-scale events
(22% annual probability, EUR 72 million expected harm), agricultural events (4%
probability, EUR 75.5 billion expected harm), and non-transmissible events (5–25%
probability, EUR 121 million expected harm). For attacks specifically, the probability that
they involve synthetic nucleic acid ordered from providers ranges from 30% to 70%
depending on event type, while for accidents the corresponding probability ranges from
6% to 17%.
The biosecurity and biodefence baselines expose a separate category of public health
vulnerability. In the domain of synthetic nucleic acid synthesis, the EU market (estimated
at approximately EUR 850 million in 2024, representing approximately 0.2% of the
European biotechnology market162) is expected to grow at an annual rate of 10-20%, but
competitiveness is shaped by the absence of a level playing field: companies that
voluntarily screen their customers face competitive disadvantages against providers that
do not screen, and as DNA synthesis prices continue to decline, the cost of screening
represents an increasing share of the final order price. Without a change in biosecurity
162 Based on Grandview Research estimates of the DNA synthesis market
https://www.grandviewresearch.com/horizon/outlook/dna-synthesis-market/europe and the Biotech market more
generally https://www.grandviewresearch.com/horizon/outlook/biotechnology-market/europe
37
policy, the annual probability of a large-scale biological attack or accident is estimated at
1%, with expected economic harm to the EU of a large-scale event of ca. EUR 20 trillion.
The risk is set to increase further as synthetic DNA and RNA continues to become cheaper
and more widely available. Meanwhile, pathogen surveillance remains reliant on clinical
surveillance networks and targeted wastewater-based monitoring for known agents, with
no systematic agnostic detection capacity for novel or engineered biological threats.
Environment and sustainability
The baseline reveals a tensionat the intersection of the EU's biotechnology regulatory
architecture and its environmental policy ambitions: while these frameworks uphold high
environmental and safety standards, certain features – such elements of their process
design and limited risk differentiation - can delay or constrain the deployment of
biotechnology applications with significant potential to advance the environmental and
sustainability objectives. This tension manifests most acutely across three intervention
areas.
The most consequential environmental baseline deficit concerns GMMs. No GMM has
been authorised for deliberate environmental release under Directive 2001/18/EC. As
innovations utilising genetic engineering are not brought to the market in the EU, the EU
is therefore entirely absent from this important segment of rapidly growing global markets
in biofertilisation (EUR 1.18 billion in 2024, growing at 12.8% CAGR), microbial
biocontrol (EUR 5.55 billion in 2025, 14.3% CAGR), bioremediation (EUR 14 billion in
2024, 9.9% CAGR), and bioleaching (EUR 8.65 billion in 2024, 8.9% CAGR), sectors
with a combined global market exceeding EUR 29 billion and projected growth rates of 9-
14% annually. In contrast, a product-based regulatory approach in the US has already
enabled commercial deployment. Under the baseline scenario, this partial market exclusion
persists indefinitely, and European companies developing GMM products will
increasingly serve non-EU markets or relocate, while the environmental benefits of GMM-
based microbial solutions for resource-efficient agriculture, pollution remediation, and
sustainable extraction remain unrealised within the EU.
In the veterinary domain, the dual-track regulatory system for GMO-containing VMPs
results in a regulatory friction that can slow the uptake of next-generation biotech vaccines
in food-producing species, with potential ramifications for animal health, farmers and food
security.
The food chain sandbox landscape is characterised by fragmentation and lack of
coherence with Union law; only a few Member States operate sandbox-type mechanisms,
none anchored in a harmonised EU framework under the General Food Law. As a result,
findings and best practices cannot be systematically integrated into the evolution of the
existing legal framework. This limits structured, pre-market testing of sustainable food
production technologies, leaving innovation potential for the food system's environmental
transition partly unexploited.
38
4 APPROACH TO THE BIOTECH ACT
4.1 Objectives of the proposal
4.1.1 General objectives
The general objective of the proposed Regulation and Directive is threefold: (i) to improve
the functioning of the internal market by establishing a framework to strengthen the
competitiveness of the health biotechnology sector, from research to production, (ii) to
create the conditions for the development and timely placing on the single market, of
biotechnology innovations, products and services, (iii) while safeguarding high standards
for the protection of human health, animal health, patients and consumers, food and feed
safety, the environment, and biosecurity.
4.1.2 Specific objectives
This general objective translates into the following specific objectives, as presented in the
proposed Regulation and Directive: (i) strengthen the biotechnology sector and reinforce
the EU’s research, development and production capabilities; (ii) support funding of,
investments in, and access to capital for, biotechnology companies and projects; (iii)
improve the EU manufacturing capacity of, and expertise in biosimilars, including through
international cooperation; (iv) facilitate the application of AI into the EU’s biotechnology
and health technology manufacturing ecosystems and frameworks, in line with the AI
Act163; (v) ensure a legislative framework that encourages innovation and takes account of
technological and scientific developments and progress; (vi) prevent the misuse of
biotechnologies and strengthen biodefence capabilities and (vii) enable the effectiveness
of the above specific objectives through a legislative framework conducive to the use of
biotechnology innovations.
4.2 Choice of the legal instruments and legal basis
4.2.1 Choice of the legal instruments
A Regulation is the most suitable for measures requiring uniform application across the
EU, such as those concerning recognition and support for heath biotechnology strategic
projects and high impact health biotechnology strategic projects, and measures to boost
EU biodefence and biosecurity and prevent biotechnology misuse. The Regulation is also
justified to amend existing EU regulations in the area of health and food law. Its directly
applicable nature ensures consistent implementation without national transposition. A
Directive is the appropriate instrument for amendments to Directive 2001/18/EC and
Directive 2010/53/EU.
4.2.2 Legal basis
The appropriate legal bases are therefore as follows:
- Article 114 TFEU is the basis for the adoption of measures that increase
harmonisation and remove fragmentation and, therefore, seek to create a level playing
163 Regulation (EU) 2024/1689, OJ L, 2024/1689, 12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj.
39
field within, and fully exploit the scale of the single market for biotechnology products
and biomanufacturing. The proposal also seeks to achieve the objective of a high level
of health and safety protection as per Article 114(3).
– Article 168(4) TFEU is the basis for the adoption of certain measures that contribute
to achieve a high level of human health protection, i.e. standards of quality and safety
of organs and SoHO, blood and blood derivatives; measures in the veterinary and
phytosanitary fields, and standards of quality and safety for medicinal products and
devices for medical use.
- Article 173(3) TFEU is the basis for measures in support of Member States’ action for
the competitiveness of the EU’s industry, in particular the provisions regarding the EU
Health Biotechnology Investment Pilot.
4.3 Subsidiarity: necessity for EU action and EU added value
Under the subsidiarity principle, the Union may act in areas of non-exclusive competence
only where the objectives of the proposed action cannot be sufficiently achieved by the
Member States.
4.3.1 Necessity for EU action
The objectives of the proposed Biotech Act cannot be achieved by Member States acting
alone, as the identified drivers are cross-border and systemic, affecting the functioning of
the single market and the global competitiveness of EU companies. These challenges may
differ in intensity across Member States and regions, but their nature is Union-wide.
Access to finance is fragmented and EU biotechnology companies lack the capacity to
access private finance at a competitive scale, including at later stages of development.
European biotechnology clusters are dispersed and lack continental scale to compete
globally. The development and deployment of AI in biotechnology remains limited, also
due to the insufficient cross-border availability and sharing of relevant data.
While several Member States have taken action, these bottlenecks persist and
improvements would remain slow and uneven. National measures alone cannot provide
the scale, coordination and speed required, although in certain areas (e.g. access to finance,
development of regional innovation ecosystems and clusters, and support to research
infrastructures, etc.), Member States may still take complementary action alongside Union
measures.
Important regulatory barriers stem from existing EU legislation, such as lack of legal
clarity, complex or outdated rules, disproportionate administrative burden and additional
national requirements. As these drivers originate in Union law, they cannot be effectively
addressed by Member States acting individually. Union action is therefore necessary to
facilitate innovation, enhance legal clarity and improve market access.
4.3.2 EU added value
The proposed actions focus on areas where there is a demonstrable value added in acting
at EU-level due to the scale, speed and scope of the efforts needed.
40
A harmonised but simplified EU regulatory framework, supported by strengthened
collaboration in selected policy areas (access to capital, AI and data) is expected to ensure
patients, users and citizens across the EU can benefit from biotechnology innovations.
A large market with a streamlined, fit-for-purpose regulatory framework ensures a level
playing field and reduces compliance costs in the single market, thereby supporting
biotechnology market uptake. Coordinated EU action in the field of biotechnologies will
generate economies of scale, reduce duplication of efforts, increase legal certainty for cross
border entrepreneurs, and unlock investments, infrastructures and skills development that
Member States alone could not achieve. Union-level coordinated action is expected to
yield higher benefits than fragmented national measures.
Regulatory streamlining and clarification measures will reduce administrative burden,
accelerate time-to-market and improve the functioning of the internal market, also by
addressing the observed diverging national interpretations and additional requirements.
The proposed Biotech Act also seeks to reinforce the EU’s strategic autonomy in a critical
technological area while fostering adequate biosecurity safeguards and biodefence
capabilities.
4.4 Intervention logic of the proposal
Figure 4.164
Figure 5 illustrates the overall architecture of the Biotech Act, highlighting the two
complementary pillars of regulatory streamlining and facilitation to accelerate time-to-
market and industrial enablers to strengthen the EU biotechnology ecosystem.
164 Revised version of the intervention logic (see first version in COM(2025) 1022 finalhttps://eur-lex.europa.eu/legal-
content/EN/TXT/?uri=CELEX:52025PC1022).
41
Figure 5. Biotech Act architecture
5 DESCRIPTION OF THE PROPOSED MEASURES AND ANALYSIS OF THEIR MAIN IMPACTS
The measures described below are outlined in the proposal for a Regulation and the
proposal for a Directive165. They are presented in 17 packages of interventions, which fall
under two categories: eight interventions related to regulatory streamlining and facilitation
measures aiming at regulatory simplification (addressing drivers 1 and 3), and nine
interventions linked to industrial enablers (addressing drivers 2 and 3). They are presented
in more detail in Annex 7.
The summary assessment of measures166 below includes tables capturing the key impacts
across standard impact categories167. Where sufficiently robust evidence is available, key
impacts are quantified and expressed using numerical estimates. Where quantification is
not feasible, impacts are assessed qualitatively using a standardised rating scale168,
indicating the direction and relative magnitude of effects. For certain measures, tables are
not used where the nature of the impacts or the available metrics are better suited to
alternative forms of presentation (e.g. narrative analysis or visual representations), to
ensure a more accurate and meaningful representation of the expected effects.
5.1 Interventions for regulatory simplification: measures and expected impacts
Chapter IX of the proposed Regulation and Directive include amendments to EU
legislative frameworks in the areas of health, food and feed safety as well as GMMs, which
aim to simplify existing procedures and accelerate time-to-market. These amendments are
165 Annex 6 presents a mapping of the policy measures and the corresponding articles in the proposed Regulation and
proposed Directive respectively. 166 The assessment of impacts draws on the supporting studies presented in Annex 1. 167 COB = conduct of business; Admin = administrative costs on businesses, including SMEs; CTI = competitiveness,
trade and investment flows; Int Mar = functioning of the internal market and competition; I&R = innovation and research;
PA = public authorities; H&S = public health and safety. 168 ++ significant positive; + moderate positive; 0/+ marginal positive; 0 negligible/neutral; 0/– marginal negative; –
moderate negative, -- significant negative.
42
needed to ensure the effectiveness of the self-standing measures on industrial enablers laid
down in the proposed Regulation.
5.1.1 Intervention n°1: Regulatory facilitation for novel health biotechnology
products
The Regulation proposal sets out the provision of regulatory assistance or support by
the EU Health Biotechnology Support Network to developers. This targeted, early-stage
support will be particularly valuable for SMEs, which often lack extensive in-house
regulatory expertise. The support will consist of facilitating information on, and access to,
applicable legislative frameworks, including procedures for seeking guidance on
regulatory status, rules applicable to products combining different technologies or
regulatory frameworks, and access to regulatory sandboxes.
Further, the Regulation proposal establishes a publicly available regulatory status
repository containing decisions, opinions and scientific recommendations regarding the
regulatory status of health innovations across the EU. This repository aims to ensure
transparency and consistency in regulatory determinations. It also aims to support advisory
bodies mandated under sectoral legislation to determine the regulatory status of health
products promptly and without undue delay, as well as to assist developers in shaping their
regulatory strategy based on existing practice.
In addition, the proposal establishes a foresight panel for emerging health innovation
comprising scientific and regulatory experts from the SoHO Coordination Board (‘SCB’),
the Medical Devices Coordination Group (MDCG), the Coordination group on Health
Technology Assessment, the EMA, and the competent authorities of the Member States.
The panel would provide early recommendations to the Commission, relevant EU
agencies, and Member State competent authorities.
Moreover, a cross-framework coordination for regulatory sandboxes in the health
area aims to allow for dialogue and information exchange among authorities operating
regulatory sandboxes for health biotechnology products across different Union legislative
frameworks (MDR, IVDR, SoHO Regulation, Pharmaceutical Regulation). Member State
and Union-level authorities operating sandboxes under different frameworks would have
to consult with each other and with the foresight panel regarding sandbox design and
implementation, ensuring the potential integration of cross-framework aspects, which is
needed given the increasing cross-cuting nature of health product innovations. The
Commission, the EMA, the MDCG and the SCB facilitate cross-framework exchanges
through the above-mentioned foresight panel, focusing on knowledge sharing (regulatory
approaches, technological challenges, best practices) and regulatory learning (identifying
implications for future legislative adaptations).
Finally, the proposal includes the possibility for regulatory sandboxes for novel health
biotechnology products. These Commission-led sandboxes are designed for products
that, due to their very early stage of development cannot be accommodated in existing
sectoral sandboxes for novel products and whose development is hindered by challenges
in identifying suitable regulatory procedures. They offer a framework – in the form of a
subsidiary sandbox – for continued engagement with regulators and eventually a
recommendation on the applicable existing framework for marketing authorisation. Upon
43
substantiated request from developers, the Commission would assess applications and
establish such a regulatory sandboxes through implementing act. These sandboxes would
operate under time-limited sandbox plans specifying objectives, scope, participants, risk
mitigation measures, and supervision arrangements. When assessing the applications for
the establishment of such a subsidiary regulatory sandbox, and when developing and
implementing the sandbox plan, the Commission may consult the EMA, the SCB, the
MDCG and the Foresight Panel. Upon termination of the regulatory sandbox, the
Commission would, upon a request from a developer, provide a recommendation on an
existing appropriate regulatory procedural pathway for authorising the placing on the
market and post-market surveillance and vigilance of the products concerned under an
existing framework and may publish reports on lessons learned from the regulatory
sandboxes.
Expected impacts:
It is crucial for research, business, investment and patients that the EU regulatory system
can efficiently and adequately assess highly innovative health biotechnology products.
With the above proposed measures, the Regulation proposal aims to introduce a
comprehensive set of regulatory tools designed to make the EU regulatory system more
predictable, efficient, and innovation-friendly without compromising safety requirements.
Conduct of business: These tools are expected to generate positive effects, as the
repository would provide guiding documented regulatory interpretations for similar
products, enabling firms to benchmark approaches. Navigation assistance by the Support
Network will deliver targeted, early-stage support particularly valuable for SMEs, which
often lack extensive in-house regulatory expertise and often rely on costly external
consultancy. The foresight panel for emerging innovation would increase the regulatory
readiness of the legislative frameworks in the health area by allowing them to integrate
approaches to new technologies in a timely way. The panel, offering a forum for structured
dialogue across the frameworks, also aims to ensure a cross-framework perspective on
emerging technologies, which is needed as innovation increasingly develops across the
silos of the different frameworks. This would make the existing frameworks more
conducive to processing products based on new biotechnologies.
Regulatory sandboxes offer a controlled environment where developers of truly disruptive
innovations are supported by regulators to identify suitable authorisation routes. Evidence
from analogous sandboxes already applicable in other sectors, notably the UK Financial
Conduct Authority study169, suggests that sandbox participation can reduce time-to-
market by 20-40%, increase funding probability by 15-50%, and improve firm
survival and patenting by 20-30%, with benefit-to-cost ratios ranging from 3/1- 10/1
over three to five years.
The measures are also expected to have a positive impact on administrative costs for
businesses (including SMEs),through reducing administrative burden and costs by
eliminating duplicative work and regulatory unpredictability for businesses and
169 “Regulatory Sandboxes and Fintech Funding: Evidence from the UK” by G. Cornelli S. Doerr L. Gambacorta O.
Merrouche (2020) act 2025: FCA Strategy.
44
innovators. The measures aim to avoid undue delays and inefficiencies in regulatory
pathways at an early stage of development.
R&I: The measures are also expected to generate positive impacts. Clearer pathways for
researchers would reduce the chilling effect that uncertainty currently has on frontier
research, encouraging more high-risk, high-novelty projects being developed and retained
in Europe. The repository and regulatory assistance would help research institutions and
firms plan development activities with confidence, while the sandboxes would ensure that
truly disruptive research in novel products is still accommodated by the regulatory system.
The foresight panel aims to connect the research world, where innovation emerges, with
regulators. This would allow to reflect collaboratively on how to process products based
on new technologies in the best way. These measures combined would guide funding
bodies and researchers toward promising areas likely to be facilitated in a system
conducive to innovation, eventually unlocking the potential for increasing EU gross
domestic expenditure on research and development and better translating scientific
breakthroughs into clinical applications.
Competitiveness, trade and investment: The Biotech Act as a whole is expected to
address structural weaknesses that currently deter investment and early-stage scaling in
Europe. Greater regulatory clarity and predictability, through the repository and navigation
assistance, should reduce perceived regulatory risk, making the EU more attractive for
biotech investment. The sandbox might signal to global investors that tailored regulatory
tools exist for disruptive innovations, providing viable pathways to market and reducing
uncertainty. The foresight panel demonstrates that the EU actively incorporates emerging
trends into regulatory planning, aligning long-term policy with cutting-edge innovation
and supporting confidence that governance and rules will adapt to technological progress.
These measures have the potential to reverse declining trends in EU biotech and partially
close the investment and commercialisation gap with the US and China.
Functioning of the internal market: Its functioning is expected to improve through
greater harmonisation and transparency, as the repository promotes convergence by
making consistent regulatory interpretations visible across Member States and reducing
divergent classifications that fragment the market and distort competition. Navigation
assistance and structured guidance minimise interpretive disputes and streamline cross-
border compliance. For public authorities, the Biotech Act is designed to improve
efficiency and preparedness by reducing duplication through the shared repository
reference base, streamlining pre-authorisation interactions through navigation assistance,
and building anticipatory capacity through the sandbox and foresight panel. Although
establishing the sandbox and operating the foresight panel require upfront investment,
these costs are limited given the expected low number of such sandboxes, borne at EU-
level with no additional burden on Member States, and are expected to be offset by
efficiency gains, reduced uncertainty, and scale effects. For public health and safety, the
combined regulatory tools aim to offer a more innovation-conducive regulatory system,
bringing more breakthrough products with potential major patient benefit to the market
through a more efficient and adapted regulatory process – without compromising safety
standards.
45
Public authorities: The proposed measures will entail only limited costs, while delivering
long-term efficiency gains, particularly through streamlined authorisation processes that
reduce administrative workload. Regulatory assistance via the support network will
leverage existing national structures, adopting an antenna approach to better coordinate
and deploy assistance providers at the national level. The regulatory status repository,
though requiring initial development, will build upon existing or planned resources—such
as the SoHO compendium or the Medical Devices Manual on Borderline and
Classification—or simply reference national publications, thereby minimising duplication
and resubmissions by developers. This, in turn, will further alleviate the burden on public
authorities by reducing uncertainty and improving procedural efficiency. The foresight
panel, while incurring marginal costs for logistical support, staff allocation, and expert
compensation, is designed to strengthen anticipatory governance, ensuring greater
preparedness for emerging technological shifts and ultimately lowering the future
regulatory burden for complex, innovative products. Though no data exists on the cost-
benefit ratio of a regulatory sandbox for novel health biotech products, its use will be
highly targeted, keeping expenses minimal. Importantly, investments to establish the
sandbox and operate the foresight panel will be fully funded by the Commission, imposing
no additional financial obligations on Member States.
On public health and safety, no impacts are expected as safety standards remain
untouched by these provisions.
Table 1. Summary assessment of the effects due to the intervention n°1
Policy measure COB Admin CTI Int mar I&R PA H&S
Union regulatory
status repository
+ + + + + n/a 0
Foresight Panel for
Emerging Health
Innovation
+ 0 + + + n/a 0
Regulatory sandboxes + + + + + n/a 0
5.1.2 Intervention n°2: Targeted regulatory reform of the General Food Law170
First, the Regulation proposal includes measures to accelerate and improve EFSA risk
assessment processes for products subject to pre-market authorisation under Union food
and feed law. These include:
- the broadening of the scope of general pre-submission advice (currently limited
to administrative and regulatory requirements) to cover scientific matters, such as
study design and testing strategies, while merging it with the renewal-related
advice into a single, unified and simplified procedure;
170 Regulation (EC) No 178/2002, OJ L 31, 1.2.2002, pp. 1–24. ELI: http://data.europa.eu/eli/reg/2002/178/oj.
46
- a shortening to three months of the procedural delay for non-compliance with
the study notification requirements at pre-submission phase;
- a targeted and limited revision of the Scientific Committee/Scientific Panel
governance while maintaining the composition of the Scientific Committee;
- the expansion of EFSA mandate to provide scientific advice on all aspects of
human nutrition.
Secondly, the proposal establishes a comprehensive regulatory sandboxes framework
within Union food law, enabling Member States to create controlled environments for
testing innovative technologies, products and substances at pre-market stage, data
requirements and alternative regulatory requirements for food production, processing and
distribution, feed produced for food-producing animals, food contact materials, and GMO-
containing products. The proposal, however, does not allow the establishment of
regulatory sandboxes for the following categories of products: (a) Novel foods:
Experience has shown that certain types of novel foods involve highly innovative processes
and complex scientific considerations, which require thorough oversight even at
testing/experimental phase. This makes such foods less suited to the flexible, experimental
nature of sandboxes. Furthermore, experience has shown that certain types of novel foods
trigger ethical or cultural concerns among various consumer segments regarding their
acceptability. Therefore, all aspects of novel foods in general are best addressed solely
within the applicable rigorous regulatory framework established by Regulation (EU)
2015/2283 of the European Parliament and of the Council and should not be subject to
regulatory sandboxes171; (b) Recycled plastic food contact materials: As regards
innovations concerning novel plastic recycling technologies for plastics intended to come
into contact with food, chapter IV of Commission Regulation (EU) 2022/1616 already
establishes a framework that is meant to encourage the development of such novel
technologies without prior authorisation. To ensure uniform rules on the development of
novel recycling technologies that safeguard the health of the consumers, it is appropriate
to exclude the development of recycling technologies from the possible use of regulatory
sandboxes and rely instead on the procedure established in chapter IV of Regulation (EU)
2022/1616;172 and, (c) GMOs regulated under Part B of Directive 2001/18/EC: For
certain GMOs legal pathways already exist to allow testing of innovations, such as under
Part B of Directive 2001/18/EC on the deliberate release of genetically modified organisms
(GMOs) for purposes other than placing on the market, and therefore there should not be
a duplication of paths in the interest of legal certainty. For this reason, regulatory
sandboxes should be restricted to products containing or consisting of GMOs subject to
authorisation under Part C of Directive 2001/18/EC.
171 Regulation (EU) 2015/2283 of the European Parliament and of the Council of 25 November 2015 on novel foods,
amending Regulation (EU) No 1169/2011 of the European Parliament and of the Council and repealing Regulation (EC)
No 258/97 of the European Parliament and of the Council and Commission Regulation (EC) No 1852/2001 (OJ L 327,
11.12.2015, p. 1, ELI: http://data.europa.eu/eli/reg/2015/2283/oj). 172 Commission Regulation (EU) 2022/1616 of 15 September 2022 on recycled plastic materials and articles intended to
come into contact with foods, and repealing Regulation (EC) No 282/2008 (OJ L 243, 20.9.2022, p. 3, ELI:
http://data.europa.eu/eli/reg/2022/1616/oj).
47
Regulatory sandboxes established in the context of Regulation (EC) No 178/2002 would
not replace or circumvent existing pre-market authorisation procedures, as any product
subject to pre-market authorisation – for example a new feed additive tested within a
sandbox – would still need to undergo the full authorisation process before being placed
on the EU market.
Expected impacts:
Conduct of business: The proposed extension of the scope of EFSA’s general pre-
submission advice to cover also scientific aspects is expected to significantly improve
application dossier quality, reduce validation timelines and limit ‘stop-the-clocks’ during
the risk assessment phase, thereby contributing to shorten time-to-market. By enabling
applicants, especially SMEs and first-time applicants, to clarify study design, endpoints
and methodologies in advance, with EFSA staff and external experts, the measures should
increase predictability without undermining the ‘non-committal’ character of the pre-
submission advice and without altering the applicant’s burden of proof or EFSA’s
independence. Shortening the procedural delay for non-compliance with study notification
obligations from six to three months further reduces procedural delays at pre-submission
phase. In parallel, the introduction of a framework for regulatory sandboxes allows
companies to test innovative technologies, products and processes in controlled
environments before pre-market authorisation procedures, helping them to understand data
requirements and regulatory expectations while maintaining oversight and safety. Overall,
the conduct of business along the food chain is expected to become more innovation-
friendly and less encumbered by avoidable procedural obstacles.
Administrative costs on businesses (including SMEs): the reform is expected to reduce
unnecessary burdens linked to incomplete or poor-quality application dossiers. The
enlarged scope of pre-submission advice should help applicants tailor their data generation
more precisely to EFSA’s requirements, avoiding mis-designed studies and decreasing the
likelihood of repeated information requests and related delays. This is particularly
important for SMEs and one-time applicants, for whom administrative and compliance
costs weigh more heavily and who currently underuse existing advice instruments. By
clarifying notification obligations and other procedural requirements at an early stage, the
reform can streamline compliance and reduce the cumulative administrative effort over the
life cycle of an application.
Competitiveness, trade and investment flows: The targeted amendments are expected to
strengthen the EU’s competitive position by making the regulatory environment more
conducive to innovation while preserving high safety standards. Faster and more
predictable risk assessment processes, fewer unnecessary administrative hurdles and
reduced non-compliance penalties should lower the cost of bringing new products to
market and make the EU a more attractive location for R&D and investment. By
facilitating the development and approval of innovative products and related technologies,
the reform supports the ability of EU firms to compete globally, leveraging the existing
reputation of EU standards as a quality benchmark and reinforcing the EU’s capacity to
shape international norms.
Functioning of the internal market and competition: the reform is not expected to
materially alter the baseline. The measures would apply horizontally and uniformly to all
48
operators and Member States, and do not change the core harmonised framework
established by the General Food Law and sectoral legislation. The level playing field across
the internal market, underpinned by common risk-analysis principles and centralised EFSA
risk assessment, would therefore remain intact.
Innovation and research: The new legislative framework for regulatory sandboxes is
expected to be potentially transformative. By allowing supervised experimentation with
technologies, products and substances in real-world conditions before pre-market
authorisation, sandboxes significantly reduce both technological and regulatory risks for
innovators, particularly start-ups and SMEs. Shorter learning cycles, direct feedback on
safety, usability and acceptance, and clearer insight into data and evidentiary expectations
should accelerate development and derisk investment in more ambitious, less incremental
innovations. Participation in regulatory sandboxes established by Member States in
accordance with the proposed amendment of the General Good Law, with visible
regulatory engagement, is also likely to signal credibility to investors and industrial
partners, facilitating access to finance and strategic collaborations. Overall, the measures
are expected to improve the innovation climate in the EU food and feed sector, while
keeping full pre-market authorisation requirements in place for products entering the
market.
Public authorities: Concerning public authorities, notably national competent bodies, as
well as EFSA, the reform is expected to improve the efficiency and the quality of scientific
and regulatory outputs. Enhanced pre-submission advice, including scientific aspects and
delivered by EFSA staff and external experts who may also support subsequent risk
assessment, should improve dossier quality, reduce the frequency and duration of stop-the-
clock procedures, and allow better allocation of EFSA’s resources along the application
process. Adjustments to EFSA’s scientific panel governance – having EFSA staff chair
panels and the Scientific Committee – are expected to reinforce coherence, methodological
consistency and timeliness across assessments. While the expanded advice function may
require some additional staff and coordination efforts, these are expected to be offset by
savings from fewer procedural delays and less remedial work on weak-quality dossiers.
For national authorities, participation in regulatory sandboxes offers a vehicle for
systematic regulatory learning, enabling them to test data requirements and alternative
regulatory approaches in a controlled setting and to feed robust evidence into EU-level
scientific guidance and regulatory standards.
Public health and safety: the targeted amendments are designed to preserve, and
potentially enhance in the longer term, the high level of safety standards currently afforded
by EU food law. The streamlining of EFSA procedures and the extension of pre-
submission advice aim to ensure that risk assessments are supplied with more relevant,
better structured data, thereby supporting robust scientific opinions within shorter
timelines. The expanded mandate of EFSA on nutrition matters, enabling EFSA to provide
advice on all nutrition matters aim at further equip EU regulators with the necessary
scientific knowledge to address challenges relating with the increasing prevalence of diet-
related health issues. The regulatory sandbox framework, under strict safeguards, is
expected to function as a regulatory learning tool, generating richer real-world evidence
on exposures, hazards, patterns of use and the effectiveness of risk-management options.
This should enable more accurate risk characterisation, more proportionate and effective
risk-management measures, and earlier detection of potential safety issues in a controlled
49
environment. Provided that capacity is available to analyse and use sandbox generated
data, the overall effect is expected to be at least the maintenance, and potentially the
strengthening, of the EU’s high standards of public, animal and plant health protection and
environmental safety.
Table 2. Summary assessment of the effects due to the intervention n°2
Policy measure COB Admin CTI Int Mar I&R PA H&S
Improved timeliness
and coherence of
EFSA risk
assessment processes
++ ++ ++ 0 0/+ ++ +
Regulatory
framework for
sandboxes in relation
to food, feed, and
GMOs
++ 0 + 0 ++ + +
5.1.3 Intervention n°3: Targeted regulatory reform of the Advanced Therapy
Medicinal Products (ATMPs) framework173
The proposed regulatory simplification and future-proofing of ATMPs includes two
interconnected changes. First, it establishes a risk-proportionate approach for clinical
trials involving ATMPs containing or consisting of GMOs. Under this approach
sponsors would be exempted from submitting environmental risk assessments (ERAs) for
products presenting no or negligible risks. Second, it aims at future-proofing the
regulatory framework by amending the definition of tissue-engineered products to reflect
technical and scientific advances, without extending the scope of the definition.
Expected impacts:
Overall, the reform is expected to strengthen the EU’s attractiveness for high-risk biotech
investment and support the growth of a rapidly expanding ATMP sector across Member
States. The proposed amendments are expected to contribute to the EU’s global
competitiveness in biotechnology. Predominantly positive impacts are expected for
businesses (in particular SMEs), research and innovation, the internal market, and public
health.
Conduct of businesses, innovation and research: The introduction of a targeted
exemption from ERA requirements during the CT application phase for clearly defined
categories of low-risk investigational ATMPs directly addresses a key barrier to
conducting clinical trials in Europe. Even where the recently agreed pharmaceutical
legislation reform addresses the fragmentation of ERA requirements across Member States
by centralising/harmonising the ERA procedure, requiring sponsors to obtain ERA
approval prior to, or alongside, a CT authorisation, imposes a disproportionate regulatory
173 Regulation (EC) No 1394/2007, OJ L 324, 10.12.2007, pp. 121–137. ELI: http://data.europa.eu/eli/reg/2007/1394/oj.
50
burden at an early stage of development where the risk profile of the product is already
well-characterised and low. This deters sponsors –particularly SMEs – from choosing the
EU as a trial location, diverting early-stage innovation to jurisdictions with more
streamlined processes. This competitive disadvantage is evident when comparing with the
US: the Food and Drug Administration grants an exclusion from ERA for the vast majority
of gene therapy Investigational New Drud (IND) applications at the clinical trial stage.
That regulatory efficiency accelerates development timelines and explains why a
significant share of ATMP clinical trials are conducted in the US rather than in the EU.
While an ERA will still be required at the marketing authorisation stage, removing this
requirement during clinical development removes a critical friction point. This provision
is expected to attract clinical research on certain categories of ATMP in the EU even if it
is not possible to quantify the precise impact at this stage.
An empowerment which would allow the Commission to amend the ATMP Regulation
via delegated acts, in order to amend the definition of tissue engineered products will
future‑proof the ATMP framework by allowing to take into consideration technical and
scientific advancements in the field of ATMPs. The need for such adaptations is
underscored by concrete cases. For example, an acellular tissue-engineered vascular graft
intended for urgent revascularisation in severe arterial injury has faced 18 years of
classification uncertainty in the EU. Its acellular nature excluded it from the existing tissue-
engineered product (TEP) definition. Meanwhile, the FDA approved the same product,
demonstrating how regulatory rigidity can drive innovation away from Europe.
Both measures are expected to lower operational costs by removing non‑value‑adding
regulatory steps, potentially removing a burden of 0.15-0.3 FTE-years per clinical trial
application, and reducing uncertainty. Together, they speed the transition from research
to clinical development, particularly for SMEs, while making the EU a more competitive
and predictable environment for ATMP innovation.
Functioning of the internal market and competitiveness: The impact of streamlining
Regulation (EU) No 536/2014, in conjunction with modifications to ERA requirements for
investigational GMO-ATMPs and amendments to ATMP definitions, is expected to be
profound and multifaceted concerning internal market dynamics and EU competitiveness.
By exempting certain investigational ATMPs containing GMOs from full ERA
submissions, this change not only facilitates faster progression from trial initiation to
product development, but also significantly influences sponsors’ decisions to conduct
clinical trials in Europe. Consequently, the EU could emerge as a leading destination for
biotech investment, accelerating the development of innovative therapies. Future-proofing
ATMP definitions allows EU to enhance its scientific and technological leadership in
biotechnology and regenerative medicine, while further cementing its reputation as a
regulator pioneer. The reform is also expected to attract more high-risk capital, support the
growth of more than 580 ATMP companies across over 20 Member States, and help
maintain EU competitiveness.
Public health and safety: The Biotech Act targets procedural simplification rather than
substantive relaxation of safety standards. The ERA exemptions only apply to ATMPs
which fall into clearly defined categories with no or negligible risks. Safety oversight is
maintained through the review of sponsor declarations within the clinical trial assessment
process, comprehensive risk–benefit evaluation and long-term follow-up requirements.
51
By reducing unnecessary procedural delays and shortening assessment timelines, the
measures are expected to facilitate earlier initiation of CTs and potentially earlier access
for EU patients to safe, effective and often transformative advanced therapies.
Furthermore, the ability to adapt ATMP definitions to scientific progress helps reduce the
risk of regulatory blind spots for emerging technologies, ensuring that innovative
therapies remain subject to the most appropriate regulatory oversight.
Table 3. Summary assessment of the effects due to the intervention n°3
Policy measure COB Admin CTI Int mar I&R PA H&S
1. targeted ERA
exemption
+ 0 + + + 0 0
2. revised definition + + + + + 0 0
5.1.4 Intervention n°4: Targeted regulatory reform of clinical trials174
The amendments to the CTR aim to shorten authorisation timelines, strengthen
collaboration between Member States, and enhance regulatory efficiency without
compromising safety, quality, or ethical standards.
The proposed amendments articulate around five pillars:
(i) Faster authorisation procedures
Authorisation timelines for initial clinical trial applications are reduced from 106 to 75
days, or from 75 to 47 days, where no additional information is requested from the sponsor.
For substantial modifications175, timelines are reduced from 96 to 47 days or from 64 to 33
days where there is no additional request for information. The additional 50-day
assessment period for ATMPs is removed.
(ii) More predictable and efficient authorisation procedures
The shorter authorisation timelines are supported by procedural changes to increase
efficiency, cooperation, and consistency across Member States. The reporting Member
State (RMS) leads the evaluation of Part I176 of the trial application, with other Member
174 Regulation (EU) No 536/2014, OJ L 158, 27.5.2014, pp. 1–76. ELI: http://data.europa.eu/eli/reg/2014/536/oj. 175 Substantial modifications as defined in the proposed amendments to Regulation (EU) No.536/2014, Art. 2 mean ‘any
change to any aspect of the clinical trial which is made after the notification of a decision referred to in Article 8 in at
least one Member State concerned and which is likely to have a substantial impact on the safety or rights of the subject
or on the reliability and robustness of data generated in the clinical trial.’ 176 The application dossier for the authorisation of a clinical trial in the EU is split into Part I and Part II. Part I contains
overarching scientific, medical, and technical information about the investigational medicinal product (IMP), the clinical
trial design and participants’ safety. The RMS leads the assessment of Part I. Part II contains the national, ethical, and
national information (e.g., informed consent, recruitment related information, site and investigator suitability, insurance)
assessed separately by each Member State concerned.
52
States concerned providing complementary considerations. For initial applications, the
validation of Part I will be carried out solely by the RMS without coordination and
consolidation steps with the other Member States concerned. It is also allowing the RMS
to initiate the assessment already during the validation phase, shortening the overall
assessment time by two weeks. The ethics committee of the
RMS will be mandatorily engaged in the review of Part I to ensure that the ethical review
is fully integrated with scientific and regulatory assessments. The scope of the ethical
review and the mandate of the Member States concerned in the assessment are clarified.
Maximum timelines are designed to allocate seven day-periods per assessment step,
ensuring deadlines do not fall on weekends and thereby avoiding automatic extensions.
This approach ensures predictability in timelines for sponsors and regulatory bodies.
Substantial modifications to Part I and/or Part II for changes that may significantly affect
participants' rights, safety, or data reliability can be assessed in parallel, with significantly
shorter assessment times.
Efficiency is further improved through the establishment and re-use of a single
investigational product core dossier containing documents common to all trials with the
same investigational medicinal product (IMP), a mandatory use of harmonised EU
templates, and by shifting translation checks from Part I to Part II. An upgraded EU portal
enhances communication between sponsors and assessing Member States during
assessments.
The amendments also encourage participation of vulnerable populations in clinical trials,
by carefully weighing the potential risks and benefits of their exclusion versus inclusion in
trials. Additionally, women who become pregnant or start breast-feeding during their trial
participation will not be automatically excluded from the trial. Their continued
participation will instead be evaluated by assessing the risks and benefits involved.
(iii) Context-specific clinical trial authorisation procedures
The Regulation proposal sets out three tailored authorisation procedures to streamline
regulatory requirements to the specific context and risks of the clinical trial.
1. It introduces a single assessment procedure for combined studies involving both
medicines and medical devices or medicines and in vitro diagnostic medical
devices, rationalising the relevant provisions of three EU regulations (i.e. CTR,
MDR, and IVDR).
2. It introduces a fast-track authorisation procedure with simplified requirements for
multinational clinical trials to ensure availability of crisis-relevant medicines to
prevent/contain health threats, provide timely treatment options, or facilitate
diagnosis in the context of an emerging or a recognised serious cross-border threat
to health at Union level177. The procedure will be automatically applicable in a
recognised serious cross-border threat to health at Union level. The Commission
would be further empowered to define, through implementing acts, transparent
criteria and a process for declaring the procedure applicable in the context of an
emerging serious cross-border threat to health.
177 In accordance with Article 23 of Regulation (EU) 2022/2371 (see footnote 40, page 9).
53
3. It strengthens the risk-proportionate approach by more precisely aligning
regulatory requirements with the level of risk associated with a clinical trial. A new
risk category, minimal intervention trials, is introduced to cover post-marketing
authorisation trials, which will require ethical review only for the authorization
itself.
(iv) Innovation and Harmonised Data Governance
The proposal facilitates the integration of AI and digital tools (e.g. e-informed consent),
reinforces direct shipment of IMPs to patients and improves trial design, execution and
oversight. It introduces regulatory sandboxes to test innovative approaches and establishes
a single legal basis under the requirements of the GDPR for processing of personal data to
provide legal clarity and streamline multinational trials.
(v) Governance and Enforcement
The proposal strengthens EU governance by improving cooperation among Member
States’ authorities and Ethics Committees by expanding the role for the Clinical Trials
Coordination and Advisory Group. National competent authorities and ethics committees
must have sufficient personnel and resources to perform assessments. National competent
authorities gain stronger inspection powers, including unannounced and joint inspections,
which may be delegated to other Member States or agencies. Harmonised guidelines
standardise IMP distribution oversight. The Commission can verify compliance within the
EU and assess whether clinical trials outside the EU meet good clinical practice and ethical
standards.
Expected impacts:
The policy measures outlined above aim to make the EU more attractive to sponsors, by
reducing administrative burden and shorten time to market, thereby increasing the number
of clinical trials conducted within the EU. The impact of the regulatory changes is assessed
both quantitatively and qualitatively through a two-step procedure (Figure 6). First, the
expected effect on the total number of EU-based clinical trials resulting from the
simplification and acceleration of the authorisation process and conduct of clinical trials is
examined. Second, the broader economic implications and public health benefits arising
from the increased number of clinical trials conducted across Member States are assessed.
Figure 6. Schematic illustration of the assessment of possible impacts of the proposed
regulatory changes to the Clinical Trials Regulation
Step 1 - Expected impact on the number of clinicals run in the EU
54
Faster, more efficient and better coordinated procedures, as well as the uptake of AI and
digital tools are expected to increase the number of clinical trials conducted in the
EU/EEA178,179 and encourage participation by a wider set of Member States. This can
reduce current concentration in a few jurisdictions, level the playing field for SMEs and
support a more integrated EU clinical research market.
According to one survey with sponsors180, the anticipated increase of clinical trial
authorisations for selected individual policy changes lies between 5% and 28%, and by
32% for a bundled sub-set of policy measures included in the proposed Biotech Act181.
Another study, based on limited empirical evidence, suggests that the proposed revision of
the CTR could increase the number of clinical trials by on average of 10%182. In addition,
sponsors believe that the regulatory change will foster multinational trials in the EU with
a broader geographic scope (see Figure 7).
To quantify the economic and public health impacts of the regulatory change, we assume
that the number of clinical trials will increase by 10% to 30%. These estimates draw on
two separate studies183. The lower bound reflects the average projected increase in clinical
trials of 10%. This estimate also aligns with the ACT EU target of having additional 500
multinational clinical trials over the next five years184. Meanwhile, the upper bound is
derived from survey responses collected from sponsors as part of the second study185. The
range was selected to reflect the differing findings of the two studies, while accounting for
the respective strengths and limitations of each. The wide disparity in these estimates
highlights the challenges in assessing the reform’s impact on clinical trial activity, given
data limitations and inherent uncertainties about future developments.
178 Regulatory Framework Study (forthcoming) 179 Between January 2022 and December 2025, on average 2,484 new trial applications were submitted per year. This
includes the transition period to the Clinical Trial Regulation which went from 31 January 2022 to 31 January 2025.
Source: EU clinical trials during the 3-year CTR transition period. 180 A survey with 48 sponsors, among those commercial sponsors, was conducted. It is to note that not all respondents
replied all questions. For further information, see Regulatory Framework Study (forthcoming) 181 In the survey, sponsors were asked to assess the impact of selected policies individually on the expected change in
clinical trials. For the policies comparably to the changes included in the proposal of the Biotech Act the impact of the
single measure lies between 5% and 28%. It is to note that the survey replies are subjective assessment from the
respondents considering the difficulties that come along with projecting the future. Nevertheless, these figures can be
used as indicative evidence. For further information see Regulatory Framework Study (forthcoming). 182 Rapid Assessment Scenario Study (forthcoming). The study, based on limited empirical evidence, distinguishes
between two hypothetical scenarios regarding the potential impact of the BioTech Act on the projected number of clinical
trials in the EU. In the first scenario, a moderate increase in the number of clinical trials by 4% to 8% is anticipated. This
is attributed to improved efficacy and attractiveness of performing clinical trials in the EU, driven by increased domestic
uptake among sponsors already operating within the region. The second scenario assumes that, in addition to increased
domestic uptake, sponsors relocate clinical trial activities from other regions to the EU/EEA as a result of the reforms in
the Biotech Act, leading to an estimated increase of 8% to 16%. As the Biotech Act is expected to simplify authorisation
processes and the conduct of trials for sponsors, it is considered plausible that some sponsors may relocate their clinical
trials to the EU following the amendments of the Regulation. Therefore, the average of both scenarios is used as a
benchmark for the lower bound.
183 Studies Regulatory Framework Study (forthcoming) and Rapid Assessment Scenario Study (forthcoming). 184 For further information, see: New targets for clinical trials in Europe | European Medicines Agency (EMA). For the
purposes of this analysis, the same 11.1% increase is also assumed for mononational clinical trials. For Q1/2026 the KPI
has been evaluated for the first time. This quarter, 19 additional multinational trial applications have been submitted. If
extrapolated annually, this would represent an 8% increase in trials without any changes to the regulatory framework. 185 Regulatory Framework Study (forthcoming)
55
Figure 7: Survey replies from sponsors to the following question: “To what extent
would each of the following policies expand the geographic scope of multinational clinical
trials in the EU, by increasing the number of participating Member States in a clinical
trial in the EU?”186
Step 2 – Economic and Public Health Impact
The subsequent section assesses the expected impact of the increase in the number of
authorised clinical trials on economic and public health outcomes. Economic impacts are
evaluated along the following dimensions: competitiveness, gross-value added (GVA),
work productivity, employment, R&D spillovers, a simplified cost-benefit analysis for
sponsors, and relevant EU and national actors involved. The public health impact is
measured by the expected change in number of enrolled participants and the composition
of the participant populations.
(a) Economic impacts
Survey responses from sponsors and Member State representatives187, including national
competent authorities, ethics committees and ministries, suggest that a subset of policy
186Regulatory Framework Study, forthcoming. In the survey, sponsors were asked to assess the impact of selected policies
individually. The policies presented in this figure are those most closely to the ones included in the Commission proposal
adopted on 16 December 2025. Please note that there is still some slight deviation between the described policy scenarios
assessed in the survey and the policy changes proposed in the Commission proposal. 187 For further information, see report Regulatory Framework Study, forthcoming. The policies presented in this figure
are those most closely to the ones included in the Commission proposal adopted on 16 December 2025. Please note that
there is still some slight deviation between the described policy scenarios assessed in the survey and the policy changes
proposed in the Commission proposal.
56
measures introduced in amendments to the CTR are expected to strengthen the EU’s
competitiveness (see Figure 8).
Figure 8: Survey replies to the following question “To what extent would the policies
increase/decrease the competitiveness of the EU compared to the baseline in terms of, e.g.
R&D expenditures in the pharmaceutical sector including revenue for healthcare
providers, number of marketing authorisations and patents granted in the EU/EEA, Gross
Value Added in the pharmaceutical sector?188
The economic impact for commercially-sponsored clinical trials is likely to differ from
that of non-commercial/academic ones due to systematic differences in their
characteristics. In particular, 71.5% of applications submitted by commercial sponsors
involve multinational trials, whereas 85.6% of applications submitted by academic
sponsors relate to mono-national trials.189 Academic sponsors are also more likely to
conduct late-phase clinical trials, particularly post-marketing authorisation trials190, which
may entail different cost structures191. These differences suggest that the economic impacts
of commercial and non-commercial clinical trials should be assessed separately.
Between January 2022 and January 2025, commercial trials accounted for 53.1% of all
clinical trials authorised in the EU. Figure 9 illustrates the incremental benefit for an
increase in clinical trials across three economic dimensions, i.e. GVA, R&D spill-over
188 Regulatory Framework Study, forthcoming. In the survey, sponsors and Member State representatives were asked to
assess the impact of selected policies individually. The policies presented in this figure are those most closely to the ones
included in the Commission proposal adopted on 16 December 2025. Please note that there is still some slight deviation
between the described policy scenarios assessed in the survey and the policy changes proposed in the Commission
proposal. 189 EU clinical trials during the 3-year CTR transition period (see p.9). 190 EU clinical trials during the 3-year CTR transition period (see p.26). 191 Fast-track landscape analyses to assess the regulatory clinical trial eco-system in the EU/EEA and in other relevant
regions (forthcoming)
57
and work productivity192 assuming an increase of 10% or 30% in commercial clinical
trials as a result of the legislative changes proposed in the amendments to the CTR. A 10%
increase in clinical trials is estimated to generate approximately EUR 3.6 billion in
economic gains and create roughly 16,500 additional jobs across the EU, while a 30%
increase could result in approximately EUR 10.7 billion in economic gains and 49,500
additional jobs193.
Figure 9. Economic impacts assuming a 10% and 30% increase in commercial clinical
trials194
The value of non-commercial trials on the economy has been recently demonstrated for
some regions and countries, such as the UK195. Due to a lack of sufficiently robust and
comparable data for the EU, this analysis does not attempt to quantify the economic
impacts of the proposed regulatory changes for non-commercial trials. Therefore, the
estimated economic impacts presented for commercial trials should be considered a lower
bound estimate of the overall economic gains associated with the increase in the number
of authorised cinical trials.
192 The GVA measures “the value of output less the value of intermediate consumption; it is a measure of the contribution
to GDP made by an individual producer, industry or sector” (OECD; National Accounts at a Glance 2009 (EN)). R&D
spill-overs measure clinical research activities creating knowledge, products, and processes which can be used by other
companies. Workforce productivity measures how improved treatment options enhance people’s health and thereby
reducing sick days (EFPIA report 2026; the-economic-impact-of-industry-clinical-trials-across-europe.pdf). 193 The values are calculated based on the following assumptions/parameters: (1) between 2022 and 2025 the annual
number of authorised industry commercial trials was 1,509(EU clinical trials during the 3-year CTR transition period);
(2) The reported values in EFPIA 2026 the-economic-impact-of-industry-clinical-trials-across-europe.pdf are used to
calculate incremental effects per trial. (3) There is a linear relationship between the increase in clinical trials and the
incremental benefits. 194 Commission own calculations based on information from EFPIA (2026) the-economic-impact-of-industry-clinical-
trials-across-europe.pdf and EU clinical trials during the 3-year CTR transition period. 195 Frontier Economics The value of non-commercial clinical research | Frontier Economics.
58
The proposed regulatory changes are expected to encourage more non-commercial trials,
particularly minimal-intervention and low-intervention trials, by simplifying authorisation
requirements and streamlining the conduct of trials typically conducted by academic
sponsors196. Survey replies support the assumption that these amendments would reduce
administrative barriers and make academic research easier, including increased availability
of data from comparative trial 197 or the Health Technology Assessment (HTA) procedures.
The primary advantages extend beyond the authorisation stage, encompassing risk-
proportionate safety reporting, more targeted monitoring, and flexible models for the
supply and distribution of investigational medicinal products.
To assess the efficiency of the amendments proposed to the Clinical Trial Regulation, a
simplified cost-benefit analysis has been carried out as part of two supporting studies.
These analyses provide a broad indication of the range of expected cost savings based on
different methodologies.
One study evaluates the impacts using estimates from sponsors and public authorities,
collected through targeted surveys, on expected changes in costs and the number of clinical
trials198. Based on these estimates annual cost savings for setting up and the conduct of
trials are approximately EUR 1.24 billion for a subset of policy measures included in the
Commission proposal. However, it should be noted that response rates for some survey
questions have been low (N<10), which may limit the representativeness of conclusions
on cost patterns. The policy measures assessed are largely aligned with, but not identical
to, those in the Commission’s proposal. Additionally, not all the proposed changes are
captured therein, and those are expected to have a positive effect on clinical trials in
Europe. Important policy changes, such as the introduction of a single assessment
procedure for combined studies, the integration of artificial intelligence, and new structures
for governance and enforcement measures, are not part of the assessment as the survey was
designed prior to the finalisation of the proposed amendments. Therefore, the calculations
can be used as suggestive evidence rather than precise estimates of the cost savings.
The assessment of a second study199 considers the total set of measures included in the
Commission proposal. It estimates direct annual cost-savings for sponsors of
approximately EUR 1.5 billion to EUR 3.1 billion through more effective administration
and faster authorisation procedures and indirect annual savings of equal amounts through
an accelerated conduct of clinical trials. The calculations are based on the assumptions that
the amendments reduce the total costs of a clinical trial by 5% due to more effective
administration, a clinical trial runs on average 2 to 2.5 years, the average costs of a clinical
trial amount EUR 30-50 million and the number of clinical trials remains unchanged. It is
to be noted that the limited data availability on the average costs of a clinical trial may
substantially impact the estimated cost reductions due to the proposed regulatory changes.
196 Over 90% of low intervention trials are conducted by non-commercial sponsors (EU clinical trials during the 3-year
CTR transition period). 197 Regulatory Framework Study (forthcoming) 198 See Regulatory Framework Study (forthcoming) 199 See Rapid Assessment Scenario Study (forthcoming).
59
(b) Expected Impact on Public Health
Clinical trials provide early access to innovative treatments for European patients, up to
five to ten years before the commercial launch. In the case of rare diseases, clinical trials
often present the only available treatment option for patients200. In this context, a crucial
indicator is not only the number of clinical trials conducted but also the number of
participants enrolled in those trials.
Between 2023 and 2025, the estimated average annual number of newly enrolled
participants was 163,643 for commercial trials and 341,632 for non-commercial trials201.
Assuming a 10% to 30% increase in the number of authorised clinical trials, with the
median number of participants per trial remaining constant, this would result in an
additional 7,847202 to 23,540 newly enrolled participants included in commercial trials and
10,381 to 31,145 in non-commercial trials per year.
The increase in the number of participants is expected to contribute to improved patient
health outcomes and quality of life, while at the same time generating more robust evidence
to inform Europe’s treatment guidelines and HTA decisions, and potentially facilitating
faster market authorisation of the medical products under investigation.
In addition to increasing access to innovative and improved treatment options through
clinical trials, the new provisions should also support efforts to reduce health inequalities.
For example, pregnant and breastfeeding women would no longer be automatically
excluded from trial participation, as is the case under the current regulatory framework.
Instead, their participation would be evaluated based on the associated risks and benefits.
Furthermore, the inclusion of vulnerable populations, such as minors and pregnant or
breastfeeding women, is encouraged, provided that the potential benefits of participation
are carefully weighed against the associated risks.
Finally, the anticipated increase in clinical trial activity is expected to foster science,
innovation, and skill development. Conducting clinical trials generates knowledge,
products, and technologies that stimulate further innovation, drive economic activity, and
contribute to the development of a more highly skilled workforce across the sector. These
spillover benefits from R&D extend beyond the returns captured by private investors,
creating broader societal gains. The associated economic impact of these spillover effects
for commercial trials is quantified and presented by the value of the R&D spillover in
Figure 9.
200 See Regulatory Framework Study (forthcoming) and EFPIA (2024) assessing-the-clinical-trial-ecosystem-in-
europe.pdf 201 The data are retrieved from CTIS and represents the estimated mean number of participants by year of clinical trial
authorisation for all initial applications between 2023 and 2025. 202 The calculations rely on the median number of participants in commercial trials (52) and non-commercial trials (78)
for 2023–2025, rather than the mean, to mitigate bias from outliers. This approach yields a more conservative estimate
than using average participant numbers (108 per commercial trial and 257 per non-commercial trial).
60
Table 4. Summary assessment of the effects due to the policy measure
Policy measures COB ADMIN CTI INT
MAR
I&R PA H&S
Accelerated and
streamlined clinical
trial authorisation
procedures
++ ++ ++ + 0/+ 0/+ +
Clinical trial
regulatory
sandboxes
0/+ + + + ++ ++ 0/+
Digital innovation
and harmonised
data governance for
clinical trials
+ ++ ++ ++ + + +
Combined Studies+ + + ++ ++ ++ 0/+
Governance and
enforcement
+ + + ++ 0/+ + ++
5.1.5 Intervention n°5: Targeted regulatory reform of Veterinary Medicinal
Products (VMPs)203
First, the regulatory framework for VMPs containing or consisting of GMOs is
streamlined by exempting from EU GMO legislation VMPs containing or consisting of
GMOs authorised or manufactured in accordance with VMP Regulation, which are to be
assessed solely under the VMP Regulation. Additionally, it is clarified that animals treated
with VMPs do not become, for this sole reason subject to the GMO legislation.
Second, the handling of variations not requiring assessment is simplified:
- For variations not requiring assessment with no impact on the product information,
submissions can be consolidated on a yearly basis.
- For all variations not requiring assessment, confirmation by the competent
authorities is no longer required.
Third, the SPC for biotechnology VMPs treating zoonoses is extended under certain
conditions:
- the product must be developed by means of a biotechnology process as defined in
Article 42(2)(a) of Regulation 2019/6;
- it must be intended to diagnose, treat, or prevent zoonotic diseases;
- it must contain a new active substance distinctly different from any authorised
medicinal product in the EU;
- it must have a mechanism of action distinctly different from existing products for
the same zoonotic disease, with at least equivalent safety and efficacy;
203 Regulation (EU) 2019/6, OJ L 4, 7.1.2019, pp. 43–167. ELI: http://data.europa.eu/eli/reg/2019/6/oj.
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- and at least one manufacturing step (excluding packaging, quality testing, and
certification) must be performed in the EU.
Fourth, the Regulation proposal establishes a regulatory sandbox framework for
innovative technologies, methods or products related to animal health.
Expected impacts:
The measure related to the VMPs containing or consisting of GMOs delivers
procedural simplification (1-3 month CT application saving; cumulative EUR 5-14.5
million in CTA administrative savings; EUR 560,000 in marketing authorisation dossier
savings over the period 2026-2040) and cross-Member States harmonisation, with a
high-value, zero-cost legal clarification on GMO status of treated animals eliminating
a latent risk. While standard marketing authorisation timelines are unaffected, the
benefit materialises under accelerated/emergency pathways (estimated at 30-60 days for
1-3 products/year). While no measurable increase of marketed products is expected, the
measure contributes to preventing the progressive offshoring of the innovation process
to other jurisdictions where next generation veterinary biotechnology would be
developed and trialled.
The proposed SPC extension for VMPs is a low to medium impact signalling instrument.
No near-term commercial benefit is expected due to the virtual non-existence of veterinary
biosimilar competition and the fact that existing data protection periods already outlast
patent/SPC terms. Therefore, the impact of this measure is not appropriately captured
through quantification of direct commercial or cost effects, because the primary function
of the SPC extension is not to deliver measurable near-term revenue protection but to serve
three signalling and future-proofing purposes:
1. Policy signalling: The measure communicates EU institutional commitment to
veterinary biotechnology innovation addressing zoonotic diseases, potentially
influencing long-term R&D allocation decisions at the margin.
2. Future-proofing: Should veterinary biosimilar competition eventually
materialise at scale (plausibly from the mid-2030s onward), the mechanism
would already be in place, avoiding the need for reactive legislative intervention.
3. EU manufacturing incentive: The requirement that at least one manufacturing
step be performed in the Union introduces an explicit industrial policy lever.
There is no centralised EU database publicly listing how many VMPs have obtained
SPCs, and national patent office data are not often broken down by human vs. veterinary
use. However, based on data provided by the EMA, out of the 28 biotechnology VMPs
for zoonotic diseases approved between 2010 and 2025, only 8 fulfilled all eligibility
criteria for the SPC extension. On average, this is 1 product for each 2 years. A forward-
looking estimate would foresee an average of 3 eligible products per year over 2026-
2040, based on the retrospective eligibility analysis (8 out of 28 over 16 years ≈ 2/year)
and adjusted upward modestly to reflect the growing share of biotech vaccines in the
pipeline. The targeted SPC extension is designed to be cost-neutral for the EMA. Given
the narrow scope of the measure, the EMA is expected to handle a very low volume of
applications.
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The possibility of using a regulatory sandbox for animal health innovation provides
a structured framework to facilitate the development and marketing or use of products,
methods or technologies that are not regulated under EU legislation. Expected
utilisation is modest (∼1 sandbox per five years; 2-3 established over 2026-2040). Its
primary value is qualitative: pathway creation, evidence generation for adaptive
regulation, and investment signalling. The proposed measure creates new
EMA/Commission responsibilities (application assessment, implementing acts,
reporting).
Finally, the reduction of burden for the handling of variations not requiring
assessment delivers the most quantifiable and immediately realised benefits with a
central estimate of EUR 22.5 million present-value cumulative staff cost savings (2025-
2040) and 45-55% reduction in submission events. This will result in approximately
EUR 2.5 million/year in fee savings for applicants. The removal of the confirmatory
step reduces the national competent authorities workload. It creates a one-off IT cost
for EMA of EUR 150,000-300,000. The measure is a purely administrative reform and
has no impact on safety or efficacy. The proposed measure has received positive
feedback from industry.
Table 5. Summary assessment of the effects due to the intervention n°5
Policy measure COB Admin CTI Int mar I&R PA H&S
1. GMO exemption + + + + + 0 +
2. Variations
revision
+ ++ 0 0/+ 0 + 0
3. SPC extension 0/+ 0 0/+ 0 0/+ 0 0
4. Regulatory
sandbox
0/+ 0 0/+ 0 + - 0/+
5.1.6 Intervention n°6: Targeted regulatory reform of the substances of human
origin (SoHO) framework204
First, the SoHO regulatory status consultation procedures is streamlined by
empowering the Commission to adopt implementing acts establishing binding time limits
for regulatory status consultation processes within the SoHO framework.
Second, the Regulation proposal establishes a regulatory sandbox framework for SoHO,
enabling Member States to create time-limited controlled environments for developing and
204 Regulation (EU) 2024/1938, OJ L, 2024/1938, 17.7.2024. ELI: http://data.europa.eu/eli/reg/2024/1938/oj.
63
testing innovative SoHO products, services, processes, or substances that cannot yet fully
comply with standard regulatory requirements.
The new regulatory sandbox framework allows a Member State (or several jointly) to set
up a regulatory sandbox upon a substantiated request from a SoHO entity, providing a
time-limited controlled environment to facilitate the development and testing of innovative
SoHO products, services, processes or substances under the supervision of one or more
competent authorities. Two eligibility conditions should be met: (a) the innovation is
expected to contribute distinctively to SoHO safety, quality, including effectiveness, or to
significantly improve patient access to treatment; and (b) applying the SoHO Regulation’s
requirements would impede or significantly delay development due to scientific or
regulatory challenges inherent to the innovation.
The regulatory sandbox is an evidence-generating mechanism: it should enable assessment
in a real-world environment under strict regulatory supervision, producing the data needed
to demonstrate safety and quality, including effectiveness, in view of subsequent
distribution decisions. Derogations from the SoHO Regulation may be included, but only
if clearly described, strictly necessary, and justified in a sandbox plan. Derogations may
take the form of adapted, enhanced, waived or deferred requirements. Sandboxes cannot
derogate from the SoHO Regulation’s standards on voluntary and unpaid donation.
Operationally, activities must follow a sandbox plan developed by the SoHO competent
authorities, informed by data and consultations with the innovation’s developers, and
specifying participants and roles; which SoHO requirements cannot be complied with and
the resulting derogations and adaptations; risk-mitigation measures; the sandbox duration;
and the monitoring framework. The competent authorities must consult the SoHo
Coordination Board (SCB) where appropriate, and the SCB is tasked with supporting and
fostering a common approach. The SCB may also collaborate with the Foresight Panel for
Emerging Health Innovation established by the Biotech Act, linking sandbox practice to
upstream horizon-scanning and cross-framework learning.
The proposed amendments create a structured route for SoHO innovations, which cannot
yet be developed in full compliance with the SoHO Regulation, or if compliance would
impede or significantly delay development due to inherent scientific or regulatory
challenges. The proposed amendments also formalise cross-authority collaboration and
information exchange, which improve transparency and comparability across Member
States while retaining core safeguards.
A SoHO preparation resulting from an innovation developed as part of a regulatory
sandbox may be distributed for human application only where authorised in accordance
with Article 38(1) of Regulation (EU) 2024/1938. The purpose of the regulatory sandbox
is therefore to make authorisation feasible by enabling supervised testing and evidence
generation in novel or complex cases where applying the current regulation’s requirements
would impede or significantly delay development. These are, for example, new
technologies for which there are currently no fitting technical safety and quality
requirements by the Expert Bodies (EDQM, ECDC); new technologies that are only
partially covered by SoHO rules.
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Sandbox-eligible cases would be a minority of cases which could not be authorised under
the SoHo Preparation Authorisations (SPA) model established in the 2024 SoHO
Regulation, but would bring in high extra value. Expert interviews suggested that SoHO
products eligible for the sandbox route likely represent 5–10% of overall SoHO activities,
i.e. 90-250 eligible cases per year205. Sandbox use cases demonstrate acceptance rate of
between 7-16% of sandbox applications, demonstrating great interest from developers in
the sandbox instrument but limited capacity of the regulators to establish sandboxes206.
Considering the high resource requirements of a regulatory sandbox, we can further
assume that only a share of eligible cases will be pursued. If all eligible cases apply for the
sandbox tool, between 6 and 40 regulatory sandboxes can be established pear year.
Expected impacts:
Since the regulatory sandboxes are a first-of-its-kind instrument, the initial take-up could
be slow, also as, in the first years, most innovations are expected to be well regulated under
the new model for SPA in the 2024 SoHO regulation.
Conduct of business: Regulatory sandboxes offer a pathway for addressing complex cases
that would otherwise not be pursued. We estimate a slowly growing interest in the
regulatory sandbox from SoHO entities, leading to regulatory sandbox requests,
particularly in strong innovation nations and for SoHO innovations where no safety and
quality requirements are prepared by the expert bodies.
Administrative costs on businesses, including SMEs: Regulatory sandbox is expected
to have similar costs to high-risk authorisations (between EUR 1,200 and EUR 6,000 per
patient) due to the need to involve a certain number of data subjects and a thorough
assessment process207. Therefore, while there would not be any extra cost for high-risk
cases, if low- or medium-risk cases are pursued using the sandbox route, the direct cost of
each case will increase. We assume that half of the cases directed to the sandbox route will
be high risk cases and half of the cases will be medium risk cases. Under the low estimate,
the additional cost of regulatory sandbox route for SoHO entities will be EUR 718,500
(under the assumption that six sandboxes are established per year) and EUR 4,790,000
(under the assumption that 40 sandboxed are established per year).
As a positive secondary effect this would allow SoHO entities to engage with authorities
early in an environment that tolerates iterative learning, prototyping, and co-development
of evidence strategies, thereby lowering the volume of redundant work and iterative back-
and-forth that currently inflates administrative burdens.
205 Rapid Assessment Scenario study, assuming that currently, a share of SoHO activities is not pursued for authorisation
due to exceedingly high costs of evidence generation and/or difficulty reaching full compliance. However, this share
could not be estimated. 206 Rapid Assessment Scenario study based on: Medicines and Healthcare products Regulatory Agency. (2025). AI
Airlock sandbox pilot programme: Report. UK Government.
https://assets.publishing.service.gov.uk/media/68ee1fb88427701993d5e02c/AI_Airlock_Sandbox_Programme_Report.
_Final.pdf and Commission nationale de l’informatique et des libertés. (2022). Dossier de presse : Bilan 2021 et enjeux
2022. https://www.cnil.fr/sites/default/files/atoms/files/dossier_de_presse_cnil_bilan_2021_et_enjeux_2022_vf.pdf. 207 Rapid Assessment Scenario Study, based on assumptions provided by the European Commission.
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Competitiveness, trade and investment flows: By providing a flexible, but coordinated
and proportionate pathway for novel SoHO activities, regulatory sandboxes will reduce
uncertainty and transaction costs for innovations. This could improve EU attractiveness
for certain R&I projects. Particularly strong competitiveness effects can be expected in the
forerunner countries with strong innovation potential. Such effects will come from two
sources. First, projects that are authorised thanks to sandbox evidence, which would not be
pursued otherwise.
Second, under the assumption that sandbox route allows for a responsible approach with
limited or more flexible types of appropriate evidence, and for less authorisations to be
obtained, innovative SoHO activities will become more attractive for SoHO entities.
Functioning of the internal market and competition: The regulatory sandboxes might
have an indirect effect if the outcomes obtained in one Member State are reused in other
Member States when assessing similar innovations. This can in particular be expected
given the central role of the SoHO Coordination Board in supporting and monitoring
sandboxes, including joint sandboxes undertaken by two or more Member States. The
overall approach of open access innovation in the largely public SoHO sector will also
contribute to a fast and harmonized roll-out of novel technologies.
Innovation and research: The regulatory sandboxes provide a pathway to authorisation
and a signal to the R&I stakeholders. As the immediate response to the sandbox measure,
we can therefore expect to see an increase in the actor activity in this segment. These
changes in risk and incentives and the reduction of the administrative burden could attract
more public entities into innovation and stimulate innovation activity in novel, borderline
cases and cases requiring cross-framework coordination.
Innovation in SoHO is continuous, often incremental and largely driven by activity in
public organisations, with knowledge diffusion through publications and professional
societies rather than patents208. In leading Member States, major public hospitals treat
research as a regular part of their activity and are linked to universities and research
institutes. This creates a favourable ecosystem for SoHO innovation, which is nevertheless
dependent on the availability of public and private research grants. However, high
administrative costs deter these actors from innovative and novel SoHO activities.
Controlled testing environments created through the regulatory sandboxes would enable
experimentation under protection from disqualification due to a mismatch with the current
framework. By allowing for adapted standards of regulatory evidence generation,
regulatory sandbox pathway can enable innovative research that might otherwise be
abandoned for fear of regulatory rejection. Therefore, these proposed amendments support
the ‘throughput’ phase of the innovation process. Innovation and research impacts at
Member State level are expected to be positive mainly via risk reduction, faster evidence
generation, increase in academic research, and regulator capability-building, but uneven
across Member States depending on capacity and ecosystem maturity.
208 Rapid Assessment Scenario Study, based on SWD(2022) 190 final.
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Regulatory sandboxes could be expected to shorten the path from innovation to safe
clinical use, especially where the baseline suffers from uncertain borderlines and divergent
evidence thresholds. In the financial technology area, firms that went through the
regulatory sandboxes had, on average, a 40% shorter time from engagement with the
regulator to market authorisation than similar firms using the standard process. In SoHO,
therefore, gains can also be expected. However, no baseline data is available for
quantification as these gains would be realised in the cases that otherwise would not be
pursued due to difficulty gathering evidence for authorisation.
Public authorities: The addition of the sandbox instrument is expected to expand the
mandate and increase the workload of public authorities in the short and medium term for
the benefit of significant cost reduction in the longer term due to achieved system
efficiency.
To quantify the operational costs of the regulatory sandboxes on public authorities, person-
day cost of the sandbox should be compared with person-day cost of the SPA model, taking
into account both the costs of learning by doing and the cost reduction expected in the
medium term due to cross-Member State learning leading to improved efficiency of
operations when novel SoHO activities are concerned. Furthermore, OECD guidance
indicates that investments are needed for regulators in terms of time, expertise, and
organisational capacity when instituting a sandbox instrument.
These costs would be borne primarily by national competent authorities but also by the
Commission due to (i) the role in supporting the regulatory sandbox activities and hosting
the EU SoHO Platform, and (ii) the engagement of the SCB as a key operational and
consensus-building mechanism. Experts interviewed for this study assessed the role of the
EU-level guidance as high for organisation of SoHO activities on the Member State
level209. Commission-defined principles and formal mandates are essential to stimulate
cross-body collaboration among relevant public authorities within Member States and to
harmonise common national procedures for multi-framework cases.
We calculate the cost of regulatory sandbox for public authorities as follows: 1) assessing
request (no change per risk category), 2) workload of regulatory sandbox (50 person-days)
and 3) assessment of clinical evidence (reduced by 40%). This brings the workload on a
medium-risk case to 75-94 person-days per case (EUR 22,575 – EUR 28,294); and on the
high-risk case to 98-149 person-days per case (EUR 29,498 – EUR 44,849).
Public health and safety: The sandbox instrument grants earlier access to therapies for
patients involved in the clinical evidence collection, before the activity is approved. As
illustrated above, regulatory sandbox has similar evidence requirements as a high-risk
authorisation process. In total, regulatory sandboxes are expected to involve 450-3,000
patients p/a. The impact of such access could be significant in the case when sandboxes
provide evidence generation for SoHO activities that would otherwise not be feasible to
authorise, for example, in the cases of rare diseases or niche treatments. Follow-up
monitoring and assessment should consider whether these patients would have been served
at all if the sandbox route did not exist, since authorisations for sandbox-eligible cases
209 Rapid Assessment Scenario Study, based on stakeholder consultation (interview).
67
would be very difficult to obtain ordinarily. A key condition of sandbox eligibility is a
significant expected public benefit, which further implies that sandboxes will address the
needs that would otherwise not be met.
Longer-term effects are expected to arise due to institutionalisation of cross-Member State
learning and publication of sandbox reports on the EU SoHO Platform. The proposal
constrains derogations to standard SoHO procedures to what is strictly necessary and
requires explicit risk mitigation and monitoring and therefore disallows derogations on
voluntary or unpaid donation standards.
Table 6. Summary assessment of the effects due to the intervention n°6
Policy measure COB Admin CTI Int mar I&R PA H&S
Regulatory sandbox ++ + 0/+ 0 + ++ +
5.1.7 Intervention n°7: Targeted regulatory reform of the Directive on the
deliberate release into the environment of GMOs210
The proposal introduces specific provisions in Part C of Directive 2001/18/EC addressing
the placing on the market of GMMs as or in products other than food and feed with the
aim of creating a tailored, more efficient and streamlined regulatory framework for the
placing on the market of GMMs as or in products, while maintaining a high safety level
for human and animal health and the environment. The proposed provisions relate to the
risk assessment, to the validity of the consent granted for their placing on the market, and
to detection methods applicable to all GMMs. In addition, the proposal introduces the
concept of low-risk GMMs and a specific set of rules for adapted information requirements
and a streamlined authorisation procedure for this subgroup of GMMs to be detailed by
way of Commission delegated and implementing acts. The requirement for post-market
environmental monitoring of low-risk GMMs is equally adapted in the proposal, providing
the possibility to a notifier, based on certain conditions, to propose to omit post-market
environmental monitoring.
Expected impacts:
Conduct of business: The proposed regulatory framework for GMMs as or in products
other than food and feed is expected to improve some framework conditions for companies
being active in the GMM field. By shifting towards more product‑specific risk assessment
criteria, introducing specific modalities for detection methods, granting unlimited validity
for market consents and creating an accelerated pathway for low‑risk GMMs, where
certain data requirements would be waived in consideration of an existing Qualified
Presumption of Safety delivered by EFSA, the intervention should shorten time‑to‑market
and reduce procedural rigidity. This is expected to pave the way for GMM-related consents
for placing on the EU market of GMMs as or in products. Earlier market entry would
210 Directive 2001/18/EC, OJ L 106, 17.4.2001, pp. 1–39. ELI: http://data.europa.eu/eli/dir/2001/18/oj.
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mitigate income losses from regulatory delays and improve the business case for
investment, particularly for SMEs and start‑ups that are more sensitive to regulatory
timelines and uncertainty.
Administrative costs on businesses (including SMEs): The impacts are expected to be
very positive. While quantitative estimates are lacking for non‑food GMMs, a qualitative
assessment indicates that a more product‑focused risk assessment and a dedicated low‑risk
GMM pathway should substantially reduce the burden associated with preparing extensive
dossiers under the current GMO regime. Streamlined, more predictable procedures, the
unlimited validity of consents and the possibility to waive post‑market environmental
monitoring where justified would lower recurring costs, especially for GMMs considered
to be low risk. This is expected to make compliance more manageable for
resource‑constrained SMEs and start‑ups, to stimulate exploration of novel products and
partnerships between large firms and smaller innovators, and to reduce the incentive to
relocate development activities to jurisdictions such as the US or China with more flexible
GMM frameworks.
Competitiveness, trade and investment flows: The new regulatory framework is
expected to act as an enabler and accelerator. By reducing regulatory costs and uncertainty
and clarifying a route to market for GMMs, the intervention could render more projects
investable, thereby supporting an expansion of the innovation pipeline in sectors such as
biofertilisation, biocontrol, bioremediation, and bioleaching. Over time, this is expected to
translate into a larger portfolio of authorised GMM products and more robust EU‑based
value chains in these areas. The more predictable pathway from laboratory to market would
likely attract additional venture capital and corporate investment and may encourage
non‑EU companies with established GMM products to enter the EU market. The number
and resilience of biotech start‑ups and SMEs operating in GMM‑related domains is
likewise expected to increase, as founders and investors gain confidence that
commercialisation in Europe can realistically be achieved within acceptable timeframes.
However, all these effects would be gradual and path-dependent, unfolding over several
years and dependent on how the regulatory scrutiny process works in practice.
Functioning of the internal market and competition: There are no adverse impacts
expected. The new regulatory framework for GMMs modifies a horizontal framework and
will apply across all Member States and to all economic operators, so no distortions of
intra‑EU trade or competition between Member States are anticipated. The analysis notes
that competition and displacement may arise between GMM‑based products and their
non‑GM counterparts; however, in the absence of concrete evidence and given that many
firms are likely to offer both types of products, no material changes in internal market
functioning or competition patterns are expected as a direct consequence of the new GMM
framework.
Innovation and research: The proposed intervention is projected to have a positive and
potentially substantial effect. By reducing administrative barriers, shortening authorisation
timelines and providing regulatory clarity, the framework could stimulate R&D investment
by universities, research organisations and companies. This is particularly important in the
EU context, where excellent early‑stage biotech research has historically struggled to
translate into scaled‑up applications and competitive firms. A more innovation‑friendly
regulatory environment is expected to improve the EU’s relative position vis‑à‑vis other
69
major innovation regions such as the US and China, increase private funding for
GMM‑related research, and help retain and attract talent in this domain. Over the longer
term, the biotechnology innovation system around GMMs could therefore become more
dynamic, better leveraging Europe’s strong scientific base.
Public authorities and their administrative workload: The effects of the new regulatory
framework for GMMs are difficult to assess. The average effort for national competent
authorities per GMO authorisation of a non‑food/non‑feed GMM would fall. However, the
extent to which burden will be reduced will fall in a wide range, resulting from the fact
that the adaptation of risk assessment (applicable to all GMMs, and expected to go further
for low-risk GMMs) will be case-by-case and may lead to considerable variability of data
requirements. In the most conservative scenario, risk assessment would require roughly
the same amount of data as today, and only a small fraction of products would qualify for
the low‑risk procedure (interviews suggested that national authorities may be cautious in
designating GMMs as low‑risk, based on a precautionary approach and no practical
experience with non‑medical GMM releases), translating in very limited gains for
competent authorities. In less conservative scenarios, the tailoring of risk assessment to
GMMs is expected to deliver efficiency gains for national authorities. In addition, the
harmonisation of criteria for low-risk products will allow the effective use of that
procedure, delivering further efficiency gains and reduction of administrative burden.
Further savings, in the phase following the initial authorisation, would result from the
unlimited authorisation validity and waivers of post‑market environmental monitoring.
These were not quantified and would accrue mainly at national level. At EU-level, the
mechanisms regarding EFSA’s role in resolving disagreements between Member States is
not modified, and the considerations above apply in those instances where -following a
disagreement- EFSA would need to conduct an assessment. Both at national and EU-level,
if application numbers rise significantly under the new framework, total administrative
effort may increase or decrease depending on how many of these applications would have
occurred under the existing regime and on the effective use of the low‑risk pathway.
Public health and safety: The proposed measures are designed to maintain the high
protection standards of the current EU GMO regime while making their implementation
more proportionate to the specific characteristics of GMMs. The intervention does not
lower safety standards or abandon mandatory risk assessment but rather tailors information
requirements and allows for more flexible approaches where risks are low and well
understood. This is expected to reduce unnecessary regulatory burdens without
compromising the high level of protection of human and animal health and the
environment.
At the same time, by enabling the deployment of beneficial GMM applications that are
currently discouraged or displaced to other regions, the new framework could help realise
environmental and sustainability benefits, for instance by supporting more
resource‑efficient agriculture, cleaner industrial processes or enhanced bioremediation. In
doing so, it may contribute to broader EU policy objectives such as the European Green
Deal and the 2030 Agenda for Sustainable Development, while preserving robust
safeguards for health and the environment.
70
Table 7. Summary assessment of the effects due to the intervention n°7
Policy measure COB Admin CTI Int mar I&R PA H&S
Regulatory
framework for
GMMs as or in
products other than
food and feed
+ + + 0 + +/0 0
5.1.8 Intervention n°8: Targeted regulatory reform of the Directive on human
organs intended for transplantation211
The proposal amends Directive 2010/53/EU to reflect technological developments in organ
preservation and processing and to provide EU-wide legal clarity and standards for
innovative practices which aim to improve organ quality and expand transplantation
opportunities.
First, the scope of the Directive is extended to explicitly include the processing of organs
prior to transplantation, with a definition of “processing” being introduced by the proposal,
encompassing any operation involving the handling of organs performed to maintain or
improve the functional status of an organ prior to transplantation.
Second, a specific authorisation regime for organ processing per processing technology
and per transplantation centre is established. A transplantation centre is to submit an
application for authorisation to the competent authorities including a benefit-risk
assessment where scientific evidence and clinical data are available. In the absence of such
evidence and data, e.g. when no other EU transplantation centre has been authorised to
apply the same organ processing technology, a clinical outcome monitoring plan must be
submitted for approval. A clinical outcome monitoring plan must also be submitted for
approval where the benefit-risk assessment identifies a significant risk. The extend of the
clinical monitoring will be proportionate to the risks identified. Detailed rules on the
authorisation procedure are to be established through Commission implementing acts and
guidance on the benefit risk-assessment is to be established by the competent authorities.
Transplantation centres must request the written agreement of competent authorities prior
to making significant changes to authorised processing steps. The competent authorities
have the prerogative to suspend an authorisation where there is reasonable ground to
suspect non-compliance. A central EU list of authorised processing techniques or with an
approved clinical outcome plan is to be established by the Commission. This will serve as
reference point to simplify later authorisations of similar processing technologies used in
other EU transplant centres, and hence to facilitate the roll-out and uptake of the same
processing technology for other centres and authorities.
211 Consolidated text: Directive 2010/53/EU, ELI: http://data.europa.eu/eli/dir/2010/53/2010-08-06.
71
Third, the proposal clarifies coordination with other Union health legislation. Where organ
processing involves medicinal products, medical devices or SoHO preparations, national
competent authorities must verify compliance under the relevant Union frameworks and
cooperate with the corresponding national competent authorities under Directive
2001/83/EC, Regulation (EC) No 726/2004, Regulation (EU) 2017/745 and Regulation
(EU) 2024/1938 to ensure coherent and more efficient oversight.
These amendments aim to provide EU-wide and cross-sector legal certainty, support
innovation in transplantation, and ensure high standards of quality and safety while
facilitating timely clinical uptake of advanced processing technologies.
Expected impacts:
Measure 1 – the enlarged scope is textually modest but legally consequential as the
foundational enabler of Measures 2 and 3. On its own, however, it generates no direct
operational requirements, administrative obligations or supervisory mandates. Its
independent effect operates through a single channel: the provision of legal certainty by
formally recognising organ processing as a regulated activity within the EU legislative
framework. This resolves the legal ambiguity identified in the problem definition and
sends a regulatory signal to transplantation centres and technology developers, but
the substantive operational, administrative, and health impacts materialise only through
Measures 2 and 3.
Measure 2 – on organ processing authorisation regime - is crucial and derives in nearly
all quantified impacts for this intervention area.
The conduct of business is assessed as moderate positive: the framework relates to the
operational model of transplantation centres by introducing a prior authorisation obligation
per centre and per processing technology. However, the net effect is positive because the
certainty channel (removing the legal ambiguity that functions as a structural drag on
adoption) outweighs the compliance channel, yielding an estimated 70-110 additional
programmes with active processing capability and approximately 1,435 additional
transplants per year by 2035.
Administrative costs on businesses are assessed as marginal negative: the per-
application cost is estimated at EUR 11,500-16,750 (Track 1/Track 2), with a cumulative
EU burden of approximately EUR 2.5 million over 2029-2035, costs that are real but
proportionate and partially offset by replacing fragmented and duplicative baseline
compliance arrangements. Moreover, only the first centre in the EU has to complete the
full pathway at the full cost, since subsequent centres can apply a shortened pathway by
using evidence from the central list. This leads to significant administrative savings for the
overall EU transplant community. Further, transitional measures are envisaged to avoid
the authorisation of practices already in place, so that these are not to be re-authorized.
Competitiveness, trade and investment flows are marginally positive: the transparent
authorisation pathway reduces the regulatory risk premium for private investment in organ
processing technologies, but the effect is indirect given the niche character of the market.
The internal market benefits from standardised authorisation procedures that create
mutual trust for cross-border exchange of processed organs, with an estimated 120-250
72
additional cross-border exchanges per year by 2035, while the published list of
authorised operations generates de facto EU-wide convergence of practice.
Innovation and research are moderate positive: the dual-track system provides a
structured pathway for next-generation technologies (Track 2 conditional authorisation),
an estimated 15-36 active monitoring plans generate structured EU-level evidence, and
the “Processing” data field in the Annex creates the taxonomic infrastructure to
disaggregate processing-attributable outcomes.
Public authorities face a marginal negative impact: the transition-phase assessment cost
is approximately EUR 850,000 over three years across the EU, declining to
approximately EUR 60,000-85,000 per year in steady state; the net incremental cost is
moderated by the replacement of ad hoc national arrangements but represents a genuine, if
manageable, expansion of the supervisory mandate.
Public health and safety is the strongest effect, assessed as significant positive: 1,435
additional transplants per year by 2035; 570-945 fewer organ discards; 57-72 waiting-
list deaths averted annually; approximately EUR 158 m in cumulative dialysis cost
savings over 2028–2035; and a structural improvement in safety oversight through the
mandatory benefit-risk assessment and clinical-outcome monitoring mechanisms.
Measure 3 addresses the multi-regulatory-domain nature of organ processing, which
require competent authorities to verify that products used in processing (medical devices,
medicinal products, SoHO preparations) are duly authorised under their respective EU
frameworks, and mandate cross-authority collaboration for the exchange of clinical
outcome data. Its impact profile is narrower and more targeted than Measure 2.
The conduct of business is marginal positive: the cross-framework verification adds a
structured step to the centre’s processing workflow but also brings EU harmonization and
reduces the ad hoc legal uncertainty that centres currently face regarding the permissibility
of specific product combinations.
Administrative costs are marginal negative: the verification dossier imposes a modest
additional documentation requirement, functionally embedded within the Measure 2
application process. However, there is a significant simplification in administration by
other centres, aiming to implement an organ processing step already authorized in other
EU transplant centres, facilitating uptake of novel processes across the EU.
Competitiveness, trade and investment flows are marginal positive: the clearer multi-
domain regulatory landscape marginally improves investment predictability for
manufacturers of perfusates, gene therapy vectors, and other products used across
regulatory frameworks.
The internal market is the principal beneficiary of this measure: the mandatory cross-
authority coordination directly addresses the regulatory silo problem identified in Section
3.2.3 and creates legally binding cooperation obligations that facilitate the acceptance of
processed organs involving multi-domain products across Member State borders.
73
Innovation and research are marginal positive: the mandated exchange of clinical
outcome data between regulatory frameworks generates research-valuable evidence on
multi-domain processing outcomes, contributing to a more coherent EU-level evidence
ecosystem.
Public authorities face marginal negative costs from establishing inter-authority
communication protocols, though Member States with existing cooperation infrastructure
will face limited marginal effort.
Public health and safety benefits indirectly but materially: the cross-framework
verification ensures that all products used in processing meet their respective EU safety
standards, and the mandated data exchange improves pharmacovigilance and device
vigilance for processing-related adverse events, closing a surveillance gap that currently
exists between regulatory silos.
Table 8. Summary assessment of the effects due to the intervention n°8
5.2 Interventions on industrial enablers: measures and expected impacts
5.2.1 Interventions n°9, 10 and 11: Strategic projects, high-impact projects and
ecosystem support framework
The proposed Regulation establishes a comprehensive framework to structure and
coordinate the selection, development and scaling-up of strategic health biotechnology
capacities and projects, encompassing:
(i) the recognition and the support of health biotechnology strategic projects
(Intervention n°9),
(ii) a targeted EU-level framework for high-impact strategic projects
(Intervention n°10)212, and
(iii) an ecosystem support framework (Intervention n°11).
212 The proposal sets out five types of high impact projects. For the purpose of the analysis in this section, two of these
project categories (biotechnology development accelerators - trusted testing or demonstration facilities with state-of-the-
art equipment and staff – and centres of excellence for advanced therapies) are taken into consideration, while three
others (concerning access to finance, AI-enabled biotechnology innovation and biodefence) are considered under the
respective intervention areas, namely Interventions 14, 15 and 17.
Policy measure COB Admin CTI Int Mar I&R PA H&S
1. Enlarged scope 0/+ 0 0/+ 0/+ 0/+ 0 0/+
2. Organ processing
authorisation regime
+ 0/– 0/+ + + 0/– ++
3. Cross-border and
cross-framework
coherence
0/+ 0/– 0/+ + 0/+ 0/– +
74
Together, these measures aim to boost the EU’s competitiveness and resilience in health
biotechnology, by strengthening biomanufacturing capacity, value chains, research and
technology infrastructures in the sector, accelerating innovation and technology
deployment and addressing ecosystem fragmentation through coordinated support
mechanisms.
Strategic projects (recognised by Member States) would benefit from administrative
support (including single points of contact at Member State level), accelerated procedures
(including for permitting, subject to a maximum ten-month deadline, as well as for dispute
resolution and litigation), a public interest status and measures to facilitate access to
funding at national and EU-level. Provisions also proposed support to pro-competitive
collaboration between projects, networks and clusters. High-impact projects (recognised
at EU level) represent a limited flagship portfolio of systemic importance, including
biotechnology development accelerators and centres of excellence for advanced therapies.
These projects benefit from similar support but with priority status, including an
accelerated eight -months permitting timeline and stronger signalling for Union financial
support.
These project-level measures are underpinned by ecosystem support instruments:
(i) a strategic mapping of the EU biotechnology ecosystem to identify capacities,
gaps and investment needs;
(ii) an EU health biotechnology support network with national and regional
antennas to assist innovators in navigating regulatory and funding pathways
and accessing scaling and networking opportunities; and
(iii) a European Health Biotechnology Steering Group to coordinate Member States
and the Commission, facilitate exchange of best practices and ensure effective
implementation for strategic and high impact health biotechnology projects.
The EU Health Biotechnology Support Network is not intended to duplicate existing EU-
level SME support structures, such as the Enterprise Europe Network or future horizontal
instruments under the European Competitiveness Fund. Rather, it operates as a sector-
specific coordination and support layer, building on existing structures where appropriate,
and providing health biotechnology-specific navigation, ecosystem coordination and
cross-border integration functions. In particular, while existing networks may support
firms on general business, innovation or internationalisation aspects, they are not designed
to provide structured support for navigating complex, multi-framework health
biotechnology regulatory pathways. The design of the Support Network is therefore
intended to remain compatible with and complementary to future EU-level SME support
architectures, including the envisaged EU for Business Network, notably by leveraging
existing capacities while ensuring the availability of specialised expertise.
Expected impacts:
Conduct of business and administrative costs: Taken together, the measures are
expected to generate significant positive impacts on conduct of business and administrative
costs for firms, with positive but more incremental contributions to competitiveness,
internal market functioning, innovation and, indirectly, public health and safety. Impacts
on public authorities are expected to be front-loaded but moderate overall due to reliance
75
on existing structures. The principal transmission channels operate at two complementary
levels. At project level, impacts arise from reduced execution risk through more predictable
and coordinated administrative handling, including time-bound permitting (ten months for
strategic projects, eight months for high-impact projects), structured single points of
contact model and facilitated access to finance. At ecosystem level, impacts arise from
reduced transaction and navigation costs, improved access to investors and infrastructures,
and strengthened cross-border collaboration through network and cluster effects.
Uptake is a key uncertainty across all components, therefore the scale of impacts should
be interpreted as proportional to the number and maturity of projects applying for
recognition and to the utilisation of ecosystem support services. This reflects the voluntary
nature of the mechanism and the fact that promoters will weigh the administrative effort
of application against the expected benefits of more predictable administrative pathway
and improved access to support, consistent with observed dynamics in comparable
strategic-project regimes213.
To illustrate the potential order of magnitude, three uptake scenarios can be defined for
each of the project categories. As a calibration point, other EU-level priority-project
frameworks214 have operated at volumes ranging from several dozen to over one hundred
projects, providing a useful order-of-magnitude reference (rather than a direct comparator)
for the potential scale of project pipelines under coordinated policy frameworks. Against
this backdrop, an indicative range for health biotechnology strategic projects could be
framed as: (i) low uptake: around 25-30 recognised projects by 2038, (ii) medium uptake:
around 60-70 projects, and (iii) high uptake: around 100-120 projects. For high-impact
projects, reflecting a limited flagship portfolio, ranges would be: low uptake (six to –eight
projects), medium uptake (12–15), and high uptake (20–25).
Conduct of business: Significant positive impacts are expected through greater
predictability, shorter effective administrative lead times for strategic and high-impact
projects, alongside reduced coordination frictions. Greater clarity and time-bound
procedures are expected to improve planning horizons, milestone sequencing and time-to-
revenue, reduce volatility in project schedules and strengthen firms’ capacity to align
procurement, construction and staffing decisions with a clearer administrative pathway.
Delay and uncertainty remain economically material for capital-intensive investments,
with an indicative benchmark suggesting that regulatory delays of more than 12 months
beyond initial projections have been associated with an average 34% increase in total
development costs, alongside a high incidence of additional funding rounds and some
programme abandonment.
213 See Commission SWD on establishing a framework of measures for strengthening Europe’s Net Zero Industry Act:
COM(2023) 219 final (https://single-market-economy.ec.europa.eu/publications/net-zero-industry-act_en). 214 E.g. projects recognised under Union frameworks with explicit strategic project provisions, such as those established
by the Net Zero Industry Act and the Critical Raw Materials Act, as well as earlier coordinated frameworks such as the
first Union list of energy Projects of Common Interest (PCIs) and Projects of Mutual Interest (PMIs) comprising 166
projects and approved IPCEIs in the microelectronics value chain comprising 100 projects across 14 Member States.
While the scale of such projects is influenced by Member State participation, fiscal capacity and policy priorities, they
remain informative as to the potential scale of coordinated project pipelines. The ranges presented here are therefore
illustrative and adapted to the specific design and incentives of the present measure.
76
For high-impact projects, these effects are reinforced through access to promoter-led
shared late-stage translation infrastructures with cross-border relevance, supporting more
efficient development and scale-up. Impacts can be evidenced through utilisation
indicators such as the number of firms served, including SMEs, the number of service
engagements (e.g. testing, validation and small-batch GMP runs), and utilisation rates,
reflecting improved coordination and access to critical capabilities.
Ecosystem support measures contribute indirectly by improving visibility of strategic
projects, facilitating collaboration and enhancing firms’ ability to navigate the EU
regulatory and funding landscape. While these effects are not directly attributable in
isolation, they reinforce the overall improvement in business conditions generated by the
project-level measures. Overall, once implementation stabilises, a significant share of
recognised projects is expected to complete permit granting within the applicable
timelines.
Administrative costs on businesses, including SMEs: Significant positive impacts on
administrative costs are expected, driven by reduced transaction costs, simplified
administrative interactions and more predictable, time-bound procedures. For strategic and
high-impact projects, reductions arise from fewer parallel interfaces, fewer iterative
information exchanges and greater reuse of existing evidence, supported by single points
of contact and structured administrative facilitation. These effects are expected to lower
compliance costs and administrative burden, with avoided delay costs for capital-intensive
investments constituting the main economic benefit.
For high-impact projects, impacts are more targeted, reflecting prioritised handling and
faster decision-making for a limited number of catalytic projects, reducing schedule
uncertainty rather than generating system-wide burden reductions. Ecosystem support
measures further reduce navigation and search costs, particularly for SMEs and start-ups,
through a single-entry point and improved preparedness for regulatory interactions.
Overall, impacts are expected to be proportionately stronger for SMEs lacking in-house
administrative capacity.
Competitiveness, trade and investment flows: Positive impacts on competitiveness,
trade and investment flows are expected through improved bankability, stronger
investment signalling and reduced time-to-market. For strategic and high-impact projects,
more predictable delivery and prioritised handling are expected to lower risk premia and
improve conversion from planning to financial close, supporting higher investment
mobilisation and leverage, particularly for mature and bankable projects. High-impact
projects are expected to generate stronger effects per project due to their scale, visibility
and systemic relevance.
Ecosystem support measures reinforce these effects by improving access to investors
through structured matchmaking and by reducing delays linked to incomplete or immature
submissions, thereby shortening time-to-market215. Overall investment mobilisation will
215 Evidence from the EIC Business Acceleration Services demonstrates that structured matchmaking can generate
measurable outcomes (over 20,000 meetings, 595 deals, EUR 350 million raised since 2021). On time-to-market, EMA
data indicates that applicant-side clock-stops represent a substantial portion of total procedure time (198 days average vs
77
depend on project maturity and uptake, but the combined framework is expected to
strengthen investment attractiveness and facilitate greater mobilisation of both public and
private capital in the Union health biotechnology sector. Existing Union financing
instruments can also amplify these effects through leverage: where support is backed by
an EU budget guarantee, this can reduce risk for implementing partners and crowd in
additional public and private investment beyond the direct Union contribution.
Internal market: Positive impacts on the functioning of the internal market are expected
through a more visible and comparable pipeline of strategic projects and reduced
information asymmetries for promoters, authorities and investors. Cross-border
recognition for projects located in two or more Member States is expected to reduce
duplicative processes and improve consistency of treatment, supporting more contestable
investment conditions across Member States, while take-up patterns will remain sensitive
to underlying administrative capacity and clustering effects. Internal market effects are
expected to strengthen as uptake increases and the pipeline becomes sufficiently broad and
geographically distributed to improve comparability and transparency across Member
States.
These effects are reinforced by improved cross-border accessibility of infrastructures and
shared capabilities in the context of high-impact strategic projects, facilitating resource
pooling and multi-country collaboration. The Support Network is expected to reduce
fragmentation of support services by providing comparable216 antennas across Member
States. Cluster networks further contribute by structuring cross-border ecosystems,
enabling access to biomanufacturing and research infrastructures and supporting the
formation of cross-border consortia217.
Innovation and research: Impacts are expected through faster and more efficient
translation of research and innovation into industrial deployment, supported by strategic
projects and reinforced by a limited number of high-impact catalytic assets addressing late-
stage bottlenecks. Strategic projects contribute through strengthening biomanufacturing
infrastructures and innovation assets, while high-impact projects further enhance the
number and speed of projects progressing through late-stage development,
particularly for advanced therapies and other complex applications.
These effects are complemented by ecosystem measures, notably cluster networks and
support structures that strengthen research-industry linkages and facilitate cross-border
collaboration, thereby enhancing firm-level innovation capacity and access to shared
infrastructures. Overall, innovation impacts are expected to scale with uptake and portfolio
composition, with the main effect being improved translation and deployment rather than
system-wide shifts in innovation performance.
204 days assessment time in 2023), with 42% of applicants requesting extensions due to immature data. By helping
SMEs come better prepared to interactions with regulatory bodies, the Support Network could address submission
readiness gaps that contribute to these delays. 216 This comparability is ensured through common selection criteria set by the Commission, standardised service
functions, and EU-level coordination via the Steering Group and strategic mapping, which together support consistent
service delivery across Member States. See Rapid Assessment Study – forthcoming – for further elaboration. 217 Evidence from the ECCP Cluster Panorama and sector comparators (e.g., Silicon Europe with 2,500+ companies)
supports the potential of cluster structures to facilitate cross-border consortia.
78
Public authorities: They are expected to be front-loaded mainly due to process design,
workload reallocation and coordination needs to operate single points of contact and
provide structured support, as well as participation in governance and coordination
structures. In many Member States, single points of contact may be established by
designating or adapting existing administrative coordination mechanisms rather than
creating entirely new structures, which may reduce upfront costs. Over time, efficiency
gains are expected as procedures standardise, and administrative experience accumulates.
Incremental impacts attributable specifically to the high-impact designation are expected
to be limited and concentrated in selection, monitoring, coordination and reporting for a
limited flagship portfolio, without duplicating cost drivers associated with general
permitting operations and routine administrative facilitation. Administrative workload will
scale with the number of recognised projects and monitoring cycles required.
The intervention also introduces additional obligations for Member States, including
participation in the Steering Group, data provision for ecosystem mapping and facilitation
of support network activities, but these are expected to build on existing structures,
resulting in marginal set-up costs. Comparable initiatives (NZIA, CRMA) estimate 1–2
FTEs for one-stop shop functions and around two FTEs for governance participation.
These initial obligations are expected to yield efficiency gains over time, as Member States
gain access to a systematic evidence base and coordination forum that should improve
national decision-making and reduce duplicative investments. At EU-level, technical
assistance appropriations of approximately EUR 2.6 million annually (EUR 18.4 million
over the MFF period) cover relevant coordination functions.
Public health and safety: Impacts are expected to be positive but indirect, mediated by
the realised project portfolio and the extent to which faster delivery translates into earlier
EU-based capacity for strategic products and a contribution to supply resilience outcomes.
The scale of both administrative workload and resilience-relevant capacity effects is
expected to increase with uptake, subject to project mix and implementation performance.
For high-impact projects, the core impact pathway will be potentially faster, safer and more
efficient development of innovative therapies, notably advanced therapies, supported by
improved access to specialised testing, validation, small-batch GMP and quality control
services and, where relevant, links to data and digital infrastructures.
Impacts are expected to materialise over the medium term and remain conditional on
uptake by developers and manufacturers, as well as on broader regulatory, reimbursement
and health system conditions affecting downstream patient access. Ecosystem support
measures are not expected to have direct effects but may indirectly reinforce these
outcomes by facilitating collaboration and improving system preparedness.
The tables below provide an illustrative, scenario-based quantification218 of the expected
impacts by 2038 under three uptake cases for the recognition and support framework for
strategic health biotechnology projects (Table 9) and for high impact health biotechnology
projects (Table 10) for each impact category. Impacts should be interpreted as orders of
218 See Annex 7 and relevant sections of the Rapid Assessment Study – forthcoming for further elaboration on the
calculations of impacts
79
magnitude and as broadly proportional to the number, maturity and operationalisation of
recognised projects over the period.
Table 9. Illustrative uptake scenarios and order-of-magnitude impacts for strategic
health biotechnology projects
Impact
category
Summary
assessment of
the effects due
to the policy
measure
Key indicators expected evolution under different project uptake
scenarios
Low uptake (25-30
projects)
Medium uptake
(60-70 projects)
High uptake
(100-120
projects)
COB ++ Projects completing permit
granting within 10 months:
~18-26
~42-60 ~70-102
Admin ++ Avoided delay costs
(cumulative): ~EUR 90-
410 million
~EUR 214-952
million
~EUR 357-
1,632 million
CTI ++ Total investment mobilised
(cumulative): ~EUR 6-12
billion
~EUR 15-28 billion ~EUR 25-48
billion
Int mar + Cross-border projects (≥2
Member States): ~3-6
~6-14 ~10-24
I&R + Projects with material
R&I or innovation
infrastructure outputs: ~5-
9
~12-21 ~20-36
PA 0/+ Recognition decisions per
year (average): ~2-3;
indicative single point of
contact capacity: ~0.5-1
FTE
~5-6; ~1-2 FTE ~8-10; ~2-3
FTE
H&S + Capacity-relevant strategic
deployments: ~8-15
~18-35 ~30-60
80
Table 10. Illustrative uptake scenarios and order-of-magnitude impacts for high
impact strategic health biotechnology projects
Impact
category
Summary
assessment of
the effects due
to the policy
measure
Key indicators expected evolution under different project uptake
scenarios
Low uptake (6-8
projects)
Medium uptake (12-
15 projects)
High uptake (20-25
projects)
COB ++ Shared-capability
throughput: ~60-120
firms/year, ~120-480
engagements/year
~120-360 firms/year,
~240-1,440
engagements/year
~240-600 firms/year,
~480-2,400
engagements/year
Admin ++ Avoided delay costs
(cumulative): ~EUR
20.4-85 million
~EUR 51-204 million ~EUR 91.8-340
million
CTI + Total investment
mobilised
(cumulative): ~EUR 2-
6 billion
~EUR 4-12 billion ~EUR 6-20 billion
Int mar + Cross-border users
supported: ~12-48
firms/year
~24-144 firms/year ~48-240 firms/year
I&R + Clinical trial
applications linked to
capability layer: ~4-
8/year
~8-24/year ~16-40/year
PA 0/+ Incremental
workload: ~6-8
recognition decisions
plus monitoring
cycles, limited multi-
country coordination
~12-15 decisions plus
monitoring, moderate
coordination
workload
~20-25 decisions
plus monitoring,
higher coordination
workload but still
bounded by
portfolio design
H&S + Therapy programmes
supported with
improved
development pathway:
~2-4/year
~4-12/year ~8-20/year
81
Table 11. Summary assessment of the effects of Intervention n°11: Health
biotechnology ecosystem support framework
Policy intervention COB Admin CTI Int Mar I&R PA H&S
Ecosystem support
measure
0 ++ + + + - 0
5.2.2 Intervention n°12: Biosimilars competitiveness framework
The proposal includes two measures focusing on biosimilars:
First, it proposes the development and update of EMA guidelines on tailored and risk-
proportionate regulatory approaches for biosimilar development, reflecting manufacturing
and analytical testing advances. Most importantly, the guidance will set out the criteria and
provide for the potential reduction of clinical data requirements for biosimilar development
and approval without affecting quality, safety and efficacy. The revision would be guided
by the assessment and conclusions of the reflection paper on tailored clinical approach in
biosimilar development by EMA and the CHMP Biosimilar Medicinal Products Working
Party (BMWP), published on 27 March 2026219. The reflection paper concludes that “a
tailored approach for clinical development of biosimilar candidates is possible.
Comparative Efficacy Studies (CES) are no longer expected to be required for approval of
biosimilars that can be thoroughly characterised using state-of-the-art analytical methods
and have demonstrated similarity in physicochemical and functional properties”.
Comparative clinical pharmacokinetics/pharmacodynamics (PK/PD) studies can in this
context provide supportive safety and immunogenicity data. Over the past three years,
applications concerning monoclonal antibodies and fusion proteins have represented more
than 90% of all biosimilar marketing authorisation applications (see Annex 5 - additional
background on the sector and problem definition). The proposed measure is therefore
expected to have a broad practical impact, as it applies to the majority of current and future
biosimilar development programmes.
Second, it proposes the establishment of a framework for the recognition and the support
of health biotechnology strategic projects focused on biosimilar research, development,
manufacturing and marketing authorisation. The support package outlined in intervention
n°9 applies to these projects. Furthermore, the proposed measure promotes international
cooperation between economic operators and biotechnology clusters active in the area of
biosimilars, including in the context of health biotechnology strategic projects.
The two measures are complementary and the intervention logic goes as follows: The EMA
guidelines are expected to reduce the evidentiary burden and associated cost and time of
biosimilar development, thereby lowering barriers to market entry. Simultaneously,
biosimilar strategic project recognition aims to provide administrative, financial, and
permitting support for biosimilar manufacturing and development projects within the EU.
219 Reflection paper on a tailored clinical approach in biosimilar development.
82
Furthermore, eligibility criteria for biosimilar strategic projects enable projects developing
analytical methodologies that reduce clinical data needs to qualify for support under the
measure, creating a feedback loop between regulatory modernisation and industrial
investment.
Expected impacts of measure 1: update and development of EMA guidelines
Conduct of business: If, following EMA guidelines, CES requirement was waived for
biosimilar mAb products where analytical similarity is comprehensively demonstrated,
developers could reduce direct Phase III clinical trial costs by an estimated EUR 19–26
million per product220, with a broader range of EUR 14–46 million across all trial types221.
Clinical development accounts for approximately 57% of total biosimilar development
costs222, with the CES representing the single largest component.
Of the 27 biosimilar marketing authorisation applications (MAAs) resolved in 2024223,
approximately 24 concerned monoclonal antibodies or fusion proteins, the product classes
for which CES have historically been required (see Annex 5)224.
On this basis, three scenarios are considered regarding the uptake of a tailored
development approach including CES waivers.
An estimated CES cost of EUR 19–26 million per product for monoclonal antibody and
fusion protein biosimilars is used to estimate the gross annual cost savings for industry.
Residual clinical requirements are expected to persist. Comparative PK/PD studies
(estimated at EUR 5.7–7.8 million per product) will remain necessary for all biosimilars,
and immunogenicity assessment will continue to be required, particularly for antibody-
based products. Accounting for these residual costs, total net savings are assumed to be
reduced by approximately 30%225.
In the near term (2025–2030), assuming 25–45 biosimilar marketing authorisation
applications (MAAs) per year, with approximately 90% relating to monoclonal antibodies
and fusion proteins, and that 50–75% of these would benefit from a tailored development
approach including a CES waiver, the gross annual cost savings for industry are estimated
at EUR 214–790 million.
220 Ranbhor, R., & Kulkarni, P. (2026). Net present value impact of FDA's Phase 3 waivers on monoclonal antibody
biosimilar development programs. Biosimilars and Targeted Therapy. https://www.dovepress.com/net-present-value-
impact-of-fdas-phase-3-waivers-on-monoclonal-antibod-peer-reviewed-fulltext-article-BTT. 221 Moore, T. J., Mouslim, M. C., Blunt, J. L., Alexander, G. C., & Shermock, K. M. (2020). Assessment of availability,
clinical testing, and US Food and Drug Administration review of biosimilar biologic products. JAMA Internal Medicine,
181(1), 52–60. https://doi.org/10.1001/jamainternmed.2020.3997. 222 Ranbhor, R., & Kulkarni, P. (2026). Net present value impact of FDA's Phase 3 waivers on monoclonal antibody
biosimilar development programs. Biosimilars and Targeted Therapy. https://www.dovepress.com/net-present-value-
impact-of-fdas-phase-3-waivers-on-monoclonal-antibod-peer-reviewed-fulltext-article-BTT. 223 Of the 27 MAAs 25 were authorised and 2 withdrawn or refused; source: EMA Medicines Database, 2026. 224 European Medicines Agency. (2026). Medicines output report [dataset]. Retrieved 2 March 2026 from
https://www.ema.europa.eu/en/medicines/download-medicine-data; European Medicines Agency. (2025). Annual report
2024. Publications Office of the European Union. https://doi.org/10.2809/7433636. 225 The share of European investment into biosimilar development, which is not allocated to CES, which in turns makes
up for the 70% as outlined above.
83
After accounting for residual clinical development requirements—primarily comparative
PK/PD studies and immunogenicity assessments net annual savings are expected in the
range of EUR 150–552 million.
Over the five-year period (2025-2030), cumulative net savings are therefore estimated
at:
Scenario Uptake Gross annual cost
savings for
industry
Total net annual
savings
Five-year period,
cumulative net
savings
Low scenario
(50%)
12 products per
year transition to
CES waivers
EUR 222–312
million
EUR 155–218
million
EUR 0.75 billion
Central
scenario (≈60–
65%)
14–15 products per
year
EUR 266–390
million
EUR 186–273
million
EUR 1.5–1.8
billion
High scenario
(75%)
18 products per
year
EUR 342–467
million
EUR 239–326
million
EUR 2.8 billion
The projected annual range of 25–45 marketing authorisation applications (MAAs) reflects
a normalisation following the exceptional peak observed in 2025, notably linked to
denosumab-related applications. At the same time, projections remain constrained by the
‘biosimilar void’ 226, 227.
The lower bound (25/year) assumes the void persists; the upper bound (45/year) assumes
that the guidance (issued by 2027) begins attracting developers. Under current conditions,
it is estimated that only around 10% of the approximately 100 biologics expected to lose
exclusivity in the EU by 2032 will face biosimilar competition228.
In the medium term (2030–2038), assuming that the tailored approach to CES waivers is
widely implemented, and that complementary investment support measures partially
mitigate the ‘biosimilar void’, it is projected that 35–55 biosimilar MAAs may be
submitted annually. Of these, approximately 90% are expected to concern monoclonal
antibodies and fusion proteins, with 70–80% benefiting from a tailored development
approach including a CES waiver.
On this basis, the gross annual cost savings for industry are estimated at EUR 418-990
million.
226 Approximately 100 biological medicines are expected to lose exclusivity in Europe by 2032. However, 79% currently
have no biosimilars in development, and only 10% of biologics nearing loss of exclusivity are likely to face biosimilar
competition in Europe when accounting for the geographic footprint of clinical trials (IQVIA, 2026). The void is
concentrated in biologics with projected global sales below USD 100 million, where current development costs remain
prohibitive. 227 IQVIA, The Impact of Biosimilar Competition in Europe, 2026, iqvia-the-impact-of-biosimilar-competition-in-
europe-2026-01-26-forweb.pdf. 228 IQVIA, The Impact of Biosimilar Competition in Europe, 2026, iqvia-the-impact-of-biosimilar-competition-in-
europe-2026-01-26-forweb.pdf.
84
After accounting for residual clinical development requirements net annual savings are
expected in the range of EUR 293–700 million.
Over a five-year period within this timeframe, cumulative net savings are therefore
estimated at:
• Low scenario: EUR 1.5 billion
• Central scenario: EUR 2.3–2.8 billion
• High scenario: EUR 3.5 billion
These projections reflect a scenario in which reduced development costs, increased
regulatory predictability, and targeted policy support measures contribute to higher
biosimilar uptake and increased market entry. As such, the economic impact of CES
waivers is expected to be significantly amplified compared to the near-term period.
Overall, the medium-term scenario suggests that the full implementation of a tailored, risk-
based regulatory approach could generate substantial and sustained cost efficiencies for
industry, while supporting improved competition and access to biological medicines in the
Union.
According to the Biosimilar Medicines Group229, a sector group of the Medicines for
Europe organisation, under the current framework, the sector’s contribution to European
clinical trials for biosimilar candidates amounts to EUR 4.9 billion over five years, with
approximately 71% allocated to CES. The implementation of CES waivers could free an
estimated EUR 3 billion over five years in clinical spending. These resources could be
reallocated to European research and development and manufacturing, including the
development of next-generation biosimilar medicines, new technological platforms (e.g.,
antibody-drug conjugates, cell and gene therapies), and modernisation of manufacturing
operations).230
While the cost impact of biosimilars has been evaluated, the potential time savings are
expected to be limited, as many development streams run in parallel rather than
sequentially. A CES waiver would accelerate one stream, while the remaining streams
continue to constrain the overall development timeline. However, shorter development
pipelines would allow developers to start later, once the originator’s market trajectory—
including geographic penetration, therapeutic positioning and real-world outcomes—is
clearer, thereby reducing commercial risk without affecting the ultimate timing of market
entry.
Administrative burden: The dominant cost saving is associated with the CES waiver and
not with the reduction in dossier preparation labour. According to reported estimates, the
preparation of a full CES-based dossier requires approximately 328 person-days (EUR
131–197 thousand), compared to 253 person-days (EUR 101–152 thousand) for a tailored
package. This represents a reduction of approximately 75 person-days (EUR 30–45
thousand) per application. Applied to 12–18 affected MAAs annually, this yields an
aggregated administrative savings of EUR 0.36–0.81 million per year at current
229 https://www.medicinesforeurope.com/biosimilar-medicines/who-we-are/ . 230 Medicines For Europe factsheet: Pillar 1-2-3-4-FOOTPRINT-SPC-Biotech-Act-facsheets-ppt.cdr.
85
conditions. While measurable, these savings are secondary relative to clinical trial cost
reductions (see Annex 5 for reported detailed dossier preparation calculations).
Innovation and research: The proposed intervention is expected to reallocate innovation
incentives toward advanced analytical science. As outlined in the section ‘conduct of
business’ above, savings generated from the elimination of superfluous comparative
efficacy studies (CES) are estimated at EUR 717 million- 2.76 billion in five years, as
regulatory reliance shifts from clinical trials to analytical comparability. According to
another recent industry report231, approximately EUR 3 billion in R&D expenditure will
be freed up over five years out of the current EUR 4.9 billion —to be reinvested in the
development of additional biosimilar products, new technology platforms, and the
modernisation of manufacturing operations.
Public health: The tailored approach is expected to accelerate patient access without
compromising safety. Therapeutic coverage is expected to expand from approximately 27
reference products to 35–45 by 2030 and to 55–75 by 2038. The cumulative number of
authorised biosimilars is expected to grow from 151 in 2024 to 250-350 between 2025-
2030232 and to 450-650 between 2030-38233. This expansion is projected to generate
significant system-level savings, increasing from approximately EUR 13 billion in 2024
to EUR 16–22 billion annually by 2030 and EUR 22–35 billion/year by 2035–2038,
driven by increased competition and broader treatment availability. The introduction of a
tailored regulatory approach is not expected to alter the underlying safety standard, as it
modifies evidentiary requirements rather than regulatory thresholds for approval234. The
safety outlook therefore remains unchanged, with no increase in withdrawals on safety
grounds anticipated.
However, the upper bounds of these projections are tempered by a structural gap in the
market. Of approximately 100 biologics expected to lose exclusivity by 2032, 79% have
231 Medicines for Europe, Biosimilar Medicines Sector Group. (2025). Reforming Regulations, Market Entry and
Competition for Biosimilar Medicines (Pillar 2) [Factsheet]. Brussels: Medicines for Europe.
https://www.medicinesforeurope.com/wp-content/uploads/2026/03/FOOTPRINT-Biotech-Act-factsheet.pdf.232 151 biosimilars already authorised in 2024. To this, we add the expected new approvals between 2025 and 2030 i.e.
between 25 and 45 new applications, of which ~89% will be successful over 5 years
- Low estimate: 25 × 5 × 0.89 = ~111 new products → total ~262
- High estimate: 45 × 5 × 0.89 = ~200 new products → total ~351 233 ~300 authorised products in 2030, to this we add 35–55 annual applications between 2030 – 38 × 8 years ~89%
success rate
- Low estimate: 35 × 8 × 0.89 = ~249 new products → total ~549
- High estimate: 55 × 8 × 0.89 = ~392 new products → total ~692 234 Risk based tailoring of clinical evidence requirements for biosimilar marketing authorisations does not lower safety
standards; it reflects the maturity of the EU regulatory framework for biosimilars and advances in analytical science
used to demonstrate comparability with the originator product. The EU has the longest global experience with
biosimilars, with the first EU biosimilar approved in 2006, and since then over 100 biosimilars authorised across around
30 reference products, with no withdrawals on safety grounds. This long-standing experience confirms the robustness of
the comparability-based regulatory approach.
At the same time, analytical methods have significantly evolved. High-resolution structural characterisation, advanced
functional assays, and improved immunogenicity testing now allow very sensitive detection to demonstrate comparability
with the originator medicinal product.
This is complemented by strong post-authorisation safety monitoring through the European Medicines Agency. In this
context, streamlined clinical requirements do not weaken safety; they align regulatory expectations with current
scientific capability while preserving continuous real-world pharmacovigilance.
86
no biosimilar versions in development and only 10% are likely to face biosimilar
competition in Europe235.
Expected impacts of measure 2: biosimilar strategic projects recognition and support
The projects this proposed measure would target benefit from the same framework
described in intervention n°9 i.e. recognition and the support of health biotechnology
strategic projects: administrative support (including through single points of contact at
Member State level), accelerated procedures (including for permitting, subject to a
maximum ten-month deadline, as well as for dispute resolution and litigation), a public
interest status and measures to facilitate access to funding at national and EU-level.
Administrative costs on businesses: As for the projects described in intervention n°9, the
greatest efficiency gain is expected to be the reduction of execution risk through more
predictable and coordinated administrative handling, notably through a structured single
point of contact model and a maximum 10-month permit-granting timeline, complemented
by facilitated access to finance.
Conduct of business: The measure is expected to mobilise additional investment in EU
biosimilar manufacturing and development infrastructures. The magnitude depends on
Member State implementation. To estimate the order of magnitude, three uptake scenarios
are used, consistent with the approach applied in the strategic projects and high impact
projects assessments. Biosimilar projects are framed as a subset of the total strategic project
pipeline:
• Low uptake: 3–5 biosimilar projects recognised by 2038 (~0.3 per year)
• Medium uptake: 8–12 biosimilar projects (~1 per year)
• High uptake: 15–20 biosimilar projects (~1.5 per year)
See annex 7 for an overview of the illustrative order-of-magnitude impacts for biosimilar
strategic projects derived by proportional scaling from the Strategic Projects of chapter II
(intervention n°9).
Competitiveness, trade and investment flows: The effectiveness of the proposed
measure is expected to scale with its uptake, with higher levels of recognised projects
leading to greater mobilisation of investment in EU-based biosimilar manufacturing. The
investment mobilisation estimated at EUR 0.9–7.6 billion cumulative by 2038 reflects
the total capital deployed in biosimilar manufacturing and development projects. This
includes private investment, STEP-supported instruments, and any national co-financing.
The per-project investment range of EUR 200–400 million is consistent with the capital
requirements for dedicated biosimilar biomanufacturing facilities, as documented by
industry sources.236
235 IQVIA, The Impact of Biosimilar Competition in Europe, 2026, iqvia-the-impact-of-biosimilar-competition-in-
europe-2026-01-26-forweb.pdf. 236Alira Health. (2025, November 6). 2025 global biosimilars report: Market size, growth drivers, regional dynamics.
https://alirahealth.com/biosimilars-market-2025-market-size-growth-drivers-regional-dynamics/
87
Further, the proposed measure supports EU based manufacturers’ competitiveness in
biosimilars, by promoting international partnerships among economic operators as a
mean to share expertise and diversifying and strengthening supply chains. Recent studies
identified an increasing number of partnerships involving ex-EU biosimilar companies that
collaborate with European manufacturers to launch products in Europe. Historically, these
partnerships were relatively uncommon, but their prevalence has increased. Between 2006
and 2013, ex-EU partnerships represented 30% of all approvals, but more recently this
figure increased to 45% (2014–2024).237 The proposal aims to leverage this trend by
encouraging promoters of biosimilar projects to establish or strengthen cooperation with
international partners, including with a view to fulfilling the conditions for the
recognition of biosimilar strategic projects.
When it comes to research and innovation (R&I), as per specific eligibility criteria
proposed in Article 29, the recognised projects could contribute to R&I through setting up
or extending infrastructures for biosimilar analytical testing; strengthening the use of
platform technologies for research, development and marketing authorisation; and
developing analytical methodologies that would reduce the need for clinical data for the
development and approval of biosimilars. The impact of the measure on R&I will depend
on how many recognised projects will focus on material research or analytical innovation
outputs. As mentioned in the conduct of business section above, biosimilar projects are
framed as a subset of the total strategic project pipeline. Out of all 3-5 biosimilar strategic
projects in a low uptake scenario, we assume 1-2 to be R&I focused; 2-4 out of 8-12 in a
medium uptake scenario; and 3-6 out of 15-20 in a high uptake scenario (see Annex 7 for
full table of scenarios uptake).
The administrative costs for public authorities are part of the overall cost analysed in
chapter II for strategic projects. The initiative does not create a separate approval
architecture for biosimilar strategic projects specifically. Efficiency gains are expected to
emerge over time as procedures standardise, and administrative experience accumulates.
By 2030–2038, as the recognition process matures and uptake increases (estimated at 8–
12 biosimilar projects under the medium scenario), the net effect is expected to be
decisively positive for the sector.
Table 212. Summary assessment of the effects due to the policy intervention
237 Troein, P., Newton, M., Stoddart, K., Travaglio, M., & Arias, A. (2025, January). The impact of biosimilar competition
in Europe. IQVIA. http://www.iqvia.com/-/media/iqvia/pdfs/library/white-papers/the-impact-of-biosimilar-
competition-in-europe-2024.pdf.
Policy measure COB Admin CTI Int Mar I&R PA H&S
1. Tailored
regulatory approach
(Art. 28)
++ + + + + - +
2. Strategic project
support (Art. 29-30)
+ +/- + + + - 0/+
88
5.2.3 Intervention n°13: SPC extension for biotechnology medicines
Supplementary protection certificates (SPCs) are an intellectual property right. They
serve as an extension to a patent right and aim to offset the loss of patent protection for
pharmaceutical that occurs due to the compulsory testing these products require prior to
obtaining regulatory marketing approval. An SPC can extend a patent right for a maximum
of five years238.
The Regulation proposal introduces an extension of 12 months of the SPC for medicinal
products developed by means of biotechnology processes and for Advanced Therapy
Medicinal Products.
Eligible medicinal products would have to contain a new active substance which is
effective via a mechanism of action distinctly different to that of any other product already
authorised in the EU for preventing or treating the same disease. The clinical trials
evaluating the efficacy of the product and supporting its marketing authorisation would
need to have been conducted in more than two Member States and at least one
manufacturing step, excluding packaging, quality and testing certification, would need to
be performed in the Union.
This provision is intended to target highly innovative biotechnology-based products that
are expected to deliver significant therapeutic advantages to patients, particularly those
who currently have limited or no treatment options.
The proposed SPC extension does not affect in any respect the existing legal framework in
Regulation (EC) No 469/2009239 or related measures, nor the ongoing reform of that
framework. In accordance with the principle of legal certainty, this includes how the SPC
extension will be applied in the future. The SPC extension has a different scope. Its purpose
is not to replace the existing SPC legal framework but to complement it.
Intended objective:
The SPC, by prolonging IP protection, provides a very robust shield from competition for
the relevant product240. Additionally, on average, products for which SPC is the last form
of protection to expire have higher revenues than medicines that rely on regulatory
protection (RP) or patent (see Annex 7 for details on protection length). This further
underscores the attractiveness and effectiveness of this incentive.241
238 Six-month additional extension is available in accordance with Regulation (EC) No 1901/2006 if the SPC relates to
a medicinal product for children for which data has been submitted according to a Paediatric Investigation Plan (PIP).
PIPs are required to support the authorisation of medicines for children. They ensure that enough data is collected on the
effects of the medicine on children. 239 Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the
supplementary protection certificate for medicinal products, OJ L 152 16.6.2009, p. 1
httphttp://data.europa.eu/eli/reg/2009/469/2019-07-01. 240 Max Planck Institute for Innovation and Competition (2018), Study on the Legal Aspects of Supplementary Protection
Certificates in the EU. 241 Impact assessment accompanying the revision of the pharmaceutical legislation
https://health.ec.europa.eu/publications/impact-assessment-report-and-executive-summary-accompanying-revision-
89
Innovation and patenting behaviour in biotechnology are closely linked to firms’
expectations around the future commercial value and appropriability of inventions.
However, intellectual property is just one part of innovators’ investment decisions. The
Biotech Act proposal includes explicit conditions to link the SPC extension to conducting
late-stage clinical trials and manufacturing in Europe, because the incentive is precisely
meant as a stimulus to modify sponsors’ behaviour at the margin, thereby helping generate
economic and societal gains for Europe.
Analysis and limitations:
It is acknowledged that modelling the costs and benefits of this measure necessitates
certain assumptions and it is subject to inherent limitations, such as the need to work with
small samples of medicines given the medicine characteristics being studied, and
simplified representations of complex real-world health biotech innovators’ behaviour.
These limitations have been mitigated by using robust data sets reflecting observations of
actual product lifecycles and market entry patterns (market data from the IQVIA MIDAS®
databases) and assessments on products eligibility (data provided by the European
Medicines Agency which will be in charge of assessing eligibility), to ensure that the
resulting estimates of the measure's potential remain grounded and reliable rather than
being based on a more theoretical model.
To make an estimation of the costs of the SPC extension, an analysis was performed of the
198 innovative medicines which lost patent or regulatory protection between 2016 and
2024 and that have not so far been withdrawn from the market. Of those medicines 31 were
found to be biologics, 12 of which rely on SPC as the last protection to expire (40%). Of
these 12, 10 fulfil the proposed Regulation’s SPC eligibility criterion of being a medicine
developed with a biotechnology process. In order not to limit the sample size unduly, the
other SPC eligibility criteria have not been used to exclude medicines from the sample as
they should not a priori affect the market characteristics of the medicine. The sample
studied was restricted to these 12 products in order to ensure that the medicines considered
are representative of those for which the SPC extension would be relevant242. The model
specifically looked at how sales volumes and prices shift when a product loses patent
protection and biosimilar versions enter the market. On this basis, the model made it
possible to calculate how much additional profit accrues to the originator and how much
additional cost is borne by the healthcare system and patients when an extra year of
protection is added.
Expected impacts:
Figure 10 charts the course of revenue and volume for the average medicine in the sample
across 20 years: 15 years before expiry of protection and 5 years after expiry. This
represents our baseline in the absence of SPC extension. As biosimilar entry drives prices
general-pharmaceutical_en supports this statement, furthermore data analysed for the impact of the SPC extension
measure confirm the same trend. Of the 31 biological products in the nine-year cohort studied, 12 had SPC as last
protection to expire and 10 had RDP. While the SPC-reliant products averaged EUR 740 million during their last year
of protection collectively, the 10 RDP-reliant medicines averaged EUR 83 million. 242 To accurately measure economic impact, we shouldn't just count all eligible products. We must isolate those where
the SPC extension is the sole factor preventing biosimilar entry (last layer of protection to expire). If other protections
remain in place after the SPC expires, the extension has no real-world economic effect.
90
down, it is associated with an accelerated increase in volume, effectively allowing for a
higher number of patients to be treated (green line). Because prices are lower, overall
revenues fall, despite the higher volumes. This process is somewhat restrained in the case
of biologics by the higher barriers to entry for biosimilars as compared to generics for small
molecules, including due to stricter regulatory pathways and more complex production
processes, resulting in a relatively shallow decrease in overall revenue.243
Figure 10. Normalised sales and volume for SPC-reliant biological medicines with
current duration of SPC
Author analysis based on IQVIA MIDAS data
To assess the impact of an additional year of protection, the same twenty-year reference
period was maintained, but with an additional year of uncontested sales with revenues and
volumes equal to those in the year before expiry and one year fewer of contested sales. The
effect is depicted in Figure 11 (light blue bar). The result is a fall in the number of patients
treated accompanied by an increase in spending.
243 For the purposes of this graph, one medicine from the sample, with particular outlier characteristics was excluded.
The product is a moderately high revenue medicine with no biosimilar entry even after several years and a far shorter
lifecycle than all the other SPC-reliant biologicals in the sample.
91
Figure 11. Normalised sales and volume for SPC-reliant biological medicines
products with a 12- months SPC extension
Author analysis based on IQVIA MIDAS data
To assess how many products per year would be eligible for the measure, data from EMA
was analysed covering the period from 2011 to 2025. If the SPC extension existed, over
the past ten years, there would have been on average 5 products per year among all those
centrally authorisedthat fulfil all the criteria to obtain the SPC extension, and 6 per year
over the past 5 years, albeit with considerable variation per year. As stated above, out of
the 31 biologics we analysed, 40% (i.e. 12 products), relied on SPC as their last effective
protection244. Thus, assuming the proportion of products relying on SPC remains constant,
the SPC extension would have an economic impact on 2-3 products per year.
Conduct of business: The average revenue of a product in the sample in the year prior to
protection expiry is EUR 740 million. Impacts in the model are calculated as a percentage
of revenues in this last protected year. Taking into account the expected impact of the
measure, as shown in Figure 11, an additional year of protection results in an additional
direct cost to public payers in the EU of approximately EUR 70 million per medicine,
corresponding to approximately EUR 210 million annually at aggregate level (considering
three medicines per year). The relatively moderate increase in spending reflects the
shallow post-expiry revenue decline characteristic of SPC-reliant biologicals.
244 To accurately measure economic impact, we shouldn't just count all eligible products. We must isolate those where
the SPC extension is the sole factor preventing biosimilar entry (last layer of protection to expire). If other protections
remain in place after the SPC expires, the extension has no real-world economic effect.
92
Functioning of the internal market and competition: For the reasons set out above,
biosimilar competition produces slower price reductions than generic competition, limiting
the price differential between the extension scenario and the baseline. Instead, the main
effect of the extension relative to the baseline is the temporary postponement of additional
product entry, implying fewer available treatment options and delayed expansion of supply
for patients during the extension period. By postponing competitive entry, the extension
maintains higher average prices for an additional year and delays the expansion of supply
associated with follow-on products.
Public health: In addition to the direct cost impact of approximately EUR 70 million per
medicine, there is a delay in the expansion of coverage (the upward pivot of the green line
is delayed by a year). This is expressed in a patient monetised loss of EUR 135 million per
product and EUR 405 million for three products (see table below) calculated as the
additional spending required to achieve baseline coverage at policy scenario prices.
Additional details in Annex 7. Additional protection for originators results in a transfer of
revenue and profit from biosimilar makers to originators as well as a transfer of economic
surplus from payers and patients to the pharma industry, as set out in the table below245.
Table 13. Impact of change of +1 SPC extension for biotechnology medicines
Source: Author analysis based on IQVIA MIDAS data246
Due to data availability and confidentiality around price negotiation, this calculation is
based on list prices and cannot capture discounts and clawback mechanisms that apply at
national pricing and reimbursement stage. If it were possible to use net prices, the cost
calculation would be lower.
Competitiveness, trade and investment flows: According to EMA data from 2016 to
2025, in addition to the 5-6 products that would have met all the criteria each year, a further
five products would have met all the criteria except the “geographic” ones, i.e. conducting
trials in more than two Member States and having part of their manufacturing in the EU.
245 As set out in Annex 11, this latter transfer can be approximated by the combined total of the monetised loss to patients
and the additional costs to the public payer of EUR 205 million per medicine. 246 Internal analysis by the authors using IQVIA MIDAS® quarterly sales data 2008-2024. Geographical coverage: EU27
without Cyprus, Malta and Denmark. which were obtained under license from IQVIA and reflect estimates of real-world
activity. Copyright IQVIA. All rights reserved. The statements, findings, conclusions, views, and opinions contained and
expressed herein are not necessarily those of IQVIA.
1 year increase in protection Per medicine Annual (3 meds)
Originator gross profit 230 m 690 m
Biosimilar gross profit -80 m -240 m
Cost to public payer 70 m 210 m
Patients monetised gains/losses 135 m 405 m
Patients + payer monetised gain/loss 205 m 615 m
93
It was assumed again that about 40% of the products are SPC-reliant. Thus, the SPC
extension could potentially be awarded to 4-5 products annually (rather than 2-3) if
developers changed their behaviour in response to the incentive i.e. conduct clinical trials
in more than one Member State and part of the production of the medicinal product in the
EU.
This measure is designed to incentivise late-stage clinical trials as part of the product’s
marketing authorisation. Clinical trials generate sizeable economic benefits in several ways
as outlined in the economic impact section of intervention n°4 (Clinical Trial Regulation
Revision). A further potential benefit of more clinical trials is avoiding the healthcare
expenditure which would normally be associated with sponsor-funded medicines,
diagnostics and monitoring. As an illustrative benchmark, Polignano et al. (2022)247
estimate a leverage ratio of 3.67, implying EUR 3.67 of avoided healthcare expenditure
for every euro of sponsor investment in industry-sponsored clinical trials. While the SPC
extension conditionality of conducting clinical trials in the EU can only impact behaviour
at the margin of a limited set of products, the combined impact with measures proposed in
the Biotech Act on streamlining clinical trials can be non negligeable248.
The measure is also designed to encourage sponsors to incorporate an EU-based
manufacturing step as part of their manufacturing and scale-up strategies. As underscored
by public consultations, literature and empirical evidence, intellectual property, including
SPC extension, is an important part of the broader set of elements that drive biotechnology
investment decisions. While the decision to invest in a biotechnology manufacturing
facility cannot be attributed to any single product or regulatory incentive, similarly to the
conditionality concerning the conduct of clinical trials in the EU, the positive impulse
created by the SPC extension could contribute to broader investment and employment
effects at the margin.
The effect of these measures is expected to be amplified and completed by other
measures set out in the Biotech Act, especially those aimed at supporting and derisking
investment in manufacturing in the EU (e.g. high impact biotechnology health strategic
projects and biotechnology health strategic projects) and the amendment to the Clinical
Trials Regulation to facilitate the conduct of multi-national clinical trials in the EU. These
changes will make the incentive to conduct clinical trial and manufacturing activity to
Europe introduced by the SPC extension more effective. It must also be noted that the
SPC extension complements other measures in the Regulation proposal and in the reform
of the general pharmaceutical legislation249 that are aimed at facilitating development of
innovative products and reducing time to market (e.g. use of AI and regulatory sandboxes,
combined trials and shortening marketing authorisation timelines).
Research & Innovation: Between 2004 and 2011, just over one product per year would
have been eligible for the SPC extension, according to EMA’s data. This number grew to
five in the last decade and to six in the last 5 years. While the long-term trend reflects a
247 Polignano, M. G., et.al. (2022). Economic impact of industry-sponsored clinical trials in inflammatory bowel
diseases: Results from the national institute of gastroenterology "Saverio de Bellis". Frontiers in pharmacology, 13,
1027760. https://doi.org/10.3389/fphar.2022.1027760. 248 Refer to the relevant section of the SWD on the Clinical Trials Regulation for a full assessment of costs and benefits 249 COM/2023/193 final and COM/2023/192 final.
94
growing health biotech pipeline, we observed high variability in product eligibility year-
over-year, reflecting the unique risk profile of the health biotech sector. With the
development of biotechnology pipelines and scientific advances, we can expect this
measure’s economic impact to increase, but in parallel it is also expected to bring new
transformative products to the market.
Administrative costs on businesses, including SMEs: Under the current regulatory
framework, companies applying for SPCs incur administrative costs associated with
preparing and submitting applications, assessing eligibility, and interacting with patent and
regulatory authorities. SPC applications require legal interpretation of patent and
marketing authorisation scope and prior use of products protected by the patent and the
medicinal product which has been authorised. They require internal legal and regulatory
staff time and, in many cases, recourse to external legal advisors. For SMEs, SPC-related
administrative and advisory costs can weigh more heavily, given their more limited in-
house legal and regulatory resources and greater dependence on outsourced expertise250.
Evidence from the impact assessment of the Commission proposals for a unitary SPC251
shows that overall administrative and advisory costs for filing SPC extensions across
multiple Member States typically range between approximately EUR 80,000 and EUR
150,000 per product.
Public Authorities: The proposed SPC extension does not introduce new standalone
administrative procedures beyond those already required for obtaining SPC protection
under the baseline framework. Companies seeking to benefit from the SPC extension
would follow the same application process as for a standard SPC, with the addition of the
documentation provided by EMA demonstrating that the eligibility criteria for the
extension are fulfilled. As these elements are largely based on information already
provided during the marketing authorisation process and associated regulatory
documentation, the additional administrative effort required from companies is expected
to remain negligible. Therefore, overall costs would remain between EUR 80,000 and
150,000 per product.
The SPC system is subject to disputes over eligibility, duration and scope, which
generate administrative and legal costs for companies, public authorities and courts252.
The proposed SPC extension, by introducing novel eligibility criteria, especially in the
early years of application might also entail the same litigation risks which currently
characterise the existing legal framework with increased risk of administrative costs and
burdens. This is because the generics manufacturers are well placed to contest any form of
SPC extension. In addition, the Court of Justice interprets the conditions for grant narrowly
250 European Commission (2023), Commission Staff Working Document – Impact Assessment accompanying the
proposals on supplementary protection certificates, SWD (2023) 118 final, Brussels, 27 April 2023, Section 2.3.2 and
Annex 6 (SME Test). 251 European Commission (2023), Commission Staff Working Document – Impact Assessment accompanying the
Proposal for a Regulation of the European Parliament and of the Council on the supplementary protection certificate for
medicinal products (recast) and the Proposal for a Regulation on the unitary supplementary protection certificate for
medicinal products, SWD (2023) 118 final, Brussels, 27 April 2023, Section 2.3.2 and Annex 5B. 252 Technopolis Group (2018) Effects of supplementary protection mechanisms for pharmaceutical products. Final report,
May 2018. Amsterdam/Vienna: Technopolis Group.
95
as it considers that all the interests at stake, including those of public health, in a sector as
complex and sensitive as the pharmaceutical sector should be considered.
Conclusions
Providing an additional year of protection for innovative biotech medicines rewards the
delivery of transformative treatments for high-burden conditions, ranging from
oncology to metabolic and neurological disorders, while sending an important signal to
companies regarding investment priorities. The geographical conditions ensure that this
additional incentive also favours investment in the EU and helps strengthen the EU’s health
biotech sector, which is crucial both for European patients and for the competitiveness of
one of Europe’s most valuable industries.
Table 14. Summary assessment of the effects due to the policy measure
Policy
interventions
COB Admin CTI Int Mar I&R PA H&S
SPC
extension
++ 0/- + - + 0 -
5.2.4 Intervention n°14: Facilitating Access to Funding
The proposed Regulation establishes an EU Health Biotechnology Investment Pilot in
order to mobilise substantial private investment into the sector. This is a partnership with
the European Investment Bank and European Investment Funds (together the “EIB
Group”) and other implementing partners, bringing together equity instruments and
venture-style debt tailored to biotechnology-specific risk profiles. In synergy with existing
EU investment initiatives, the Pilot would support the full lifecycle of health biotechnology
companies and projects. As early as 2026 and 2027, the EIB Group will aim to mobilise
EUR 10 billion of total investment into the sector through the BioTechEU initiative.
Projects that contribute to an EU late-stage Capital Booster Pilot will be recognised by
the Commission as high-impact health biotechnology strategic projects. These projects are
expected to strengthen cross-border investment, mobilise long-term and institutional
capital, improve investor access and issuer visibility, and enhance biotechnology-specific
investment expertise.
More broadly, health biotechnology is recognised as a strategic technology eligible for
Union and national financial support in line with applicable rules, including State aid rules.
High-impact health biotechnology strategic projects may receive particular consideration
under relevant Union programmes and may combine Union funding with financing from
the EIB Group, national promotional banks and private investors, in line with applicable
96
rules253. These measures aim to address structural financing gaps, particularly at late
development stages, and to crowd in private capital.
Expected impacts:
Over the last 10 years, health biotechnology was a strategic financing priority for the EIB
Group, underpinned by close cooperation with the European Commission through EU
budgetary resources254 and complementary EIB Group own resources. Over the period
2015-2025, the Group has scaled its activity across the full financing chain, combining (i)
EIF-backed investments into specialised venture capital and growth equity funds ('fund of
funds' approach) to support more than 1000 health biotechnology projects and emerging
startups with (ii) direct EIB loans to more than 145 later-stage innovative SMEs and
midcaps ('venture loans') or (iii) established pharma companies ('corporate loans').
With all these investments, the EIB Group mobilised more than EUR 100 billion for the
benefit of the health biotech sector over this period. Table 15 summarises this activity
across instruments, including the EU budget guarantee backing those investments and how
much funding the original EIB Group investment mobilised by crowding in private capital.
Figures are reported as annualised run rates over the 2015-2025 period. These are
indicative averages only and should be interpreted with caution: actual annual
volumes vary significantly from year to year, driven by market conditions, pipeline
timing and the availability of EU budgetary guarantees.
Table 15. Average annual EIB Group contribution to health biotech financing and
investment mobilisation (2015–2025)
Instrument EU guarantee/year EIB Group
Investment/year
Total Investment
mobilised/year
Venture debt EUR ~150 million/yr EUR ~350-400 million EUR ~3.1-3.5 billion
Corporate loans EUR ~70 million/yr255 EUR ~730 million EUR ~1.9 billion
EIF fund investments EUR ~100 million/yr EUR ~520 million EUR ~5.5 billion
Total EIB Group EUR ~320 million/yr EUR ~1.6 billion EUR ~10.8 billion
However, the EIB estimates that an annual investment gap of EUR 40 billion remains
between the EU and US Biotech sectors256. To address this gap, the Biotech Act proposes
the creation of a dedicated EU Health Biotech Investment Pilot. The pilot would deploy a
toolbox of financial instruments, tailored to the specific risk and maturity profile of health
253 Regulation (EU, Euratom) 2024/2509 of the European Parliament and of the Council of 23 September 2024 on the
financial rules applicable to the general budget of the Union, OJ L, 2024/2509, 26.9.2024. 254 InvestEU guarantee in the current MFF, EFSI and COSME-EFG in the previous MFF. 255 Over the time period 2015-2025, out of the EUR 7 billion EIB corporate life-sciences loans (730/year), only EUR 2
billion (EUR 200 million/year) were backed by a guarantee of EUR 700 million (EUR 70 million/year). The remaining
EUR 5 billion were financed from EIB own resources. 256 The EIB Group uses industry data of EUR 69.7 billion investment for the US vs EUR 26.5 billion in the EU in 2021,
resulting in a gap of ca. EUR 40 billion.
97
biotech companies. With the support of these instruments, the pilot aims to crowd in
substantially more private capital and respond more effectively to unmet market needs
across the financing chain.
Table 16 outlines three scenarios for the pilot across different ambition levels. The
scenarios assume a positive review after an initial two-year pilot period, and initial
evaluation of crowd-in ratios, after which it will continue for a total of seven years. A
longer time horizon helps with attracting substantial private investment, particularly from
institutional investors such as pension funds, insurers and corporates, and reflects the long
investment and value-creation cycles characteristics of the health biotechnology sector. In
addition, sustained and predictable public support is critical for investor confidence, while
sufficient time is needed to deploy and test the different instruments in the toolbox and
adjust the mix in response to market uptake, geopolitical shifts and observed outcomes.
The first scenario assumes a continuation of the level of EIB Group's average investment
level over the last 10 years, with the second and third illustrating the additional level of EC
guarantees and investment by the pilot needed to mobilise sufficient investment to close,
respectively, 25% or 50% of the EUR 40 billion annual investment gap in the Health
Biotech sector.
These scenarios are illustrative sensitivity cases rather than forecasts and depend on strong
assumptions: linear scalability of deployment by the investment pilot over seven years,
with the same distribution of investment across instruments as the EIB Group over the last
10 years, sufficient absorption capacity in the EU health biotech pipeline, no material
displacement of private finance and no binding implementation constraints (including risk
appetite, deal flow, administrative throughput and the availability of EU budgetary
guarantees).
Table 16. Scenarios for the EU Health Biotechnology Investment Pilot
Scenario EC guarantee over 7
years
Direct investments by
the pilot over 7 years
Total investment
mobilised over 7 years
Continuation scenario EUR 2.2 billion EUR ~10.4 billion EUR ~70 billion
Closing 25% of EU-US
investment gap
EUR 4.5 billion EUR ~20.7 billion EUR ~140 billion
Closing 50% of EU-US
investment gap
EUR 6.7 billion EUR ~31.1billion EUR ~210 billion
5.2.5 Intervention n°15: Use of Artificial Intelligence and Data
The Regulation proposal provides for the publication and regular update of EMA
guidance, in agreement with the Commission,on the use of advanced technologies,
including AI, in the lifecycle of medicinal products. This guidance is expected to establish
overarching principles to enhance clarity on the use of advanced technologies across the
lifecycle, including development, manufacturing, regulatory evaluation and approval, and
post-authorisation monitoring. The proposal also provides for the recognition of high-
impact health biotechnology strategic projects in the form of trusted AI-enabled
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biotechnology testing environments (to facilitate integrated experimentation and
translational validation) and biotechnology data quality accelerators to support the
curation, standardisation and annotation of high-quality datasets required for the training,
testing and validation of AI systems used in biotechnology applications.
Expected impacts:
The effects of the proposed measure are driven by several mechanisms:
• the establishment of common principles for the clarity of the use of AI across the
medicinal product lifecycle, supporting consistent validation approaches and
alignment of regulatory expectations;
• the complementing and structuring of case-by-case regulatory interactions
through publicly available guidance, improving predictability and supporting the
consistent deployment of AI across the medicinal product lifecycle;
• the provision of shared AI-enabled biotechnology testing environments
combining experimental, computational and data-driven capabilities, reducing
firm-level constraints and facilitating faster validation and scale-up of
innovations;
• the improvement of data quality for AI applications, through the curation,
annotation, standardisation and provenance of datasets to support the training,
testing and validation of AI systems in biotechnology.
These mechanisms are interdependent and reinforce each other, with outcomes scaling
with the number and maturity of recognised projects in the form of testing environments
and data quality accelerators.
By combining improved regulatory clarity, enhanced validation infrastructure and higher-
quality datasets, the measures are expected to help address key structural bottlenecks that
currently limit the translation of Europe’s scientific excellence into scalable innovation
and thereby facilitate the translation of research into scalable innovation and contribute to
strengthening the EU’s competitiveness in AI-enabled biotechnology257.
Uptake of high-impact projects (testing environments and data quality accelerators) is a
key variable, and the scale of effects should be interpreted as proportional to the number,
capacity and maturity of recognised projects. This reflects the project-based nature of the
intervention and the reliance on public and private co-investment, which make different
uptake scenarios possible.
Conduct of business: These impacts include less regulatory uncertainty and better access
to validation and scale-up capacity. The guidance introduces a shift from case-by-case
regulatory interactions to a publicly available reference point, replacing confidential and
non-reusable exchanges and reducing transaction costs and internal deliberation time. This
allows firms to take development decisions earlier and with greater confidence. Testing
environments and data quality accelerators address the limitations in terms of access to
shared pilot and scale-up infrastructure, with time-to-access effects being material. Under
257 See further findings in the Study to support the rapid assessment of policy scenarios to strengthen innovation and
competitiveness in the field of biotechnology in the EU, Rapid Assessment Scenario Study.
99
baseline conditions, firms must independently finance or secure validation capacity, which
entails high fixed costs, long lead times and coordination challenges. Shared infrastructure
converts firm-level capital expenditure into pooled capacity, reducing delays in accessing
pilot-GMP capacity and limiting the risks of overall project delay. Providing access to such
infrastructure operates as an enabling condition for commercialisation.
Administrative costs on businesses, including SMEs: These costs are expected to evolve
in a balanced manner. While guidance can reduce repeated clarification processes and
improve predictability, care may be needed to ensure sufficient flexibility in its application.
Participation in testing environments and data quality accelerators may entail certain
administrative steps, such as application, reporting and knowledge-sharing; however, these
are expected to be proportionate and to support transparency, collaboration and the
generation of shared evidence. Appropriate design of support frameworks, including
streamlined procedures, can help facilitate participation and ensure that administrative
processes remain aligned with the pace of technological development.
Competitiveness, trade and investment flows: These reflect the availability of validation
infrastructure and AI-ready data. Testing environments contribute by addressing key R&D
constraints, providing integrated capacity for validation and supporting development of
such activities within the Union. Data accelerators contribute by reducing ‘data friction’,
improving data usability, interoperability and quality, and thereby lowering costs
associated with fragmented datasets. Both interventions require sustained capital and
operational support to ensure effective utilisation and maximise their impact on innovation
and investment decisions.
Functioning of the internal market and competition: Changes in data readiness and
interoperability across Member States are expected, with fragmentation and heterogeneity
in data readiness remaining significant. Legal access to data does not ensure technical
usability, due to differences in formats, metadata and validation criteria. Data accelerators
help enlarge the effective market for data-driven development by improving
standardisation, curation and interoperability. At the same time, differences in absorptive
capacity and digital maturity across Member States may lead to uneven uptake in certain
instances. This underlines the importance of ensuring coordinated implementation over
time, so that these measures support convergence and avoid the emergence of a multi-
speed internal market.
Innovation and research: Impacts are expected to reflect changes in regulatory
uncertainty, validation capacity and data usability. The guidance helps reduce the ‘option
value of waiting’, thereby accelerating investment decisions in R&D. Testing
environments contribute through addressing limitations in access to integrated validation
capacity, enabling validation activities under more efficient and coordinated conditions,
and supporting improved validation timelines, regulatory submissions and standardisation,
including platform effects. Data quality accelerators contribute through improving data
quality and reducing dataset fragmentation, and interoperability, reducing the data
preparation burden, generating research productivity effects, and enabling discoveries that
fragmented datasets cannot support.
Public authorities: These stakeholdersmay need to support supervision, coordination,
infrastructure maintenance and the development of specialised human capital in relation to
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testing environments and data quality accelerators. This includes ensuring appropriate
technical capacities and skills of their staff, as well as the ability to adapt to evolving
technological developments. Data quality accelerators require sustained investment in
high-quality data curation and annotation capacities. This highlights the importance of
ensuring continuity and coordination of funding mechanisms to support their long-term
operation and maximise their impact.
Public health and safety reflect changes in the validation of AI-enabled biomedical tools
prior to deployment. Testing environments contribute by reducing the real-world
performance gap, improving reliability through structured multi-system validation, and
supporting the use of more diverse datasets. In combination with the guidance, this
supports the consistent application of validation and risk management principles across the
lifecycle of AI-enabled medicinal products. These developments align with evolving
regulatory validation frameworks and support safer deployment of AI-enabled tools.
Table 17. Summary assessment of the effects of Intervention n°15: Use of Artificial
Intelligence and Data
Policy intervention COB Admin CTI Int Mar I&R PA H&S
Use of Artificial
Intelligence and Data ++ 0/+ ++ + ++ 0/- +
Scenario-based quantification of the expected impacts under different uptake cases has also
been developed258 to illustrate such potential impacts, which should be interpreted as
proportional to the scale, maturity and utilisation of recognised projects.
Table 18. Illustrative uptake scenarios and order-of-magnitude impacts and
estimation of associated impacts
Impact Category Low uptake Medium uptake High uptake
What this scenario
entails
2–3 recognised testing
environments (Art. 32)
and 2–3 data quality
accelerators (Art. 33);
upgrade-focused
investment in existing
facilities; primarily
public funding with
limited private co-
investment
5–8 recognised testing
environments and 5–8
data quality accelerators;
mix of upgrades and new
greenfield investments;
mixed public-private
funding on PPP model
10–15 recognised testing
environments and 10–15
data quality accelerators;
industrial-scale
greenfield and upgraded
facilities; public-private
leverage at the largest
nodes
Direct employment
created
160–420 FTE (testing
environments + data
accelerators)
1,000–2,640 FTE 3,300–7,500 FTE
Companies and
data users served
per year
120–495 (20–45
companies; 100–450
data users)
1,100–3,400 (100–200
companies; 1,000–3,200
data users)
4,250–12,600 (250–600
companies; 4,000–
12,000 data users)
258 See Annex 7 and relevant sections of the Rapid Assessment Study – forthcoming – for further details.
101
Total
infrastructure
investment (public
and private
CAPEX combined)
EUR 85 million –EUR
205 million
EUR 650 million– EUR
1.3 billion
EUR 2.4 billion–EUR
7.2 billion
Annual
operational
funding required
EUR 6–18 million/year
(data accelerators) +
testing environment
OPEX
EUR 40–120
million/year + testing
environment OPEX
EUR 150–450
million/year + testing
environment OPEX
EU-level
supervisory
burden
1–3 FTE 2.5–8 FTE 5–15 FTE
Regulatory
interaction cost
avoided per firm
(Article 31)
Reduction in regulatory
interaction costs and
timelines through
publicly available
guidance; effects
consistent across
scenarios
same across all scenarios same across all scenarios
SME
infrastructure
barrier addressed
82% of SMEs currently
unable to self-finance
validation; shared access
reduces per-firm fixed
costs
same direction; scales
with number of
environments
same direction; scales
with number of
environments
Data usability gap
addressed
87% of biomedical
datasets currently not
readily usable for ML;
accelerators begin
conversion to AI-ready
scales with number of
accelerators
scales with number of
accelerators
Key
implementation
risk
Limited number of
environments and
accelerators reduces
coverage and
competitiveness signal
Need to ensure efficient
access conditions and
interoperability
alignment; OPEX
sustainability
Need for continuous
technological upgrading
and balanced. access
conditions across users
5.2.6 Intervention n°16: Prevention of biotechnology misuse
The proposed Regulation sets out a regulatory framework for customer screening of
biotechnology products of concern, focused on custom-made and potentially dangerous
sequences of synthetic DNA or RNA (synthetic nucleic acids, synthetic ‘NA’). Custom
NA synthesis is a small but crucial part of the biotech sector, representing around 0.1% of
the European Biotech market259. The EU is home to around 100 companies in scope of the
Chapter’s provisions (ca. 20% of global NA synthesis companies) 260, with companies
outside the EU selling custom nucleic acids to the Union market also in scope.
259 Estimations based on GrandViewResearch estimates of the overall EU DNA synthesis market
https://www.grandviewresearch.com/horizon/outlook/dna-synthesis-market/europe and EU Biotech market
https://www.grandviewresearch.com/horizon/outlook/biotechnology-market/europe, assuming 50% of the overall EU
DNA synthesis market (0.2% of the Biotech sector) is custom DNA synthesis, based on the number of companies – see
footnote 260 and Annex 4 Additional methodological information on specific measures for details. 260 IBBIS has identified 215 companies in the NA synthesis market in the EU, of which 66 companies performing custom
synthesis, including oligos and data storage. The EU also has 4 benchtop manufacturers and 40 third-party vendors. The
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The exponential decrease in the cost of synthesising DNA and RNA has transformed
biotechnology and made innovation more accessible. However, it has also increased the
risk of misuse. A particular concern is that, given information on the genomes of viruses
and other pathogens is publicly available, access to the physical DNA or RNA is an
increasingly eroding chokepoint to create and weaponise pathogens to carry out biological
attacks. These could have consequences similar to, or worse than, those seen during
the Covid-19 pandemic, with economic costs of EUR 20 trillion for the EU alone. In
2024, MIT researchers demonstrated the ability to order synthetic genetic fragments
sufficient to reconstruct the 1918 pandemic influenza virus, with their order fulfilled in
almost all attempts261.
Williams et al. (2025) estimate the near-future annual probability of biological attacks at
1% and accidents from their use at 1.5%. In recent years, multiple individuals in the EU
attempted to carry out biological attacks by weaponising biological agents262. As synthetic
NA continues to become cheaper and more widely available, this increases the risk that
future biological attacks could be much more damaging, using transmissible viruses
instead of toxins.
Table 19. Estimated risk from accidents with or misuse of Synthetic Nucleic Acids263
Type of events Annual likelihood Expected monetised harm to EU if event occurs
Large scale event264 1% EUR 19.6 trillion
Small scale event265 22% EUR 72 million
Agricultural event 4% EUR 75.5 billion
Non-transmissible events 5-25% EUR 121 million
To reduce this risk, the Biotech Act introduces a mandate for custom NA synthesis
companies to verify the identity and legitimacy of customers purchasing potentially
dangerous NA sequences. Companies that make benchtop NA synthesis devices available
would also be obligated to implement a screening mechanism to prevent the synthesis of
biotechnology products of concern with the device.
In the Biotech Act Call for Evidence266, several industry representatives were supportive
of such harmonised rules on NA synthesis screening at EU-level, given the significant
share of EU synthetic DNA providers is calculated following IBBIS number, namely 215 over 1,023 globally identified
providers. 261 Esvelt K. (2024), https://drive.google.com/file/d/1hNUnU8i2yubt5uesmmV17aTJXhYYDgTY/edit?pli=1 262https://jamestown.org/ricins-round-two-germany-prevents-another-islamic-state-motivated-bioterrorism-
attack/, https://www.dw.com/en/germany-teens-home-searched-over-suspected-ricin-plot/a-72272711,
https://health.ec.europa.eu/document/download/1be3e462-bd50-4c64-b147-add9d1d5a580_en?filename=com_2025-
529-1_act_en.pdf on page 5. 263 RAND 2026. 264 Large-spreading events, global pandemics on the scale of COVID-19 or the 1918 influenza 265 Expected to result in 65 deaths in case the event happens. 266 https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/14627-Biotech-Act/F3565340_en
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heterogeneity in security practices267 and the difficulty in complying with diverging rules
across Member States268. Customer screening for potentially dangerous NA synthesis
orders is frequent industry practice, with companies representing over 50% of global NA
synthesis capacity being members of the International Gene Synthesis Consortium269, an
industry association that supports its members to follow its harmonised screening protocol.
However, companies implementing such biosecurity measures risk being undercut on price
and turnaround time by providers without such measures. While the cost of screening for
companies is currently minimal, as the cost of NA synthesis will continue to decline, the
‘fixed’ cost of screening could represent an increasing share of the final order price270,
further worsening this dynamic.
The provisions in the Biotech Act would aid to prevent such a ‘race to the bottom’ on
biosecurity practices and enable competition by removing burden for companies that
screen271. The RAND study assumes that a mandate would result in companies screening
98% of EU synthesis orders, while also indirectly increasing screening rates for non-EU
orders by around 10%. This is modelled to reduce misuse risk by 35% and accident
risk by 86%272. This risk reduction would result in expected annual monetised
benefits273 of EUR 2.9 billion in 2027, increasing to EUR 5.5 billion in 2036. Around
EUR 1.2 billion of the benefits in 2027 stem from accident prevention, while around EUR
1.8 billion stem from attack prevention. This risk reduction would indirectly also benefit
the biotech sector itself, avoiding severe regulatory backlash or a research pause as a
consequence of such an event, which RAND estimates could represent EUR 10 billion in
lost future research value.
These benefits significantly outweigh the estimated costs of the measure. Screening
measures represent a minor cost for NA synthesis companies. In a Commission workshop
on biosecurity274, an EU NA synthesis SME who screens all their orders and customers
highlighted how screening is practical and efficient for them, not hindering innovation or
commercial timelines. Industry interviews suggest that SMEs of 40-50 staff dedicate
around 0.5-1 FTE to biosecurity screening measures275. For cost calculations, we assume
30% of the ca. 100 custom NA synthesis companies in the EU already have customer
267 https://pmc.ncbi.nlm.nih.gov/articles/PMC11319849/ 268 See IBBIS mapping of explicit and implicit rules on NA synthesis screening across countries:
https://globalsynthesismap.bio/policy?country=FRA. 269 Harmonized screening protocol v2.0 (2017). International Gene Synthesis Corporation.270 If not matched by a similar decrease in the cost of screening with advancements in AI, as investigated in Acelas et al.
(2026) cited below. 271https://www.weforum.org/publications/biosecurity-innovation-and-risk-reduction-a-global-framework-for-
accessible-safe-and-secure-dna-synthesis-582d582cd4/ 272 Zakaria, S. et al. (2026). Cost–benefit analysis for synthetic nucleic acid screening in the European Union. Santa
Monica, CA: RAND Corporation, 2026. https://www.rand.org/pubs/research_reports/RRA4805-1.html; The analysis is
conducted over ten years and assumes a mandatory screening policy for all synthetic nucleic acids longer than 50bp
bought and sold in the EU. 273 The benefits quantify the reduction in the probability of biological events, such as another pandemic or an agro-
terrorism attack, and the resulting reduction in expected public health and economic costs. 274 Held on the 18th February 2026 in the context of stakeholder consultations for the Rapid Assessment Scenario Study
(forthcoming). 275 Evidence from SME expert interviews.
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screening policies in place276. We estimate the direct costs for the remaining 70% of EU
companies in scope to hire an additional biosecurity FTE, implement IT tools to screen
sequence orders277 and direct compliance costs for the regulatory introduction and
adjustment efforts are estimated at EUR 10.5 million annually, compared to a market size
of roughly EUR 500 million278.
The RAND Europe study estimates costs on a per-order rather than per-company basis,
taking the full NA synthesis market as a basis. Adjustingtheir model to only cover the
custom NA synthesis market in scope of the regulation and EU wages, direct legitimacy
screening costs are estimated at EUR 22.2 million279. However, per-order costs are
expected to significantly decrease with AI tools becoming more powerful and more widely
available, with Acelas et al. (2026) estimating their cost to decline from EUR 1 to EUR
0.20 per customer as the verification step becomes increasingly automated280.
For researchers and other customers, mandatory screening introduces additional
administrative costs linked to documentation, procurement adjustments, and compliance
procedures. For custom NA synthesis orders, these costs are estimated at approximately
EUR 16.4 million annually. Public sector implementation costs should remain relatively
small at around EUR 15 million (for EU and MS together), as the provisions do not rely
on a licensing regime and costs for both the EU and Member States would be mostly
limited to monitoring and inspection activities.
Table 20. Annual direct costs of screening measures281
EU enforcement cost EUR 1.3 million
MS enforcement cost EUR 14 million
Direct costs to companies EUR 10.5 - 22.2 million
Direct cost to customers EUR 16.4 million
Total EUR 42.2 – 53.9 million
276 Estimation based on the average between minimum (15%) and maximum (45%) values of the proportion of EU gene
companies that voluntarily screen now, from the RAND analysis. The number is also in line with the global results of
the survey conducted by Sentinel Bio on major screening tool providers and Response to the European Biotech Act -
Call for Evidence. See details on methodology in Annex 4 Additional methodological information on specific measures
for Intervention No 16. 277 Assumed to be relatively moderate at EUR 1.5 million for all companies, given the availability of free tools to screen
for sequences of concern: https://github.com/ibbis-bio/common-mechanism; and Response Call for Evidence for EU
Biotech Act. 278 Estimations based on https://www.grandviewresearch.com/horizon/outlook/dna-synthesis-market/europe. Assuming
50% of the overall DNA synthesis market is custom NA synthesis. 279 Estimations based on RAND analysis, but adjusted for EU average labour costs, number of custom providers, and
orders by the share of the market belonging only to custom providers (110 custom providers/215 total companies in the
synthetic DNA= 0.51). 280 Acelas, A., Palya, H., Flyangolts, K., Fady, P. E., & Nelson, C. (2026). Evaluating AI-Assisted Customer Verification
for Synthetic Nucleic Acid Screening. bioRxiv. https://www.biorxiv.org/content/10.64898/2026.02.27.708645v1?ct= 281 Calculation based on 2027 numbers. Costs may rise in the long run as the market also continues growing.
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In addition to these direct costs, a screening mandate may also result in different types of
indirect costs which are more difficult to estimate. It might produce a “chilling effect” on
research activities if some organisations delay or abandon projects due to concerns about
delays or rejected orders. RAND Europe estimates potential research losses at EUR 97
million annually under very conservative assumptions. It assumes around 10% of
researchers shifting to in-house synthesis, which carries significantly higher costs per
order. In addition, introducing an additional regulation, even if not very costly to follow,
may result in productivity loss for custom NA synthesis companies due to higher
‘regulatory intensity’, estimated at EUR 12.3 – 24.8 million.
Table 21. Comparing annual costs and benefits
Estimated benefits EUR 2,900 million
Estimated costs (conservative estimate282) EUR 176 million
Even taking those conservative estimates of indirect costs into account, the estimated
benefits are 16 times higher than estimated costs. This reflects the expected reduction
in the probability of a biological attack with catastrophic public health and economic
consequences, achievable through a targeted intervention with minimal costs for
businesses and innovation.
5.2.7 Intervention n°17: Biodefence
The proposed Biotech Act establishes two categories of high-impact strategic projects for
biodefence. Article 42 covers biodefence capability projects with a broad mandate,
supporting activities from misuse prevention to surge capacity for diagnostics and
countermeasures. Article 41 creates a more targeted instrument: the EU Biothreat Radar,
focused on detection, characterisation, identification, analysis and assessment of biological
threats, including novel, unknown and engineered pathogens, and on pathogen-agnostic
cross-border surveillance.
These measures respond to a deteriorating threat environment. The ongoing Russia
invasion on Ukraine283 and war in Iran has raised concerns about the risk of pathogen
release from biological weapons programmes284, while advances in AI and biological
engineering lower barriers to designing or modifying pathogens285. The assessment of
impacts focuses on the EU Biothreat Radar, which provides a sufficiently detailed project
scope for structured impact analysis.
Expected impact:
282 Taking the upper bound of all cost estimates and including the relatively high RAND estimate of indirect costs. 283 Russia has expanded site of past bioweapons research, satellite images show - Washington Post. 284Nelson, C., The Threat No One is Talking About in Iran, RUSI Commentary, 23 March 2026. 285Williams et al. (2025), Forecasting LLM-Enabled Biorisk and the Efficacy of Safeguards, Research Forecasting
Institute.
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Deploying a surveillance system geared towards novel and engineered pathogens would
represent a significant change from current systems focused on surveillance of known
communicable diseases, with significant upfront and operational costs. By building on
existing EU surveillance capacities and initiatives, ECDC estimates that coordinating
Biothreat Radar activities at EU-level over seven years would require an operational
budget of EUR 25 million for coordination, governance, and information-sharing
platforms and 10 FTEs for the full period. A possible EU Reference Laboratory for
Biothreat Security is estimated to cost EUR 20 million for the 7-year period.
The larger cost lies in updating and integrating existing surveillance infrastructure:
syndromic, clinical, laboratory and environmental surveillance combined with
metagenomic sequencing. The Biotech rapid assessment scenario study uses a model by
SecureBio Detection (2025)286 for a US pathogen surveillance system287 at ~USD 52
million/year as a basis. Adapting this to the EU288 yields two scenarios: Scenario 1 scales
proportionally to EU transport and wastewater networks as complementary surveillance
activities (~EUR 46.5 million/year), while Scenario 2 expands environmental collection
and sequencing capacity as investing in traditional public health surveillance (~EUR 110
million/year).
Table 22. Estimated annual costs of pathogen surveillance systems
Cost component US model (EUR) EU Scenario 1
(EUR)
EU Scenario 2
(EUR)
Traveller genomic surveillance 19,516,259 22,635,734 7,543,733
Sequencing, processing & analysis 23,967,648 23,470,428 101,883,439
Environmental detection 425,610 416,374 832,748
Total (annual) 43,909,518 46,522,536 110,259,919
Traveller Genomic Surveillance (aircraft wastewater + nasal swabs). Sequencing/processing covers
metagenomic sequencing, bioinformatics and analysis. Scenario 1 scales the US model proportionally.
Scenario 2 expands environmental sampling and sequencing while discontinuing passenger swabbing. US
figures from SecureBio Detection (2025) converted to EUR.
Benefits are harder to quantify but potentially substantial. Despite gaps in EU-wide
standardised evaluation frameworks analysing the benefits of surveillance, studies exist
that have quantified the number of infections prevented, deaths avoided, and costs saved
in specific hospital and outbreak settings289. The advantages of early detection (through
modelling) and the impact of infection control interventions informed by pathogen
agnostic sequencing have been documented. However, whereas genomic and
epidemiological surveillance are likely to deliver greater real-world value, they are much
286SecureBio Detection (2025), Scaling US Pathogen Detection. See details on methodology in Annex 4 Additional
methodological information on specific measures for Intervention No 17. 287Based on swabs of airport travellers, municipal monitoring and aircraft wastewater analysis. 288See Methodology Annex for scenario descriptions and cost calculations. 289 Nascimento de Lima, P. et al. (2024), The value of environmental surveillance for pandemic response, Scientific
Reports, 14, 28935.
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harder to measure in economic terms. On the other hand, environmental surveillance is
population and ecosystem-wide by design, produces early signals and is easy to plug into
economic models. There are thus more quantified studies available proving the value of
this type of surveillance.
Empirical evidence from European wastewater surveillance studies documents lead times
of 5 to 19 days for SARS-CoV-2 detection relative to clinical identification.290 Modelling
by Nascimento de Lima et al. (2024) shows that an environmental surveillance system
providing a five-day early warning relative to clinical detection could reduce deaths from
149 to 134 per 100,000, lower illness costs from ~EUR 1,271 to ~EUR 1,118 per person,
and shorten lockdowns from 121 to 89 days in the first year of a COVID-19-type
pandemic.291
Set against the broader costs of pandemics, these gains are substantial. Global viral
epidemics cause estimated annual mortality of ~3.3 million people292, and COVID-19
alone caused economic losses in the trillions across the EU. For a pathogen-agnostic
system capable of detecting novel and engineered threats, the marginal benefit could be
substantially higher, as limited surveillance currently exists for novel threats.
Beyond public health, the Biothreat Radar would generate indirect gains in research
capacity and technological sovereignty, through investments in metagenomic
infrastructure, bioinformatics pipelines and EU-based data sharing via the European
Nucleotide Archive.
6 CUMULATIVE ECONOMIC, SOCIAL, ENVIRONMENTAL AND OTHER IMPACTS OF THE
PROPOSAL
While many of the measures included in the proposed Biotech Act are technical and
targeted in nature, their combined effect has the potential to be transformative. Together,
they create a framework for competitiveness where regulatory simplification, investment
mobilisation and innovation all support and reinforce one another.
This interaction is expected to generate impacts that are materially greater than the sum of
each measure assessed in isolation, because it addresses the key structural bottlenecks
affecting the EU biotechnology sector simultaneously. The measures also ensure that the
sector contributes more effectively to societal objectives, such as economic growth, job
creation and improved health outcomes.
The proposed Biotech Act’s impacts materialise across four interconnected areas. The first
three: regulatory simplification, competitiveness and investment attractiveness, and
innovation and research, capture the primary economic impacts. They also generate
indirect social impacts through employment creation, skills development and better access
to innovative treatments driven by faster innovation. They address, respectively, the cost
of operating within the EU regulatory environment, the EU’s capacity to retain and attract
290 ECDC (2025), Framework for integration of wastewater-based surveillance; Viviani et al. (2025). 291 Nascimento de Lima, P. et al. (2024), The value of environmental surveillance for pandemic response, Scientific
Reports, 14, 28935. 292 Bernstein, A. S. et al. (2022), The costs and benefits of primary prevention of zoonotic pandemics, Science Advances,
8(5).
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productive capital, and the conditions needed to translate scientific excellence into
marketable products. These areas are causally sequenced: regulatory simplification lowers
the cost base, which strengthens the investment proposition, which in turn accelerates
innovation throughput. The fourth area, public health and safety, captures the Act’s
ultimate societal return in terms of health outcomes, safety and resilience, complemented
with an assessment of the expected environmental impact. The combined effects of the
preceding areas materialise in benefits such as earlier patient access, supply resilience, and
proactive biosecurity governance. The following assessment draws on 17 intervention-
level assessments of impacts presented above, synthesising quantitative estimates and
directional findings into a coherent account of the Act’s expected effects. The estimates
presented below should be interpreted in light of several cross-cutting factors that may
influence their magnitude, while not changing the overall direction of the effects identified.
First, the magnitude of investment mobilisation critically depends on the availability of EU
budgetary guarantees under the next MFF, with estimates for the EU Health Biotechnology
Investment Pilot and strategic projects frameworks assuming sufficient budgetary
headroom. Second, the realisation of benefits depends on consistent implementation by
Member States, particularly for clinical trials, the organ processing authorisation regime,
strategic project permitting, and biosecurity screening, among others. Third, uptake-
dependent measures, such as strategic and high-impact project recognition, regulatory
sandboxes, and the AI and data framework, are presented under illustrative scenarios (low,
medium, high). Actual impacts will be determined by the number, quality and maturity of
projects. Finally, estimates assume broadly stable global market conditions; significant
shifts in competitor jurisdictions' regulatory frameworks could alter the EU's relative
competitive position.
6.1 Regulatory simplification and administrative burden
The Biotech Act delivers its most immediate effects in two distinct but mutually
reinforcing ways: by eliminating procedural duplication across intersecting regulatory
frameworks, and by shortening authorisation timelines. Where the Act removes entire
procedural layers, it also shortens the remaining ones. Because these savings compound
over multiple applications, modifications, and jurisdictions, the cumulative reduction
across a full clinical development programme is substantially larger than any individual
measure assessed alone293. These effects complement other simplification efforts in related
Union frameworks. For instance, the pharmaceutical and medical devices legislation, in
combination with the Biotech Act, are expected to generate significant simplification
effects for the biotechnology sector294.
293 The cumulative programme-level impact results from a combination of a) measure stacking within a single application
(e.g., a single clinical trial application can benefit from several reforms simultaneously); and b) lifecycle accumulation
(i.e., the same per-application saving recurs across many transactions and jurisdictions in one clinical development
programme. 294 The indicated complimentary simplification effect stems for example from: a) the revised Pharma Package, which
has already transferred ERA for investigational medicinal products from the GMO legislation to the CTR, and which the
Biotech Act builds directly on by introducing risk-proportionate ERA derogations for specified categories of low-risk
GMO-ATMPs; b) the Commission's proposal of 16 December 2025 on the MDR and IVDR, which the Biotech Act's
combined-studies measure complements by replacing parallel CTR-MDR/IVDR tracks with a single coordinated
assessment; and c) for novel biotechnology products that currently span pharmaceutical, medical devices, and SoHO
frameworks simultaneously, the Biotech Act's regulatory status repository and Foresight Panel resolve cross-framework
classification ambiguity that neither the pharmaceutical nor the medical devices reforms can address in isolation.
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Significant burden reduction is expected in clinical development, one of the most cost-
intensive stages of the biotech value chain295. For human medicinal products, the
proposed amendments to the CTR are expected to reduce authorisation timelines from
106 to 75 days (47 without a request for information) and to simplify and streamline the
authorisation procedure, as well as the conduct of clinical trials. Key improvements include
a new single assessment procedure for combined studies involving medicinal products and
medical devices or in-vitro diagnostics, a new single investigational product core dossier,
and the possibility of submitting applications for substantial modifications to the clinical
trial in parallel after the notification of the authorisation decision. It is expected to yield
direct cost savings in EU sponsor expenditure of approximately 5% (EUR 1.5-3.1 billion
per year). Indirect savings of a similar order are anticipated through shorter time-dependent
costs, yielding aggregate annual financial gains for sponsors potentially exceeding
EUR 5 billion. Applying the Standard Cost Model (SCM), each multinational trial stands
to save approximately EUR 2,700-4,500 in sponsor administrative costs through alone a
reduction in the staff time for regulatory interactions by 15-25%. Additionally, electronic
submission and digitalisation measures are estimated to generate EUR 112-225 million in
industry savings over fifteen years. A simplified version of the cost-benefit analysis,
considering a subset of the policy measures included in the Biotech Act, suggests an overall
annual cost-saving of EUR 1.24 billion296. The Biotech Act proposal is expected to result
in an increase in commercial clinical trials by 10% to 30%, estimated to generate
approximately EUR 3.6 billion to 10.7 billion in economic gains and 16,500 to 49,500
additional jobs.
These gains extend into adjacent product domains, where parallel reforms are addressing
sources of procedural duplication there. In the biosimilars domain, the rationalisation of
Comparative Efficacy Studies requirements removes EUR 19-26 million in direct trial
costs per product and shortens development timelines by 12-24 months, translating into
sector-level savings of EUR 222-467 million annually for the 12-18 affected MAAs per
year. Thus, combined annual regulatory cost relief for health biotech sponsors across
clinical trial and biosimilar reforms approach (and potentially exceed) EUR 5.2-5.5
billion per year. Regarding ATMPs, eliminating the additional 50-day assessment period
and granting risk-proportionate ERA exemptions for qualifying GMO-ATMPs is expected
to reduce regulatory timelines and remove non-value-adding procedural steps, potentially
removing a burden of 0.15-0.3 FTE-years per clinical trial application, a reduction that
disproportionately benefits the SME-dominated ATMP developer base, and is also
expected to significantly influence sponsors’ decisions to conduct clinical trials in Europe.
For VMPs containing GMOs, the single regulatory pathway eliminates 30-90 days of
process delay per CTA, aggregating to 240-1,350 product-days of delay removed annually
at current pipeline volumes, with cumulative administrative cost savings of EUR 5-14.5
million till 2040. The uniform handling regime for variations not requiring assessment adds
a further EUR 22.5 million in present-value savings over the same period.
295 Farid et al. (2020) Benchmarking biopharmaceutical process development and manufacturing cost contributions to
R&D - PMC. 296 See Regulatory Framework Study (forthcoming). The simplified costs-benefit analysis focus on operational costs, not
considering costs arising from transitioning to new regulatory requirements.
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Beyond clinical development, the Act addresses the regulatory fragmentation that so
often compounds costs. Divergent national practices in risk classification, product
categorisation, and procedural interpretation currently force applicants to navigate several
different Member State-specific requirements for what is nominally the same regulatory
procedure. The Act responds by establishing shared infrastructure, harmonising regulatory
pathways, reducing legal ambiguities, and offering regulatory and procedural guidance.
Within this context, the Act's benefits are structurally tilted toward SMEs and start-ups,
for whom the reforms remove barriers to participation rather than merely reducing costs
of ongoing operations. This happens in two distinct ways. First, regulatory simplification
measures reduce fixed-cost compliance burdens (e.g., legal support, regulatory affairs
staffing, dossier preparation, external consultancy, multi-jurisdictional coordination) that
are largely invariant to firm size and therefore represent a substantially higher share of total
expenditure for smaller firms. This is particularly pronounced in ATMPs, where SMEs
constitute the majority of developers, and in GMMs, where SMEs and start-ups represent
the predominant developer base. Second, the Act addresses infrastructure and data access
barriers that structurally exclude smaller firms from the innovation pipeline, most
pronouncedly in the AI and data domain.
These regulatory simplification gains for businesses come with new governance
obligations for public authorities and Member States. The Act introduces an expanded
public sector role in certain areas, which includes new coordination and project permitting
responsibilities, more clinical trial governance and enforcement, biosecurity screening and
inspection obligations, and ecosystem coordination through the Steering Group and
Support Network. The resulting costs are expected to be front-loaded with activities such
as designating competent authorities, establishing or adapting single points of contact,
resource permitting functions, and developing sector-specific expertise. However, the
Act’s provisions are also designed in a way that limits the incremental burden to the extent
possible by designating or adapting existing administrative coordination mechanisms
rather than creating entirely new institutions. Over time, efficiency gains are expected as
procedures standardise, digital handling matures, and coordination platforms reduce the
unit cost of multi-authority interactions, partially offsetting the initial burden. Thus, the net
balance is structurally positive: by removing procedural layers, the Act generates savings
for businesses and healthcare systems that substantially exceed the incremental
institutional costs and administrative burdens borne by public authorities.
Aggregated across the full package of simplification interventions, the Act delivers direct
annual cost savings for businesses in the order of EUR 5.2-5.5 billion, driven
overwhelmingly by the clinical trials reform and biosimilars CES rationalisation, and
supplemented by cumulative electronic-submission savings and VMP-related
administrative and variation savings. Under the One-In-One-Out (OIOO) accounting, new
administrative burdens on businesses of approximately EUR 16.6 million/year (dominated
by biosecurity customer-side compliance) are partially offset by removed burdens totalling
approximately EUR 4.3-8.0 million/year, yielding a net administrative increase of
approximately EUR 8.6-12.4 million/year. In parallel, adjustment costs on businesses
amount to EUR 8.16-27.32 million/year, with a further EUR 48.6-112.6 million/year in
recurrent monetised costs falling on public administrations, mainly stemming from
biodefence collection infrastructure (EUR 46-110 million/year).
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Even at the upper bound of identified incremental costs, and before accounting for the Act's
downstream health, supply-resilience and innovation-enabling benefits, the direct
business-level savings from regulatory simplification far exceed the full sum of
monetised countervailing items, confirming that, in cumulative terms, the Biotech Act
operates as a substantial net simplification instrument for the EU biotechnology sector,
with the residual OIOO increase concentrated in a single, security-motivated intervention
whose justification rests on a distinct benefit-side case (biosecurity risk prevention
monetised at EUR 2.9 billion/year in 2027, rising to EUR 5.5 billion/year by 2036).
Distributional impacts
While the aggregate cost-benefit balance of the package is firmly positive, the Act
produces material intra-EU transfers whose direction warrants explicit recognition (see
Annex 3). The principal redistributive vector is the SPC extension, which is explicitly
designed to transfer approximately EUR 690 million/year in additional originator gross
profit from biosimilar developers (around EUR 240 million/year in foregone profits) and
from payers and patients (combined social cost of around EUR 615 million/year), in
exchange for conditional EU-based manufacturing and multi-Member State trial
commitments. A second, structural transfer runs across firm size: because fixed
compliance costs are largely size-invariant, simplification gains in clinical trials, ATMPs,
GMMs and the AI and data framework accrue disproportionately to SMEs and start-ups,
for whom they typically remove barriers to participation rather than merely reduce
operating costs. A third runs across the public-private interface: businesses and
healthcare systems capture the bulk of regulatory and efficiency savings, while Member
State authorities absorb front-loaded governance costs, which nonetheless remain orders
of magnitude smaller than the corresponding business-side relief and associated prevention
benefits. Crucially, the combination of measures generates additional distributional effects
not visible at intervention level: CES rationalisation and strategic-project eligibility partly
offset the SPC-driven loss to biosimilar developers; the SPC geographical conditionalities
recycle part of the payer-to-originator transfer back into EU clinical and manufacturing
activity; and the Support Network and cluster infrastructure narrow the capacity gap that
would otherwise leave smaller firms less able to exploit complex regulatory architectures.
On balance, patient welfare is strongly positive, as biosimilar-driven healthcare savings
outweigh the SPC-related delay costs.
6.2 Competitiveness and investment attractiveness
The competitiveness rationale for the Biotech Act rests on a well-documented structural
deficit297, as evidenced by the EU’s limited capacity to scale innovative firms, and a
persistent investment gap (estimated at EUR 40 billion annually) in the EU biotechnology
sector. Regulatory simplification is a necessary condition for closing this gap, but it is not
enough on its own. The Act therefore deploys a set of instruments that collectively alter
the return profile for biotech investments in the EU by targeting the specific stages and
segments where market failures are most acute. The Act's competitiveness provisions are
designed to address a structural erosion of the EU's position relative to its principal global
297 See section 3 for further elaboration.
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competitors and to reverse specific competitive disadvantages on the dimensions that drive
investment and location decisions.
The project recognition frameworks (strategic and high-impact) turn what is currently
an opaque, variable permitting landscape into a bounded, time-limited pathway, directly
improving the bankability of industrial-scale deployments. The combined potential for
investment mobilisation is substantial. Strategic project recognition alone could mobilise
EUR 15-28 billion cumulatively by 2038 (under medium uptake; 60-70 recognised
projects), while the high-impact flagship tier adds a further EUR 4-12 billion (medium, 12-
15 projects) targeting catalytic infrastructure with cross-border reach, such as integrated
biotech testing and scale-up facilities and centres of excellence for advanced therapies.
Together, these frameworks could mobilise EUR 19-40 billion in total investment by 2038,
depending on uptake and project composition, and avoid combined delay costs of EUR
265 million-1.16 billion (under medium uptake). Critically, these project pipelines also
serve a signalling function; creating a structured ‘investability’ channel that did not
previously exist, facilitating faster financial close and more crowding-in of private capital.
The financing instruments reinforce this logic. The proposed EU Health Biotechnology
Investment Pilot targets the sector's structural EUR 40 billion annual investment gap, as
estimated by the EIB. The already launched BioTechEU initiative backed by InvestEU is
expected to mobilise up to EUR 10 billion in biotechnology investments in 2026-2027
alone. Under the medium-ambition scenario (closing 25% of the EU-US investment gap),
the Pilot would result in approximately EUR 6.2 billion in direct investments over two
years, supported by EC budgetary guarantees. It is expected to raise total investment
mobilisation to approximately EUR 41.6 billion over the same period (compared with
approximately EUR 21.6 billion under the baseline), consistent with reducing the annual
investment gap by approximately EUR 10 billion per year.
A distinct competitive dimension concerns biosimilars, where the EU holds the world’s
largest market (approximately EUR 17 billion at list prices298), but is experiencing
manufacturing migration to Asia. Streamlining CES requirements serves a competitiveness
objective: by reducing the cost threshold for biosimilar development, it accelerates market
entry by 12-24 months per product and strengthens EU-based developers against
jurisdictions already formalising such flexibility. Strategic project eligibility for biosimilar
manufacturing reinforces this supply-side effect. While the share of EU-headquartered
companies in EU biosimilar MAs is 49% in 2025, projected to fall to 40-50% without
intervention, it can be potentially maintained at 45-55% with the proposed measures. On
the other hand, the SPC extension incentivises a very targeted set of innovative
biotechnology medicines. The SPC extension could potentially be awarded to about three
products annually299. According to EMA’s data from 2016 to 2025, the three products
could grow to about five per yearif developers changed their behaviour in response to the
incentive (i.e. conducting part of their clinical trials and manufacturing in the EU), thus
bringing new transformative products to the market and a marginal positive impact on
the conduct of clinical trials and manufacturing in the EU.
298 IQVIA Institute for Human Data Science (2026), The Impact of Biosimilar Competition in Europe, estimating the EU
biosimilars market at approximately USD 18 billion (list prices). 299 The average is 2-3 products per year rounded to 3 for ease of illustrating the systemic impact.
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The extension comes with an additional gross economic gain of approximately EUR 230
million per qualifying medicine per year, and a direct payer expenditure and monetised
cost of delayed patient access which together amount to approximately EUR 205 million
per medicine. This corresponds to a cost of approximately EUR 615 million every year at
aggregate level, based on an average of three qualifying medicines per year.
The extension focuses specifically on rewarding innovations that bring the greatest value
to patients300, sending an important signal to companies regarding investment priorities.
The geographical conditions ensure that this additional incentive also favours investment
in the EU and helps strengthen the EU’s health biotech sector.
Clinical research is equally critical to the competitiveness proposition. Despite significant
global growth in clinical trials between 2013 and 2023, the EU’s share of global
commercial trials halved from 22% to 12%, failing to capture the proportional share of the
growth. Improved regulations, including simplified and more predictable procedures, as
well as sandboxes work in concert to make the EU/EEA more attractive for sponsors as a
location for conducting clinical trials. Consequently, a better regulatory environment is
expected to increase the number of clinical trials in the Union and possibly, depending on
the development in other regions, reverse the structural decline of the EEA share of global
trials. The increase in trials is expected to range between 10% and 30% based on two
studies supporting the assessment301. Together, these interventions form a coordinated
competitiveness package.
6.3 Innovation and research
The EU’s core innovation challenge in biotechnology is not insufficient scientific output.
European research organisations rank among global leaders in biotechnology publications,
but there are persistent barriers to translate that output into clinical and commercial
development. This is reflected in significantly weaker late-stage financing and a persistent
investment gap in the EU compared to global peers302. While the competitiveness measures
described above address the conditions under which capital is deployed in the EU, the
innovation provisions target the conditions under which scientific discoveries are
developed, validated and translated across the full R&D continuum, including clinical
research and scale-up activities, ensuring that innovation can progress effectively from
early-stage research to market deployment in the Union. The Act addresses this structural
translation gap through three mutually reinforcing channels.
300 Example of the value for patients of biotechnology medicines include: Jönsson B, Hampson G, Michaels J, Towse A,
von der Schulenburg JG, Wong O. Advanced therapy medicinal products and health technology assessment principles
and practices for value-based and sustainable healthcare. Eur J Health Econ. 2019 Apr;20(3):427-438. doi:
10.1007/s10198-018-1007-x. Epub 2018 Sep 18. PMID: 30229376; PMCID: PMC6438935.
Ohashi T. The impact of monoclonal antibody drugs on healthcare economics in the treatment of multiple sclerosis and
neuromyelitis optica spectrum disorders. Clin Exp Neuroimmunol. 2022;13(3):166–171.
https://doi.org/10.1111/cen3.12718. 301 According to one study (Regulatory Framework Study forthcoming), the number of clinical trials is expected to
increase by 32% considering the outcomes of a survey with sponsors. A second study (Rapid Assessment Scenarios
study, forthcoming) suggests an average increase of 10 %. Additionally, the lower bound aligns with the ACT EU target
of an increase of 11.1% of multinational clinical trials in the EU in the next five years. 302 US biotech firms have raised approximately 870% more Series C capital over the past decade and 945% more in IPO
proceeds (USD 53 billion versus USD 5 billion), while EU venture capital in biotech and healthcare fell from 34% of
global share in 2013 to 18% in 2022.
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First, introducing regulatory sandboxes across clinical trials, food and feed, SoHO, and
veterinary products creates, for the first time, structured pathways for innovations that
currently face regulatory uncertainty or do not fit neatly into existing EU frameworks. In
the absence of such mechanisms, highly novel products risk delays, fragmented
assessments or the absence of a clear route to market, constraining their development and
deployment in the Union and delaying or preventing the Union from capturing benefits in
terms of patient outcomes, innovation and economic activity.
Second, the Biotech Act addresses late-stage attrition by combining dedicated financing
instruments with catalytic infrastructure. The EU Health Biotechnology Investment Pilot
targets the sector’s EUR 40 billion annual funding gap, as estimated by the EIB, building
on the EUR 10 billion in mobilisation expected in 2026-2027 through the BioTechEU
initiative and illustrative scenarios projecting a gap reduction of EUR 10-20 billion per
year at full scale. Simultaneously, high-impact project infrastructures are expected, under
illustrative uptake scenarios, to support 4-40 additional clinical trial applications per year
and serve 60-600 firms annually. These ranges reflect very low to very high uptake
scenarios, with impacts driven by de-risking translation services and compressing
development cycles. Together, the sandboxes are expected to resolve pathway uncertainty
for novel products, while financing instruments and catalytic infrastructure ensure that
developers of products with a clear regulatory route can access the capital and facilities
needed to reach the market.
Third, the AI and data framework addresses a cross-cutting enabler that conditions the
effectiveness of the first two channels. Depending on uptake, the recognised testing
environments and data quality accelerators could serve approximately 1,100-3,400
companies and data users annually (under medium uptake projections), and trigger
infrastructure investments of EUR 650 million to EUR 1.3 billion. Along with the
harmonised guidance on deployment and use of systems based on advanced technologies,
including AI in the lifecycle of medicinal products, these measures are expected to deliver
an 14-month average reduction in development timelines versus fragmented multi-vendor
outsourcing, with best-case savings of up to 34 months across Phase I–III303 , with potential
trial timeline reductions of 18% as AI integration matures, collectively positioning the EU
to capture a greater share of the rapidly expanding AI-enabled drug discovery market.
Together, these three channels constitute the most comprehensive intervention the EU has
undertaken to address the structural disconnect between its scientific output and its
capacity to translate that output into clinical and commercial innovation. The Act
strengthens the EU's capacity to innovate in biotechnology by simultaneously lowering
the three barriers that currently determine whether a viable scientific discovery acquires a
path to market in the EU: regulatory pathway uncertainty (addressed by sandboxes, the
regulatory status repository, and the Foresight Panel), capital scarcity at the translation
stage (addressed by the Investment Pilot and high-impact project infrastructure), and the
absence of shared enabling infrastructure for AI-enabled development (addressed by
testing environments and data quality accelerators). These interventions could also create
303 Evidence from integrated shared-facility models, based on DiMasi, J., Dirks, A., & Getz, K. (2025). "The Net
Financial Benefits of Single Vendor Integrated CDMO and CRO Drug Development Services." Tufts Center for the
Study of Drug Development. Announced June 16, 2025.
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synergies with other Union initiatives, including potential Important Projects of Common
European Interest (IPCEIs304), where relevant.
6.4 Public health and safety
The regulatory and economic reforms described in the preceding sections are not ends in
themselves; their ultimate justification lies in their capacity to deliver measurable public
health benefits. The Biotech Act’s public health impact comes through three reinforcing
channels: accelerating patient access to biotechnology-derived treatments, strengthening
supply resilience for essential medicines, and establishing a preventive framework against
biosecurity risks.
The most quantifiable patient-access gains come from biosimilars and organ
transplantation. Accelerating and widening biosimilar competition is projected to increase
annual healthcare system savings from approximately EUR 13 billion in 2024 to EUR 22-
35 billion per year by 2035-2038 (cumulative EUR 300-450 billion), while preserving an
unblemished safety record; no biosimilar has been withdrawn on safety grounds in 19
years. In parallel, reforms to organ processing standards are estimated to yield
approximately 1,435 additional transplants per year by 2035, set against a waiting list
exceeding 52,000 patients and approximately 3,366 waiting-list deaths annually,
generating cumulative dialysis cost avoidance of approximately EUR 158 million. Beyond
these gains, the organ processing reforms are expected to prevent 570-945 organ discards
per year and avert 57-72 waiting-list deaths annually by 2035 (248-311 cumulatively over
2028-2035, valued at approximately EUR 285-537 million using the Commission's
standard value of a statistical life year). Thus, the total monetised public health benefit of
organ processing reforms over 2028-2035 is approximately EUR 443-695 million.
The reforms to clinical trial authorisation and the ATMP framework compound these
effects. Given that around 5% to 10% of clinical trials result in a medicinal product
reaching the market (an average of 8%), the proposed amendments to the Clinical Trial
Regulation could enable roughly 100 of the 2,500–3,000 products tested annually to launch
up to six months earlier, while ATMP reforms accelerate access to potentially curative
therapies in high-unmet-need areas where the EU already lags behind competing
jurisdictions. The biosimilars framework further strengthens both access and affordability:
by reducing the cost threshold for biosimilar development, the Act addresses a ‘biosimilar
void’; some 79% of the approximately 100 biologics losing exclusivity by 2032 have no
biosimilars in development.
On supply resilience, the strategic projects framework is expected to deliver 18-60
capacity-relevant EU-based biomanufacturing deployments by 2038 (depending on
uptake), directly countering the structural vulnerability created by growing import
dependence, currently increasing at 12% annually for biosimilars alone.
Supporting these four impact areas is a set of ecosystem-level enabling measures,
comprising the EU Health Biotechnology Support Network, networks of health
304 E.g. three Important Projects of Common European Interest (IPCEI) in the biotechnology domain are currently under
design (https://competition-policy.ec.europa.eu/state-aid/ipcei/design-support-hub_en#ipcei-candidates-in-the-design-
support-hub).
116
biotechnology clusters, the strategic mapping of the EU’s biotechnology ecosystem, and
the European Health Biotechnology Steering Group, which provide the coordination,
advisory, and connectivity infrastructure needed to translate individual regulatory reforms
into system-level outcomes. The Support Network provides a single, locally accessible
entry point for health biotechnology developers (particularly SMEs and start-ups) to
navigate regulatory pathways, identify funding instruments, and connect with investors,
while cluster networks facilitate cross-border collaboration, infrastructure access, and
knowledge transfer. Together, these mechanisms reduce the transaction costs that would
otherwise limit the uptake and cumulative impact of the substantive reforms.
Finally, the biosecurity framework introduces a screening framework for synthesised
nucleic acids, addressing the specific risk that arises as biotechnology products become
more accessible and AI lowers barriers to misuse.
6.5 Environmental impacts
Beyond its primary economic and public health objectives, the Act is expected to generate
material environmental and sustainability co-benefits across several interventions. The
GMM regulatory reform enables the deployment of microbial applications in
biofertilisation, biocontrol, bioremediation, and bioleaching (sectors with a combined
global market exceeding EUR 29 billion and projected growth rates of 9-14% annually),
which are currently entirely blocked in the EU, where no GMM has been authorised for
deliberate release under the existing framework. The veterinary medicines reform
facilitates uptake of next-generation biotech vaccines in food-producing species, reducing
reliance on antimicrobials in support of the EU's target of halving antimicrobial sales by
2030; empirical evidence associates a 10% reduction in livestock disease levels with an
800 million tonne decrease in greenhouse gas emissions, equivalent to the annual
emissions of 117 million Europeans. The biosecurity screening framework provides a
direct environmental safeguard: mandatory nucleic acid screening, modelled to prevent
35% of deliberate attacks and 86% of accidental releases, yielding expected benefits of
EUR 2.9 billion in 2027, rising to EUR 5.5 billion by 2036,set against implementation
costs that are orders of magnitude smaller. In addition, the biothreat radar and biodefence
provisions address the extreme tail of biological risk where market mechanisms cannot
ensure preparedness. Meanwhile, the food chain sandbox framework creates structured
pathways for pre-market testing of sustainable food production technologies, such as GM
food, food enzymes, as well as methodologies thereof, such as new approach
methodologies for risk assessment. These provisions collectively position the Act as a
contributor to the EU's broader sustainability commitments under the European Green Deal
and the 2030 Agenda for Sustainable Development.
Taken together, these effects position the Biotech Act as a structural enabler of a
more competitive, innovative and resilient EU biotechnology ecosystem, while
contributing to societal objectives and embedding safeguards against emerging
biosecurity risks, with system-level benefits materialising over time. While the
magnitude of these benefits will depend on uptake, implementation and broader
market conditions, the assessment indicates that the cumulative benefits of the
package are expected to significantly outweigh the associated costs.
117
6.6 Digital by default principle
The Biotech Act supports the digital transformation of the EU biotechnology ecosystem
by embedding a digital-by-default approach across regulatory, scientific and
administrative processes. Through measures dedicated to AI and data, but also other
measures embedded across the act, digitalisation operates as a horizontal enabler that
amplifies the effectiveness of the regulatory simplification, competitiveness and
innovation interventions described in the preceding sections.
Measures under the Biotech Act promote the use of electronic submissions and coordinated
approaches to data governance. This contributes to reducing administrative costs for
businesses and streamlining interactions with public authorities.
The AI and data framework (Intervention n°15) establishes a coherent structure for the
development, validation and regulatory use of advanced technologies, including AI, across
the lifecycle of medicinal products. The provision of non-binding guidance at Union level
reduces uncertainty around data requirements and validation standards, enabling
developers to design evidence generation strategies more efficiently and with greater
regulatory certainty. In parallel, trusted testing environments and biotechnology data
quality accelerators are bound to create shared infrastructures that allow companies,
particularly SMEs and start-ups, to access high-quality datasets and computational
resources that would otherwise remain out of reach.
Taken together, these contribute to strengthening innovation and research capacity and
shortening timelines for innovations to reach the market, reinforcing the competitiveness
and investment effects described in Section 6.2 by improving the risk-return profile of
data-driven biotechnology projects and increasing the attractiveness of the Union as a
location for AI-enabled development.
For public authorities, the transition to digital-by-default entails upfront adjustment costs
related to the development of digital infrastructures, data governance frameworks and
technical expertise. These costs are expected to be largely offset over time as procedures
standardise, digital handling matures and coordination across authorities improves. As
systems scale, the unit cost of regulatory processing is expected to decline, contributing to
greater administrative efficiency and more consistent decision-making.
Overall, through measures touching upon both regulatory and innovation aspects, the
digital-by-default approach therefore acts as a systemic multiplier across the Biotech Act.
7 MONITORING AND EVALUATION
Five years after the Regulation proposal’s entry into application, and every five years
thereafter, the Commission will evaluate its implementation, effectiveness and impact. As
regards the proposed Directive, it will also be evaluated in accordance with Better
Regulation policy.
Progress towards the objectives of the proposed Regulation would be monitored using a
set of quantitative and qualitative indicators. This assessment will draw on the strategic
mapping of the EU’s biotechnology ecosystem that will be established and periodically
118
updated by the Commission. It will also be based on continuous data and other information
available through the implementation of existing legislation and initiatives in the
Commission and the European Medicines Agency.
Such monitoring shall be based on key performance indicators:
Indicator Source
Venture-capital investment flows in biotechnology in the Union305 Invest Europe Annual activity
statistics
Number of strategic projects and high-impact strategic projects European Commission
Number of products granted a supplementary protection certificate National patent offices
Number of additional multinational clinical trials authorised in the
Union over the 5-year period of the reporting, compared to the
average number of such clinical trials authorised per year in the
Union as of 2025
Clinical Trials Information
System (CTIS)
Number of clinical trials concerning ATMPs authorised in the EU Clinical trials information
system (EMA)
Number of ATMPs with EMA authorisation in the EU EMA annual report
Number of GMM products authorised under Directive 2001/18/EC to
be placed on the EU market
European Commission
305 Calculation methodology to ensure that short-term volatility and year-to-year fluctuations do not distort the
assessment of underlying investment trends, such as by using three-year moving average of annual investment flows.
EN EN
EUROPEAN COMMISSION
Brussels, 26.5.2026
SWD(2026) 450 final
PART 2/2
Addendum to
COM(2025) 1022 and COM(2025) 1031 adopted on 16.12.2025
COMMISSION STAFF WORKING DOCUMENT
European Biotech Act
Accompanying the documents
Proposal for a Regulation of the European Parliament and of the Council on
establishing a framework of measures for strengthening Union's biotechnology and
biomanufacturing sectors particularly in the area of health and amending Regulations
(EC) No 178/2002, (EC) No 1394/2007, (EU) No 536/2014, (EU) 2019/6, (EU) 2024/795
and (EU) 2024/1938 (European Biotech Act)
and
Proposal for a Directive of the European Parliament and of the Council amending
Directives 2001/18/EC and 2010/53/EU as regards the placing on the market of
genetically modified micro-organisms and the processing of organs
{COM(2025) 1022 final} - {COM(2025) 1031 final}
Table of contents
ANNEX 1: PROCEDURAL INFORMATION ................................................................................ 2
ANNEX 2: STAKEHOLDER CONSULTATION........................................................................... 4
ANNEX 3: WHO IS AFFECTED AND HOW? ............................................................................ 16
ANNEX 4: ANALYTICAL METHODS ....................................................................................... 47
ANNEX 5: ADDITIONAL INFORMATION ON BACKGROUND ON THE SECTOR AND
PROBLEM DEFINITION .................................................................................................... 77
ANNEX 6: OVERVIEW OF THE PROPOSED MEASURES AND ARTICLES OF THE
PROPOSED REGULATION AND DIRECTIVE .............................................................. 101
ANNEX 7: ADDITIONAL INFORMATION ON MEASURES AND EXPECTED IMPACTS 111
ANNEX 8: COMPETITIVENESS CHECK ................................................................................ 244
ANNEX 9: SME CHECK ............................................................................................................ 247
2
ANNEX 1: PROCEDURAL INFORMATION
1. Lead DG, Decide Planning/CWP references
The legislative proposal for the European Biotech Act was prepared under the lead of the
Directorate-General for Health and Food Safety (DG SANTE). In the DECIDE Planning
of the Commission, the process is referred to under item PLAN/2025/176. The Act was
announced in the political guidelines for the European Commission 2024-2029.
2. Organisation and timing
An Inter-Service Coordination Group (ISCG) assisted DG SANTE in the preparation of
legislative proposal. It included Commission services of Directorate-Generals AGRI,
BUDG, CLIMA, CNECT, COMP, DEFIS, ENER, ENV, GROW, HERA, JRC, REGIO,
RTD, TAXUD, TRADE, together with the Commission’s Legal Service and Secretariat
General.
Three Interservice Coordination Groups have been organised between February and
November 2025, informing the preparation of the proposed Act.
A Call for Evidence was open for feedback between 14 May and 11 June 2025. A Public
Consultation was published on 4 August 2025 and closed on 10 November 2025.
An ISCG meeting on the analytical Staff Working Document took place on 23 March 2026.
3. Consultation of the RSB
The RSB was not consulted on an impact assessment. Considering the politically urgent
need to address the policy challenges identified, an impact assessment could not have been
delivered in the timeframe available before the proposal. A derogation from the
accompanying impact assessment was granted and this analytical Staff Working Document
(SWD) explains the proposal and presents the underlying evidence and impact analysis,
including cost-benefit assessment.
4. Evidence, sources and quality
The major competitiveness gap in biotechnology and the market and regulatory barriers
faced by European companies were identified in the Commission Communication
‘Building the future with nature: Boosting Biotechnology and Biomanufacturing in the
EU’1 and in the Draghi and Letta reports2.
External studies have been commissioned by the Commission which have been used to
prepare the SWD:
1 COM(2024) 137 final/2. 2 Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe, European Commission,
9 September 2024.; Enrico Letta, Much more than a Market. April 2024.
3
- ‘Analysis of the Regulatory Framework for Biotechnology and
Biomanufacturing in the EU’3 (Regulatory Framework Study, forthcoming). This
study was announced in the Commission Communication ‘Building the future with
nature: Boosting Biotechnology and Biomanufacturing in the EU’ and was
launched in December 2024. It provides a mapping of the main pieces of EU and
national legislation that apply to biotechnology and biomanufacturing products and
processes – whether they are horizontal or sector-specific – and identifies related
challenges, their causes and the consequences for stakeholders. The study also
assesses the impacts of policy measures related to the EU rules applicable to
clinical trials and genetically modified micro-organisms.
- ‘Landscape analysis study of the biotechnology sector in the Union with a view
to foster its competitiveness and innovation’4 (Landscape analysis study,
forthcoming): This study, launched in August 2025, provides an analysis of the
challenges faced by the various biotechnology sectors, an overview of the market
as well as a landscape of EU and national measures supporting competitiveness and
innovation of the sector and the resulting successes and gaps.
- ‘Study to support the rapid assessment of policy scenarios to strengthen
innovation and competitiveness in the field of biotechnology in the EU’5 (Rapid
Assessment Scenarios study, forthcoming): The study, launched in December 2025,
assesses all significant impacts of measures for the proposed European Biotech
Act.
- ‘Study supporting the Evaluation of the European Food Safety Authority
2017-2024’6: This study supports the Evaluation of EFSA, covering the evaluation
criteria of effectiveness, coherence, EU added value and relevance.
- JRC case study7 and pipeline analysis on GMMs8.
- Scientific opinions from EU agencies have been considered where relevant to
specific areas of the Act (see e.g. Annex 7, intervention n°7 on GMMs).
- ‘Fast-track landscape analyses to assess the regulatory clinical trial eco-
system in the EU/EEA and in other relevant regions’9 (forthcoming).This study
supports the assessment of the clinical trial eco-system in the EU and other regions
and its impact on the economy, public health, and skill formation.
3 "Analysis of the Regulatory Framework for Biotechnology and Biomanufacturing in the EU" Deloitte, empirica et al.,
(forthcoming). 4 Technopolis et al, Landscape analysis study of the biotechnology sector in the Union with a view to foster its
competitiveness and innovation, (forthcoming). 5 PPMI (part of the Verian Group), Fraunhofer ISI, Study to support the rapid assessment of policy scenarios to
strengthen innovation and competitiveness in the field of biotechnology in the EU, (forthcoming). 6 Intellera, Ipsos, Tetra Tech, Study supporting the Evaluation of the European Food Safety Authority 2017-2024, Final
Report, December 2025 (forthcoming). 7 Burren, S., Palacios, J., Areal, F.J., Rodriguez-Cerezo, E., Barreiro-Hurle, J. (2026). The potential of genetically
modified microorganisms to reduce nitrogen loads in the EU agricultural sector. JRC Technical Report, Publications
Office of the European Union, Luxembourg (publication forthcoming). 8 Lowe, C.R., Ponferrada, V., Ruiz Aquino C., Compaño, R., Nanda, A.K. (2026). Current and future market applications
of genetically modified microorganisms (GMMs) to be placed on the market or for environmental release. JRC Technical
Report, Publications Office of the European Union, Luxembourg (publication forthcoming). 9 This study has been conducted by Technopolis Consulting Group.
4
ANNEX 2: STAKEHOLDER CONSULTATION
1. Introduction
The synopsis report covers all consultation activities that have been conducted to support
the preparation of the proposal for a European Biotech Act and this analytical SWD.
Information was collected through consultations via a Call for Evidence (CfE), Public
Consultation (PC), and Targeted Consultations (TC).
The feedback period of the CfE ran from May 2025 to June 2025 and the PC was opened
for contributions from August 2025 to November 2025. These were complemented by
targeted consultation activities between December 2024 and March 2026. The first two
stakeholder consultations were carried out by the Commission services but were analysed
by an external contractor (see Landscape Analysis Study below and presented in Annex
1). The targeted consultation activities were carried out, among others, in the context of
the following three studies (see Annex 1 for more details on the studies):
• Analysis of the Regulatory Framework for Biotechnology and Biomanufacturing
in the EU
• Landscape Analysis Study of the biotechnology sector in the Union with a view to
foster its competitiveness and innovation
• Study to support the rapid assessment of policy scenarios to strengthen innovation
and competitiveness in the field of biotechnology in the EU
The consultation was addressed to citizens, innovators, entrepreneurs, industry, financial
institutions, investors/venture capitalists, researchers/research organisations, civil society
(including consumer, patient and environmental organisations), other users of
biotechnologies (e.g. farmers and foresters), trade unions, national and regional authorities,
and other stakeholders.
2. Methodology of the consultation activities
Call for Evidence (CfE)
The CfE was launched on the Commission’s Have Your Say platform10. It received 222
valid responses11 and 149 attachments. Participants were primarily based in Belgium (33%,
74/222), Germany (12%, 29/222) and France (9%, 20/222). Responses from non-EU
countries came mainly from the US (5%, 10/222), Switzerland (3%, 7/222) and the UK
(2%, 4/222).
10 https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/14627-Biotech-Act_en 11 3 submissions were received from a single respondent and have been counted as 1 response. 2 further submissions
were received from another respondent and have been counted as 1 response. Thus, the total number of responses
considered in this analysis is 222 instead of 225.
5
With respect to the type of stakeholder groups12, responses came from business
association13 (60), companies or businesses (50), non-governmental organisations (44),
academic, research institutions (20), public authorities (14) and from EU-citizens (14). No
campaign was identified. All feedback and position papers were analysed in the context of
the Landscape Analysis Study.
Public Consultation (PC)
The PC was published on the Commission’s Have Your Say14 platform. A total of 464
answers were received and 119 attachments were submitted. The majority were position
papers, while some included answers to open questions. Most of the responses were
submitted by respondents from France (20%, 91/464), Belgium (19%, 87/464) and
Germany (12%, 54/464). Contributions from non-EU countries mainly came from the US
(3%, 12/464), followed by Switzerland (2%, 8/464). With respect to the type of stakeholder
groups15, most respondents were from individual companies or businesses (25%, 114/464),
followed by business associations (19%, 89/464), and citizen (16%, 73/464). Among
businesses, most identified themselves as SMEs (55%, 63/114)16. Among public
authorities, 14 self-identified as national, ten as regional respectively, two as local, and
three as international.
The questionnaire consists of nine sections, which can be roughly divided into three
thematic blocks: The first block (Sections 1–3) addresses general views on biotechnology,
the presence of businesses in the EU market, and the regulatory environment in the EU.
The second block (Sections 4–6) focuses on biomanufacturing, specifically biotechnology
clusters, production, and the availability of workforce. The third block (Sections 7–9)
centres on data and artificial intelligence, defence, and security, and a final section to
submit attachments.
Duplicates or campaigns from stakeholders had not been identified. All feedback and
position papers were analysed in the context of the Landscape Analysis Study.
A Factual Summary Report has been published on 23 December 2025, based on 359
responses on the Have Your Say webpage17. This report presents the outcome of the Public
Consultation based on all 464 contributions received.
12 Among the stakeholders who reported themselves as ‘other’ are notably network organisations, multi-stakeholder
platforms, and non-profit organisations. Given their non-commercial nature and similarities with NGOs, these
respondents were grouped together with NGOs for the purposes of the analysis. 13 3 respondents identified as trade unions but are analysed as business associations as they represent industries. 14 https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/14627-Biotech-Act/public-consultation_en 15 5 self-reported trade unions were analysed under business associations, and 1 contribution self-reported public
authority was analysed coming from an EU citizen. 16 Comprising: 16 medium, 19 small-, and 28 micro-sized enterprises. 17 https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/14627-Biotech-Act/public-consultation_en
6
Targeted Consultation (TC)
Analysis of the Regulatory Framework for Biotechnology and Biomanufacturing in the
EU
The Regulatory Framework Study consists of two Pillars.
• Pillar A focused on the assessment of impacts of policy scenarios defined by the
EC. It consists of a supporting assessment of impacts related to genetically
modified micro-organisms (GMM) and a supporting assessment of impacts related
to clinical trials in Europe (CT).
• Pillar B focused on mapping the relevant EU and national legislations related to
biotechnology and biomanufacturing; identifying regulatory challenges, causes and
consequences relevant for the biotechnology and biomanufacturing ecosystems;
and identifying policy areas for potential simplification and streamlining.
Targeted stakeholder consultations were carried out across all the listed activities:
On genetically modified microorganisms (GMM), targeted stakeholder interviews and a
consultation of subject matter experts were conducted. It included 25 interviews
comprising seven large enterprises, six SMEs, five public authorities, one EU agency, four
EU business associations, one national business association, and one NGO.
On clinical trials (CT) in Europe, targeted interviews, surveys and consultations with
the study team’s subject matter experts were conducted. Two rounds of stakeholder
interviews were conducted, comprising a total of ten interviews with nine stakeholders,
representing four industry associations, two large enterprises, and one each from a
European agency, a research network, and a private non-profit organisation.
On CTs, three surveys were also launched. One survey targeted sponsors and contract
research organisations (CROs) involved in clinical trials. It received 48 responses, 32
from commercial sponsors, six from non-commercial sponsors, three from CROs, and
seven from other stakeholders (including non-profits, hospital owners, advocacy groups,
research infrastructures, trade associations, and life sciences providers). Thus, the response
rate for this survey was approximately 23.8% (48/202). A second survey was directed at
public authorities (including ethics committees and national competent authorities). It
yielded 44 responses from public authorities with approximate response rate of 32.6%,
including 20 responses from ethics committees and national competent authorities each,
three responses from ministries or government bodies, and one respondent identified as
both a ministry and an ethics committee. A third survey aimed at patient representative
organisations, collecting only one response from a national, disease-specific patient
organisation active in clinical trials across eight EU Member States and two third countries.
This resulted in a response rate of 8.3% (1/12).
With regards to Pillar B of the study (see above), two surveys were conducted, along with
ten interviews and five workshops. One survey was focused on public authorities
across the EU Member States. A second survey was broader in scope and covered all types
of stakeholders (e.g. NGOs, business associations at EU and national levels, industry,
academia, etc.). In total, 334 responses were received in both surveys. Considering
7
duplications in entries from stakeholders, 274 responses were considered for the analysis.
Ten interviews were carried out to understand the regulatory challenges that stakeholders
encounter, the legislation currently impacting them, and potential policy areas for
simplification. Five workshops were carried out to gather insights into regulatory
challenges that stakeholders face and identify potential legislation that brings such
challenges. Each workshop focused on a specific sector, i.e. health/pharma,
agriculture/environment, food and feed, bio-based chemicals and plastics, and bio-based
materials. For each sector, relevant actors active in the specific field of the workshop were
invited to participate.
Landscape Analysis Study of the biotechnology sector in the Union with a view to foster
its competitiveness and innovation
The Landscape Analysis Study draws on evidence from the CfE, PC and targeted
stakeholder interviews, workshops and case studies. It includes 28 interviews with
organisations, covering the five pillars Access to Finance (eleven interviews, five with
private sector funders and six with public sector funders), AI and Data (six interviews, two
businesses, one trade association, two research organisations and one public-private
partnership), Cluster (three interviews with clusters), Skills (four interviews with research
and training, and education organisations/infrastructures), and Security and Defence (five
interviews with two private sector companies and three research intermediaries).
Four workshops18 were conducted on Access to Finance (three public funders, four private
funders, one institutional investor, two industry associations), Skills (11 research
organisations and research infrastructure, two businesses, one intermediary, five business
associations), Clusters (eight representatives of European and regional cluster
organisations, one infrastructure provider, one ecosystem intermediary and one EU
institution), AI and Data (three businesses, four research organisations, two industry
associations, one public organisation) respectively.
Study to support the rapid assessment of policy scenarios to strengthen innovation and
competitiveness in the field of biotechnology in the EU
As part of the study, the project team carried out a stakeholder consultation programme
comprising three targeted workshops and a series of semi-structured interviews.
Consultations were conducted between January and March 2026 and covered the main
policy intervention areas addressed in the study
The online workshops were organised to gather stakeholder views on specific thematic
areas of the European Biotech Act: Clusters and Strategic Projects Workshop (11
participants), AI and Data Workshop (eight participants), Biosecurity Workshop (Ca. 100
participants).
18 The AI and Data and Cluster workshops were organised jointly with the contractor on the Rapid Assessment Scenario
study, with dedicated sessions focusing separately on the topics of each study.
8
34 interviews (including one written response) were conducted across seven policy
intervention areas of the proposed European Biotech Act. Interviews were held between
January and March 2026.The policy intervention areas were:
• SPC extension for biotechnology medicines (four interviews)
• Biosecurity and Recognition and support of high impact biodefence projects (six
interviews)
• Targeted regulatory reform of Veterinary Medicinal Products (eight interviews)
• Regulation of novel health biotechnology products, ATMPs framework and
Targeted regulatory reform of clinical trials framework (seven interviews)
• Regulatory framework for genetically modified micro-organisms (GMMs) in
products other than food and feed (four interviews)
• Regulatory framework on the substances of human origin (SoHO) (two interviews)
• Regulatory framework on standards of quality and safety of human organs intended
for transplantation (three interviews)
The interviews were distributed across the following stakeholder groups: industry (ten
interviews), regulatory authorities (EU and national, 12 interviews), academia and research
(four interviews), policy experts and think tanks (five interviews), and other (three
interviews).
Other targeted consultation activities
On clinical trials, evidence has also been collected through three workshops19 organised
by the European Commission in June, September, and November 2025, with
representatives of national competent authorities and ethics committee members from each
Member States across the EU to exchange views with experts to inform how policy options
would be defined.
Finally, targeted consultation activities were also conducted as part of the supporting study
for the evaluation of EFSA (see Annex 1 for information the study).
3. Overview of Responses
The regulatory environment
Respondents to the PC perceive significant regulatory barriers across the authorisation,
testing and commercialisation chain in the biotechnology sector. The EU framework is
considered complex and cost-increasing compared with non-EU countries despite ensuring
high safety standards.
Three-quarter of the respondents indicated regulatory barriers in the assessment and market
authorisation (77%, 357/464). About 70% (326/464) indicated pre-commercial testing or
clinical trials, 68% (314/464) noted impediments in commercialising products and 67%
(311/464) in scaling-up production or manufacturing, while 64% (298/464) signalled
regulatory barriers in product development matters. Regarding other stages and cross-
19 CTAG: Clinical Trials Advisory Group; MedEthics-EU, the Clinical Trials Coordination Group of the Heads of
Medicines Agencies (HMA) was also invited to the workshop. The EMA is an observer to the CTAG.
9
cutting aspects, between 44% (204/464) and 49% (226/464) agreed or strongly agreed that
EU rules lead to regulatory barriers in early-stage or pre-clinical development, techno-
economics (outside health), health technology assessments, and post market activities.
Stakeholders also provided views as part of the feedback to the CfE. On Clinical trials,
submissions highlighted delays, fragmentation, and excessive bureaucracy as key barriers.
Stakeholders argued that protracted timelines, divergent national requirements, and
administrative burdens (e.g., for trial modifications or ethics reviews) undermine Europe’s
competitiveness and delay patient access to innovative therapies. Pharma and biotech
industry groups also pointed to the lack of coordination between Member States, proposing
centralised approval systems, binding deadlines, and digital tools (e.g., CTIS optimisation)
to cut duplication and speed up trials.
Research institutes and SMEs pushed for regulatory sandboxes for advanced therapies
(ATMPs) and simplified rules for academic studies (e.g., reduced fees, streamlined
exemptions), while patient organisations stressed the need for real-world data (RWD) and
cross-border collaboration (e.g., for rare diseases) to enable faster, patient-centred trials.
Individual biotech firms additionally called for early scientific dialogue with regulators
and prioritised pathways for breakthrough therapies to boost investment confidence.
Stakeholders also addressed Advanced Therapy Medicinal Products (ATMPs),
highlighting their transformative potential but also critical barriers to development and
patient access.
The overarching consensus emphasised that regulatory complexity, fragmented approval
pathways, and funding gaps (especially for rare/ultra-rare diseases) hinder ATMP
innovation in the EU. Stakeholders called for streamlined, risk-based frameworks,
including regulatory sandboxes, harmonised GMO/clinical trial rules, and centralised
ethics reviews, to accelerate development while ensuring safety.
Industry groups called for simplified manufacturing rules (e.g., decentralised production,
platform-based assessments) and financial incentives (e.g., innovation procurement, social
impact funds) to offset high costs. Academics and research bodies demanded dedicated
pathways for non-profit developers, including reduced fees and tailored regulatory support,
while patient advocates stressed equitable cross-border access via harmonised Hospital
Exemption rules and EU-wide reimbursement alignment. Regulatory experts proposed
joint GMO/CTR reforms and ATMP-specific sandboxes to cut redundancy and enable
faster, scalable therapies.
On the Supplementary Protection Certificate (SPC), some stakeholders underlined that
the current SPC framework needs reform to compensate for regulatory delays, enhance
competitiveness, and ensure robust intellectual property protection in the EU, while their
proposals differ in scope and specificity.
Some stakeholders addressed Substances of Human Origin (SoHO), flagging critical
regulatory gaps in its interaction with other frameworks (e.g., GMO, ATMPs, medical
devices). The overarching concern is fragmentation and legal uncertainty, which is seen as
to stifle innovation in human-derived therapies like cell/gene therapies and microbiome-
based products.
10
In the context of the consultations for the study on the regulatory framework for
biotechnology and biomanufacturing in the EU, SMEs but also larger companies identified
the complexity of the legislation governing genetically modified organisms (GMOs) in the
EU, together with the complexity of the risk assessment and authorisation procedures as
aspects posing challenges for biotech innovation, including for bringing innovative
products to the EU market. The regulation of genetically modified micro-organisms
(GMMs) was identified as one concrete example in this regard. In addition, when consulted
on concrete policy scenarios for the authorisation of products containing, consisting of or
produced from GMMs, many stakeholders, including public authorities, considered that a
more product-centric approach that differentiates between low-risk and other GMMs has
the potential to provide faster, more cost-effective assessments of GMM products. These
stakeholders also considered that the biological properties of a GMM and the status of
qualified presumption of safety (QPS) would be suitable to determine the category of a
GMM, i.e. low-risk or other, and with that the regulatory path of a GMM product.
Access to capital
The different stakeholder consultation activities (CfE, PC and targeted consultations) draw
a consistent picture of the challenges in Europe’s biotechnology sector, particularly
regarding access to risk-tolerant capital. The findings show that Europe’s biotech industry
suffers from a chronic shortage of long-term financing, which limits the ability of start-ups
and SMEs to scale, innovate, and compete globally.
According to the CfE, there is broad agreement that Europe lags behind the U.S. and China
in biotech financing, with only a fraction of global venture capital available. Fragmented
and risk-averse capital markets force European companies to seek funding abroad,
jeopardizing technological sovereignty and contributing to offshoring. Early-stage firms,
especially those without clinical data, struggle due to long development timelines, high
capital expenditures (CAPEX), and regulatory uncertainty. Stakeholders are calling for a
comprehensive financial and regulatory framework that would mobilize public and private
investment while reducing structural barriers to funding. Proposed solutions include the
creation of dedicated EU biotech funds with a mix of grants, convertible loans, and
guarantees, the establishment of an EU Biotech/Life Sciences Index or NASDAQ-style
exchange to improve equity access, and Fund-of-Funds mechanisms to de-risk early-stage
innovation. Additionally, public-private partnerships (PPPs) and Important Projects of
Common European Interest (IPCEIs) are recommended as tools to attract private co-
investment.
The PC reinforces these findings with concrete data on the accessibility of financing
instruments. Only 19% of respondents state that public grants or subsidies are easy to
access, while for other public funding types, agreement drops to below 10%. Nearly 50%
of respondents disagree that public financing instruments are easily accessible. For private
investments, strategic research or sales partnerships (21%) and angel investors (15%) are
perceived as the most accessible, while venture capital in the expansion stage was seen as
particularly lacking (43.5%). The high number of “don’t know” or “N/A” responses
suggests a lack of awareness or clarity regarding available funding options.
As key drivers for biotech investments, respondents highlight groundbreaking technology,
regulatory certainty, innovative science, and strong IP protection (up to 80% agreement),
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followed by experienced management teams, robust supply chains, and solid financial
projections (67–71% agreement). Access to data held by public sector bodies is identified
as a less prominent driver, with 49% of respondents agreeing or strongly agreeing that it
influences investment decisions.
The Landscape Study emphasizes that biotech financing is influenced by a complex
interplay of economic factors and sector-specific risks. While some challenges, like the
structure of financial markets, require systemic shifts, others could be addressed through
targeted policy interventions. As part of this Study, a workshop was held with
representatives from EU institutions, industry associations, venture capital investors, and
institutional investors. The key finding of the workshop was that while the EU has a strong
biotech research base, it faces critical financing gaps, particularly at early-stage.
Biotechnology clusters
The five most critical challenges recognised by respondents to PC, which hamper EU
biotechnology clusters in achieving their full potential, were: insufficient financial support
(58%, 270/464), insufficient public support (54%, 251/464), incapacity to reach a critical
mass of stakeholders (46%, 215/464), insufficient collaboration among existing clusters
(46%, 213/464) and insufficient start-up incubators or business support infrastructure
(45%, 209/464).
Biomanufacturing
The responses gathered from both the CfE and the PC reveal several critical challenges
and priorities related to biomanufacturing, with stakeholders across industry, academia,
and research institutions highlighting key areas for improvement.
A major concern is infrastructure and facility capacity, with NGOs and “other”
contributors (16 submissions in the CfE) stressing the need for better-equipped
biomanufacturing sites, particularly those compliant with Good Manufacturing Practices
(GMP). They also called for interoperable digital platforms, such as the European Health
Data Space (EHDS), and clinical trial networks to support scalable production).
Additionally, some contributions emphasised the importance of resilient supply chains,
suggesting decentralised or point-of-care biomanufacturing as a potential solution.
The PC responses reinforced these concerns, with 58% to 67% of stakeholders identifying
global competition, lengthy permitting processes for new facilities, scaling challenges
from pilot to industrial production, high energy costs, and expensive raw materials as the
most significant barriers. Around half of respondents also highlighted supply chain
vulnerabilities and inconsistent sustainability policies as major obstacles.
Financing and investment risks were another recurring theme. In the CfE, businesses
pointed to weak late-stage capital and the need for targeted incentives, guarantees, and de-
risking tools to support pilot, demonstration, and full-scale manufacturing projects. The
PC similarly underscored high operational costs as a key challenge, further complicating
scaling efforts.
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Business associations called for training in advanced biomanufacturing, among other
needs. A few companies specifically advocated for EU-wide multidisciplinary training
programmes, while academic and research institutions stressed the need for co-created
curricula, including modular courses, vocational training, and industry placements in
Contract Development and Manufacturing Organisations (CDMOs).
Finally, sustainability and innovation in manufacturing were addressed, with one academic
respondent (EU citizen) highlighting plant-based production and microbial technologies
as promising but currently hindered by inadequate infrastructure and regulatory
frameworks.
AI and data
The results of several stakeholder consultation activities (CfE, PC, targeted consultations)
emphasize the critical role of AI and data in Europe’s biotechnology sector, while exposing
significant barriers that hinder their effective deployment. Across all stakeholder
consultation activities, a recurring theme emerges data access, governance, and
interoperability represent the most pressing bottlenecks, compounded by regulatory
uncertainty, infrastructure limitations, and skills shortages, which together threaten
Europe’s ability to compete globally in AI-driven biotechnology innovation.
The CfE responses reveal broad consensus that Europe’s biotech sector suffers from
fragmented, non-interoperable data and ambiguous governance frameworks, severely
limiting the potential of AI applications. Despite rapid advancements in AI technologies,
their adoption remains constrained by these structural barriers. Stakeholders emphasize the
need for EU-wide bio-data infrastructures, European biotechnology dataspaces, and secure
computing resources, particularly to support SMEs and start-ups that lack the infrastructure
to leverage AI effectively. They also call for FAIR-aligned data-sharing ecosystems
tailored to genomics, proteomics, synthetic biology, and clinical data, alongside federated
datasets, supercomputing resources, and AI testing facilities.
Stakeholders in the CfE also stress the importance of AI-ready data formats, reliable data
connectors, and harmonized metadata standards to enable seamless integration of AI tools.
They advocate for aligning the proposed European Biotech Act with existing frameworks
such as the AI Act, GDPR, European Health Data Space (EHDS), and AI in Science
Strategy, while demanding clarity on rules governing AI model training, validation, and
deployment, particularly in highly regulated sectors like pharma and healthcare. The PC
quantifies these challenges, with 61% of stakeholders citing technological barriers and
58% pointing to difficulties in implementing regulatory frameworks as the primary
obstacles to AI adoption in R&D. Over half of the respondents view these issues as the
main barrier to deploying AI-based biotechnology products, underscoring the need for
regulatory sandboxes to facilitate safe testing of AI-driven tools in areas like drug
discovery and clinical trials.
A cross-cutting concern is the shortage of interdisciplinary talent, namely individuals
proficient in both data science and biotechnology. The PC quantifies this gap, with
stakeholders ranking skills development as the top priority (65%) for supporting AI
adoption in biotech, followed by access to annotated datasets (64%), partnerships with
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public research institutions or AI hubs (63%), dedicated funding (62%), regulatory
sandboxes (59%), and roadmaps for AI implementation (65%).
Despite these challenges, stakeholders in the CfE highlight AI’s transformative potential
across the biotech value chain, including drug discovery, bioprocessing, healthcare,
agriculture, and cosmetics.
To address these barriers, stakeholders propose investing in trusted data-sharing
ecosystems and European-scale bio-data infrastructures, as well as developing harmonized
standards for interoperability and security. They also advocate for targeted support for
SMEs, including dedicated funding, AI testing centres, and collaborative projects,
alongside promoting open science and FAIR principles as guiding frameworks.
Security and defence
The results of stakeholder consultation activities (CfE, PC, and targeted consultations)
highlight the dual-use risks, biosecurity challenges, and strategic vulnerabilities associated
with Europe’s biotechnology sector, while emphasizing the need for proportionate
governance frameworks that balance innovation with safeguards. Stakeholder responses
reveal a shared concern that while biotechnology offers transformative potential for
defence, healthcare, and food security, its misuse, fragmented regulation, and supply chain
dependencies pose significant threats to Europe’s strategic autonomy and public safety.
The CfE responses underscore that biotechnology’s rapid advancement brings ethical
dilemmas and dual-use risks, particularly in areas like synthetic DNA, AI-driven biotech,
and data exploitation. Stakeholders stress the need to embed ethical principles and
standards from the outset to prevent misuse, protect societal trust, and ensure public
acceptance of biotech innovations. However, they caution against excessive security-
driven regulation, which could stifle innovation if not designed proportionately. Key
proposals include screening customers of synthetic DNA orders, regulatory sandboxes for
controlled testing of novel biotechnologies, and tiered risk-based frameworks for GMOs
and recombinant therapeutics. There are also calls for a European Biotechnology Security
Strategy to enhance supply chain resilience and intellectual property protection, alongside
international coordination to address dual-use risks globally. Stakeholders further advocate
for harmonized EU rules to ensure consistency across Member States, while warning
against overly restrictive approaches that could impede progress.
The CfE highlights the need for proportionate, risk-based governance that integrates
security considerations without imposing unnecessary burdens. The PC identifies strategic
autonomy risks, cybersecurity threats, supply chain vulnerabilities, and biosecurity
concerns as the top challenges, with 50% of stakeholders citing risks to biomanufacturing
autonomy and medical countermeasures, followed by cybersecurity risks (45%), supply
chain vulnerabilities (44%), and biosecurity threats (40%). Conversely, stakeholders see
opportunities in innovative medical countermeasures (45%), biological threat detection
(45%), and enhanced food security (53%).
To address these challenges, stakeholders propose EU-wide governance frameworks that
align with international best practices, such as the Australia Group Biological Agent List
and IGSC Harmonised Screening Protocol.
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The responses from PC further emphasize the need for risk-based, innovation-friendly
regulation that keeps pace with advances in synthetic biology and AI, while the response
from CfE call for strategic autonomy in biomanufacturing and resilient supply chains to
mitigate dependencies.
Skills
The results of all stakeholder consultation activities (CfE, PC, and targeted consultations)
highlight the critical skills challenges facing Europe’s biotechnology sector, with
stakeholders across all three sources underscoring the need for targeted interventions to
develop a workforce capable of driving innovation and competitiveness.
In the CfE responses, stakeholders reveal broad consensus that developing a skilled
workforce represents a central challenge for Europe's competitiveness in biotechnology.
Industrial companies identify skills development as a key priority for the biotech
ecosystem, particularly highlighting the need for competencies in data and AI alongside
traditional biotech skills. This perspective is echoed by healthcare and pharmaceutical
companies, which similarly underscore the urgency of skills development, while business
associations consistently prioritize building a skilled workforce as fundamental to sectoral
growth. Third-country stakeholders reinforce these themes, particularly emphasizing skills
development as part of a broader package that includes regulatory and financing
improvements. A dominant concern across these responses is the need to address skills
shortages through specialized training programs, effective talent attraction strategies, and
entrepreneurial education initiatives, with human capital widely regarded as foundational
to Europe's competitive position in the global biotech landscape. Third-country research
organizations align with EU institutions in calling for targeted investment in skills at the
intersection of biotechnology, artificial intelligence, and data science, recognizing that
future competitiveness will depend on mastery of these converging disciplines. Academia
and research institutions place particular emphasis on skills development and talent
retention, advocating for EU-level initiatives that support career mobility and foster
interdisciplinary education bridging biotechnology with digital and engineering
competencies. NGOs similarly stress the necessity for stronger skills infrastructure to
underpin sectoral advancement. Companies and businesses highlight skills as a critical
factor in 24 separate contributions, while business associations, through 14 dedicated
submissions, call for comprehensive training programs in regulatory science, AI
applications, data management, and advanced biomanufacturing techniques,
complemented by measures to attract and retain global talent. Third-country contributors
mirror concerns raised within the EU-27, consistently emphasizing investment in skills as
a core requirement for sustainable biotech development.
The PC provides validation of these insights, with stakeholders demonstrating strong
alignment regarding the specific skills challenges confronting the EU workforce. The
consultation reveals particularly acute shortages in financial and entrepreneurial skills
(57%, 263/464), vocational skills for biotechnology and biomanufacturing (53%,
247/464), regulatory and quality assurance expertise (53%, 244/464), and digital and data
science competencies (45%, 211/464). These findings underscore the breadth of skills gaps
across both technical and managerial domains, suggesting that Europe's biotech sector
faces multifaceted workforce challenges that extend beyond scientific competencies to
include commercial and operational capabilities.
15
As part of the Landscape Study, a targeted workshop was organised, gathering EU
institutions, industry associations, research infrastructures, universities, hospitals, training
institutes, and individual companies, providing perspectives across the full biotechnology
value chain. The workshop aimed to validate, prioritise, and add granularity to preliminary
findings. Discussions highlighted shortages in specialised roles, limited hands-on
industrial experience in higher education, and the need for scalable, competency-based
training models, while emphasising EU-level opportunities modular lifelong learning,
industry-academia collaboration, and shared training infrastructures as horizontal enablers.
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ANNEX 3: WHO IS AFFECTED AND HOW?
1. Practical implications of the initiative
Businesses and the research community
The proposed amendments to the Clinical Trials Regulation shorten clinical trial
authorisation timelines from 106 days to 75 days, or to 47 days where no request for further
information is issued. They also simplify and streamline both the approval process and the
conduct of clinical trials.
Applying the Standard Unit Cost Model suggests that these efficiencies could cut
administrative time—the period sponsors spend engaging with regulators—by 15–25%,
equating to savings of EUR 2,700 to EUR 4,500 per multinational trial application. Such
reductions in administrative costs would particularly benefit SMEs, which face a
disproportionately higher regulatory burden. Electronic submission and digitalisation
measures contribute a further EUR 112 to 225 million cumulatively over fifteen years.
At an aggregated level considering the total set of measures included in the Commission
proposal, the economic impact of the Biotech Act’s reform for sponsors can be
approximated using current baseline data. Around 2,500 clinical trials are conducted
annually in the EU, at an average cost of EUR 30–50 million per trial and a duration of 2–
2.5 years, implying total annual sponsor expenditure of roughly EUR 30–62.5 billion.
Streamlined approvals and reduced administrative burdens are expected to yield direct cost
savings of about 5% (EUR 1.5–3.1 billion per year) and indirect savings of a similar order
through faster technical execution (around a 0.1-year reduction in time-dependent costs).
Combined, these efficiencies could generate several billion euros in annual financial gains
for sponsors, with total savings potentially exceeding EUR 5 billion. Considering a
potential increase in the number of trials, these gains would increase proportionally.
The reforms are also expected to improve the EU's attractiveness for clinical research.
Current projections suggest that the number of clinical trials in the EU could rise between
10% and 30%, compared with the existing volume of trial applications. These estimates
draw on two separate studies: one, based on sponsor survey data, forecasts a 32% increase,
while the other, relying on limited empirical evidence, projects a more modest growth of
4% to 16%20. The wide disparity in these estimates highlights the challenges in assessing
20 Rapid Assessment Scenario Study (forthcoming). The study, based on limited empirical evidence, distinguishes
between two hypothetical scenarios regarding the potential impact of the Biotech Act on the projected number of clinical
trials in the EU. In the first scenario, a moderate increase in the number of clinical trials by 4% to 8% is anticipated. This
is attributed to improved efficacy and attractiveness of performing clinical trials in the EU, driven primarily by increased
domestic uptake among sponsors already operating within the region.. The second scenario assumes that, in addition to
increased domestic uptake, sponsors relocate clinical trial activities from other regions to the EU/EEA as a result of the
reforms in the Biotech Act, leading to an estimated increase of 8% to 16%. As the Biotech Act is expected to simplify
authorisation processes and the conduct of trials for sponsors, it is considered plausible that some sponsors may relocate
their clinical trials to the EU following the amendments of the Regulation. Therefore, the average of the both scenarios
is used as a benchmark for the lower bound
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the reform’s impact on clinical trial activity, given data limitations, and inherent
uncertainties about future developments. To account for these constraints, the evaluation
of the impact adopts a broad range of potential outcomes.
Costs to sponsors are limited and front-loaded. One-off investments in harmonised
standard operating procedures are not quantified but are expected to be absorbed within
existing budgets. Sandbox participation introduces upfront overhead, though the net
lifecycle direction is a reduction in burden. The proposed measures restructure conditions
for new applications rather than imposing new obligations on active trials, limiting
compliance exposure for sponsors with existing portfolios.
SMEs and start-ups
SMEs and start-ups are disproportionately exposed to the current regulatory landscape:
administrative expenses account for 11 to 29% of total clinical trial costs, and this burden
falls proportionally harder on smaller entities with limited internal capacity. The proposed
measures therefore carry a higher marginal value for this group than for large sponsors.
Benefits operate through two channels. On ecosystem navigation, the EU Health
Biotechnology Support Network provides a dedicated support channel for health
biotechnology innovators as regards regulatory pathways, funding, and investor
connections across EU27. Firms receiving comparable network support report 14
percentage points higher knowledge sharing and collaboration capability than unsupported
firms (69% versus 55%). Articles 32 and 33 address a further structural barrier: 82% of
SMEs cannot self-finance the validation infrastructure required for AI-enabled
biotechnology development. At medium uptake, shared testing environments and data
quality accelerators are expected to serve 1,100 to 3,400 companies and data users per
year.
On direct regulatory relief, the elimination of the additional 50-day ATMP assessment
period and the reduction of substantial modification timelines from 96 to 47 days benefit
a developer base of which over 60 % are SMEs. ERA exemptions for qualifying GMO-
ATMPs remove a further 0.15 to 0.3 FTE-years per application. The harmonised AI
guidance under Article 31 replaces bilateral EMA interactions currently valued at EUR
89,000 per qualification request and 160 to 250 days per interaction with freely accessible
public guidance, a measure whose value is asymmetrically concentrated in smaller actors
that cannot absorb bilateral engagement costs.
Costs to SMEs are limited by design. Strategic project participation is voluntary, and
biosecurity compliance obligations fall on nucleic acid synthesis providers rather than the
broader SME research and development population.
Biosimilar developers
Biosimilar developers are affected by three intersecting mechanisms that do not all pull in
the same direction.
Following EMA guidelines adoption, Comparative Efficacy Studies (CES) requirement
may be waived for biosimilar products where analytical similarity is comprehensively
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demonstrated. The CES removal would deliver the most economically significant relief,
eliminating EUR 19 to 26 million in direct trial costs per product (20 to 30 per cent of total
development expenditure for standard indications, up to 50 to 60 per cent for complex
monoclonal antibody biosimilars) and shortening timelines by 12 to 24 months. Across 12
to 18 marketing authorisation applications per year where the tailored clinical package
reform applies, aggregate annual savings are estimated at EUR 222 to 467 million. The
competitive dimension is equally important: South Korea, the UK, the US, and Canada are
all moving toward CES flexibility, and without this reform the EU would risk regulatory
disadvantage. EU-based companies currently hold approximately 49 per cent of EU
biosimilar authorisations, a share under increasing pressure from South Korean and Indian
developers. The strategic project framework reinforces these gains on the supply side,
projecting stabilisation of the EU-based companies share at 45 to 55 per cent through 2038
and mobilising EUR 0.9 to 7.6 billion in cumulative biosimilar manufacturing investment
by 2038.
The SPC extension works in the opposite direction. The additional year of originator
exclusivity is estimated to reduce biosimilar gross profits by approximately EUR 80
million per qualifying medicine (sensitivity range EUR 60 to 110 million), or EUR 240
million annually at three qualifying medicines per year. Development programmes are
unlikely to be abandoned over a one-year delay, but marginal programmes targeting
smaller or more uncertain markets face a measurably reduced return on investment. The
net balance across the two instruments is positive in aggregate, but the distributional effect
varies depending on product class and the overlap between SPC-eligible originators and
active biosimilar pipelines.
Remaining costs to developers are limited to voluntary strategic project recognition, which
entails preparation and reporting costs of one to two FTEs per project per year, equivalent
to approximately one to two per cent of project value.
Originators and SPC-holding companies
The SPC extension generates approximately EUR 230 million in additional gross profit
per qualifying medicine (sensitivity range EUR 140 to 290 million). With the measure
being relevant for about 3 medicines per year, aggregate additional originator gross profit
is estimated at approximately EUR 690 million annually.
According to EMA data from 2016 to 2025 and assuming the proportion of SPC reliant
medicines remain constant, the SPC extension could potentially be awarded to 4-5 products
annually (rather than 2-3) if developers changed their behaviour in response to the
“geographical” condition of the incentive i.e. conduct clinical trials in more than one
Member State and part of the production of the medicinal product in the EU.
The principal costs fall on biosimilar developers, payers, and patients through delayed
competitive entry, addressed in the respective sections. The measure is explicitly
redistributive, transferring value from follow-on developers and healthcare systems to
originators while incentivising manufacturing and trial location.
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SoHO entities and organ processing establishments
SoHO entities using the regulatory sandbox face evidence generation costs of EUR
718,500 per year under the low scenario (six sandboxes per year) and EUR 4,790,000 per
year under the high scenario (40 sandboxes per year), with per-case costs comparable to
high-risk SoHO authorisations at EUR 1,200 to 6,000 per patient. Medium-risk cases
directed through the sandbox will incur higher costs than under the standard route. These
costs are concentrated in a small subset of novel applications that would otherwise lack a
viable pathway.
For organ processing establishments, the authorisation framework introduces per-
application costs of approximately EUR 11,500 for full authorisation and EUR 16,750 for
conditional authorisation, with a weighted average of EUR 12,800 during the transition
phase. At 60 to 145 applications across EU27 over 2029 to 2031, the aggregate transition-
phase burden is EUR 768,000 to EUR 1,856,000, rising to a cumulative EUR 1.2 to 2.5
million by 2035. Establishments under conditional authorisation additionally face
mandatory clinical outcome monitoring costs of approximately EUR 9,000 per monitoring
plan per year, aggregating to EUR 405,000 to EUR 980,000 across EU27 over the
transition phase.
These costs are substantially outweighed by the benefits. The authorisation regime is
expected to generate 1,435 additional transplants per year by 2035, with 570 to 945 fewer
organ discards annually. Total monetised benefits are estimated at EUR 443 to 695 million,
comprising EUR 285 to 537 million in statistical lives saved from 248 to 311 cumulative
waiting-list deaths averted over 2028 to 2035, and EUR 158 million in cumulative dialysis
cost avoidance derived from the reduction in the dialysis-dependent population by 2035,
attributable to additional kidney transplant recipients who would otherwise have remained
on dialysis.
GMM developers, veterinary medicine companies, and food chain operators
The Act creates the most structurally transformative change for GMM developers: the
introduction of a viable EU market authorisation pathway where none currently exists. The
EU has zero authorised GMMs for deliberate release, a direct consequence of a regulatory
framework designed for genetically modified plants and ill-suited to micro-organisms. The
reform introduces a tailored, product-based pathway with an accelerated route for low-risk
GMMs, unlocking potential access to biofertilisation, biocontrol, bioremediation, and
bioleaching sectors. These collectively represent a combined global market for microbial
products of EUR 29.1 to 33.4 billion growing at 9 to 14% per year, though GMM-specific
products constitute only an emerging share of these totals and the figures should be
understood as indicative of the upper bound of commercial opportunity rather than
immediately accessible demand.
For veterinary medicine companies, three measures deliver quantifiable gains. The single
GMO pathway for VMPs removes 30 to 90 days per clinical trial application, eliminating
240 to 1,350 product-days of aggregate delay annually and generating cumulative
administrative cost savings to 2040 estimated at EUR 5 to 14.5 million. Uniform handling
of VMP variations not requiring assessment yields present-value savings of EUR 15 to 30
million to 2040 (central estimate EUR 22.5 million). The VMP sandbox creates an entirely
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new pathway for innovative products outside existing categories, with utilisation expected
at approximately one sandbox every five years; its primary value lies in pathway creation
and investment signalling rather than immediate commercial volumes.
Food chain operators benefit from the sandbox mechanism for pre-market testing of
sustainable food production technologies, including GMO-containing products. The
exclusion of novel foods from sandbox scope, whilst justified on grounds of scientific
complexity and consumer sensitivities, - as explained in Section 5.1.2 of the Staff Working
Document represents a genuine constraint on the benefits available to this group and has
been characterised by industry stakeholders as a missed opportunity.
Sequence synthesis providers
Providers of nucleic acid synthesis services face the most direct and quantifiable
compliance burden under the biosecurity provisions. Mandatory sequence and legitimacy
screening obligations impose direct annual compliance costs estimated at EUR 10.5 to 22.2
million per provider sector, comprising legitimacy screening (EUR 19 million in 2027
rising to EUR 34 million by 2036), sequence screening (EUR 1.6 million rising to EUR
2.8 million), and procedure introduction and regulatory adjustment costs (EUR 1.7 million
rising to EUR 2.5 million). Customers and researchers face additional compliance costs of
approximately EUR 16.4 million per year for documentation, procurement adjustments,
and per-order verification. Indirect costs compound these figures: research chilling effects
from concerns about order delays or rejections are estimated at EUR 97 million in 2027
rising to EUR 170 million by 2036, whilst productivity losses to providers from
compliance intensity are estimated at EUR 8.6 to 24.8 million per year. Approximately
10% of researchers may shift to in-house synthesis at substantially higher per-order costs.
These costs must be assessed against a strongly asymmetric benefit profile. The mandatory
screening regime is estimated to prevent 35% of deliberate bioattacks and 86 % of
accidental release events, generating expected annual prevention benefits of EUR 2.9
billion in 2027 rising to EUR 5.5 billion by 2036. A further EUR 10 billion in future
research value is preserved by averting the regulatory backlash that would follow a major
biosecurity incident. The compliance burden, whilst material, represents well under
one precent of the prevention benefits the regime is expected to deliver.
Applicants for strategic and high-impact projects
Entities seeking recognition under either framework face preparation, submission, and
ongoing reporting costs estimated at one to two FTEs per project per year, equivalent to
approximately one to two % of total project value. In the most demanding governance
configurations, worst-case participation costs might reach EUR 700,000 to 800,000 per
firm (as an upper bound). Participation is entirely voluntary.
The returns are substantial. The strategic project framework is expected to mobilise EUR
15 to 28 billion in total investment at medium uptake (60 to 70 projects), with the high-
impact tier adding a further EUR 4 to 12 billion (12 to 15 projects), yielding a combined
EUR 19 to 40 billion by 2038. Both frameworks additionally reduce permitting delay costs,
with cumulative avoided delay-related capital costs estimated at EUR 265 million to
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EUR 1.16 billion by 2038 across the two tiers at medium uptake, concentrated in the most
capital-intensive projects where schedule adherence directly affects bankability and time-
to-revenue.
Public authorities
European Medicines Agency
The proposed EU Biotech Act would generate a series of incremental workload increases
for EMA, none of which are individually large. Finalisation of the biosimilar draft
reflection paper into adopted guidance is estimated at 0.5 to 1.0 FTE-year as a one-off cost,
with ongoing maintenance at 0.2 to 0.5 FTE-year. SPC eligibility verification introduces a
maximum annual workload of 28 to 30 working days across the Agency, at approximately
one working day per application. Lifecycle-wide AI guidance development under Article
31 requires one-off capacity building and training at Union and national levels, not yet
quantified. For VMPs, adaptation of the Union Product Database to remove the
approve/reject functionality for national competent authorities is estimated at EUR
150,000 to 300,000 for a three-to-six-month IT engagement.
These costs are partially offset by two workload reductions. CHMP verification of sponsor
declarations for qualifying GMO-ATMP clinical trial applications, submitted in place of
full ERA dossiers, represents a net reduction in assessment workload relative to the
baseline. Additionally, the CES removal for biosimilars reduces the number of multi-
country Phase III trial authorisations requiring ethics committee review and GCP
inspection oversight across Member States, easing NCA burden across the network. In
aggregate, EMA's incremental costs under the Act are modest and absorbable within
existing institutional capacity.
National competent authorities
NCAs face new and expanded obligations across several distinct areas, the most significant
of which is the biosecurity enforcement mandate. Member State enforcement and
coordination costs for the biosecurity screening regime are estimated at approximately
EUR 14 million per year in 2027, rising to EUR 21 million per year by 2036, requiring
approximately three FTEs per Member State for policy coordination, reporting, and
enforcement activities.
For the strategic and high-impact project frameworks, steady-state staffing requirements
for single points of contact range from 0.3 to 0.9 FTEs per Member State under low uptake,
0.7 to 1.8 FTEs under medium uptake, and 1.1 to 3.0 FTEs under high uptake. These are
incremental rather than structural costs: in most Member States, existing authorities are
expected to be designated rather than new structures created, with the primary burden
concentrated in front-loaded process design and workload reallocation.
SoHO sandbox supervision increases NCA workload materially on a per-case basis, with
medium-risk sandbox cases requiring 75 to 94 person-days per case (EUR 22,575 to EUR
28,294, a 57 to 114% increase over standard authorisation) and high-risk cases 98 to 149
person-days (EUR 29,498 to EUR 44,849, a 10 to 63% increase). Cross-Member State
learning is assumed to offset these elevated unit costs over the medium term. For organ
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processing, per-assessment costs are estimated at EUR 7,000 to EUR 10,000, with
aggregate EU27 transition-phase assessment costs of EUR 420,000 to EUR 1,450,000 over
2029 to 2031, declining to EUR 60,000 to EUR 85,000 per year in steady state. Monitoring
oversight for Track 2 conditional authorisations adds EUR 63,000 to EUR 216,000 per
year during transition.
Finally, participation in the European Health Biotechnology Steering Group requires
approximately two FTEs per Member State per year, and strategic ecosystem mapping data
provision approximately 0.25 FTEs per year. These governance obligations are ongoing
but modest relative to the biosecurity and sandbox functions.
European Commission
The Commission's recurring fiscal commitment under the Act is dominated by the
biodefence and biosecurity components. Total annual operational costs of the combined
biodefence surveillance system and biosecurity screening oversight are estimated at EUR
86 to 190 million per year across Union and Member State budgets, with the biodefence
component alone accounting for EUR 46 million per year under Scenario 1 and EUR 110
million per year under Scenario 2. EU-level biosecurity coordination and oversight
specifically is estimated at EUR 1.3 million per year in 2027 rising to EUR 1.9 million in
the long term, corresponding to approximately 11 FTEs. These commitments should be
read against EUR 2.9 to 5.5 billion in annual prevention benefits the two instruments are
jointly expected to deliver.
Beyond biosecurity, Commission-level costs are more modest. Operating the Steering
Group secretariat, conducting strategic mapping, and coordinating the Support Network
requires approximately EUR 2.6 million annually, equivalent to EUR 18.4 million over the
MFF period. EU-level supervision of high-impact strategic projects requires 1 to 3 FTEs
under low uptake, 2.5 to 8 FTEs under medium uptake, and 5 to 15 FTEs under high uptake.
Sandbox establishment under clinical trials and novel health products
each require approximately EUR 4.3 million over approximately three years as an order-
of-magnitude reference, with adopting implementing acts for VMP sandboxes representing
an additional unquantified legislative workload over 2026 to 2040.
Citizens, patients, and consumers
Earlier access to medicines
The acceleration of clinical trial authorisation procedures and the removal of the biosimilar
CES requirement are expected to result in approximately 100 products reaching the market
up to six months earlier than under the baseline, applying an approximate 8% average
launch rate to the 2,500 to 3,000 products tested annually in EU trials. ATMP procedural
reforms are expected to accelerate access in high unmet-need areas, though patient-level
quantification is not yet available.
Organ transplantation
On the regulatory changes proposed to organ processing, the moderate-scenario projection
of 1,435 additional transplants per year by 2035 translates into 57 to 72 fewer waiting-list
23
deaths annually, or 248 to 311 cumulative deaths averted over 2028 to 2035, valued at
EUR 285 to 537 million. A further EUR 158 million in cumulative dialysis cost avoidance
is attributable to approximately 3,295 additional patients living with a functioning
transplant by 2035 who would otherwise have remained on dialysis.
Patient access and the SPC extension trade-off
The SPC extension entails a direct and quantifiable cost on patients and payers. The
additional year of originator exclusivity delays biosimilar competition, resulting in a
combined social cost of approximately EUR 205 million per qualifying medicine (range
EUR 140 to 290 million), comprising EUR 135 million in delayed patient access value and
EUR 70 million in direct payer expenditure. At three medicines per year, aggregate annual
social costs amount to approximately EUR 615 million. The cost is driven primarily by the
delay in the expansion of patient coverage rather than by direct price effects: coverage
expands upon loss of protection, and the main social cost of the extension therefore consists
in the temporary postponement of this expansion.
Biosecurity and public safety
RAND (2025) estimates that mandatory NA synthesis screening prevents 35% of
deliberate bioattacks and 86% of accidental release events, generating expected annual
prevention benefits of EUR 2.9 billion in 2027 rising to EUR 5.5 billion by 2036. A further
EUR 10 billion in future research value is preserved by averting the regulatory backlash
that would follow a major biosecurity incident.
Consumer and environmental interests
Consumers benefit indirectly from the long-term competitive effects of a stronger EU
biosimilar market supporting pricing pressure at patent expiry, and from sustainable food
production technologies enabled through the food law sandbox. Environmental gains
materialise through GMM applications in biofertilisation, biocontrol, and bioremediation,
and through expanded veterinary biotech vaccine uptake supporting antimicrobial
resistance reduction targets. A 10 % reduction in livestock disease levels is empirically
associated with an 800 million tonne reduction in GHG emissions, equivalent to the annual
emissions of 117 million Europeans. No direct costs are anticipated for ordinary consumers
beyond the payer-side cost of the SPC extension, which manifests primarily through public
health system expenditure.
2. Summary of costs and benefits
I. Overview of Benefits (total for all provisions)
Description Amount Comments
Direct benefits
Elimination/reduction of duplicative
regulatory obligations across
intersecting/overlapping legal
frameworks
EUR 5.2–5.5 billion/year
Combined annual savings (clinical trials + biosimilars)
EUR 2,700–4,500
Per multinational trial (SCM; admin costs only)
~EUR 2.8–4.7 million/year aggregate (derived: ~1,050
multinational trials/year × per-trial saving)
The EUR 5.2–5.5 billion/year figure covers these annualised streams:
• clinical trial reform (EUR 1.5–3.1 billion/year in direct sponsor savings, ~5%;
aggregate indirect savings raise the total to >EUR 5 billion/year)
• the VMP single GMO pathway removes EUR 5–14.5 million in cumulative
administrative costs to 2040
• biosimilar CES rationalisation (EUR 222–467 million/year across 12–18
MAAs/year)
• electronic submission and digitalisation measures yield EUR 112–225 million
cumulatively over 15 years (~EUR 7.5–15 million/year annualised.
Three further components are additional to this figure but presented on different units:
• the SCM-derived per-trial saving of EUR 2,700–4,500 (15–25% reduction in
sponsor administrative costs per multinational trial through reduced staff
time).
• ATMP reforms additionally remove 0.15–0.3 FTE-years per CTA.
Reduction of regulatory
fragmentation across Member States
Qualitative Harmonised templates, single GMO pathways for VMPs, shared infrastructure, and the EU
Support Network reduce Member State divergence in risk classification, product
categorisation, and procedural interpretation.
Enhanced predictability and legal
certainty in permitting and project
development
EUR 265 million – 1.16 billion
Combined avoided delay costs (medium uptake, to 2038)
~EUR 22–97 million /year simple annual average21
Strategic project recognition (60–70 projects, medium uptake) and high-impact flagship tier
(12–15 projects) together yield EUR 265 million – 1.16 billion in avoided permitting delay
costs by 2038.
Converts an opaque, variable permitting landscape into a bounded, time-limited pathway,
directly improving the bankability of industrial-scale deployments and creates a structured
"investability" channel that previously did not exist.
21 The annualised figure should be interpreted as a simple average over the implementation period; actual annual benefits are back-loaded, materialising primarily as projects reach permit-
granting maturity in the 2030–2038 window.
25
Streamlined authorisation
procedures and compressed
timelines in clinical development
106 → 75 days (47 without RFI)
EUR 1.5–3.1 billion/year direct sponsor savings (~5%)
Aggregate savings potentially exceeding EUR 5
billion/year
Clinical trial authorisation timeline compressed from 106 to 75 days (47 without RFI), with
harmonised templates and parallel modification submissions.
Direct cost savings of ~5% of annual EU sponsor expenditure yield EUR 1.5–3.1
billion/year; indirect savings through faster technical execution raise the aggregate to
potentially above EUR 5 bn/year.
Electronic submission saves EUR 112–225 million over 15 years.
Streamlined risk assessment
processes
12–24 months shorter per product (biosimilars)
(monetised annual figure already accounted for under the
first benefit)
50-day assessment period eliminated; modification
timelines cut from 96 to 47 days (ATMPs)
0.15–0.3 FTE-years per CTA removed (ATMPs)
30–90 days per CTA removed (VMPs)
EUR 22.5 million PV savings, central estimate (EUR 15–
30 million range) (VMP variations, to 2040). The central
annual saving in the base year is approximately EUR 1.46
million/year rising to EUR 3.07 million/year by 2040.
Biosimilar CES removal shortens development by 12–24 months and removes EUR 19–26
m in direct trial costs per product (representing 20–50% of total development expenditure
depending on molecule complexity), with the timeline reduction enabling developers to start
later in the originator's market protection period and reducing commercial risk.
For ATMPs, the elimination of the additional 50-day assessment period and the reduction
of substantial modification timelines from 96 to 47 days are the principal procedural gains;
ERA exemptions for qualifying GMO-ATMPs additionally remove 0.15–0.3 FTE-years per
CTA in administrative burden, concentrated in regulatory affairs and project management
functions, with benefits disproportionately accruing to the SME-dominated developer base.
For VMPs containing GMOs, the single regulatory pathway removes 30–90 days per CTA
(240–1,350 product-days of delay eliminated annually at current pipeline volumes; EUR 5–
14.5 million in cumulative administrative cost savings to 2040). The uniform handling
regime for VMP variations not requiring assessment yields a further EUR 22.5 million in
present-value savings to 2040 (range EUR 15–30 million), derived from a 10–20%
efficiency gain on VNRA processing workload applied across the sector.
Anchoring late-stage investment and
scale-up activity in the EU
EUR 19–40 billion
Total investment mobilised by 2038 (project frameworks)
~EUR 1.6–3.3 billion/year annual average22
Investment mobilised:
• Strategic project framework: EUR 15–28 billion (medium uptake, 60–70 projects).
• High-impact flagships: EUR 4–12 billion (medium uptake, 12–15 projects).
22 Cumulative EUR 19–40 billion ÷ 12 years; not uniform, because investment mobilisation is ramp-up dependent with bulk of activity concentrated in 2030–2038 as project pipeline matures.
26
EUR 10 billion mobilised in 2026–2027 (BioTechEU /
InvestEU)
EUR 230 million/year additional originator gross profit
per qualifying SPC medicine
• Combined EUR 19–40 billion by 2038.
Pending full establishment, the BioTechEU initiative under the current MFF and InvestEU
programme will mobilise up to EUR 10 bn in biotechnology investments in 2026–2027.
Additionally, the SPC extension, operating via a distinct IP protection mechanism rather
than project recognition or financing instruments, generates:
• an estimated EUR 230 million in additional originator gross profit per medicine
benefitting from the incentive per year (sensitivity range EUR 140–290 million),
• corresponding to approximately EUR 690 million/year in aggregate at an average
of three medicines per year.
• the associated combined payer expenditure and monetised cost of delayed patient
access amounts to approximately EUR 205 million per medicine (EUR 615
million/year in aggregate at three medicines).
• if developer behaviour changes in response to the incentive, up to five products
per year could benefit from the incentive rather than up to 3.
Strengthening the EU's global
competitive position in biosimilars
45–55%
EU-based share of biosimilar MAs maintained
(vs projected 40–50% without intervention)
12–24 months faster market entry per product
Without intervention, the EU-based share of biosimilar MAs is projected to fall from 49%
(2025) to 40–50% as manufacturing migrates to Asia and competitor jurisdictions accelerate
their own regulatory streamlining.
CES removal would arrest this decline by reducing the cost threshold for EU-based
biosimilar development, accelerating market entry by 12–24 months per product and
enabling EU developers to respond more quickly to patent expires.
Strategic project eligibility for biosimilar manufacturing reinforces this effect on the supply
side by improving the bankability of EU-based biomanufacturing deployments.
Together these measures can contribute to stabilise the EU-based company share at 45–55%
Improving the EU's attractiveness as
a location for commercial clinical
research
350–700 additional trials over 3–4 years (domestic
scenario; 4–8% increase)
If the Act enters into force swiftly, a one-off domestic increase of 4–8% over 3–4 years is
considered feasible, yielding 350–700 additional trials; The average economic activity
27
Up to 700–1,400 additional trials (relocation scenario; 6–
16% increase)
14 products from 2016-2025 identified as marginal cases
for conducting multi country clinical trials in Europe (SPC
extension conditional incentive)
value associated with this scenario is EUR 40–80 million/year and broader economic
spillovers are estimated at EUR 316–695 million/year.
If relocation effects also materialise, total additional trials could reach 700–1,400, though
this depends on factors beyond regulation including HTA and reimbursement conditions.
The average economic activity value associated with this scenario is EUR 80–160
million/year and broader economic spillovers are estimated at EUR 630–1,400 million/year.
Additionally, the SPC extension is expected to influence trial location at the margin:
between 2016-2025, of 100 products within scope of the eligibility incentive, 14 met all
conditions except the multi-Member State trial requirement, representing the marginal case
for developers to modify their behaviour in response to the incentive and conduct part of
their clinical trials for marketing authorisation in more than 2 EU MS.
Enabling innovation and supporting
new market entrants through
regulatory sandboxes
6–40 SOHO sandboxes established per year (90–250
eligible cases/year; 7–16% acceptance rate)
40% shorter time from regulator engagement to market
authorisation
For SOHO, sandbox-eligible cases are estimated to represent 5–10% of overall SOHO
activities, corresponding to 90–250 eligible cases per year; given observed acceptance rates
of 7–16% in comparable sandbox regimes, between 6 and 40 sandboxes are expected to be
established per year.
Evidence from FinTech sandboxes indicates participants achieve on average 40% shorter
time from engagement with the regulator to market authorisation than comparable firms
using standard processes; analogous gains are expected in SOHO though not yet
quantifiable against a baseline given the absence of comparable EU precedent.
For VMPs, the baseline is zero as no EU-level veterinary sandbox currently exists; the
measure therefore creates an entirely new pathway rather than improving an existing one.
Accelerating the translation of
research into clinical and
commercial development
4–40 additional CTAs/year (low to high uptake via high-
impact infrastructure)
60–600 firms served annually (low to high uptake via
high-impact infrastructure)
High-impact infrastructure uptake scenarios assume 2 projects with shared late-stage
translation capability under low uptake, 4–6 under medium, and 8–10 under high, driving
the CTA and firms-served ranges proportionally.
The 60% SME share is consistent across all uptake scenarios.
The 24-product SPC manufacturing effect reflects products meeting all other eligibility
conditions except an EU-based manufacturing step at time of approval; the incentive is
28
24 products from 2016 -2025 identified as marginal cases
for EU manufacturing step inclusion (SPC extension
conditional incentive)
expected to influence incremental production network decisions at the margin, not drive
fundamental manufacturing relocation.
Building the enabling infrastructure
for AI-driven biotechnology
innovation
EUR 89,000 per EMA qualification request replaced by
free public guidance;
160–250 days saved per interaction (Article 31)
120–495 companies and data users/year (low uptake);
1,100–3,400/year (medium uptake); 4,250–12,600/year
(high uptake) (Articles 32 and 33)
EUR 85–205 million cumulative CAPEX (low); EUR 650
million – 1.3 billion (medium); EUR 2.4–7.2 billion (high)
over 5–15-year build-out period. Annualised CAPEX
during build-out: EUR 17–41 million/year (low); EUR
65–130 million/year (medium); EUR 160–480
million/year (high)23
Article 31 harmonised AI guidance replaces costly one-off bilateral EMA interactions
(currently EUR 89,000 per qualification request and 160–250 days per interaction) with a
single publicly accessible reference point, disproportionately benefiting SMEs and
academic developers.
Articles 32 and 33 establish shared testing environments and data quality accelerators across
three uptake scenarios, serving:
• 120–495 companies and data users/year (low; 2–3 environments and 2–3
accelerators),
• 1,100–3,400/year (medium; 5–8 each), and
• 4,250–12,600/year (high; 10–15 each).
Total CAPEX ranges from EUR 85–205 million (low) to EUR 650 million – 1.3 billion
(medium) to EUR 2.4–7.2 billion (high) over the project build-out period.
Direct employment: 160–420 FTE (low) to 1,000–2,640 FTE (medium) to 3,300–7,500
FTE (high).
Mitigating biosecurity risks arising
from the wider accessibility of
biotechnologies
EUR 2.9 billion expected benefits (2027): EUR 1.8 billion
attack prevention + EUR 1.2 billion accident prevention
EUR 5.5 billion by 2036: EUR 2.9 billion attack
prevention + EUR 2.7 billion accident prevention
35% deliberate attacks prevented; 86% accidental releases
prevented
EUR 10 billion avoided future research value
Benefits split: EUR 1.8 billion (attack prevention) + EUR 1.2 billion (accident prevention)
= EUR 2.9 billion in 2027; rising to EUR 2.9 billion + EUR 2.7 billion = EUR 5.5 billion
in 2036, reflecting increased screening coverage over time.
The 35% attack prevention rate reflects that malicious actors can still order through non-
EU suppliers; the 86% accident prevention rate reflects near-complete coverage of
accidental misuse pathways.
_
23 Annualised CAPEX assumes 5-year build-out under low uptake, 10-year under medium, and 15-year under high.
29
The EUR 10 billion avoided research value represents RAND's estimate of lost future
research value from a regulatory backlash following a major biosecurity event.
Indirect benefits
Earlier and broader patient access to
biotechnology-derived treatments
~100 products reaching market up to 6 months earlier
1,435 additional transplants/year by 2035
57–72 waiting-list deaths averted/year by 2035; 248–311
cumulatively (2028–2035); valued at EUR 285–537
million
EUR 158 million cumulative dialysis cost avoidance
(2028–2035) ; ; EUR 19.75 million/year average.
EUR 443–695 million total monetised benefit (EUR 285–
537 million + EUR 158 million); EUR 55 – 87
million/year average.
Clinical trials reform: ~8% average launch rate applied to 2,500–3,000 products tested
annually yields ~100 products potentially reaching market up to 6 months earlier.
ATMP reforms expected to accelerate access in high-unmet-need areas, however not
quantified.
Organ processing: 1,435 additional transplants/year by 2035 (approximately 847 kidney,
357 liver, 99 lung) derived from a moderate-scenario 1.5–2.5 percentage point reduction in
the all-organ discard rate; set against a baseline waiting list of 52,488 patients and 3,366
waiting-list deaths annually (6.4% annual mortality rate).
570–945 fewer organ discards/year by 2035.
Deaths averted: 57–72/year applying a conservative 4–5% marginal mortality rate to
marginal transplant recipients; 248–311 cumulative over 2028–2035, valued at EUR 285–
537 million.
Dialysis cost avoidance: EUR 158 million cumulative (2028–2035), based on ~3,295
additional patients living with a functioning transplant by 2035.
Strengthening supply chain
resilience for essential
biotechnology medicines
8–60 capacity-relevant EU biomanufacturing
deployments by 2038 (low: 8–15; medium: 18–35; high:
30–60)
Of which 1–10 biosimilar-specific manufacturing
deployments (low: 1–2; medium: 3–5; high: 5–10)
Strategic project framework delivers 8–15 (low), 18–35 (medium), and 30–60 (high)
capacity-relevant EU-based biomanufacturing deployments by 2038, assuming
approximately 30–50% of recognised projects translate into capacity-relevant outputs.
Biosimilar manufacturing constitutes a distinct subset: 1–2 (low), 3–5 (medium), and 5–10
(high) capacity-relevant biosimilar deployments, mobilising EUR 0.9–7.6 billion in
cumulative investment by 2038.
30
EUR 0.9–7.6 billion cumulative investment in biosimilar
manufacturing by 2038 (low to high uptake); on average
EUR 75 – 633 million/year.
Environmental and sustainability
benefits
EUR 29.1 billion+ combined microbial market across
biofertilisation, biocontrol, bioremediation, bioleaching
(9–14%/year growth; GMM-specific share not separately
quantified; currently zero EU authorisations for GMM
deliberate release)
800 million tonnes potential GHG reduction (10%
livestock disease reduction via biotech vaccines).
Equivalent to annual emissions of 117 million Europeans
GMM regulatory reform unlocks market access across four application sectors:
biofertilisation (USD 1.38–3.1 billion; 10.9–12.8% CAGR), biocontrol (USD 6.5 billion;
14.3% CAGR), bioremediation (USD 16.45–18.08 bn; 9.93–13.0% CAGR), and
bioleaching (USD 10.14–11.19 billion; 8.9–9.06% CAGR) - combined USD 34–39 billion.
The EU currently has zero authorised GMMs for deliberate release.
Veterinary biotech vaccine uptake enabled by VMP reform supports the EU's target of
halving antimicrobial sales by 2030.
10% reduction in livestock disease levels is empirically associated with an 800 m tonne
GHG decrease, equivalent to the annual emissions of 117 million Europeans.
Food chain sandbox creates structured pathways for pre-market testing of sustainable food
production technologies across all stages of production, processing and distribution, food
contact materials, and GMO-containing products.
Ecosystem-level coordination and
connectivity infrastructure
Qualitative; functions as a cross-cutting enabler of all
other interventions
14 pp higher knowledge sharing and collaboration
capability for firms receiving network support vs
unsupported firms
Four interconnected mechanisms underpin uptake of all substantive reforms:
• The EU Health Biotechnology Support Network is a single entry point for
SMEs and start-ups to navigate regulatory pathways, access funding and
scaling-up resources, and connect with investors across EU27;
• Networks of health biotechnology clusters for cross-border collaboration,
infrastructure access, and knowledge transfer;
• The European Health Biotechnology Steering Group for strategic
coordination between Member States and the Commission; and
• strategic mapping of the Union's biotechnology ecosystem for evidence base
covering industrial capacity, infrastructure, capital access, and skills gaps
informing all other measures.
31
EEN benchmark: firms receiving network support report 14 pp higher knowledge sharing
and collaboration capability than unsupported firms (69% vs 55%).
I. Overview of Benefits (Totals)
Amount Components Comments
Direct benefits
~EUR 8.3–11.3
billion/year
Duplication removal savings: EUR 5.2–5.5 billion/year
VMP procedural savings: ~EUR 1.5–3.1 million/year
Permitting predictability: ~EUR 22–97 million/year
Biosecurity screening: EUR 2.9–5.5 billion/year
Sum of directly quantified annual benefit figures drawn from intervention-level assessment of
impacts. . The EUR 10 billion biosecurity avoided research value is also excluded from the annual
total as it represents a one-off expected loss avoided rather than an annual flow, and is therefore not
additive to annual benefit figures. All figures are subject to uptake, implementation, and market
conditions as described in the benefits table above.
Indirect benefits
~EUR 55–87
million/year
Patient access monetised benefits: EUR 55–87 million/year
average (EUR 443–695 million cumulative 2028–2035)
Covers organ processing reforms only (VSL valuation of deaths averted + dialysis cost avoidance).
Clinical trial and ATMP patient access effects are not separately monetised. Supply chain resilience
benefits are not directly monetised as deployment counts and investment figures serve as proxies
only. Environmental and ecosystem benefits are qualitative.
32
II. Overview of costs
Citizens/Consumers Businesses Administrations
One-
off
Recurrent One-off Recurrent One-off Recurrent
Action
(a)
Direct adjustment
costs n/a.
Clinical trials:
- Initial investment in harmonised
standard operating procedures to meet enforcement expectations
across National Competent
Authorities and ethics committees. Not quantified -
low.
Substances of Human Origin:
- One-off costs of adjusting to the
sandbox route for SoHO entities. Not quantified – low.
Responsible use of AI and data
management:
- Adaptation of internal governance, validation
procedures and documentation to
comply with new EMA lifecycle guidance on AI. Not quantified –
medium.
Substances of Human Origin:
- Evidence generation within
sandbox route: total additional
cost to SoHO entities EUR 718,500/year (low estimate, 6
sandboxes per year) to EUR
4,790,000/year (high estimate, 40 sandboxes per year).
- Sandbox costs comparable to
high-risk SoHO authorisations (50-100 patients, EUR 1,200–
6,000 per patient), assuming
half medium-risk and half high-risk cases. If medium-risk
cases use the sandbox route,
direct cost per case increases relative to the standard SPA
route.
Organ processing:
- Ongoing data collection, analysis and reporting under
mandatory clinical-outcome
monitoring plans, estimated at approximately EUR 9,000 per
monitoring plan per year.
Aggregate across EU-27
during the transition phase
(approximately 15–36 active
monitoring plans): EUR 405,000–980,000 over three
years (2029–2031), or circa
EUR 135,000–327,000/year.
Biotech ecosystem:
- Designation of single
points of contact for health biotechnology; source
notes this is a scope
extension of structures already established under
the Net-Zero Industry Act
and Critical Raw Materials Act, resulting in
marginally lower set-up
costs than those benchmarks; not
quantified – low.
Biosimilars:
- Article 28: finalising the
Draft Reflection Paper into adopted guidance;
estimated at 0.5–1.0 full-
time equivalent-year at EMA. Cost can be
considered negligible.
Novel health biotechnology
products:
- Setting up the regulatory
sandbox and establishing
the foresight panel; borne
by the Commission only.
Approximately EUR 4.3
million over approximately 3 years is
an order-of-magnitude
reference. Or approximately EUR 1.4
million/year over the
Biotech ecosystem:
Member State level: - Steering Group participation: approximately 2
full-time equivalents per Member State per year;
- Facilitation of Support Network tasks (Article
19(7)): not separately quantified - low.
Commission level:
- Operating Steering Group secretariat, conducting strategic mapping and coordinating Support
Network: approximately EUR 2.6 million
annually (EUR 18.4 million over the MFF period).
Biosimilars:
- Article 28: ongoing maintenance of tailored biosimilar guidance and handling of tailored
scientific advice requests; estimated at 0.2–0.5
full-time equivalent-year at EMA.
Novel health biotechnology products:
- Operating the regulatory sandbox and running the foresight panel (Commission); not quantified –
low to medium.
General food law reform:
- Additional staff and coordination effort in EFSA for expanded scope of pre-submission advice. The
costs are expected to be offset by efficiency gains
from fewer stop-the-clock procedures and less remedial work on poor-quality dossiers. Not
quantified - low.
- Member State national competent authorities: establishing and supervising regulatory sandboxes
and submitting annual reports to the Commission
on sandbox results. Not quantified - low.
Access to funding:
- Monitoring and reporting of the Pilot, evaluation of leverage and additionality across instruments.
33
initial three-year setup
period.
Clinical trials:
- Setting up sandbox
ecosystem infrastructure approximately EUR 4.3
million over
approximately 3 years as an order-of-magnitude
analogy. Or approximately
EUR 1.4 million/year over
the initial three-year setup
period.
- Separate sandbox from Novel health
biotechnology products,
but similar cost expected.
ATMP:
- Commission preparation of delegated acts to update
the tissue engineered
product definition,
including consultations
with EMA and the Substances of Human
Origin Coordination
Board. Not quantified - negligible.
VMP:
- EMA: one-off
development of SPC
eligibility assessment guidance and criteria. Not
quantified - negligible.
- Commission: adopting implementing act(s)
establishing the regulatory
sandbox rules and limits; one per sandbox
established; approximately
2–3 over 2026–2040. Not quantified - negligible.
Not quantified - negligible (largely absorbed
within existing EIB structures).
Responsible use of AI and data management:
- Arts. 32 & 33: continuous technology refresh to
maintain state-of-the-art status for recognised testing environments and data quality accelerators:
15–20% of initial capital expenditure annually;
30–40% of software stacks require major replacement or updates every 18–24 months.
- Article 33: accelerator-grade data curation uplift
beyond EHDS baseline obligations -
approximately 15% added to experimentation
costs for AI-readiness; EUR 100,000–500,000 per
project for accelerator-grade data provision.
Biodefence:
Sampling and collection costs (NWSS municipal sites plus transport gateway sampling):
- EU Scenario 1 approximately €23 million per year
total collection; EU Scenario 2 approximately €8 million per year total collection (no nasal swabs).
Metagenomic sequencing, processing and
bioinformatics analysis (BIORADAR
component): EU Scenario 1 approximately €23
million per year; EU Scenario 2 approximately €102 million per year.
- Total annual operational costs including overhead:
approximately €46 million per year (EU Scenario 1) to approximately €110 million per year (EU
Scenario 2).
Biosecurity:
- Total direct compliance costs for providers
implementing mandatory sequence and legitimacy screening.
o Lower-bound estimate: approximately
EUR 7.3 million per year. o Upper-bound estimate: 22.2 million
- Only legitimacy screening: estimated EUR 19
million in 2027 rising to EUR 34 million in 2036; - Only sequence screening: EUR 1.6 million rising
to EUR 2.8 million in 2036
34
- EMA: adapting the Union
Product Database to
remove the approve/reject functionality for National
Competent Authorities.
Estimated at EUR 150– 300K (3–6 months, one IT
team).
Substances of Human Origin:
- NCA upfront sandbox
capability setup; Not
estimated – low to
medium.
- Commission costs for hosting EU SoHO
Platform and SCB
engagement. Not estimated – low.
Organ processing:
- National competent
authority capacity
building, comprising
recruitment or training of
multidisciplinary assessment staff,
establishment of
cooperation channels with pharmaceutical, medical
device, and SoHO
authorities, and development of internal
procedures and assessment
templates. Not quantified – low to medium.
- Commission: adopting
implementing acts to establish the detailed
authorisation procedure
(Article 6a(12)). Not quantified - negligible.
Access to funding:
- Only costs for procedure introduction and
regulatory adjustment: EUR 1.7 million in 2027
rising to EUR 2.5 million in 2036.
35
- Design and establishment
of the Investment Pilot by
end-2026, including instrument structuring,
biotech tagging and KPI
comparability arrangements across
instruments. Costs
moderate. Not quantified - low.
Responsible use of AI and
data management:
- Developing lifecycle-wide
AI guidance across the medicinal product
lifecycle; capacity-
building and training costs borne at both Union and
national levels. Not
quantified – low to medium.
Biodefence:
- Expansion of collection
infrastructure to strategic locations (airports, train
stations, schools,
hospitals) beyond existing wastewater treatment sites.
- Cost minimal as it would
rely on existing wastewater plants where
available.
Direct administrative
costs
n/a. - n/a.
Strategic projects & High impact
strategic projects (including
Biosimilars and AI):
- Preparation and submission of the recognition for (high impact)
strategic project application: staff
time, external consultancy and legal fees, reporting and
administrative tasks.
ATMP:
- Submission of a simplified
declaration per clinical trial
application explaining the applicable negligible-risk
categorisation, in lieu of a full
ERA dossier. New information obligation; net direction
relative to baseline is a
Strategic projects & High
impact strategic projects:
- Front-loaded setup: process design, workload
reallocation and service
standards to establish and operate single points of
contact. In many Member
States, existing authorities may be designated rather
Strategic projects & High impact strategic projects
& Biosimilars:
- Reporting on recognised project pipeline to
Commission under updated Strategic Technologies for Europe Platform information
flows. Not quantified - negligible.
Biotech ecosystem:
Member State level
36
- Central estimate: 1–2 full-time
equivalents per project per year,
corresponding to approximately 1–2% of total project value
(upper bound: 1–3 full-time
equivalents where State-aid- intensive governance applies).
Worst-case participation cost:
EUR 700,000–800,000 per firm (upper bound only; source
explicitly states this is not
representative of the Act's default
recognition-and-coordination
pathway).
- This is a voluntary cost.
Clinical trials:
- initial upfront planning and
reporting effort for sandbox
participation. This "initial overhead"; net direction over the
product lifecycle is expected to
be a reduction24. Not quantified -
low.
Organ processing:
- Full authorisation, Article 6a(2):
approximately EUR 11,500 per application.
- Conditional authorisation with
clinical-outcome monitoring, Article 6a(3)): approximately
EUR 16,750 per application.
reduction. Not quantified –
negligible.
Organ processing:
- Steady-state from
approximately 2032 onwards: approximately 7–10 new
applications per year EU-27 at
~EUR 12,800 each: EUR 90,000–128,000 per year;
- Recurrent monitoring
reporting costs EUR 16,000–
22,500 per year;
- Total steady-state
approximately EUR 106,000– 150,500 per year.
Access to funding:
- Marginal compliance and
reporting costs associated with
participation in supported instruments. Source explicitly
characterises these as the only
business-side effect and the
overall administrative cost
impact as neutral. Not quantified.
SPC extension:
- Demonstrating eligibility for
the SPC extension to EMA per
application. Negligible cost; EMA assessment relies largely
on regulatory information
than new structures
created. Not quantified –
low to medium.
- Data provision for strategic mapping on
Commission request: approximately 0.25 full-time
equivalents per Member State per year.
Novel health biotechnology products:
- Maintaining the regulatory status repository (Commission information system); not quantified
- low.
Organ processing:
- Commission: maintaining publicly accessible list
of authorised processing operations (Article
6a(11));
- facilitating exchange of clinical outcome data
between competent authorities (Article 8, as amended). Not quantified – negligible.
24 Initial overhead for the limited number of available sandboxes may increase upfront planning and reporting effort, but net administrative burden over the product lifecycle is expected to
fall—primarily through implementation of tested innovative approaches by SMEs, avoiding failed submissions and protocol overhauls while mitigating high consultancy and learning
costs. Initial overhead for sandbox participation may increase upfront planning and reporting effort, but net administrative burden over the product lifecycle is expected to fall where
sandboxes avoid failed or heavily delayed applications‑submissions and protocol overhauls for SMEs, which currently face high consultancy and learning costs. Initial overhead for sandbox
participation may increase up‑front planning and reporting effort, but net administrative burden over the product lifecycle is expected to fall where sandboxes avoid failed or heavily delayed
applications.
37
- Weighted average during
transition (~75% Track 1 / ~25%
Track 2): approximately EUR 12,800.
- Total transition-phase burden
EU-27 (~60–145 applications, 2029–2031; central estimate
~100): EUR 768,000–1,856,000.
- Cumulative burden 2029–2035: approximately EUR 2.5 million.
approximately EUR 256,000–
619,000/year during the
transition phase (2029–2031).
already available to the
Agency.
Biosecurity:
Compliance costs for customers and
researchers (documentation, procurement adjustments, internal
compliance procedures, per-order
verification): approximately EUR 16.4 million per year.
Direct regulatory fees and charges
n/a. n/a. n/a. n/a. n/a. n/a.
Direct
enforcement costs n/a.
Strategic projects including Biosimilars:
- Single points of contact dealing with recognition
applications, queries, permitting coordination and
dispute-settlement information. Indicative steady- state staffing needs (caveat: figures illustrate scale,
not a precise prediction):
o low uptake (25–30 projects by 2038): 0.3–0.9 full-time equivalents per
Member State;
o medium uptake (60–70 projects): 0.7–1.8 full-time equivalents per Member State;
o high uptake (100–120 projects): 1.1–3.0 full-time equivalents per Member State.
High Impact strategic projects (including AI):
- EU-level supervision of recognised high-impact
strategic projects: recognition, monitoring,
compliance verification and cross-border coordination. 0.3–0.5 full-time equivalents per
single-country project per year; 0.5–1 full-time
equivalent per multi-country project: o 1–3 full-time equivalents under low
uptake (2–3 projects);
o 2.5–8 full-time equivalents under medium uptake (5–8 projects);
o 5–15 full-time equivalents under high
uptake (10–15 projects).
General food law reform:
38
Member State national competent authorities
- Ongoing supervision and enforcement of
established sandboxes; ensuring sandbox activities remain within defined parameters and do not
jeopardise public health. Not quantified – low to
medium.
ATMP:
- CHMP verification of sponsor declarations submitted in place of full ERA dossiers, as part of
the centralised clinical trial and marketing
authorisation procedure. Not quantified -
negligible (verification of simplified declarations
is incremental to the existing CHMP centralised
procedure; no new assessment infrastructure required).
- .
VMP:
EMA/Commission
- Application assessment, scientific advice, risk- benefit assessment, and two-year assessment
report per established sandbox. Not quantified –
negligible (2–3 assessments over 14 years).
Substances of Human Origin:
- Additional NCA workload per sandbox case
relative to standard SoHO preparation
authorisation, at EUR 301/person-day: medium- risk sandbox case 75–94 person-days total (EUR
22,575–28,294), a 57–114% cost increase over
standard authorisation; high-risk sandbox case 98– 149 person-days total (EUR 29,498–44,849), a
10–63% cost increase.
- Alternatively, approximately EUR 156,000– 219,000/year under low uptake (6 sandboxes);
approximately EUR 1.04–1.46M/year under high
uptake (40 sandboxes). - Learning-by-doing costs and medium-term
efficiency gains from cross-Member State learning
are assumed to cancel out.
Organ processing:
- National competent authority assessment of applications. Per-assessment cost approximately
39
EUR 7,000–10,000 (central estimate ~EUR
8,500), comprising: internal assessment staff 15
working days at EUR 350–450 per day (EUR 5,250–6,750); external expert consultation 3–5
days at EUR 400–500 per day (EUR 1,200–2,500);
administrative overhead EUR 500–750. - Transition phase (2029–2031): aggregate EU-27
approximately EUR 420,000–1,450,000 over
three years (central estimate ~EUR 850,000, approximately EUR 280,000 per year).
- Steady state (from approximately 2032):
approximately EUR 60,000–85,000 per year EU-
27.
- Ongoing monitoring oversight for Track 2
authorisations: approximately 12–20 working days per active monitoring plan per year (3–5 days
per quarterly reporting cycle); aggregate
approximately EUR 63,000–216,000 per year during transition, declining in steady state.
- Alternatively, annually: Transition phase (2029–
2031): approximately EUR 140,000–483,000/year EU-27 (central estimate ~EUR 280,000/year).
Steady state (from approximately 2032):
approximately EUR 60,000–85,000/year EU-27.
Ongoing Track 2 monitoring oversight:
approximately EUR 63,000–216,000/year during transition, declining in steady state.
SPC extension:
EMA:
- Eligibility verification per application, estimated
at approximately 1 full-time equivalent working day per application. Given that between 15 and 28
biotech products are authorised annually (not all
would qualify), the maximum annual workload is estimated at approximately 28–30 working days
per year EU-wide.
Biosecurity:
Member State level:
- Approximately EUR 14 million per year in 2027, rising to approximately EUR 21 million per year
in 2036.
- Estimated staffing requirement: approximately 3 full-time equivalents per Member State for policy
40
coordination, reporting, and enforcement activities
including inspections.
EU level: - Approximately EUR 1.3 million per year in 2027,
rising to EUR 1.9 million per year in the long term;
- corresponding to approximately 11 full-time equivalents for the lead Directorate-General plus
supporting coordination and technical functions.
Indirect costs n/a. SPC extension:
- Delayed access to
biosimilar/competition
during the additional
protection year.
Estimated combined social cost of
approximately EUR
205 million per medicine (EUR 615M
annually at 3
qualifying medicines per year);
- Delayed patient
access: ~EUR 135 million per medicine
(~EUR 405 million
annually at aggregate level);
- Direct payer expenditure: ~EUR 70
million per medicine
(~EUR 210 million annually)
Biosecurity:
- Research loss from chilling
effect (researchers abandoning
or deferring projects due to
concerns about order delays or
rejections) - Approximately 10% of
researchers may shift to in-
house synthesis at substantially higher per-order costs.
- Indirect productivity loss to
providers from regulatory compliance intensity: EUR 8.6
million per year to EUR 24.8
million per year.
41
II. Overview of costs (Totals)
Citizens/Consumers Businesses Administrations
One-
off
Recurrent One-off25 Recurrent One-off Recurrent
Action
(a)
Direct
adjustment
costs
n/a. n/a.
- Not
quantifiable;
qualitatively low
to medium
- EUR 8.16–27.32
million/year (SoHO
EUR 0.72–4.79
million+ organ
processing EUR
0.14–0.33 million +
biosecurity
providers EUR 7.3–
22.2 million);
- AI recurrent
maintenance not
monetised,
qualitatively
assessed as medium.
- EUR 8.75–8.9 million
monetised (Novel
health products sandbox
EUR 4.3 million +
clinical trials sandbox
EUR 4.3 million +
VMP UPD EUR 0.15–
0.3 million ; each spread
over approximately 3
years);
- Remainder qualitatively
negligible to low to
medium.
- EUR 48.6–112.6 million
/year monetised
(Biodefence EUR 46–110
million + Biotech
ecosystem Commission
EUR 2.6 million);
- AI technology refresh and
curation uplift not
monetised; qualitatively
assessed as medium to
high.
Direct
administrative
costs
n/a. n/a.
- EUR 0.77–1.86
million
monetised (organ
processing
transition
applications
2029–2031);
- Strategic project
recognition
applications not
monetised as
- EUR 16.51–16.55
million/year
monetised
(Biosecurity
customers EUR 16.4
million + organ
processing steady-
state EUR 0.11–0.15
million );
- ATMP declaration,
access to funding,
- Not monetised;
qualitatively low to
medium (strategic
projects SPC front-
loaded setup)
- Not monetised in EUR;
qualitatively negligible to
low (Biotech ecosystem
0.25 FTE/MS data
provision; STEP
reporting; repository
maintenance; organ
processing Commission
list)
25 One off costs were left not annualised, because they occur once, so by design they do not repeat throughout the years.
42
aggregate;
voluntary cost
SPC eligibility:
negligible
Direct
regulatory fees
and charges
n/a. n/a. n/a. n/a. n/a. n/a.
Direct
enforcement
costs
n/a. n/a. n/a. n/a. n/a.
- EUR 15.52–25.06
million/year (Biosecurity
MS EUR 14–21 million+
Biosecurity EU EUR 1.3–
1.9 million + SoHO NCA
EUR 0.16–1.46 million+
organ processing NCA
EUR 0.06–0.70 million ,
higher during transition
2029–2031, declining
from 2032);
- Strategic projects FTEs
and AI EU supervision not
monetised; qualitatively
assessed as low to
medium.
Indirect costs n/a. - EUR 615 million/year
(SPC extension combined
social cost at 3 qualifying
medicines/year;
comprising delayed
patient access EUR 405
million /year + direct
payer expenditure EUR
210 million /year)
n/a. - n/a. n/a. - EUR 105.6–194.8 million
/year (Biosecurity
chilling effect EUR 97–
170 million /year +
productivity loss EUR
8.6–24.8 million /year)
Grand Total
(monetised
costs only)
n/a. EUR 615 million/year EUR 0.77 – 1.86
million
EUR 24.7 – 43.87
million/year
EUR 8.75 – 8.9 million EUR 169.7 – 332.5 million
/year
43
III. Contribution to the administrative burden reduction targets
Administrative
costs
[EUR million]
New recurrent costs
(INs)
(nominal values per
year)
Removed recurrent costs (OUTs)
(nominal values per year)
Net cost(INs –
OUTs)
(nominal values per
year)
New one-off costs (INs)
(annualised total net present
value over the relevant
period)
Removed
one-off costs
(OUTs)
(annualised
total net
present value
over the
relevant
period)
All businesses
(Organ processing)
Authorisation
application per
processing technique
(steady state from
~2032): ~7–10
applications/year EU-
27 at ~EUR 12,800
each; annual value:
~EUR 0.09–0.13
million/year.
(Biosecurity) Per-order
verification,
documentation and
procurement
compliance: EUR 16.4
million/year (EUR 3.56
million gene orders +
(ATMP) Full ERA dossier and parallel
national GMO submission obligations
replaced by a simplified declaration per CTA.
Saving: ~0.15–0.3 FTE-year per CTA
application. GMO-specific workload of ~0.3–
0.5 FTE-year per CTA is reduced by 50–70%.
At ~8–15 CTAs/year subject to dual-track
burden, and an indicative EU regulatory
affairs cost approx. EUR 16,800–33,600 per
CTA. Annual value: ~EUR 0.13–0.50
million/year
(VMP) VNRA batching: 45–55% reduction in
submission events for ~31,875 non-SPC
VNRAs/year. Staff time saving: 14,930–
29,859 hours/year saved sector-wide at ~EUR
65/hour. Annual value: ~EUR 0.97–1.94
million/year (central: ~EUR 1.46
million/year)
~ + EUR 6.9–
11.4M/year (net
increase, driven
primarily by Action
17 biosecurity
customer compliance
at EUR 16.4
million/year)
(Organ processing)
Authorisation applications
for organ processing
techniques during transition
phase (2029–2031): total
EUR 0.77–1.86 million
(approx. 60–145
applications EU-27 at
weighted average EUR
12,800 each); annualised
NPV over 11-year
assessment period (2028–
2038): approximately EUR
0.08–0.20 million.
None
44
EUR 12.85 million
oligo orders)
(multiple) Ongoing
reporting, knowledge-
sharing and
participation
compliance obligations;
recognised strategic
project applications;
SPC eligibility
demonstrations; clinical
trial sandbox reporting.
Not quantified.
Approx. EUR 16.5
million/year
(VMP GMO exemption) Elimination of
requirement to compile Annex III GMO
documentation under Directive 2001/18/EC
for GMO-containing VMP marketing
authorisation applications. Saving:
approximately EUR 7,000 per MA dossier. At
approximately 5–10 GMO-VMP MA
applications per year: annual aggregate value
approximately EUR 0.035–0.070 million/year.
(Biosimilars) Reduced MAA dossier
preparation burden where CES is eliminated:
~75 person-days saved (EUR 30K–45K) per
eligible MAA. At ~12–18 MAAs/year
qualifying during 2025–2030. Annual
aggregate value: ~EUR 0.36–0.81
million/year (12–18 MAAs × EUR 30–45
thousand).
(GMMs) Reduced standard GMO dossier
requirements for low-risk pathway
applications: source explicitly estimates ~1%
reduction per application (589 vs 593 working
days NCA burden). Near-zero applications
currently (no authorised non-food GMMs
under current framework); net saving
negligible at present
(Clinical trials) Reduced administrative FTE
time per multinational clinical trial
application through streamlined authorisation
procedures: approximately EUR 2,714–4,496
per application (Standard Cost Model; 15–
25% reduction in time spent with regulators).
45
At approximately 1,050 multinational
trials/year: approximately EUR 2.8–4.7
million/year.
(Clinical trials) Elimination of duplicate
parallel submissions for combined studies
(medicinal products and medical
devices/diagnostics). Coordinated assessment
reduces excess submissions by approximately
30%; 381–748 excess submissions eliminated
per year at EUR 2,239 processing cost per
Member State. Annual value: approximately
EUR 0.8–1.6 million/year.
Approx. EUR 5.1–9.6 million/year
- in which
SMEs
Public
administrations
Not monetised;
qualitatively negligible
to low:
Biotech ecosystem: data
provision for strategic
mapping on
Commission request
(~0.25 FTE/MS/year)
Strategic projects and
biosimilars: reporting
on recognised project
pipeline under STEP
information flows
(Biotech ecosystem) Maintaining and
updating strategic mapping outputs and
reporting on recognised project pipeline
under STEP information flows. Cost
absorbed within EUR 2.6 million/year
Commission coordination appropriation
reported under adjustment costs; not
separately quantified to avoid double-
counting.
Negligible
(qualitatively
assessed)
(Strategic projects and
high-impact strategic
projects) Front-loaded
setup of single points of
contact: process design,
workload reallocation and
establishment of service
standards. Not quantified,
assessed qualitatively as
low to medium.
None
46
Novel health products:
maintaining the
regulatory status
repository
Organ processing
(Commission):
maintaining publicly
accessible list of
authorised processing
operations; facilitating
exchange of clinical
outcome data between
competent authorities
Citizens None None None None
3. Relevant sustainable development goals
IV. Overview of relevant Sustainable Development Goals
Relevant SDG Expected progress towards the Goal Comments
SDG 3 ‘Good health and well-being: Ensure healthy lives and promote well-
being for all at all ages’
Expected increase of patients’ access to clinical trials in the EU and innovative
products on the single market, including rare diseases.
SDG 9 ‘Industry, innovation and infrastructure: Build resilient infrastructure,
promote inclusive and sustainable industrialisation and foster innovation’
Increased access of biotechnology companies to capital through the different stages of
their development;
EU’s capabilities in research, development and production are reinforced.
SDG 12 ‘Responsible consumption and production: Ensure sustainable
consumption and production patterns’
Biotechnology products placed on the market (such as microbial biocontrol and
microbial fertilisers) will have the potential to replace products potentially harmful for
the environment.
ANNEX 4: ANALYTICAL METHODS
Overarching analytical framework
This section describes the overarching analytical framework applied across the 17 policy
intervention assessments that together constitute the evidence base for the analysis26.
While each intervention-specific analysis was tailored to its thematic context, regulatory
domain, and relevant data, all assessments followed a common methodological
architecture.
1. Alignment with the EU Better Regulation framework
The baseline is constructed as a counterfactual scenario depicting how identified
challenges would evolve absent the proposed intervention, rather than a static description
of current conditions. The analysis of impacts is a standardised set of impact dimensions
derived from the Better Regulation Toolbox’s analytical categories, and the depth of
analysis is calibrated to the significance of each intervention and the availability of
evidence. The analytical phases follow the following sequence: policy mapping
(translating the legislative text into structured analytical units), baseline development
(establishing the counterfactual), assessment of impacts (evaluating costs, benefits, and
broader effects against the baseline), and compilation of findings (including cumulative
impacts).
2. The policy intervention as the unit of analysis
The policy intervention was defined as the primary unit of analysis, translating the articles
of the proposed Regulation and of the proposed Directive into 17 policy interventions,
each encompassing one or more underlying policy measures that share common policy
objectives, target stakeholders, and implementation mechanisms. The mapping operated at
three hierarchical levels: broader policy areas corresponding to the structure of the
proposed European Biotech Act, policy interventions representing the intended aims of the
proposed initiatives, and policy measures detailing the specific legislative changes. For the
purpose of the SWD, the impacts of interventions n°9, 10 and 11 are presented together in
the main report.
The 17 policy interventions span six thematic areas: strategic projects and clusters
(including biosimilars), time-to-market regulatory proposed changes, access to capital,
intellectual property, AI and data, and biodefence and biosecurity. This grouping ensured
coherence by combining related policy measures under unified assessment frameworks
while maintaining sufficient granularity to capture intervention-specific dynamics. For
each policy intervention, a dedicated baseline was established, a thorough assessment of
the impacts of the proposed measures was conducted.
3. Impact framework development
The assessment of each intervention is anchored in an intervention-specific impact
framework that sets out the logic chain linking the proposed policy measures to their
expected effects, the indicators selected to track those effects, the expected direction of
26 Rapid Assessment Scenarios study (forthcoming).
48
change, and the data sources available for baseline calibration and impact estimation. The
impact framework serves as the analytical blueprint for the entire assessment, ensuring that
the subsequent baseline and impact analysis are focused on the channels through which the
intervention is expected to operate.
Seven standardised impact dimensions were applied across all 17 assessments,
providing a common analytical structure:
• Conduct of business.
• Administrative costs on businesses, including SMEs.
• Competitiveness, trade and investment flows.
• Functioning of the internal market and competition.
• Innovation and research.
• Administrative costs to public authorities.
• Public health and safety.
All dimensions were screened for relevance for each intervention, with the analysis
emphasising the most pertinent dimensions for each case while maintaining a minimum
level of coverage across all seven to ensure comparability for the cumulative assessment.
This standardised structure enables the cumulative impact analysis to aggregate findings
by impact dimension across interventions and to identify synergies, trade-offs, and
emergent systemic effects.
For each impact dimension, the framework specifies indicators that are, to the extent
possible, quantitative and measurable, together with the data sources used for baseline
calibration. Where quantitative indicators could not be established due to data constraints
(a frequent occurrence, particularly for novel instruments such as regulatory sandboxes,
the biothreat radar, and the foresight panel), qualitative indicators based on directional
assessments were used. This approach ensured that the absence of quantitative data did not
result in the exclusion of important impact channels from the analysis.
4. Baseline construction
Consistent with the Better Regulation Toolbox (Tool #60), the baseline for each
intervention describes the counterfactual scenario: how identified problems and current
conditions would evolve in the absence of the proposed policy intervention (see Annex 7).
The baseline is a dynamic projection that takes account of existing trends, recent
Commission proposals, autonomous market developments, and foreseeable changes in the
regulatory or technological environment. This dynamic character is essential because it
establishes the reference point against which incremental impacts of the proposed
intervention are measured.
Across the 17 assessments, a common baseline architecture was applied. Discussion of the
time horizons adopted for baseline and assessment of impacts is provided below.
Across all interventions, the baseline is also based on explicit assumptions, which are
presented into details in the supporting study (Rapid Assessment Scenario Study).
49
5. Evidence base and data collection methods
The assessments draw on a multi-layered evidence base assembled through three
complementary data collection methods: desk research, targeted stakeholder consultations,
and analysis of the public consultation and call for evidence responses.
6. Proportionality and analytical transparency
While the overarching framework is common, its application was adapted to the thematic
and context of each intervention. This adaptation reflects the proportionality principle:
the depth and method of analysis were calibrated to the significance of the intervention,
the novelty of the proposed measures, and the availability and quality of evidence.
The adaptations occurred for example, on the degree of measure-level disaggregation.
These varies across interventions. Interventions encompassing multiple distinct policy
measures with separable effects, such as the VMPs intervention (four distinct measures:
GMO exemption, SPC extension for zoonotic products, regulatory sandbox, and VNRA
burden reduction) or the general food law intervention (EFSA procedural revision and food
chain sandboxes), conduct assessments at both the measure level and the intervention level,
enabling the identification of measure-specific effects. Interventions consisting of a single
unified measure or a tightly integrated package (such as the SPC extension or the
biosecurity framework) are assessed primarily at the intervention level.
The use of scenario analysis and comparator evidence was also deployed selectively.
Where the intervention creates new instruments without direct EU precedent (such as
regulatory sandboxes, strategic project recognition, or the biothreat radar), the analysis
draw on comparator evidence from analogous frameworks in other jurisdictions (e.g.,
the UK FCA sandbox, the US Nucleic Acid Observatory, the Net-Zero Industry Act) or
from other policy domains (e.g., InvestEU) to calibrate assumptions and bracket
plausible ranges. Where the intervention amends existing procedures with observable
cost parameters, the analysis relies more directly on existing regulatory data and
stakeholder-validated estimates.
Finally, a principle of analytical transparency was applied throughout. Each analysis
explicitly identifies data limitations, evidentiary gaps, and areas of uncertainty (see the
Rapid Assessment Scenario study for more information). Where assumptions cannot be
empirically validated, they are flagged as such. Where quantitative estimates are derived
from proxy data or comparator evidence, the degree of approximation is stated.
7. Time horizon for baseline and assessment of impacts
A default temporal framework structured around two projection periods was adopted: a
near-term horizon of 2025-2030 and a medium-term horizon of 2030-2038, with 2025
serving as the base year (T0). The selection of 2038 as the default medium-term endpoint
reflects two reinforcing considerations: alignment with the EU Multiannual Financial
Framework (MFF) programming cycle, which provides the institutional and budgetary
context within which the proposed European Biotech Act's instruments will operate, and
the expectation that a period of approximately ten years from the expected regulatory
transposition at EU and national levels date (likely by 2028) represents a reasonable
timeframe for the proposed policy measures to produce observable impacts across the
50
majority of intervention areas (also accounting for institutional establishment, stakeholder
adaptation, and the initial materialisation of structural effects).
Within this common framework, a principle of intervention-specific temporal
calibration was applied, whereby the precise time horizons were adapted to the causal
logic, sectoral dynamics, and primary evidence base of each intervention. This approach
reflects a deliberate methodological choice to prioritise analytical coherence and evidential
integrity within each assessment over rigid temporal uniformity across the portfolio. Three
categories of adaptation were applied.
• First, two assessments extended the baseline projection horizon to 2040: the
veterinary medicinal products framework and the organ processing directive.
In both cases, the extension was driven by the sector-specific product development
and adoption cycles that define the relevant causal pathways. The veterinary sector
is characterised by lengthy product development pipelines and a small,
commercially constrained market in which effects of the proposed regulatory
changes on innovation throughput require longer observation windows to
materialise in measurable form. The organ processing assessment relies on
compound annual growth rate (CAGR) projections of transplant volumes in a
sector where substantial shifts in supply-demand dynamics are unlikely. However,
when it came to the cumulative impacts, a more conservative time horizon (until
2035) was adopted since the proposed measures are highly contentious on the pace
of technological development in organ processing and the ability of the
legal/regulatory environment to cope with such technological shifts.
• Second, the biosecurity framework assessment employed a distinct set of
temporal milestones: short term (~2027), medium term (~2031), and long term
(~2036).
• Third, five assessments: the biotech ecosystem, general food law, SoHO sandbox,
AI and data guidance, and biodefence, employ qualitative temporal descriptors
(short-term, medium-term, longer-term) without specifying year ranges. These
interventions share a common feature: they establish enabling institutional
frameworks, coordination structures, or guidance mechanisms whose effects are
inherently structural and emergent rather than discrete and time-phased.
This differentiated approach to temporal framing remains consistent with the
proportionality principle that governs the overarching methodology.
8. Impact estimation and modelling approaches
The 17 intervention-specific assessments employed a differentiated set of approaches to
impact estimation, reflecting the heterogeneous nature of the interventions, the maturity
and availability of evidence, and the directness of the causal chains linking proposed
measures to observable outcomes.
Spectrum of quantification approaches
No single modelling framework was imposed across all 17 assessments. The overarching
analytical framework prescribed a common architecture of impact dimensions, baseline
construction, and qualitative summary ratings, but left the choice of estimation technique
to the intervention-specific context. Five broad categories of estimation approach can be
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identified, arranged along a spectrum from formal quantitative modelling to qualitative
directional assessment.
Category A: Formal quantitative modelling
The analysis of three interventions employed dedicated quantitative modelling
frameworks. For the biosecurity assessment, its core cost-benefit analysis draws directly
on an external quantitative model developed by RAND Europe, itself adapted from the
Centre for Long-Term Resilience (CLTR) framework for the United Kingdom. The RAND
model estimates costs (provider screening costs, customer compliance costs, research
productivity losses, public enforcement costs) and benefits (attack-prevention and
accident-prevention value, derived from probabilistic risk modelling) over a ten-year
horizon, producing monetised net benefit estimates at defined temporal milestones (short-
term ~2027, medium-term ~2031, long-term ~2036).
The organ processing assessment deployed a modelling framework constructed in the
context of the supporting study. It uses a triangulated estimation approach combining three
analytical pillars: CAGR-proxy logic (deriving an incremental policy acceleration effect
of +0.95 percentage points per annum from observed pre- and post-Directive transplant
growth rates), programme-level adoption modelling (projecting the share of EU transplant
programmes adopting processing technologies under three scenarios at 25%, 50%, and
100% of the gap between baseline plateau and clinical ceiling), and organ-level intensity
logic (estimating the shift from selective to systematic processing within adopting
programmes). Baseline projections to 2040 used compound annual growth rates anchored
to EDQM trend data, and impact estimation applied scaling factors to the identified
adoption headroom. This three-pillar approach was necessitated by the absence of a
directly comparable historical precedent for the proposed regulatory intervention.
The VMPs assessment employed bottom-up process-level cost estimation, calculating
per-unit administrative savings (FTE-equivalents, person-days, cost per regulatory action)
for each of its four policy measures and aggregating these over a 15-year horizon (2025-
2040) with a 3% social discount rate to produce cumulative present-value estimates. It
quantified product-day delays eliminated, VNRA redistribution effects across the sector,
and staff-time savings using stakeholder-validated parameters.
Category B: Market-level quantification
The impacts of two interventions were quantified by scaling product-level or firm-level
data to the sector, without deploying formal multi-year projection models with discount
rates. The biosimilars assessment estimated per-product development cost savings from
CES elimination and scaled these to sector-level annual aggregate savings using observed
MAA submission volumes and transition-rate assumptions. It drew on published
cumulative healthcare savings data, published IQVIA market data on therapeutic-area
price reductions, and EMA pipeline activity trends to construct a quantified baseline
against which incremental effects were assessed. The SPC extension assessment used
revenue-profile analysis drawing on the European Commission modelling based on a
cohort of 198 innovative medicines for which data on the value and volume of sales were
drawn from IQVIA MIDAS, last layer of protection was determined through IQVIA Patent
Intelligence and product eligibility though EMA data, manufacturing footprint analysis
using EudraGMDP data (624 manufacturing and import authorisations, 2012–2025), and
clinical trial location data from EMA databases to construct a quantified baseline of the
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IP-protection landscape. Impact estimation combined these empirical baselines with
published evidence on loss-of-exclusivity revenue dynamics and patenting trends.
Category C: Scenario-based order-of-magnitude estimation
The analysis of three interventions employed scenario-based approaches to generate
illustrative order-of-magnitude ranges, without claiming the precision of formal modelling.
The strategic projects and high-impact projects assessments used a common estimation
architecture: three uptake scenarios (low, medium, high) defined in terms of project
numbers by 2038, combined with monetisation calibrations for avoided delay costs (using
an illustrative project value range and a 34% cost-overrun assumption for delays exceeding
12 months) and investment mobilisation ranges (using observed leverage multipliers from
EU financial instruments, e.g. ~1.3x for loans, ~4.8x for guarantees). These produced
cumulative order-of-magnitude ranges (e.g. millions in avoided delay costs for strategic
projects under different uptake scenarios). The access to funding assessment similarly
used published financial benchmarks (VC round sizes, EIB mobilisation data, institutional
capital estimates) to calibrate plausible impact ranges, while noting that attribution of
incremental effects to the specific policy measures remains sensitive to the broader
financing environment.
Category D: Benchmark-anchored partial quantification
The analysis of two interventions embedded specific quantified parameters within
predominantly qualitative frameworks. The clinical trials assessment drew on published
cost-modelling evidence to anchor key parameters: administrative expenses accounting for
11-29% of total clinical trial costs, an indicative net present value return of approximately
five times the investment for phase II decentralised trials and approximately thirteen times
for phase III, and time savings of 1-3 months from decentralised elements. However, it did
not construct a cumulative cost-benefit model, instead using these benchmarks as
illustrative reference points within a qualitative assessment of each policy measure. The
novel health products assessment adopted a similar approach, using comparator evidence
from analogous frameworks (notably the UK FCA regulatory sandbox) to calibrate
expectations, while acknowledging the absence of directly comparable EU-level precedent
for the proposed instruments.
Category E: Qualitative directional assessment
The analysis of sever interventions relied predominantly on qualitative assessment. These
cover the biotech ecosystem, general food law, ATMPs, SoHO sandbox, GMMs, data and
AI, and biodefence. Their interventions either create entirely new institutional structures
without quantifiable precedent (the biothreat radar, the SoHO sandbox, the foresight
panel), establish enabling or coordination frameworks whose value is inherently structural
and emergent (the biotech ecosystem support network, the AI guidance mandate), or
operate in regulatory domains where the primary effects are qualitative changes in
regulatory coherence, clarity, or flexibility rather than directly monetisable cost or revenue
changes (ATMP classification proposed changes, GMM-specific risk assessment criteria,
EFSA procedural proposed changes). The analysis relied on causal-chain reasoning
grounded in intervention logic, comparator evidence from analogous frameworks in other
jurisdictions or policy domains, stakeholder-validated assumptions, and the standardised
qualitative rating scale (strongly negative to strongly positive) applied across all seven
impact dimensions.
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Cross-cutting methodological features
Several methodological features cut across the categories described above and merit
specific note.
First, all 17 analyses applied the same qualitative summary rating (from ++ to - -) across
the seven impact dimensions. This ensures that the cumulative impact analysis can draw
on a consistent set of structured qualitative judgements even where quantified estimates
are unavailable.
Second, where scenario analysis was employed (Categories A-C), the scenarios were
explicitly labelled as illustrative and designed to bracket plausible ranges under different
assumptions about uptake, implementation pace, and market response, rather than as
probabilistic forecasts.
Third, the use of comparator evidence from analogous frameworks, whether from other
EU instruments or from other jurisdictions, was deployed selectively across the spectrum:
as calibration input for quantitative models in Categories A-B, as anchor points for scenario
ranges in Category C, and as the primary basis for directional assessment in Categories D-
E.
Fourth, assumptions are explicitly stated (see the supporting study), with each impact
dimension within each analysis opening with a clearly delineated assumptions box.
Approach to cumulative impact
1. Outline of the overall approach
The analysis was organised in terms of the impact areas that are reflected in the 17
analyses:
• Conduct of business
• Administrative costs on businesses, including SMEs
• Competitiveness, trade and investment flows
• Functioning of the internal market and competition
• Innovation and research
• Administrative costs to public authorities
• Public health and safety
In each impact area, the following question was asked: through what distinct mechanism
does the proposed European Biotech Act change this dimension? Each mechanism is
driven by a specific combination of interventions, some of which are direct movers, some
as conditions or amplifiers.
To prepare the analysis the following steps were followed:
Step 1. Identification of the mechanisms operative in this impact area:
Each impact area has 2-3 distinct mechanisms. These are distinct processes, driven by
different combinations of interventions, producing different types of competitive effect.
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Step 2. For each mechanism, identification of the intervention combination that
drives it:
Each mechanism identified in Step 1 is driven by a combination of multiple interventions.
This is where multiplier effects become visible from the interventions that do not lead to
impacts themselves but enable other interventions.
Step 3. Assessment of the cumulative effects mechanism by mechanism:
This step involves combining the analyses from the individual intervention and arriving at
a comprehensive narrative. For each mechanism relevant information corresponding to
impact area was identified. For example, when working on “Reduction of overlapping
regulatory obligations across frameworks”, the analyses under Conduct of business for the
proposed ATMP revision, Vet medicinal product proposed amendments, proposed clinical
trial coordinated assessment for combined studies, and the proposed EU Health
Biotechnology Support Network were used.
In the cumulative assessment, impacts are analysed indicator by indicator. This is
necessary because the interventions generate heterogeneous types of impacts and
indicators, which cannot be combined using a single quantitative methodology. Several
mechanisms may affect the same indicator (e.g. administrative costs to authorities, clinical
trial timelines, investment levels). In such cases, impacts are combined only where they
arise from distinct regulatory drivers.
Double counting is avoided by distinguishing between:
• Independent policy drivers, where different interventions create separate cost or
benefit effects affecting the same indicator. In such cases, the impacts are treated
as additive (for example, administrative workload generated by AI-related
regulatory guidance and workload generated by SPC-related measures affecting
the same authority).
• Shared administrative or regulatory processes, where several measures rely on
the same underlying procedure or institutional activity. In these cases, the impact
is counted once, even if multiple policy measures refer to that process (for
example, different categories of strategic project designation relying on the
same workflow).
This distinction ensures that cumulative impacts reflect the true incremental effects of
policy measures, while avoiding artificial inflation of costs or benefits where measures
operate through the same administrative mechanism.
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2. Mapping of the mechanisms of change and interventions
Causal chain for each of the impact area and mechanisms is presented into details in the
supporting study (Rapid Assessment Scenario Study), together with a precise narrative,
assumptions, and implications.
Conduct of Business
Change mechanism 1: Reduction of overlapping regulatory obligations across
frameworks
Biotech companies developing products that span multiple regulatory regimes (ATMPs
with GMO components, organ-derived products, combination products involving devices
and diagnostics, veterinary medicinal products with GMO elements) currently face parallel
and often duplicative assessments under separate legal frameworks. The proposed Act aim
at addressing this through five distinct regulatory channels. The changes in the ATMP
framework eliminates procedural duplication in the relationship between the ATMP and
general medicinal product frameworks. The proposed clinical trial framework introduces
a coordinated assessment pathway for combined studies that span the CTR and IVD/MDR
frameworks simultaneously. The proposed intervention on VMPs creates a single 'one-
stop-shop' pathway for GMO veterinary medicinal products, eliminating the need for a
separate GMO environmental risk assessment alongside the marketing authorisation
procedure. The intervention on organ transplantation expands the scope of the
transplantation directive to cover organ processing and establishes a clear authorisation
regime for processing techniques, resolving a currently unaddressed overlap with tissue
and cellular frameworks. The regulatory status repository addresses a foundational source
of framework overlap: uncertainty about which legal regime governs a given product,
which currently forces companies to engage with multiple frameworks simultaneously as
a precautionary measure.
Each proposed intervention reduces a specific source of overlap; together they address the
full landscape of cross-framework friction. The EU Health Biotechnology Support
Network and AI guidance framework amplify the proposed measures by reducing the
navigation costs that persist even after formal regulatory overlap has been removed.
Emergent effect: Firms developing complex biotech products face a qualitatively more
coherent regulatory environment, not just an incrementally less burdensome one.
Risk: Proposed interventions are enacted under different frameworks at different speeds;
residual fragmentation may persist where one intervention advances and another stalls.
Change mechanism 2: Predictability and certainty in permitting and project
development
Regulatory uncertainty operates as a material business risk when firms cannot form reliable
expectations about the timeline, applicable pathway, or outcome of their regulatory
interactions. The proposal addresses this across several distinct dimensions. Strategic
project recognition introduces mandatory timelines, single points of contact, tacit approval
provisions, and highest national significance status, converting a previously discretionary
and variable permitting process into a structured, time-bounded one. The regulatory status
repository and Foresight Panel reduce a further category of uncertainty: firms developing
genuinely novel products currently face extended pre-application periods of regulatory
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status ambiguity, during which they cannot reliably plan development timelines. By
establishing clear classification procedures and expert horizon-scanning, this mechanism
resolves pathway uncertainty before the formal application process begins. In the area of
organ transplantation, the proposed organ processing authorisation regime provides legal
certainty and a clear regulatory pathway for transplantation centres and national
authorities, replacing ad hoc national practices with a structured authorisation procedure.
Recognition must be granted and classification must be completed before the predictability
benefits materialise; the quality of Member State implementation determines the actual
gain.
Emergent effect: Firms can make capital allocation decisions based on a known permitting
and pathway horizon rather than an open-ended one, materially changing project feasibility
assessments.
Risk: Dependent on Member State implementation quality; tacit approval provisions may
create legal uncertainty in some jurisdictions.
Change mechanism 3: Reduced friction for SMEs, start-ups and scale-ups in
accessing regulatory and market pathways
SMEs and start-ups face disproportionate burdens from regulatory complexity because
they lack the in-house capacity that large firms use to navigate it. The proposal creates
dedicated support through three direct mechanisms: strategic project recognition includes
mandatory dedicated communication channels and personalised administrative support for
smaller firms; high-impact project recognition maintains and extends these provisions with
particular attention to scale-ups and biotechnology development accelerators; and the EU
Health Biotechnology Support Network provides regulatory navigation, IP support,
investor connection, and AI integration assistance targeted specifically at developers who
lack these capabilities in-house.
Four further interventions amplify these direct measures by reducing the underlying
complexity that smaller firms must navigate: the regulatory status repository reduces the
cost of pathway determination; the changes in the ATMP framework simplify a product
category where SMEs are disproportionately represented as innovators; the proposed
clinical trial framework reduces the variable costs of multinational trial applications; and
AI tools under the AI and data guidance framework provide technology-enabled
efficiencies that partially substitute for human regulatory capacity.
Emergent effect: Smaller firms can access the same regulatory pathways and support
infrastructure that were previously accessible mainly to large, well-resourced companies.
Risk: Effectiveness depends on the Network's actual operational quality and coverage,
which is difficult to guarantee at design stage.
Administrative Costs on Businesses, including SMEs
Change mechanism 1: Direct reduction of procedural steps and timelines in clinical
development
The changes in the ATMP and clinical trial frameworks each reduce direct administrative
costs in clinical development through distinct but complementary procedural interventions.
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The revised ATMP framework eliminates the additional 50-day ATMP assessment period
that currently applies to advanced therapy products within the clinical trial procedure,
removing a time and cost burden specific to this product category. The proposed clinical
trial framework delivers broader reductions across all multinational trials: authorisation
timelines fall from 106 to 75 days (47 days without a request for information), substantial
modifications from 96 to 47 days; harmonised templates for Part II applications reduce
drafting costs; parallel submission of distinct modifications eliminates sequential
procedural bottlenecks; and the investigational medicinal product core dossier enables
reuse of validated documentation across multiple trials.
These direct procedural reductions are amplified by three enabling conditions. The EU
Health Biotechnology Support Network reduces the cost of inadequate dossier preparation
by providing early navigation support and connecting developers to relevant expertise. The
regulatory status repository reduces pre-application uncertainty costs by ensuring
developers enter the formal procedure with a confirmed regulatory classification. AI tools
under the AI and data guidance framework enable technology-assisted dossier preparation
and submission management, reducing the variable cost per application. Each procedural
intervention reduces a distinct category of administrative cost independently.
Emergent effect: The cumulative reduction across a full clinical development programme
is substantially larger than any single timeline saving, as the savings compound across
multiple applications, modifications, and Member States.
Risk: Realisation depends on consistent implementation across all Member States; variable
quality of reporting Member State performance could erode the gains.
Change mechanism 2: Streamlined/improved risk assessment processes for GMMs,
food, feed and food chain inputs and promotion of innovation in the food chain
EFSA's general pre-submission advice to applicants upon request is expanded to cover
study design and testing strategies, replacing also the existing renewal pre-submission
advice, reducing the cost of inadequate study design at the application stage. The
procedural delay for non-compliance at pre-submission phase (study notification
requirement) is shortened from six months to three months. The governance of EFSA's
Scientific Panels and Scientific Committee is adapted (EFSA staff chairing with no voting
rights) to strengthen the coherence of risk assessment while EFSA's mandate on nutrition
matters is expanded to cover all nutrition matters. A harmonised framework for the set-up
of regulatory sandboxes is also introduced to test products and technologies as well as data
and alternative regulatory requirements for food (except novel foods), feed, all GMO uses,
and food contact materials (except recycled plastics).
For companies developing biotech products pertaining to the food chain, the cumulative
effect of these targeted amendments is expected to reduce both direct assessment costs and
the indirect costs of prolonged authorisation procedures, as well as the costs of testing
innovative technologies and products. Regulatory sandboxes allow risk assessors and risk
managers to harvest useful evidence from testing data and alternative regulatory
requirements, contributing to their faster adaptation. In the area of GMMs in products for
deliberate release into the environment, the authorisation procedure is adapted to better
suit micro-organisms, to reduce some disproportionate burden, and to accelerate and
streamline the procedure for some low-risk products, without lowering the level of safety.
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Emergent effect: The combination of expanded pre-submission guidance, shorter
procedural delays, and governance proposed changes to Scientific Panels could reduce the
total cost of a food/feed biotech application (especially for SMEs) more than either
intervention alone, while ensuring the coherence of risk assessment.
Risk: EFSA capacity to absorb expanded pre-submission advice tasks is a constraint and
should not be detrimental to its core business (risk assessment tasks).
Competitiveness, Trade and Investment Flows
Change mechanism 1: Shifting late-stage investment and scale-up decisions towards
the EU
The EU currently loses late-stage investment to the US and other regions primarily because
the risk-adjusted return on EU-domiciled scale-up is inferior: regulatory timelines are
longer, permitting is unpredictable, capital is scarcer, and the return horizon is shorter. The
proposal addresses all four dimensions simultaneously through four direct mechanisms.
Strategic project recognition directly changes the investment calculus by de-risking the
permitting pathway that investors price into their return expectations: mandatory timelines,
single points of contact, and priority status convert a variable and opaque process into a
bounded and transparent one. High-impact project recognition extends and enhances these
effects, adding Commission-level recognition and Union-level financial support
mechanisms. The changes to the clinical trial framework shorten the development timeline,
directly improving time-to-market projections. The investment pilot and late-stage capital
booster address the capital availability dimension, providing financial instruments
specifically designed for the scale-up phase where EU funding gaps are most acute.
The proposed SPC extension amplifies the returns generated by all four direct mechanisms
by extending the period of protected commercialisation, making the full investment
package more financially attractive. No single instrument shifts the investment calculus;
the combination does. Emergent effect: A fundamentally different risk-adjusted return
profile for EU-domiciled biotech investment, sufficient to change location decisions at the
margin for a non-trivial number of companies.
Change mechanism 2: Strengthening the EU's global competitive position in
biosimilars
The EU has strong existing expertise in biosimilars but has not converted that expertise
into dominant manufacturing capacity. The biosimilars competitiveness framework is the
direct driver of this mechanism, operating across three dimensions: EMA guidance on
tailored regulatory approaches potentially reduces clinical data requirements; a dedicated
strategic project track for biosimilars manufacturing provides the full administrative and
financial support package available to strategic projects, focused specifically on the
biosimilars category; and international partnership provisions encouraging partnership
among economic operators. This addresses both the regulatory cost competitiveness of EU
biosimilars development and the strategic visibility of the EU as a biosimilars
manufacturing hub.
Change mechanism 3: Improving EU attractiveness for commercial clinical research
The EU's share of global commercial clinical trials has fallen from 22% to 12% in a decade.
This is primarily a competitiveness problem: sponsors locate trials where authorisation is
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fastest, most predictable, and most administratively manageable. The changes to the
clinical trial framework are the direct driver, addressing the principal factors sponsors use
to make trial location decisions: multinational authorisation timelines, administrative
harmonisation, digital infrastructure for trial management, and operational flexibility
through parallel modifications and electronic consent.
Four interventions amplify the competitiveness effect of the proposed clinical trial
framework by improving associated conditions. Changes to the ATMP framework make
EU clinical development for advanced therapies more operationally attractive, addressing
a category where sponsors currently face additional procedural burden relative to other
jurisdictions. Financing instruments improve the financial attractiveness of EU-domiciled
trial investment by providing capital instruments oriented toward the biotech development
stage at which sponsors make location decisions. SPC extension increases the commercial
value of products developed through EU clinical programmes, strengthening the financial
case for EU-based development. AI guidance reduces the operational cost of trial
management, an increasingly important factor in sponsor location decisions. Emergent
effect: The EU becomes competitive on the factors sponsors actually use to make trial
location decisions, reversing a decade-long structural decline.
Functioning of the Internal Market and Competition
Change mechanism 1: Reducing regulatory fragmentation across Member States
The internal market for biotech products is currently impaired by divergent national
implementation across multiple regulatory domains. The proposal introduces
harmonisation through four direct regulatory interventions, each targeting a distinct layer
of fragmentation. The proposed clinical trial framework introduces mandatory harmonised
templates, strengthened reporting Member State roles, and mutual trust and reliance
principles, directly reducing the degree to which clinical trial authorisation operates as 27
separate systems under a nominal common framework. The changes to the veterinary
medicinal products framework create a single 'one-stop-shop' regulatory pathway for GMO
veterinary medicinal products, eliminating the divergent dual-track national procedures
that currently apply. The changes to the General Food Law harmonise EFSA procedures
and governance, reducing divergent national approaches to food and feed biotech risk
assessment. The biosecurity framework establishes common screening, verification, and
reporting rules for biotechnology products of concern, replacing the patchwork of
divergent or absent national rules that currently creates an uneven regulatory environment
across Member States.
Four further interventions amplify the fragmentation-reduction effect. The regulatory
status repository provides a shared reference point that reduces divergent national
interpretations of applicable frameworks. SoHO regulatory status coordination extends
coherence to the substances of human origin domain. The changes to the organ
transplantation EU rules reduce fragmentation in organ processing authorisation practices
across Member States. The biodefence framework adds a cross-Member State intelligence-
sharing dimension that reinforces the common biosecurity rules.
Emergent effect: A meaningfully more integrated regulatory space across multiple biotech
product categories, reducing the effective cost of operating simultaneously across multiple
Member States.
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Change mechanism 2: Levelling the competitive playing field through common
biosecurity rules
Currently, divergent or absent national rules on screening biotechnology products of
concern create an uneven competitive environment: companies in jurisdictions with stricter
national rules face higher compliance costs than those in jurisdictions with weaker rules,
without any corresponding public safety justification. The proposed Act harmonises these
rules at Union level, establishing common screening, verification, and reporting
obligations applicable to all economic operators across all Member States.
The EU Biothreat Radar amplifies the level-playing-field effect by providing the ongoing
intelligence and monitoring infrastructure that enables consistent updating of the products-
of-concern list across Member States, ensuring that the common rules remain current and
are not systematically circumvented through product redesign.
Emergent effect: A genuinely common competitive environment for the handling of dual-
use biotech products, replacing a patchwork of national regimes that currently distorts
competition and compliance costs.
Change mechanism 3: Enabling/supporting new market entrants through regulatory
sandboxes and clarified pathways
Novel biotech products that do not fit existing regulatory categories face a structural
market access barrier: the absence of a clear pathway either prevents market entry or forces
products into ill-fitting categories that impose disproportionate requirements. The proposal
creates structured routes to market through four direct mechanisms. The novel health
biotechnology framework establishes a Commission-led sandbox for health biotech
products not falling under other existing sandbox regimes and provides the regulatory
status repository and Foresight Panel that reduce classification uncertainty across all
categories. The revision of the General Food Law introduces a harmonised sandbox
framework covering food (except novel foods), feed, all GMO uses, and food contact
materials (except recycled plastics). The proposed veterinary medicinal products
framework establishes a sandbox for innovative technologies, methods, or products related
to animal health. The proposed SoHO framework introduces a regulatory sandbox
framework for substances of human origin.
Three interventions amplify market entry enablement without operating dedicated sandbox
frameworks of their own. The EU Health Biotechnology Support Network helps
developers identify, access, and navigate sandbox procedures and clarified pathways. The
changes in the ATMP framework reduce the cost of accessing the advanced therapy
pathway, lowering the threshold for products approaching but not yet qualifying for ATMP
classification. The GMM framework provides an accelerated low-risk pathway that
functions analogously to a sandbox for a specific product category. The cross-framework
sandbox coordination mechanism ensures that the four sandbox regimes do not create
regulatory arbitrage opportunities between themselves.
Emergent effect: A structured route to market for product categories that currently have no
viable pathway, increasing competitive diversity in the biotech market.
Risk: Sandboxes create temporary regulatory accommodations that may advantage
sandbox participants over non-participants, raising competition concerns within the
transition period.
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Innovation and Research
Change mechanism 1: Accelerating the translation of research into clinical
development
The EU's core innovation problem is not insufficient scientific output but insufficient
translation of that output into clinical and commercial development. The proposal
addresses the translation gap through three simultaneous direct levers. The regulatory
status repository and Foresight Panel reduce the regulatory pathway uncertainty that
currently delays translation decisions: developers currently face extended periods of
ambiguity about which framework governs their product and what evidence requirements
apply, before they can plan a development programme. By resolving classification and
establishing forward-looking pathway guidance, this mechanism removes a structural pre-
application barrier that currently delays translation even before costs are formally incurred.
The changes in the ATMP framework directly reduce the regulatory distance between
research-stage advanced therapy products and clinical entry, eliminating duplicative
procedural steps for a product category where the translation gap is most acute. The
changes in the clinical trial framework reduces the cost and time of the clinical entry point
itself, lowering the threshold at which a translation decision becomes financially viable for
developers.
Three amplifying interventions improve the conditions under which the direct mechanisms
operate. High-impact project support provides resources, priority access, and
administrative support specifically for projects in the translation phase, accelerating
progress without shortening the formal regulatory pathway. Financing instruments reduce
the capital constraints that prevent translation decisions from being taken even when the
regulatory pathway is clear. AI tools accelerate evidence generation, reducing the time
between the translation decision and the first regulatory submission.
Emergent effect: The translation gap narrows structurally, not just for products that happen
to fit existing pathways but also for genuinely novel products that currently have no viable
translation route.
Risk: The Foresight Panel's effectiveness depends on the quality and independence of its
expert composition; a poorly functioning Panel could increase rather than reduce pathway
uncertainty.
Change mechanism 2: Building the infrastructure for AI-enabled biotechnology
innovation
AI has transformative potential for biotech R&D across functions such as target
identification, molecule design, clinical trial optimisation and manufacturing process
development, but its application is currently constrained by fragmented data, limited
testing environments, and unclear governance. The proposed Act establishes three direct
infrastructure components through the AI and data guidance framework: EMA guidance
on AI deployment across the medicinal product lifecycle, which resolves the regulatory
acceptance uncertainty that currently limits use of AI-generated evidence in submissions;
biotechnology testing environments, which provide the controlled infrastructure needed to
develop and validate AI tools for biotech applications; and a data quality accelerator, which
addresses the data fragmentation and quality constraints that currently limit AI model
development and training.
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Three interventions amplify this infrastructure by creating demand-side conditions for its
use. High-impact project recognition includes AI integration as a qualifying criterion,
creating institutional incentives for AI adoption among project promoters. The Foresight
Panel explicitly addresses AI-biotech convergence in its horizon-scanning mandate,
ensuring that emerging AI-biotech applications are mapped to regulatory pathways before
they reach market-ready stage. The clinical trial framework introduces AI-specific
provisions including AI use in trial design and electronic consent, creating a regulated
application domain within which AI tools can be deployed and validated against real
regulatory requirements.
Emergent effect: A functioning infrastructure for AI-enabled biotech research that does
not currently exist in a coherent form, enabling a category of research acceleration that is
otherwise blocked by infrastructure and governance gaps.
Administrative Costs to Public Authorities
Change mechanism 1: Increased administrative burden from new coordination and
governance obligations
The proposal creates substantial new institutional infrastructure across four direct sources
of burden on public authorities. Strategic project recognition frameworks require each
Member State to designate competent authorities, establish single points of contact,
process recognition applications, manage priority status grants, coordinate with the
European Health Biotechnology Steering Group, and provide ongoing administrative
support to recognised projects (including dedicated channels for SMEs and start-ups).
High-impact project recognition extends these obligations and adds Commission-level
recognition processes, coordination with EU-level financial instruments, and additional
reporting requirements. The proposed clinical trial governance and enforcement
framework expands the mandate of the CTAG, requires Member States to designate
national contact points, strengthens ethics committee coordination obligations, introduces
new inspection and Union control provisions, and creates the operational requirements for
the expanded EU Portal. The biosecurity enforcement framework requires Member States
to designate national inspection authorities for products of concern, implement verification
of legitimate need procedures, establish benchtop equipment screening obligations, create
suspicious transaction reporting systems, and participate in Commission-coordinated
enforcement and audit activities.
Three further interventions amplify the aggregate administrative load without
independently generating major new institutional structures. The veterinary framework
adds coordination obligations for the single GMO/VMP pathway and sandbox
administration. AI guidance creates new EMA obligations for guidance production and
ongoing revision as technology evolves. The biodefence framework adds monitoring and
intelligence-sharing obligations that build on but exceed the structures established by the
biosecurity enforcement framework.
Emergent effect: A significantly expanded public sector role in biotech governance,
requiring new capacities in regulatory coordination, scientific expertise, investment
facilitation, and biosecurity enforcement simultaneously.
Risk: Member States vary substantially in their existing administrative capacity; the
proposed Act's obligations may be feasible for large Member States and seriously
burdensome for smaller ones, creating implementation asymmetry.
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Change mechanism 2: Enhanced coordination capacity and reduced duplication
through common platforms and tools
Against the burden generated by Mechanism 1, the proposed Act also creates tools that
reduce the unit cost of coordination between authorities. Three direct infrastructure
elements provide the core shared platforms. The EU Health Biotechnology Support
Network and cluster framework creates structured coordination channels between national
authorities, the Commission, and ecosystem actors, reducing the transaction costs of multi-
authority interactions and providing a shared operational layer for implementation. The
regulatory status repository and Foresight Panel serve as shared reference points that
reduce the need for each authority to develop independent interpretive positions on novel
product classifications, reducing duplication of analytical effort across Member States. The
EU Portal development plan and expanded CTAG mandate provide the digital
infrastructure and governance forum that reduce the cost of multi-Member State clinical
trial administration.
Four interventions amplify coordination capacity without themselves constituting primary
shared infrastructure. Strategic project support and high-impact project support generate
structured coordination needs that the shared platforms are designed to address, creating
demand for the infrastructure while also feeding it with standardised information from
recognised projects. The veterinary single pathway reduces coordination friction between
marketing authorisation and environmental risk assessment authorities. AI tools enable
technology-assisted coordination functions across the shared platforms.
Emergent effect: Over time, the coordination tools reduce the marginal cost of managing
an increasingly complex regulatory environment, partially offsetting the burden from
Mechanism 1.
Risk: The offset is likely to be partial and delayed; in the short term, building new
institutions and tools imposes costs before they generate savings.
Public Health and Safety
Change mechanism 1: Earlier and broader patient access to innovative biotech
therapies
Two direct mechanisms drive earlier patient access. High-impact strategic project support
accelerates access along two pathways: the 'centres of excellence for advanced therapies'
designation creates specialised infrastructure that brings cutting-edge therapies to patients
in settings that currently lack access, while the high-impact recognition criteria explicitly
include therapies addressing unmet medical needs, ensuring that the full administrative and
financial support package is directed toward the products where access delay has the
greatest clinical consequence. The clinical trial framework reduces the time between a
therapy's first clinical evidence and its availability to patients by shortening authorisation
timelines, eliminating duplicative assessments, enabling faster evidence generation
through combined studies, and introducing digital innovations that reduce trial setup and
operational burden.
Three amplifying mechanisms extend the breadth and sustainability of patient access
improvements. The novel health biotechnology sandbox creates pathways for therapies
that currently have no viable route to patients because they do not fit existing regulatory
categories, thereby expanding the range of products that can reach clinical and ultimately
64
market-ready stage. Financing instruments sustain investment in therapeutic categories
where commercial incentives are weakest, including rare diseases, advanced therapies and
precision medicine, and access delays are greatest. SPC extension maintains the
commercial incentives to bring innovative therapies to EU patients, rather than prioritising
markets where protected return periods are longer.
Emergent effect: A structurally faster and more inclusive pathway to patient access,
particularly for the advanced therapy categories where the EU currently has the greatest
access delays relative to other jurisdictions.
Change mechanism 2: Strengthening supply resilience for critical biotech medicines
Strategic project recognition explicitly includes supply resilience as a qualifying criterion
for both standard and high-impact strategic projects, ensuring that manufacturing capacity
and supply chain security are weighed alongside scientific and clinical merit in project
support decisions. The biosimilars competitiveness framework strengthens EU
manufacturing capacity in a product category where supply concentration creates structural
vulnerability: a more competitive EU biosimilars market directly reduces dependence on
a small number of dominant external suppliers.
Financing instruments amplify by supporting the scale-up of domestic manufacturing
capacity for projects meeting the resilience criterion. The EU Biothreat Radar and
biodefence framework address the specific resilience gap in medical countermeasures
against biological threats, representing the extreme tail of supply risk where commercial
market mechanisms cannot be relied upon. Strategic project support builds general
manufacturing resilience; the biosimilars framework addresses a specific product category
where EU capacity is underutilised; biodefence projects address the emergency scenario.
Emergent effect: A more resilient EU supply base for biotech medicines across normal
market conditions and emergency scenarios, reducing dependence on external suppliers in
both contexts.
Risk: Supply resilience measures may increase costs for healthcare systems that currently
benefit from lower-cost external supply; the public health gain in resilience may come at
a cost to healthcare budget efficiency.
Change mechanism 3: Mitigating biosecurity risks from the wider accessibility of
biotechnologies
As biotechnology tools become more accessible and AI lowers barriers to misuse, the
public health risk from deliberate or accidental release of dangerous biological materials
increases. The proposed Act's biosecurity framework addresses this through a
comprehensive suite of direct regulatory tools: product-of-concern regulation establishing
common definitions and obligations, benchtop device screening requirements, transaction
verification and verification of legitimate need, suspicious transaction reporting
obligations, national inspection authorities with enforcement powers, penalties, and AI
model monitoring provisions for biological applications.
The EU Biothreat Radar amplifies the framework established by the intervention n°17 by
providing the ongoing intelligence and monitoring infrastructure that keeps the regulatory
response current: the Biothreat Radar identifies emerging threats and technologies that
should be added to the products-of-concern list before they reach widespread availability,
65
enabling the biosecurity framework to operate proactively rather than reactively. The
Advisory Group on Biosecurity and the Commission guidance on legitimate need
assessment ensure that the common rules are interpreted and applied consistently across
Member States.
Emergent effect: A proactive rather than reactive biosecurity governance system, capable
of responding to technological change rather than only to known threats.
Risk: The effectiveness of the framework depends heavily on keeping the products-of-
concern list current; a static list rapidly becomes obsolete in a fast-moving technological
landscape. The AI monitoring provisions are novel and their practical implementation is
untested.
Additional methodological information on specific measures:
1. Intervention n°13: SPC extension for biotechnology medicines
While in line with the overall methodology used for impact quantification of the other
measures on the Biotech Act proposal, the methodology to assess the SPC extension also
draws from the model used for the impact assessment of the pharmaceutical legislation. To
provide a more complete overview and comprehensive background to the approach
utilised, we provide further details in this dedicated section.
The assessment of the proposed 12-month extension of the Supplementary Protection
Certificate (SPC) for biotechnology medicines is based on a structured analytical
framework combining quantitative modelling, empirical data analysis and supporting
qualitative evidence. The objective of the methodology is to estimate the economic,
budgetary and public health impacts associated with extending the effective period of
protection for a defined subset of innovative biotechnology-derived medicinal products.
The modelling undertaken draws on a cohort of 198 innovative medicines (other than
vaccines) that lost patent or regulatory protection between 2016 and 2024 and that have
since remained on the market. Within this broader sample, a sub-sample of 31 biological
medicines was identified, of which 1227 products rely on the SPC as the last form of
protection to expire.
The policy scenario introduces a one-year extension of SPC protection for eligible
products. The modelling is carried out over a 20-year product lifecycle horizon. In the
baseline, the twenty years began fifteen years before loss of exclusivity (most SPC-reliant
medicines lose exclusivity after fifteen years) to four years after loss of exclusivity, i.e.
five years of contested sales including year zero. In the policy scenario, this timeline is
adjusted to incorporate one additional year of uncontested sales, during which revenues
and volumes are assumed to remain at the level observed in the final year prior to expiry.
At the same time, the period of post-expiry competition is reduced by one year.
Data on the value and volume of sales of the products used for the sample products were
drawn from IQVIA MIDAS for the years 2008 to 2024, while to determine the last layer
27 One of the products with particularly outlier characteristic was removed from the sample for the purpose of the cost
calculation, however factored into the sensitivity analysis set out in Annex 7 to give a range of possible impacts.
66
of protection, data were drawn from IQVIA Patent Intelligence.28 The twelve medicines
considered were authorised between 2003 and 2009 with loss of protection
correspondingly between 2017 and 2024. Thus, for all medicines, there were data available
for the year preceding loss of protection (year -1). However, for a number of medicines
that were used for the years -15 to -1, the years after loss of protection were not available.
Conversely, for some of those used for years 1 to 4, only a few years were available before
loss of protection. Thus, the model is, by necessity, based on a ‘moving cohort’.
Nonetheless, the data for the different years are comparable because for each medicine, the
data are normalised, i.e. expressed as a percentage of the value/volume in year -1, the year
before loss of protection. It was then possible to take the average of these normalised
quantities.
The results are presented in the graphs below. A full table of results are presented at the
end of this Annex for both scenarios.
Figure 1. Normalised sales and volume for SPC-reliant biological medicines with current
duration of SPC
28 Internal analysis by the authors using IQVIA MIDAS® quarterly sales data 2008-2024. Geographical coverage: EU27
without Cyprus, Malta and Denmark. which were obtained under license from IQVIA and reflect estimates of real-world
activity. Copyright IQVIA. All rights reserved. The statements, findings, conclusions, views, and opinions contained and
expressed herein are not necessarily those of IQVIA.
67
Figure 2. Normalised sales and volume for SPC-reliant biological medicines with a
12-month SPC extension
For the purposes of calculating profits, unit manufacturing, marketing and distribution
costs were assumed to be equal to 20% of the price in the year before expiry for originators
and 33% of that price for biosimilars.
Spending by payers in the SPC extension scenario is compared to spending in the baseline.
In addition to this direct cost to payers, the increase in price results in fewer doses being
bought by payers and consequently fewer patients being treated. To quantify the cost to
patients resulting from this lower coverage, we calculate the additional spending that
would be required to achieve the volume that is reached at the lower prices seen in the
baseline.
The impacts in normalised amounts, i.e. set out as a multiple of the value in the year
preceding loss of protection, are presented in the table below. The change is multiplied by
average sales in year -1 for SPC-reliant biological medicines (e.g. for the impact on
originator sales, we take 36% of average sales in year -1).
Table 1. Comparison of key indicators in the two scenarios summed over the 20-year
reference and expressed in terms of revenues in the year before loss of protection
(revenues in y-1=100)
Source: author analysis based on IQVIA MIDAS
Baseline SPC+1 Change % change
Originator sales1395 m1432 m 36 m 2.6%
Originator gross profit 1135 m 1166 m 31 m 2.7%
Biosimilar sales 68 m 41 m -27 m -39.2%
Biosimilar gross profit 30 m 19 m -11 m -35.9%
Cost to public payer1463 m1473 m 10 m 0.7%
Volume (patients treated)14161395-21 m-1.5%
Patients + payer monetised
gain/loss (cost of baseline volume)
1463 m1491 m28 m1.9%
68
When applied to an average sales value for an SPC-reliant biological medicine in the year
prior to expiry of EUR 740 million, these proportions give the following results in euro
terms:
Table 2. Impact of change of +1 SPC extension for biotechnology medicines
Source: author analysis based on IQVIA MIDAS
To assess whether behavioural changes would be expected on the part of developers in
response to the measure, we analysed EMA data on products authorised between 2016 and
2025 to determine which of them would have fulfilled the criteria for being awarded the
SPC extension. The information on these products is derived from the Agency’s European
public assessment reports (EPAR)for each product, the Agency’s internal databases and
own analysis.
The results of this assessment were as follows: According to EMA data from 2016 to 2025,
in addition to the 5-6 products that would have met all the criteria each year, a further five
products would have met all the criteria except the “geographic” ones, i.e. conducting trials
in more than two EU Member States and having part of their manufacturing in the EU. We
assume again that about 40% of the products are SPC-reliant. Thus, the SPC extension
could potentially be awarded to 4-5 products annually (rather than 2-3) if developers
changed their behaviour in response to the incentive.
The modelling framework is subject to a number of assumptions and limitations. The use
of list prices rather than net transaction prices implies that cost estimates may be
overstated, as they do not capture confidential discounts and rebate mechanisms applied at
national level. In addition, the distribution of revenues among pharmaceutical products is
highly skewed, implying limitations on inferences that can be drawn from averages.
Further limitations arise from the small sample size and the need to simplify complex real-
world behaviours, including firm investment decisions, clinical trial location choices and
manufacturing strategies.
These limitations are mitigated through the use of multiple data sources (EMA databases,
IQVIA datasets) and consistency checks with the broader literature and European
1 year increase in protection Per med Annual (3 meds)
Originator gross profit 230 m 690 m
Biosimilar gross profit -80 m -240 m
Cost to public payer 70 m 210 m
Patients monetised gains/losses 135 m 405 m
Patients + payer monetised gain/loss 205 m 615 m
69
Commission previous evaluations29 and studies touching upon SPC and other types of
regulatory and patent protection30.
29 These include European Commission, Inception Impact Assessment on Supplementary Protection Certificates, 2017
(roadmap for SPC reform and evaluation); Impact Assessment accompanying the revision of the EU pharmaceutical
legislation (pharma package), 2023 (including analysis of SPC-related incentives and their effectiveness); Legislative
proposals on the Unitary Supplementary Protection Certificate and centralised SPC procedure, 2023. 30 These includes: Technopolis Group (2018) Effects of supplementary protection mechanisms for pharmaceutical
products. Final report, May 2018. Amsterdam/Vienna: Technopolis Group, European Parliament. (2023). The potential
impact of the unitary Supplementary Protection Certificate on access to health technologies (PE 753.104). Policy
Department for Citizens’ Rights and Constitutional Affairs, Directorate-General for Internal Policies of the Union,
European Commission (2018) “Study on the economic impact of supplementary protection certificates (SPCs),
pharmaceutical incentives and rewards in Europe” (Copenhagen Economics) and Study on the legal aspects of
supplementary protection certificates in the EU, European Commission (Max Planck Institute for Innovation and
Competition), 2018.
Table 3. Normalised values for the baseline31
Year from
expiry -15 -14 -13 -12 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4
Originator
sales 5 14 23 40 54 63 69 73 80 86 93 98 100 100 100 95 88 80 71 64
Biosimilar
sales 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 6 12 20 27
Total sales 5 14 23 40 54 63 69 73 80 86 93 98 100 100 100 98 94 92 91 90
Originator
volume 4 10 16 28 37 46 54 60 69 77 85 92 97 99 101 97 92 85 78 73
Biosimilar
volume 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 9 20 35 49
Total
volume 4 10 16 28 37 46 54 60 69 77 85 92 97 99 101 101 101 105 114 122
Originator
profit 4 12 20 35 46 54 59 61 66 71 76 79 81 80 80 76 70 63 56 49
Biosimilar
profit 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 3 6 9 11
Total
profit 4 12 20 35 46 54 59 61 66 71 76 79 81 80 80 77 73 68 64 60
Originator
price 1.18 1.40 1.48 1.46 1.43 1.37 1.29 1.21 1.16 1.12 1.09 1.06 1.03 1.01 0.99 0.98 0.96 0.94 0.91 0.87
Biosimilar
price 0.72 0.67 0.62 0.58 0.55
Average
price 1.18 1.40 1.48 1.46 1.43 1.37 1.29 1.21 1.16 1.12 1.09 1.06 1.03 1.01 0.99 0.97 0.94 0.88 0.81 0.74
31 Four-year moving average.
71
Table 4. Normalised values for the policy scenario32
Year from expiry -16 -15 -14 -13 -12 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3
Originator sales 5 14 23 40 54 63 69 73 80 86 93 98 100 100 100 100 95 88 80 71
Biosimilar sales 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 6 12 20
Total sales 5 14 23 40 54 63 69 73 80 86 93 98 100 100 100 100 98 94 92 91
Originator volume 4 10 16 28 37 46 54 60 69 77 85 92 97 99 101 101 97 92 85 78
Biosimilar volume 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 9 20 35
Total volume 4 10 16 28 37 46 54 60 69 77 85 92 97 99 101 101 101 101 105 114
Originator profit 4 12 20 35 46 54 59 61 66 71 76 79 81 80 80 80 76 70 63 56
Biosimilar profit 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 3 6 9
Total profit 4 12 20 35 46 54 59 61 66 71 76 79 81 80 80 80 77 73 68 64
Originator price 1.18 1.40 1.48 1.46 1.43 1.37 1.29 1.21 1.16 1.12 1.09 1.06 1.03 1.01 0.99 0.99 0.98 0.96 0.94 0.91
Biosimilar price 0.72 0.67 0.62 0.58
Average price 1.18 1.40 1.48 1.46 1.43 1.37 1.29 1.21 1.16 1.12 1.09 1.06 1.03 1.01 0.99 0.99 0.97 0.94 0.88 0.81
Cost of baseline
volume 5 14 23 40 54 63 69 73 80 86 93 98 100 100 100 100 98 98 100 98
32 Four-year moving average.
2. Intervention n°16: Prevention of biotechnology misuse
Costs for providers
Two approaches are used to estimate costs for providers. The first provides a lower-bound
estimate, capturing the additional cost for non-screening providers of one full-time
equivalent (FTE), based on industry interview evidence. The second applies a more
complex calculation, incorporating both direct and indirect costs for providers. The latter
is based on the RAND Europe (2025)33 model but adjusted to the custom nucleic acid
synthesis market and EU labour costs. It provides an upper-bound estimate as it doesn’t
account for companies that are already screening.
Concerning the first approach, the estimation of compliance costs for non-screening
providers is based on assumptions derived from industry evidence and existing models.
First, evidence collected through industry interviews indicates that biosecurity screening
activities can be integrated into routine operations with relatively limited resource
requirements. In particular, SMEs with approximately 40–50 employees that already apply
biosecurity screening typically allocate around 1 one full-time equivalent (FTE) to
screening-related tasks. This benchmark is used as the standard unit of labour input for
providers that currently do not perform screening.
Based on IBBIS data, the total number of EU custom NA synthesis providers is 110 (66
custom providers, 40 third party providers, and 4 benchtop manufacturers). Based on
available evidence, an average of 70% of these providers are assumed not to conduct
biosecurity screening at present.34
For each of the 70% of providers, one FTE is allocated to screening activities. This FTE is
modelled as a composite of two occupational profiles: 50% managerial staff (ISCO-1) and
50% research staff (ISCO-2). The corresponding hourly labour costs are estimated at EUR
54.9 for managerial staff and EUR 40.5 for research staff.35 Assuming a standard annual
workload of 2,000 hours, the annual labour cost per provider is estimated at EUR 95,400.
Aggregating across all non-screening providers, total direct compliance costs are
calculated as:
110 × 0.7 × 1 FTE × EUR 95,400 ≈ EUR 7.3 million per year.
In addition to direct labour costs, indirect costs due to productivity loss are incorporated
following the methodology applied in the RAND analysis. Indirect costs are estimated
using a multiplier of 1.17 applied to direct costs. Therefore, indirect costs are estimated as:
EUR 7.3 million × 1.17 ≈ 7.3 million × 1.17 ≈ 7.3 million × 1.17 ≈ EUR 8.6 million per
year.
33 Zakaria, S. et al. (2026). Cost–benefit analysis for synthetic nucleic acid screening in the European Union. Santa
Monica, CA: RAND Corporation, 2026. https://www.rand.org/pubs/research_reports/RRA4805-1.html. 34 Estimation based on the average between minimum (15%) and maximum (45%) estimates in the RAND analysis
(2026) of the proportion of EU gene companies that voluntarily screen currently. 35 Source: Eurostat Structure of earnings survey, Labour Force Survey data for Non-Wage Labour Costs.
73
Concerning the second approach, the RAND model36 was adapted to better cover the
actual targeted companies by the biosecurity provisions in the proposed EU Biotech Act.
The RAND model takes into account companies of the NA synthesis market, without
distinguishing between custom and non-custom providers. The biosecurity provisions in
the proposed EU Biotech Act target only the custom DNA synthesis market, i.e. orders of
NA fragments which could be assembled into dangerous pathogens synthesised without
templates.37
To adapt the model and estimations accordingly, the following corrections were applied
based on the outlined assumption:
- Since the costs are calculated based on the expected increase in orders, it is
assumed that the share of these orders belonging to the custom NA synthesis
market is 51%. This assumption is based on the share of the custom NA
synthesis companies in the EU, 110, over the total number of NA synthesis
providers in the EU, which is 215, based on IBBIS data.38 This entails
multiplying orders in the cost’s calculations by 0.51.
- Therefore, the number of companies involved in the model (between 66 and
126) is also changed with the minimum number corresponding to only custom
NA synthesis providers, and 126 corresponding to synthesis providers identified
on the IBBIS map in Europe (for which we have sure information on 110, but
as maximum number we keep 126).
- To have comparable estimations, the labour costs are adapted to the European
averages, allocating the time to senior staff (ISCO 1-managers and ISCO 2-
professionals, as upper and lower bound), and non-senior staff corresponding to
ISCO 3, as technicians and associate professionals.39
Costs for customers
The cost estimation for customers (research organisations, private companies, and
individual researchers) follows a labour-cost-based approach derived from the CLTR
model.40 The methodology captures both fixed compliance costs (learning, training,
documentation) and variable costs (per-order verification).
The initial compliance cost is defined as the time required to learn and implement the
screening procedure. This is allocated across two staff categories: senior staff (ISCO 2)
and junior staff (ISCO 3). Senior staff account for 1.5 hours and junior staff for 2 hours,
with respective hourly labour costs of EUR 40.5 and EUR 32.7.41 This results in a one-off
initial cost of EUR 126.15 per customer. To reflect ongoing compliance, an annual
36 Zakaria, S. et al. (2026). Cost–benefit analysis for synthetic nucleic acid screening in the European Union. Santa
Monica, CA: RAND Corporation, 2026. https://www.rand.org/pubs/research_reports/RRA4805-1.html. 37 i.e. “Molecules of polymeric nucleic acids that have been synthesized de novo (without template), Annex 1 of the
Biotech Act. 38 IBBIS (2026), Global DNA Synthesis Map. https://globalsynthesismap.bio/ 39 Source: Eurostat Structure of earnings survey, Labour Force Survey data for Non-Wage Labour Costs. 40 Fady, P. et al. (2025). Cost-Benefit Analysis of Synthetic Nucleic Acid Screening for the UK. The Centre for Long-
Term Resilience. doi.org/10.71172/kyey-h0ya. Calculations based on the Customer TAB
https://docs.google.com/spreadsheets/d/1oBzXTGxIRHLTF9CSiLRV6kk7EyetcX-
xF1Y4ekWn5Z0/edit?gid=428955976#gid=428955976 41 Source: Eurostat Structure of earnings survey, Labour Force Survey data for Non-Wage Labour Costs.
74
“refresh” cost is included, consisting of 0.5 hours of senior staff time and 1 hour of junior
staff time, amounting to EUR 52.95 per year. The total compliance cost is then annualised
over a 10-year period, leading to an annual labour cost of EUR 65.57 per customer. In
addition, a marginal cost per order is included to capture the time required to verify
suppliers. This is estimated at 3 minutes (0.05 hours) of junior staff time per sequence,
corresponding to an additional EUR 1.635 per order.
These costs are then allocated across different types of orders using CLTR estimates of
average ordering behaviour. For gene sequences, each customer is assumed to place 20
orders per year. The annualised fixed cost (EUR 65.57) is distributed across these orders,
resulting in a fixed cost of EUR 3.28 per sequence. Adding the per-order verification cost
(EUR 1.635) yields a total cost of EUR 4.91 per sequence for customers not already
compliant. Indeed, to account for existing practices, an adjustment is introduced: 60% of
customers are assumed to already follow compliance procedures and therefore incur only
10% of the full cost. This leads to an expected cost of EUR 2.26 per gene sequence.
For long oligonucleotides, the same structure is applied but with 1,000 annual orders per
customer. This results in a much lower fixed cost per sequence (EUR 0.0197), and a total
cost of EUR 1.65 per sequence for non-compliant customers. After applying the same
compliance adjustment (with an additional correction that 70% of oligo customers already
order genes and thus partially internalise compliance costs), the expected cost per oligo
sequence is EUR 0.76.
Aggregating these per-sequence costs across total estimated order volumes yields total
annual customer costs of approximately EUR 3.56 million for gene orders and EUR 12.85
million for oligo orders. The combined total cost for customers is therefore estimated at
EUR 16.41 million per year. To have comparable and consistent numbers across the report,
we use the order volumes based on the RAND model but still adapted to 51% to only
account for custom NA synthesis market.
3. Intervention n°17: Biodefence
The surveillance cost estimates adapt a 2025 model by SecureBio Detection42 for scaling
US pathogen detection to the EU context. The US model combines three sampling streams:
aircraft wastewater via triturator sampling at major airports, passenger nasal swabs at
airports, and municipal wastewater sampling through the National Wastewater
Surveillance System (NWSS).
EU Scenario 1 (proportional scaling). Scales the US model to European transport and
wastewater infrastructure while maintaining comparable coverage. Based on 2024
European airport passenger volumes (~1 billion/year, ~2 million movements/day),
approximately 6 major airports plus 10 additional airports are needed to match US
coverage. For wastewater, 5–10 large urban treatment plant catchments replicate the US
NWSS coverage of ~2.5 million individuals. Triturator-based aircraft wastewater
sampling, currently in limited European pilots only, would require new deployment.
42 SecureBio Detection (2025), Scaling US Pathogen Detection.
75
EU Scenario 2 (expanded environmental sampling). Discontinues passenger swabbing
and expands triturator-based sampling to 20 major airports with increased processing
capacity. Significantly scales up sequencing and bioinformatics infrastructure (EUR 102
million for this component alone vs. EUR 23 million in Scenario 1), resulting in higher
overall costs.
Cost adjustments. Salaries for laboratory managers, analysts, technicians and
bioinformaticians are adapted to EU standards using Eurostat average values for ISCO-1,
ISCO-2 and ISCO-3 professional profiles. Equipment and processing costs are assumed
internationally comparable and converted from USD to EUR at the applicable exchange
rate.
Benefits estimation. Public health benefits draw on Nascimento de Lima et al. (2024),
which models the first year of a COVID-19-type pandemic under varying early-warning
lead times. The model estimates mortality, illness costs and lockdown duration across
scenarios of 0 to 10 days of advance detection. The five-day scenario is used as the central
reference, consistent with empirical findings of 5–19 day lead times from European
wastewater surveillance.
Table 5. Inputs adapted from the US model
Inputs US model EU 1st scenario EU 2nd scenario
NWSS
Number of municipal sites in
mature system
5 5 10
TGS
SWABS
Number of swab airports 13 16 20
Daily swabs per airport 400 400 0
TRITURATORS
Number of total triturator
airports
13 16 20
Of these, number of new
triturator airports
10 16 20
Individuals contributing to each
triturator
7,500 7,500 7,500
INDIVIDUAL PLANES
76
Number of individual plane
airports
2 2 2
Daily individual planes sampled
per site
25 25 25
PROCESSING
Number of sites 2 2 15
Source: https://securebio.org/blog/biothreat_radar/ ;
https://docs.google.com/spreadsheets/d/1ay2cFWjGjjnPOTBXqD-
X2Kh32R4hAW4GHMUSxZxG_8g/edit?gid=1660342520#gid=1660342520
77
ANNEX 5: ADDITIONAL INFORMATION ON BACKGROUND ON THE
SECTOR AND PROBLEM DEFINITION
1 BACKGROUND ON THE SECTOR
Figure 1. Distribution of EU biotech startups across biotechnology domains
(founding year ≥2015; active in 2025)
Source: Technopolis Group based on Crunchbase (Landscape analysis study).
Figure 2. Sector GVA comparison (index = 100 in 2015)
Source: Technopolis Group based on Prodcom; Eurostat (Landscape analysis study).
78
Figure 3. Global biotechnology exports (billion EUR)
Source: UN Comtrade (Landscape analysis study); Note: East Asia does not include
China.
Figure 4. Biotechnology export share
Source: UN Comtrade (Landscape analysis study).
79
Focusing on the relative technological specialization in biotechnology within the EU, the
study conducted by the JRC “Exploring the global landscape of biotech Innovation:
preliminary insights from patent analysis”, points out a few statements.
Firstly, Germany, France, The Netherlands, Denmark and Italy are the five Member States
with the highest share of biotechnology patents during the study period (from 2001 to
2020), which accounted for 74.9% of the total EU biotechnology patents (see Figure 5).
Secondly, the number of white and red biotechnology patents represents the majority of all
biotechnology patents, whereas the number of green biotechnology patents is extremely
low.
Thirdly, Germany and France are the Member States that account for the highest number
of biotechnology patent applicants. In fact, the two countries represent more than 50% of
all EU biotechnology patents (see Figure 5).
Lastly, it is also important to note that The Netherlands is the only country that shows clear
specialisation in green biotechnology. Italy has the highest specialisation index in red
biotechnology and Denmark has the highest index values for white biotechnology.
Figure 5. Geographic distribution of applicants within the EU-27
Source: Orbis IP, calculation: Technopolis Group (Landscape analysis study) Note: the
number of distinct patent publications are represented with a log scale to account for
strong disparities across countries. The geographical dimension is analysed based on the
inventors’ location.
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2 PROBLEM DEFINITION - SUPPORTING EVIDENCE TO AND DETAILED EXPLANATIONS
OF THE PROBLEM AND DRIVERS
2.1 Supporting evidence to the overall problem
Figure 6. Global distribution of biotechnology startups founded since 2015
Source: Technopolis Group based on Crunchbase (Landscape analysis study).
Figure 7. VC investment per biotechnology area in the EU, 2015 – 2025
Source: Technopolis Group based on Crunchbase (Landscape analysis study).
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2.2 Supporting evidence on the problem and drivers across selected health and food
biotechnology sectors
2.2.1 Authorisation of clinical trials
Europe faces growing challenges in maintaining its competitive edge due to lengthy
regulatory timelines and higher administrative requirements compared to other regions. As
a result, sponsors43 increasingly favour jurisdictions that offer faster regulatory timelines,
simpler and more streamlined approval processes, and improved access for the recruitment
of patient populations, contributing to a widening in the competitive gap.
(i) Longer timelines for the authorisation of clinical trials in EU/EEA compared to
other regions
The average time from submission to decision for the authorisation of Part I of
multinational clinical trials in the EU/EEA is 117 days, with relatively little variation
across Member States (Standard Deviation= 6 days). In contrast, mono-national clinical
trials are generally authorised more quickly, with an average duration of 91 days, but this
varies substantially across Member States (Standard Deviation= 19). Approval times range
from approximately 60 days in Belgium, the Czech Republic, and Portugal to around 120
days in Slovakia, Ireland, and Poland (see Figure 8). Additionally, the low share of ATMP
trials in the EU/EEA (~3.8% of the applications) may be attributed to long and complex
approval timelines.
Figure 8. Duration in days from submission to decision for mono-national clinical
trials in the EU/EEA44
Note: The Figure illustrates
the average duration in days
from submission to decision
for mono-national trials
between January 2022 and
May 2025.
Overall approval timelines
appear to be systematically
longer in the EU/EEA
compared to the USA,
Australia, and Canada across
various therapeutic areas. In
the USA, authorisation
typically takes approximately
1–3 months, accounting for the Food and Drug Administration's 30-day Investigational
43 Sponsors are the individual, company, institution or organisation which takes responsibility for the initiation, for the
management and for setting up the financing of the clinical trial. 44 Calculations done by the European Commission based on data from CTIS.
82
New Drug review period and parallel Institutional Review Board approval.45 China has
progressively streamlined its clinical trial approval procedures, and recent 2025 reforms
establish an expedited 30-working-day review pathway for eligible Class I innovative
drugs, representing a significant acceleration relative to the standard 60-working-day
implicit approval timeline introduced around 2018–2019 under China’s silent approval
mechanism.46 In the EU/EEA, these longer timelines are driven by several factors,
including the Member State with the longest assessment period, limited reliance on
existing assessments, and duplication of assessment by the Reference Member State
(RMS) and Member States concerned (MSC).
Beyond, in situation of public health emergencies, multi-national clinical trials offer the
advantage of involving large groups of investigators across different regions, facilitating
the achievement of required sample sizes within a shorter timeframe and mitigating the
impact of regional or local variations in participant eligibility. However, experience during
the COVID-19 pandemic has demonstrated that slow assessment and authorisation of
clinical trial applications in the EU/EEA have hindered the rapid setup of multinational
clinical trials, where timely and scientifically sound decisions are crucial.
(ii) Comparatively higher administrative burdens/costs associated with the clinical
trials authorisation process and conduct in clinical trials in the EU/EEA due to a
fragmented clinical trial environment and regulatory complexity.
Within the EU regulatory framework, diverse national systems and intricate administrative
requirements add layers of complexity for sponsors, possibly impacting the EU’s ability to
remain competitive in the rapidly advancing global pharmaceutical sector.47 In contrast to
the centralised regulatory framework in the US, China, or Australia, the authorisation
procedure for multinational clinical trials in the EU requires close coordination and
cooperation across multiple Member States. Sponsors for multinational clinical trials
currently face increased administrative burden associated with diverging national
requirements and approaches, insufficient reliance across Member States in the scientific
and ethics reviews contributing to duplicative and complex documentary submission
requirements, unpredictable timelines, language translation requirements, and a lack of
harmonised personal data protection requirements48. Additionally, current regulatory
authorisation requirements for postmarketing trials, such as treatment optimisation trials,
may impose disproportionate obligations on sponsors, often academics, and thus, hinder
trial conduct in the EU, despite the potential for these trials to reduce costs of the public
health system. Compared to the EU, other jurisdictions, such as the US and China, show a
45 EFPIA (2024) assessing-the-clinical-trial-ecosystem-in-europe.pdf; Start-Up Timelines Across Global Regions in
Clinical Trials – Clinical Research Made Simple 46 Tan et al (2025) Current landscape of innovative drug development and regulatory support in China | Signal
Transduction and Targeted Therapy 47 Tan et al. (2025) Current landscape of innovative drug development and regulatory support in China | Signal
Transduction and Targeted Therapy 48 It is to note that there is only limited data available on the cost structures across comparative regions. However,
feedback from sponsors indicates that diverging costs are driving the sponsor’s choice of the location for conducting
clinical trials.
83
higher emphasis on earlier-stage development, reflected in its relatively high share of
Phase 1 trials, underscoring its central role in early clinical innovation49.
This regulatory fragmentation is also evident in the uneven distribution of annual clinical
trial applications across Member States. Although the majority of clinical trials take place
in large-population countries such as France, Germany, Italy, and Poland (see Figure 9a),
per-capita figures reveal that some medium-size Member States—including Belgium,
Denmark, the Czech Republic, and Austria—exhibit comparatively higher clinical trial
activity (Figure 9b). This uneven distribution points to structural, regulatory inefficiencies
and may lead to the underutilisation of population potential for clinical trials in several
Member States, highlighting the need for more coordinated policy approaches at EU level.
Figure 9. Number of clinical trials applications in 202450
Figure 9a. Total number of clinical
trials in 2024
Figure 9b. Number of clinical trial
applications per 100,000 inhabitants in
2024
2.2.2 Advanced Therapeutical Medicinal Products (ATMPs)
Dual regulatory burden for investigational GMO-ATMPs
Clinical trials involving investigational ATMPs containing GMOs are currently regulated
under both Regulation (EU) No 536/2014 and the GMO legislation, creating a dual
regulatory burden. Sponsors must submit both a clinical trial authorisation application and
a separate GMO submission, leading to administrative complexity, delays, and increased
49 Fast-track landscape analyses to assess the regulatory clinical trial eco-system in the EU/EEA and in other relevant
regions (forthcoming) 50 Calculations done by the European Commission based on data from CTIS.
84
costs due to varying national GMO dossier requirements across Member States. This
fragmented system undermines the competitiveness of EU-based ATMP developers
compared to US and Asian markets and makes the EU a less attractive location for clinical
trials and investments for foreign sponsors.
Recent progress under the revision of the EU pharmaceutical legislation
The recently agreed revision of the EU pharmaceutical legislation introduces a centralised
EU-wide procedure for GMO submissions. It transfers authorisation requirements,
including Environmental Risk Assessments (ERAs), from GMO authorities to the EMA
and its Committee for Medicinal Products for Human Use (CHMP). However, the revision
does not provide for risk-based derogations from GMO requirements for specific
categories of investigational ATMPs, particularly where EU experience demonstrates
negligible environmental risk.
Outdated definitions hamper innovation
Definitions in the ATMP Regulation (Regulation (EC) No 1394/2007) encompass gene
therapy medicinal products, somatic cell therapy medicinal products, and tissue-
engineered products (TIEPs). However, scientific and technological advances are
outpacing this framework, driving the development of new ATMPs that may challenge
existing definitions. The current definition of TIEPs is outdated and fails to capture
emerging modalities such as in vivo tissue generation, acellular therapies, and bio-
synthetic hybrids.
This leads to regulatory gaps and classification uncertainty, placing EU ATMP developers
at a disadvantage compared to jurisdictions with more adaptable regulatory frameworks.
Prolonged assessment timelines
Under the Clinical Trials Regulation, ATMPs are subject to additional assessment time
beyond that for conventional medicinal products. The current rules allow up to 50 extra
days for ATMP clinical trial application assessments, with further extensions for
substantial modifications. These prolonged and less predictable timelines undermine
global competitiveness, as developers in other regions, such as the US, often face shorter
assessment periods and can secure earlier market access. Extended timelines also increase
development costs for EU-based companies and delay patient access to potentially curative
therapies.
Consequences of inaction
Without intervention the EU risks falling further behind global competitors in ATMP
development, compromising its leadership in this critical sector. This regulatory lag could
lead to poorer patient outcomes, increased healthcare costs, and limited access to effective
treatments across Europe.
85
2.2.3 Veterinary medicine products
(i) Duplicative, not-fit-for purpose regulatory framework applicable to veterinary
medicinal products that contain or consists of GMOs
Veterinary medicinal products that contain or consist of GMOs, developers are not only
required to comply with the Regulation (EU) 2019/6, which ensures the safety of veterinary
medicinal products as regards the treated animal, the user of the veterinary medicinal
product, the consumer (in case of food-producing animals) and the environment but also
with Union GMO legislation51, which also aims at ensuring the protection of human and
animal health and the environment. Challenges on the application of the GMO legislation
to medicinal products has been consistently identified as a hurdle for the development of
novel medicinal products52. Actions to address this have focused on human medicinal
products, leaving veterinary products unaddressed.
Clinical trials with veterinary medicinal products containing or consisting of GMOs are
subject to a double authorisation procedure: approvalby competent authorities
responsible for veterinary medicines in accordance with applicable national laws and Good
Clinical Practice which includes the protection of the environment, and also compliance
with the Union GMO legislation. The latter has not been designed for veterinary medicinal
products, resulting in complex compliance requirements and delays. Additionally, the
GMO legislation is not applied in a harmonised way throughout the Union, leading to
an unequal level playing field for operators across the EU and increased costs and time
for multinational trials.
For marketing authorisation of such products, applicants must include technical
documentation and an environmental risk assessment in accordance with Directive
2001/18/EC. The content of this technical file does not account for the specific
characteristics of veterinary medicinal products and overlaps with other parts of the
marketing authorisation application. Moreover, competent authorities under Regulation
(EU) 2019/6 are required to hold consultations with competent authorities under Directive
2001/18/EC. Experience shows that these consultations increase burden for the assessors
of marketing authorisation applications and can be challenging in case of accelerated
procedures.
Additionally, the lack of legal certainty on the status of animals that are treated with
certain novel biological veterinary medicinal products can deter the use thereof. While
the GMO legislation specifically excludes that humans treated with medicinal products are
regarded as GMOs, clarification as regards the legal status of animals that are administered
medicinal products does not currently exist in Union legislation.
(ii) Disproportionate administrative burden of the handling of variations non
requiring assessment
51 Directive 2001/18/EC, OJ L 106, 17.4.2001, pp. 1–39. ELI: http://data.europa.eu/eli/dir/2001/18/oj and Directive
2009/41/EC, OJ L 125, 21.5.2009, p. 75-97. ELI: http://data.europa.eu/eli/dir/2009/41/oj 52 See for example, the Explanatory Memorandum to Regulation (EU) 2020/1043 [COM(2020) 261 final] or the
Pharmaceutical Strategy for Europe [COM(2020) 761 final].
86
Variations to the marketing authorisation happen routinely during the life-cycle of any
medicinal product; the number of variations being typically higher for biological veterinary
medicinal products. Regulation (EU) 2019/6 created the category of variations not
requiring assessment. This category of variations was established with a view to reduce
administrative burden, allowing notification of changes without formal procedure or cost.
Experience with the implementation of the Regulation shows that this objective has not
been achieved. The obligation to notify all variations non requiring assessment within 30
days has led to an overall increase in the number of notifications by marketing
authorisation holders, thus increasing administrative burden for operators. The
obligation for competent authorities to record the rejection or approval of the variation
resulted in the assessment by competent authorities of the submission, leading to
administrative burden also for public authorities. In some Member States the
confirmation by the authority is associated with a fee, further increasing for operators.
(iii) Future innovation
Regulatory uncertainty represents a serious hurdle to the marketing or use of novel
technologies, methods or products. While advances in biotechnology enable the
development of novel concepts, this innovation may never reach the market due to the lack
a clear regulatory framework which secures access to the Union market. While regulatory
sandboxes have been proposed for human medicine and in other areas, no such framework
exists for animal healthcare, which would deter the development of new technologies,
methods or products in the EU.
(iv) Regulatory protection
The regulatory protection for biological VMPs comprises two strong distinct and
interacting approaches: regulatory data protection (Articles 39-40 of Regulation 2019/6)
and intellectual property (IP) protection (patents and Supplementary Protection
Certificates (SPCs) under Regulation (EC) No 469/2009).
Nevertheless, the veterinary pharmaceutical market presents distinctive challenges for
innovation, such as fragmented species-specific markets, low prices, a small overall market
size.
In this context, there is a need for enhanced incentives as a way of supporting the
development of biotech VMPs to diagnose, treat or prevent zoonotic diseases.
2.2.4 Novel health biotechnologies
(i) Union legislative frameworks not adapted to complex and hybrid emerging health
biotechnology products
While existing EU regulatory frameworks in the health area (including recent or
forthcoming revisions) ensure a high level of health and safety protection, these
frameworks operate largely in silos, each addressing specific product categories with
insufficient flexibility. In practice developers of complex and hybrid emerging novel
health biotechnology products must navigate several regulatory frameworks, including
their specific differing logic, evidence requirements and language. This is a particular
87
challenge for smaller companies, often start-ups working on a breakthrough product, as
they lack the regulatory expertise and resources to optimally navigate regulatory options.
Current mechanisms for addressing complexities related to the novelty of health
biotechnology products focus on individual products on a case-by-case basis, without
structural cross-framework dialogue on emerging innovation. This reactive, product-
specific approach lacks systematic coordination across Union legislative frameworks and
prevents regulators from identifying patterns, preparing for emerging innovations, and
developing consistent approaches. Without horizontal foresight and structured horizon-
scanning activities, regulators remain perpetually reactive rather than proactive, and
therefore less efficient than they could be.
It is also cannot be excluded that in the future innovative health biotech products may not
find fully suitable regulatory pathways in the existing EU legal frameworks, including the
regulatory sandboxes foreseen in those frameworks, resulting in products getting ‘stuck’
in the system.
Taken together, these elements lower the perceived innovation-friendliness of the EU
regulatory system, making the EU less attractive for cutting edge research, investments in
breakthrough innovation, and as an early launch market for complex but clinically
impactful products.
(ii) Lack of legal certainty on products classification and evaluation
Developers, particularly smaller entities, also lack easy access to consolidated information
about available regulatory options and guidance, and on how similar products have been
classified and evaluated under various frameworks. While opinions, recommendations,
and decisions exist, they are not systematically compiled or made accessible in a way that
enables developers and authorities to learn from precedents and ensure consistency.
Especially for SMEs, start-ups, and scale-ups, there is a significant gap in regulatory
expertise. These entities often cannot afford dedicated regulatory affairs specialists and
struggle to understand which frameworks apply, what adaptations might be needed, and
how to efficiently navigate procedures.
2.2.5 Biosimilars
The current EU regulatory framework for biosimilars can include unnecessary, lengthy and
costly multi-country clinical trials. A tailored development approach, where robust
analytical and in vitro characterisation reduce clinical data requirements without
compromising quality, safety, or efficacy—could accelerate approvals, as also being
considered by the U.S. Food and Drug Administration.
Biosimilar development currently entails costs of approximately EUR 85.5–256 million
and timelines of 6–9 years53, 54 Europe is the leading region for biosimilar clinical trials
53 IQVIA, The Impact of Biosimilar Competition in Europe, 2026, iqvia-the-impact-of-biosimilar-competition-in-
europe-2026-01-26-forweb.pdf 54 Medicines for Europe, European Biosimilar Medicines Sector: Delivering Impact Beyond Health – Economic,
Scientific & Strategic Contribution, Biotech Act Factsheet Series, March 2026, Pillar 1-2-3-4-FOOTPRINT-SPC-
Biotech-Act-facsheets-ppt.cdr
88
with 83 trials conducted between 2020–202 and roughly EUR 0.7 billion with 71%
allocated to comparative efficacy studies (CES).
Regulatory practice has already begun to evolve toward a risk-based approach. For well-
characterised, simpler products with accepted pharmacodynamic biomarkers the EMA has
accepted PK/PD-based clinical packages without Phase III CES for many years. From the
EMA Medicines Database, 41 of 151 authorised biosimilars (27.2%) are simple biologics
in this category, but in the past 3 years, their share fell to below 10%.55. For monoclonal
antibodies and fusion proteins, Phase III CES with clinical efficacy endpoints was included
in 100% of the 36 MAAs evaluated by EMA between July 2012 and November 202256.
However, evidence shows that negative regulatory outcomes were linked to quality
deficiencies rather than clinical efficacy results, indicating that CES has had limited
regulatory impact in determining approval outcomes57.
Table 1. The EMA Medicines Database records the following biosimilar CHMP
opinions per year, disaggregated by molecule type:
2018 2019 2020 2021 2022 2023 2024 2025 Cum. Total
Total opinions 13 4 9 6 7 8 25 40 151
Simple biologics 5 2 4 0 4 0 1 3 41
mAb / fusion
proteins 8 2 5 6 3 8 24 37 110
% mAb/FP 62% 50% 56% 100% 43% 100% 96% 93% 72.8%
Source: The EMA Medicines Database (extracted 2 March 2026) records 151 authorised biosimilars in the EU (over
160 including subsequent approvals through Q3 2025; IQVIA, 2026; Medicines for Europe, 2025).
Table 2. Biosimilar Authorisation Activity in the EU
2018 2019 2020 2021 2022 2023 2024 2025 Cum.
Total
Trend
Opinions 13 4 9 6 7 8 25 40 151 ↑↑
New ref. products 1 0 1 1 1 5 3 2 27 ↑
Source: EMA Medicines Database (extracted 2 March 2026). “New ref. products” = active substances receiving their
first EU biosimilar authorisation in that year. 2025 data includes CHMP opinions to date.
The acceleration from 8 opinions in 2023 to 25 in 2024 and 40 in 2025 is the most
significant volume increase in EMA biosimilar history. The 2024–2025 period is
dominated by mAb/fusion protein classes (93–96%), driven by the denosumab (29),
aflibercept (12), and ustekinumab (12) cohorts. Nine new reference product classes
entered the biosimilar market after 2022, compared with 18 in the preceding 19 years -
55 European Medicines Agency. (2026). Medicines output report [dataset]. Retrieved 2 March 2026 from
https://www.ema.europa.eu/en/medicines/download-medicine-data 56 Kirsch-Stefan, N., Guillen, E., Ekman, N., Barry, S., Knippel, V., Killalea, S., Weise, M., & Wolff-Holz, E. (2023).
Do the outcomes of clinical efficacy trials matter in regulatory decision-making for biosimilars? BioDrugs, 37(6), 855–
871. https://doi.org/10.1007/s40259-023-00631-4 57 Kirsch-Stefan, N., Guillen, E., Ekman, N., Barry, S., Knippel, V., Killalea, S., Weise, M., & Wolff-Holz, E. (2023).
Do the outcomes of clinical efficacy trials matter in regulatory decision-making for biosimilars? BioDrugs, 37(6), 855–
871. https://doi.org/10.1007/s40259-023-00631-4
89
indicating a broadening of the biosimilar pipeline including into new therapeutic areas.
The denosumab cohort (29 products) is the largest single-reference-product biosimilar
wave in EU history.
The EMA published a Reflection Paper on a Tailored Clinical Approach in Biosimilar
Development (2026) concluding that “Based on the advancements in analytical technology
and the regulatory experience gained, a tailored approach for clinical development of
biosimilar candidates is possible. CES are no longer expected to be required for approval
of biosimilars that can be thoroughly characterised using state-of-the-art analytical
methods and have demonstrated similarity in physicochemical and functional properties.
Comparative clinical PK studies are still essential elements in biosimilar development and
can provide supportive safety and immunogenicity data. This tailored clinical approach is
expected to be applicable for the majority of biosimilar candidates. A regulatory option
that, under certain conditions, allows authorisation of biosimilars based on demonstrated
comparability at the analytical level with a limited clinical data package streamlines the
development process without compromising efficacy and safety.”58 Building on this
conclusion, the revised guidance for biosimilars is expected to set out the conditions and
provide for more tailored approach for CES requirements for complex biosimilar products.
This is particularly relevant in light of recent regulatory trends. Over the past three years,
applications concerning monoclonal antibodies and fusion proteins have represented more
than 90% of all biosimilar marketing authorisation applications (see Annex). The revised
approach is therefore expected to have a broad practical impact, as it applies to the majority
of current and future biosimilar development programmes. The finalised Reflection Paper
supports rapid advancement already in the interim, currently several scientific advices as
well as 2 marketing authorisation application assessments are ongoing, which propose
tailored CES approach.
This risk-based approach aligns with international regulatory convergence. The U.S. Food
and Drug Administration has removed switching study requirements and expanded
flexibility in clinical evidence (2024–2025)59, while Canada is consulting on CES
elimination for most biosimilars60. South Korea already applies CES waivers in practice61,
and Japan is expected to adopt similar flexibility by 2028. In this context, the EMA plays
an active role in international regulatory dialogue and outreach. Ensuring that the EU
approach is effectively promoted at global level will be important to support convergence
towards a harmonised, tailored and streamlined approach to biosimilar development, in
particular with regard to the reduced reliance on Comparative Efficacy Studies.62, 63
Under the baseline, the EMA is expected to continue a gradual shift toward tailored, risk-
based approaches without the revision of the current biosimilar guidance portfolio for a
more systematic and predictable procedure for unnecessary CES elimination, as
58 Reflection paper on a tailored clinical approach in biosimilar development 59 U.S. Food and Drug Administration. (2024). Considerations in demonstrating interchangeability with a reference
product: Update (draft guidance). Silver Spring, MD: FDA. 60 Smart & Biggar. (2025, July 4). Update on biosimilars in Canada – June 2025.
https://www.smartbiggar.ca/insights/publication/update-on-biosimilars-in-canada-june-2025 61 Kang, H. N., Thorpe, R., Knezevic, I., et al. (2020). The regulatory landscape of biosimilars: WHO efforts and progress
made from 2009 to 2019. Biologicals, 65, 1–9. https://doi.org/10.1016/j.biologicals.2020.02.005 62 ICH_M18_Final_Concept_Paper_MCEndorsed_2025_1119.pdf 63 IPRP_BWG_Final IPRP Scientific Workshop Summary Report_2024_0506.pdf
90
appropriate. The formal regulatory standards for safety, quality, or efficacy are and will
remain maintained. At the same time, global competitors streamline evidentiary
requirements more rapidly. As a result, EU competitiveness in biosimilar development is
expected to weaken, with developers prioritising earlier submissions in jurisdictions with
lighter requirements, potentially delaying EU market entry.
The EU and the United States combined hold the vast majority of the global biosimilar
market by revenue. However, the EU’s relative share is declining as the US market expands
rapidly. The US biosimilar market grew from EUR 6.07 billion in 2020 to an estimated
EUR 10.1 billion in 2024, while the Asia-Pacific region - driven primarily by China - grew
from EUR 1.54 billion to approximately EUR 4.53 billion over the same period64. The EU
biosimilar market projected to grow at a compound annual growth rate (CAGR) of
approximately 17%, increasing from EUR 13.2 billion in 2025 to EUR 62.9 billion by
203565 driven primarily by patent expiries and expanding therapeutic applications. The
estimated cumulative savings of EUR 75 billion from biosimilar competition since 2006
with EUR 13 billion in 2024 continues to grow. Advances in analytical sciences are
expected to further strengthen the scientific consensus that Phase III CES provides limited
additional value for well-characterised biosimilars. However, as development shifts toward
more complex products (e.g. monoclonal antibodies, bispecific antibodies, antibody–drug
conjugates), a proportion of applications will continue to require clinical data, particularly
for immunogenicity assessment.
Table 3. Biosimilar MAA pipeline efficiency: submission-to-authorisation outcomes
in the EU centralised procedure, 2003–2026 (EMA Medicines Database, extracted 2
March 2026; EMA Annual Report 2024).
VALUE SOURCE
Total biosimilar MAAs (2003–2026) 173 EPAR Database
Authorised 151 (87.3%) EPAR Database
Withdrawn/Refused 22 (12.7%) EPAR Database
Success rate 2020–2026 92.7% (101/109) EPAR Database
2024 biosimilar MAAs resolved 27 (25 auth + 2 W/R) EPAR Database
EMA scientific advice requests 2024 635 (all products) EMA Annual Report 2024
2.2.6 12-month extension of Supplementary Protection Certificates (SPC) for
biotechnology medicine
The EU faces increasing global competition in the field of biotechnology. Patent data,
geographic distribution of clinical trials and biologic manufacturing reflect this reality and
support the need for urgent action to boost Europe’s competitiveness in health biotech
through a combined set of regulatory and industrial policy measures. These include the 12-
64 Precedence Research. (2025, August 13). Biosimilars market size to hit USD 175.99 billion by 2034.
https://www.precedenceresearch.com/biosimilars-market 65 Precedence Research. (11 Mar 2026). Biosimilars Market Size, Share and Trends 2026 to 2035.
https://www.precedenceresearch.com/biosimilars-market
91
month SPC extension, a very attractive and effective patent incentive that extends the IP’s
effect, thereby providing a very robust shield from competition for the relevant molecule66.
First, table 4 below shows that the EU accounts for a limited share of global earliest biotech
patent filings between 2012–2024, representing around 4% of patent families worldwide.
When restricting the analysis to patent families owned by European companies, however,
the EU appears more prominent as an early filing location, accounting for around 33% of
earliest filings over 2012–2024, while multiple-jurisdiction filings including the EU
represent around 39%.
Table 4. Biotech patents in 2012-2024
All PATSTAT patents Patents filed by EU-based companies
EU 4% 33%
Multiple (incl. EU) 11% 39%
US 7% 6%
China 60% 3%
All other 17% 20% Source: PATSTAT data, compiled by PPMI group
Second, the geographical distribution of clinical trials has shifted, with the EU losing
ground relative to other regions such as the United States and China. The EU/EEA's share
of commercially sponsored clinical trials fell from 22% in 2013 to 12% in 2023, with
absolute Phase III commercial trial in the EEA declining from 439 in 2018 to 327 in 202367.
This decline is prominent in the biotech segment as well, where, for instance, Europe’s
share of cell and gene therapy trials went from 25% in 2013 to 10% in 2023 (see problem
driver 2.2 for further context).
Third, manufacturing capacity within the EU has expanded over time, as illustrated by the
increasing number of manufacturing authorisations and sites recorded in EudraGMDP
data68. The table below shows a marked increase in manufacturing authorisations,
particularly in recent years, with strong growth in both the number of sites and the number
of organisations involved.
Table 5. Annual authorised biological manufacturing footprint in the EU (2012-2025)
Year New MIAs (flow)New sites (LOC IDs)New organisations (ORG IDs)
2012 6 6 6
2013 6 4 4
2014 16 10 10
2015 14 8 7
66 Max Planck Institute for Innovation and Competition (2018), Study on the Legal Aspects of Supplementary Protection
Certificates in the EU. 67 IQVIA. (2024). Assessing the clinical trial ecosystem in Europe: Final report. European Federation of Pharmaceutical
Industries and Associations (EFPIA) & Vaccines Europe. https://www.efpia.eu/media/3edpooqp/assessing-the-clinical-
trial-ecosystem-in-europe.pdf 68 Manufacturing investment proxied by regulatory data: Manufacturing and import authorisations (MIAs, i.e. regulatory
authorisations issued by national competent authorities allowing the manufacture or import of medicinal products or
active substances in the EU) and biological manufacturing sites, as recorded in the EudraGMDP database for biological
medicinal products, are used as proxies for manufacturing footprint in the EU. These indicators capture the presence and
location of investment but not production volumes or economic value, within globally integrated value chains.
92
2016 18 11 11
2017 10 4 4
2018 13 5 5
2019 17 10 10
2020 15 9 9
2021 30 19 18
2022 55 43 42
2023 77 70 64
2024 158 138 128
2025 192 174 148
Total 624 511 466 Source: EudraGMDP data; compiled by PPMI group
While such data point at a positive trend for manufacturing in the EU, it is key to consider
the evolving global context. Asia is emerging as a major competitor not only in the
production of generics and active pharmaceutical ingredients, but also in the
manufacturing of complex biologics and innovative biotechnology products. A recent
study by McKinsey describes Asia as “the emerging epicentre” of global
biopharmaceutical activity, noting that the region has expanded its share of the global
innovative medicines pipeline from 28% to 43% within five years, surpassing both Europe
and the United States.69
Given the current competitive international environment in which various jurisdictions are
actively enhancing their appeal to innovators—it is essential that the EU provides a clear
signal of its commitment to support innovation and attract health biotech investments in
research, development and manufacturing.
2.2.7 Food and feed products and other food chain inputs
Union law requires pre-market authorisations/approvals for several categories of food and
feed products and related food chain inputs – the so-called ‘regulated products’70. In those
cases, the European Food Safety Authority (EFSA) must conduct a scientific risk
assessment under the applicable sectoral legislation before risk managers at EU and/or
national level decide upon granting a pre-market authorisation/approval. To this end,
applicants must comply with the specific procedural requirements set out in the relevant
sectoral legislation and with certain general provisions set out in the General Food Law
Regulation71 (GFL) as regards the pre-submission and validation phases. Delays have been
observed in both validation and risk assessment phases. Two main regulatory drivers have
been identified for those delays:
(i) Dossier deficiencies and limited effectiveness of pre-submission advice
In the context of the risk assessment of regulated products, and when application dossiers
are incomplete or insufficiently substantiated), EFSA requests additional information or
data from applicants either in the context of the validation process or during the risk
69https://www.mckinsey.com/industries/life-sciences/our-insights/the-emerging-epicenter-asias-role-in-biopharmas-
future?utm_source=chatgpt.com 70 E.g. substances used in food and feed (such as additives, enzymes, flavourings, and nutrient sources), novel foods,
food contact materials, genetically modified organisms, plant protection products etc. 71 Regulation (EC) No 178/2002, OJ L 31, 1.2.2002, pp. 1–24. ELI: http://data.europa.eu/eli/reg/2002/178/oj.
93
assessment process. These iterative exchanges interrupt the overall process and contribute
to prolonged timelines before an authorisation is decided upon.
Although the General Pre-Submission Advice (GPSA) and Renewal Pre-Submission
Advice (RPSA)72 were introduced in 2021 to improve dossier quality, their uptake by
applicants and their effectiveness have been limited. The scope of GPSA has been
perceived as too narrow, as it cannot include advice on technical/scientific issues, e.g. on
study design, to fulfil data requirements and/or testing strategies. GPSA is therefore less
attractive for potential applicants, especially for SMEs and start-ups who request new
authorisations, reducing the potential for improving the quality of the application dossiers.
In a similar vein, the uptake of RPSA has been of limited use and value as applicants of
renewals are largely familiar with the application process and do not particularly need
support from EFSA at pre-submission phase. Moreover, the applicable pre-conditions for
RPSA combined with the absence of any procedural penalties for the non-notification of
intended studies, exacerbate the low uptake of RPSA.73
The uptake of pre-submission advice mechanisms has been limited and therefore their
potential for reducing subsequent delays at validation and risk assessment phases by
improving dossier quality has yet to materialise, contributing to persisting delays linked
with subsequent requests for additional data and subsequently to delays to ‘time to
market’.74 Long risk assessment periods reduce regulatory predictability in a sector
characterised by rapid technological development and significant R&D investment. This
may discourage investment especially for SMEs, delay scale-up and limit the
commercialisation of biotechnology-based food and feed solutions and other related inputs
within the Union.
(ii) Procedural consequences linked to study notification requirements
Since 2021, additional delays have arisen, following non-compliance with the obligation
to notify commissioned studies during the pre-submission phase and the imposition of
procedural consequences (Article 32b GFL), in which case applications are declared non-
valid and resubmitted applications are subject to a six-month delay before validation.75
Between 2021 and 2024, 47 applications were deemed non-valid on this basis,
predominantly in the novel food sector.76 In certain cases, the combination of extended
72 GPSA is provided by EFSA, upon request to all applicants (both for new authorisations/approvals and for renewals)
at pre-submission phase; this advice is limited by law on the applicable legal framework and the content for an
application. RPSA is only available to applicants for renewals of existing authorisations/approvals subject to a
notification of intended studies to EFSA, including information on how such studies will be carried out to ensure
compliance with regulatory requirements, and following a public consultation carried out by EFSA on the intended
studies. This advice can also cover scientific aspects (e.g. studies design). 73 Intellera, Ipsos, Tetra Tech, Study supporting the Evaluation of the European Food Safety Authority 2017-2024, pp.
51-5292, 154-155 (forthcoming). 74 Id. 75 Article 32b of GFL requires applicants of regulated products to notify EFSA during the pre-submission phase of any
studies once they are commissioned, without delay, with a view to support a future application dossier. The purpose of
this requirement is to ensure that EFSA is aware of all studies performed including those that may result in unfavourable
outcomes. In case an unjustified non-compliance with the notification requirement is detected when an application is
submitted, the application is considered non-valid; applicants can resubmit, but the validation process may only be
initiated six months after the non-compliance is addressed. 76 Intellera, Ipsos, Tetra Tech, Study supporting the Evaluation of the European Food Safety Authority 2017-2024
(forthcoming)
94
validation exchanges and the imposition of the procedural consequences have resulted in
significant postponements in confirming application validity.
(iii) Governance constraints relating to Scientific Committee/Scientific Panels
The current configuration of EFSA’s Panel-based governance model, consisting of eleven
Panels and one Scientific Committee77 and operating autonomously without reporting to
EFSA’s management, has ensured scientific independence and has leveraged dedicated
experts to provide advice of high scientific excellence. Nevertheless, the lack of flexibility
in the governance model (e.g. Panel chairs/vice chairs are reserved only for experts)
constrained by provisions in the General Food Law and in other rules and procedures,
restricts EFSA’s ability to keep its risk assessment work both swift, coherent, timely and
fit for purpose.78
(iv) Limited regulatory flexibility in a context of rapid technological advancement
The food and feed sector is experiencing rapid technological advancements, including in
areas such as biotechnology, AI, smart farming techniques and circular economy practices
promoting resource efficiency and waste reduction. Public consultation activities carried
out in the context of the European Innovation Act79 indicate broad, cross-sectoral support
for the use of regulatory sandboxes as a tool to facilitate innovation while maintaining
appropriate safeguards. In this context, there is a growing recognition among stakeholders
and Member States of the potential added value of a more coordinated approach at Union
level. In the absence of a coordinated framework, innovative solutions may face regulatory
uncertainty and fragmentation when attempting to fit within existing authorisation
procedures. This may lead to delays in innovative approaches to product development,
particularly in areas characterised by rapid technological advancement. Furthermore, the
current framework provides limited structured opportunities to test alternative data
requirements, such as new methodological approaches instead of animal testing – and/or
alternative regulatory requirements such as digital labelling instead of physical labelling
affixed on food products.
Taken together, dossier deficiencies, limited effectiveness of existing pre-submission
procedures, rigid procedural consequences relating to non-compliances at pre-submission
phase, governance constraints and the limited availability of harmonised regulatory
sandboxes create procedural complexity that slows the authorisation process and delays
market entry of regulated food and feed products and other food chain inputs.
77 The members of the Panels/Scientific Committee are appointed for a fixed term and act in their personal capacity
(experts). They are supported by EFSA staff, specialised Working Groups, and external contractors. The Scientific
Committee, as the highest-ranking group compared with the Panels, promotes consistency and harmonisation in
assessment methods across the Panels. 78 Intellera, Ipsos, Tetra Tech, Study supporting the Evaluation of the European Food Safety Authority 2017-2024
(forthcoming) 79 https://ec.europa.eu/info/law/better-regulation/have-your-say/initiatives/14593-European-Innovation-Act/public-
consultation_en
95
Taken together, these patterns show that the EU’s competitiveness gap in biotech is not
primarily a science deficit, but a translation and scale-up deficit shaped by long, uncertain
and capital-intensive pathways from research to market.
2.2.8 Organs80
The existing regulatory framework
Organ transplantation is among the highest-value therapeutic interventions available in
modern medicine. For patients with end-stage organ failure, transplantation is frequently
the only curative option. In the case of kidney failure, organ transplantation is also
substantially more cost-effective in the long term than chronic dialysis. In 2024, over
32,000 organ transplants were performed across the EU, comprising 19,170 kidney
transplants, 8,015 liver transplants, 2,416 heart transplants, 2,221 lung transplants, 525
pancreas transplants, and smaller numbers of small bowel and vascularised composite
tissue (hand, face) procedures. Despite this activity, a persistent and widening gap between
the supply of transplantable organs and clinical demand remains as of 31 December 2024,
over 52,000 patients were registered on transplant waiting lists across the EU. 81
Directive 2010/53/EU establishes common quality and safety standards for human organs
intended for transplantation across the EU, setting minimum requirements applicable
throughout the entire chain from donation to transplantation (i.e., donation, testing,
characterisation, procurement, preservation, transport, and transplantation of organs). This
framework is complemented by technical guidance from the European Directorate for the
Quality of Medicines and HealthCare (EDQM) and by binding international principles
(equitable access, the prohibition of financial gain from organs and tissues of human origin,
and consent requirements for donation)82, as well as EU rules on cross border information
exchange (Directive 2012/25/EU83).
The technological transformation
Since the adoption of Directive 2010/53/EU, the field of organ transplantation has
undergone a profound technological transformation that has altered the nature of what
happens to an organ between its procurement from a donor and its transplantation into a
recipient.
The traditional approach to organ handling, and the one implicitly assumed by the
Directive when it was drafted, is static cold storage (SCS). Under this method, a procured
organ is flushed with a cold preservation solution, packed in ice, and transported to the
recipient hospital as quickly as possible. SCS slows cellular deterioration by cooling the
organ to approximately 4°C, but it buys only limited time before ischaemia-reperfusion
80 Analysis largely based on Rapid Assessment Scenario Study - forthcoming 81 SANTE-SoHO/D2 - European Commission. (2026). Introducing “organ processing” into directive 2010/53/EU
[Unpublished slideshow]. 82 under the Council of Europe Convention on Human Rights and Biomedicine (ETS No. 164), with its Additional
Protocol Concerning Transplantation of Organs and Tissues of Human Origin (ETS No. 186) 83 European Commission. (2012). Directive 2012/25/EU of 9 October 2012 laying down information procedures for the
exchange, between Member States, of human organs intended for transplantation. https://eur-lex.europa.eu/legal-
content/EN/TXT/PDF/?uri=CELEX:32012L0025&from=EN
96
injury renders the organ unsuitable. These narrow time windows constrain the
geographical reach of organ exchange, creating intense pressure on surgical teams. This
means that organs from so-called “marginal” or “expanded criteria” donors (i.e., organs
that are not in ideal condition but could still be clinically useful) are frequently discarded
because there is insufficient time to assess or rehabilitate them.
Ex-vivo machine perfusion represents a different paradigm. Rather than passively
preserving an organ on ice, ex-vivo machine perfusion places it on a device that
continuously pumps an oxygenated, nutrient-rich perfusate through its vasculature,
maintaining the organ in a metabolically active, near-physiological state outside the body.
Machine perfusion can be performed under hypothermic conditions (1–8°C),
subnormothermic conditions (typically 20-35°C), or normothermic conditions (34-38°C,
essentially body temperature). The clinical consequence is transformative: ischaemia time
constraints are dramatically relaxed, the organ’s function can be assessed in real time, and,
for regulatory purposes, the extended ex-vivo window opens the possibility for active
interventions on the organ.
These interventions go well beyond mere preservation. They include reconditioning
damaged organs (e.g., reducing fat content in steatotic livers through defatting protocols
during normothermic perfusion), administering pharmacological therapies directly to the
organ (such as chemotherapy to treat cancer cells, antibiotics to clear infections, or anti-
inflammatory agents to reduce ischaemia-reperfusion injury), performing surgical
procedures on the organ while it is on the perfusion machine (e.g., ex-vivo tumour
resection from a liver), and even delivering gene therapies via viral vectors in the perfusate.
Taken together, these activities constitute what the proposed legislation terms
“processing”: active operations designed to maintain or improve the functional status of an
organ prior to transplantation. They transform the organ from a passively preserved
specimen into one that is actively managed, assessed, and improved during the ex-vivo
period.
The most established clinical application of EVMP is ex-vivo lung perfusion (EVLP), first
introduced clinically in 2001 and now widely adopted in major transplantation centres
across Europe and globally. Machine perfusion for kidneys, livers, and hearts has similarly
progressed from experimental to routine or near-routine clinical use in leading centres. As
a result, the global organ preservation market is expanding rapidly, driven by increasing
adoption of perfusion machines.
Problem definition specific to this area of intervention
The central problem that the proposed amendments seek to address is that the regulatory
framework established by the Directive has been overtaken by clinical and technological
practice. The Directive was designed for an era in which the primary ex-vivo activity was
preservation. Thus, it contains no provisions for authorising, overseeing, or ensuring the
quality and safety of the active processing operations that are now being performed
routinely in transplantation centres across the EU. This regulatory gap gives rise to a series
of interconnected problems.
97
Legal uncertainty and absence of a dedicated authorisation framework
Directive 2010/53/EU, as currently in force, refers to “preservation” in its scope provision
(Article 2(1)) and in its definitions (Article 3(l)), but it contains no reference to
“processing.” It has no framework for authorising processing operations, no mechanism
for benefit-risk assessment of these interventions, and no provisions requiring
transplantation centres to seek prior approval before applying a specific processing
technique.
This absence of legal clarity generates uncertainty for all actors in the transplantation chain.
Transplantation centres lack a clear legal framework for the processing activities they
perform, making it difficult to establish uniform standards, allocate responsibilities, or
demonstrate compliance. Competent authorities have no EU-level mandate or guidance for
overseeing these operations. Pharmaceutical and medical device companies face
regulatory ambiguity regarding the use of their products in the novel context of ex-vivo
organ treatment, a context in which the patient (the organ recipient) is not the direct subject
of the pharmacological intervention, but the organ is. The risk of different national
regulatory approaches would bring a significant barrier for cross border exchange of
organs, which is essential to optimize the donor/organ-recipient matching and the
consequent transplant outcome.
Patient safety risks from unregulated processing
Organ processing, precisely because it involves active intervention on the organ,
introduces new categories of risks that are not captured by the existing quality and safety
framework. The administration of drugs to an organ during perfusion, the performance of
surgery on an organ outside the body, or the use of biological agents in perfusates all carry
the potential for adverse effects on the organ and, ultimately, on the transplant recipient.
Without a systematic authorisation mechanism requiring benefit-risk assessment before
processing operations are applied, there is no structured safeguard ensuring that these risks
are identified, evaluated, and managed. The Directive’s existing serious adverse event and
reaction (SAE/SAR) reporting system (Article 11) was designed for the traditional
donation-to-transplantation chain and does not specifically address risks attributable to
processing operations.
Organ processing techniques also vary significantly in their maturity and evidentiary base,
ranging from well-established hypothermic machine perfusion of kidneys to highly
experimental ex-vivo gene therapy. The absence of a tiered regulatory approach, one that
distinguishes between well-evidenced and novel processing techniques and calibrates
oversight, accordingly, means that in practice both established and experimental
interventions are, at the EU level, equally unregulated.
Fragmentation across Member States
In the absence of EU-level rules on organ processing, Member States have been left to
develop their own approaches, or, in other cases, to not develop any specific framework at
all. Some Member States have begun to address organ processing within their national
transplant legislation or through administrative guidance from their competent authorities;
others left processing activities to occur under the general authority of the transplantation
98
centres themselves without specific regulatory oversight. This patchwork creates divergent
standards across the EU, with direct implications for the need for cross-border exchange
of organs that the Directive was originally adopted to facilitate.
When a processed organ crosses a national border, the receiving centre and competent
authority currently have no common EU standard against which to assess the safety and
quality of the processing that was performed. This could over time create de facto barriers
to the cross-border exchange of organs within the EU. Over the last three years, the cross-
border exchange rate of allocated organs fluctuated between 20-23%84. European organ
exchange organisations such as Eurotransplant and Scandiatransplant, which coordinate
allocation across multiple Member States, noted particular difficulties in the absence of
harmonised processing standards.
Cross-framework coordination gaps
Organ processing is inherently a multi-regulatory-domain activity. A single processing
operation may simultaneously involve a medical device (the perfusion machine, regulated
under Regulation (EU) 2017/745), a medicinal product (a drug administered to the organ,
regulated under Directive 2001/83/EC or Regulation (EC) No 726/2004), and a substance
of human origin (blood products in the perfusate, regulated under Regulation (EU)
2024/1938). The current Directive 2010/53/EU contains no mechanism for coordination
between the organ transplant competent authority and the competent authorities operating
under these other legislative frameworks. As a result, valuable clinical outcome data
generated from the use of medicinal products or devices in the novel context of ex-vivo
organ treatment may be lost between regulatory silos. For instance, when a chemotherapy
agent is used to treat cancer cells in a liver during perfusion, the outcome data is relevant
both to the transplant authority (was the organ safe and effective?) and to the
pharmaceutical authority (how did the drug perform in this unprecedented application?).
Without a legal obligation to share and coordinate this data, neither authority has a
complete picture. Furthermore, it necessarily to trial a medicinal product or medical device
in the transplant setting, to have the engagement of the organ authorities with whom
protocols are to be developed on which organs can and will be made subject to the trial,
avoiding putting fully functional organs at risk while aiming to improve and recover less
functional organs.
Furthermore, the recently adopted SoHO Regulation (EU) 2024/193885 has introduced a
comprehensive SoHO Preparation Authorisation model based on benefit-risk assessment
and clinical outcome monitoring. Solid organs are explicitly excluded from the scope of
this Regulation. Yet the processing techniques being applied to organs are often analogous
to those applied to tissues and cells and may involve the same types of products and
substances. The absence of an equivalent authorisation mechanism within the organ
Directive creates an asymmetry in the EU’s regulatory architecture for substances of
human origin, where tissues and cells are subject to a modern, risk-based authorisation
84 See Rapid Assessment Scenario Study 85 Consolidated text: Regulation (EU) 2024/1938 of the European Parliament and of the Council of 13 June 2024 on
standards of quality and safety for substances of human origin intended for human application and repealing Directives
2002/98/EC and 2004/23/EC. ELI: http://data.europa.eu/eli/reg/2024/1938/2024-07-17
99
system while organ processing remains entirely outside any EU-level authorisation
framework.
Barriers to innovation uptake and equitable access
The regulatory vacuum does not only affect patients, but it also acts as a brake on
innovation and contributes to inequitable access to advanced transplantation technologies.
In the absence of a clear, harmonised EU framework for authorising organ processing,
transplantation centres in Member States with less developed regulatory capacity, or in
countries that have not established any national processing oversight regime, may be
reluctant to adopt new processing technologies. This creates the risk of a two-tier system
in which patients in some Member States benefit from organs improved through advanced
processing while patients in others continue to rely on static cold storage alone.
The broader economic and competitive implications are also relevant. Many of the most
advanced organ processing technologies are fundamentally biotechnological in nature: ex-
vivo gene therapy delivered through machine perfusion, the use of bioengineered
perfusates, and AI-driven perfusion assessment systems all sit at the intersection of
biotechnology and transplantation. Many of the new technologies are developed by
academia and spin-offs, while several SMEs are offering these processing technologies to
transplant systems. Without regulatory clarity and a transparent authorisation pathway,
developers or providers of these technologies face uncertain market conditions, which may
deter investment and delay the clinical translation of innovations that could expand the
pool of transplantable organs.
Problem drivers
The problems identified above share a common origin: the Directive was drafted and later
adopted in 2010 on the basis of the then-prevailing clinical paradigm, in which the ex-vivo
handling of organs was essentially limited to passive cold preservation. At that time, the
legislative choice to include “preservation” but not “processing” in the Directive’s scope
was reflecting the state of the art. Machine perfusion existed in experimental form, but its
clinical deployment was limited and the prospect of routine ex-vivo organ treatment was
still largely theoretical.
Over the subsequent fifteen years, the technology matured faster than the legislative
framework evolved. Three principal drivers underpin the current regulatory gap. First, the
pace of clinical and technological innovation in ex-vivo organ management has
accelerated dramatically, with machine perfusion transitioning from experimental to
routine or near-routine use in major centres across Europe. The technology has also shifted
qualitatively, from simple hypothermic perfusion (which is functionally closer to
preservation) to normothermic perfusion and active organ treatment (which are clearly
beyond the concept of preservation). Second, the original legislative design chose a
Directive as its instrument type, establishing minimum standards that Member States
transpose into national law. While this approach provided flexibility, it also meant that the
resulting national divergences in approach to transplantation and processing were not
counterbalanced by common EU rules. Third, the absence of a legislative review
mechanism capable of responding to technological change within the Directive itself
meant that the framework could not self-correct. Unlike some other EU health legislation,
100
Directive 2010/53/EU did not include a built-in mandate for periodic review or adaptation
to scientific and technical progress, contributing to the widening gap between law and
practice.
Furthermore, the GAPP Joint Action, which brought together competent authorities from
17 European countries to develop a common approach to the authorisation of preparation
processes for substances of human origin. The organ processing authorisation model
proposed in new Article 6a of the Directive 2010/53/EU is modelled on the SoHO
Preparation Authorisation framework that emerged from this work and was subsequently
codified in Regulation (EU) 2024/1938.86 This lineage is significant: it means the proposed
regulatory model is not an untested construction but rather an adaptation of a framework
that has been developed, piloted, and validated through extensive multi-country
collaboration in the closely related SoHO sector.
Scope of the problem
The regulatory gap identified above affects multiple categories of stakeholders.
Transplantation centres are the primary operators of organ processing technologies and
bear the most immediate consequences of the legal uncertainty, as they perform these
activities without a clear EU-level legal or authorisation framework. National competent
authorities designated under the Directive lack the EU mandate, tools, and in many cases
the technical capacity to oversee processing activities, even as these activities become
increasingly common within their jurisdictions. Pharmaceutical and medical device
companies developing and marketing products and services for organ processing face an
ambiguous market environment in which the regulatory pathway for their products in this
novel application is unclear. European organ exchange organisations such as
Eurotransplant and Scandiatransplant, which coordinate cross-border organ allocation,
confront the practical challenge of managing organs that have been processed under
divergent national regimes.
Ultimately, however, the most significant affected group is patients, both those on
transplant waiting lists and those who receive transplants. The 52,488 patients on EU
waiting lists at end-2024 stand to benefit from any regulatory intervention that safely
expands the pool of transplantable organs by enabling the rehabilitation of marginal organs
through processing. Conversely, they are at risk from both the absence of processing
oversight (unregulated processing may introduce undetected safety risks) and from the
uneven uptake of processing technologies across Member States (which may result in
inequitable access to the benefits of organ processing depending on where a patient lives).
86 See proposed Article 6a of the amended Directive 2010/53/EU, in COM(2025) 1031 final, Article 2.
ANNEX 6: OVERVIEW OF THE PROPOSED MEASURES AND ARTICLES OF THE PROPOSED REGULATION
AND DIRECTIVE
No. Policy
intervention
Policy
measure(s) Covered provision(s)
Simplifi-
cation
measure
New
policy
intervention
Strategic projects and clusters, incl. biosimilars
1
Recognition
and support of
strategic health
biotechnology
projects
Support package
for strategic
health
biotechnology
projects
Chapter II, Section 1: Art. 3: Health biotechnology strategic projects ; Art.
7: Designation of competent authority ; Art. 8: Application for recognition ;
Art. 9: Recognition by Member States
Chapter II, Section 2: Art. 11: Single points of contact ; Art. 12: Priority
status; Art. 13: Administrative support ; Art. 14: Financial and technical
support
Chapter IX: Art. 60: Amendments to Regulation (EU) 2024/795 (STEP) -
projects deemed to contribute to STEP objectives
Recitals (12)-(14), (27)-(30), (54)-(56)
X
2
Recognition
and support of
high impact
strategic health
biotechnology
projects
Support package
for high impact
strategic health
biotechnology
projects,
including for
'biotechnology
development
accelerators' and
'centres of
excellence for
advanced
therapies'
Chapter II, Section 1: Art. 4: High impact health biotechnology strategic
projects; Art. 5: Biotechnology development accelerators ;Art. 6: Centres of
excellence for advanced therapies; Art. 7: Designation of competent
authority; Art. 8: Application for recognition ; Art. 10: Recognition by the
Commission
Chapter II, Section 2 : Art. 11: Single points of contact; Art. 12: Priority
status; Art. 13: Administrative support ; Art. 14: Financial and technical
support
Chapter IX - Amendments: Art. 60: Amendments to Regulation (EU)
2024/795 (STEP) - projects deemed to contribute to STEP objectives
Recitals (14)-(16), (24), (52)-(56)
X
102
3
Health
biotechnology
ecosystem
support
framework
Networks of
health
biotechnology
clusters
Chapter II, Section 2: Art. 15: Networks of health biotechnology clusters
Recitals (25)-(26)
X
EU Health
Biotechnology
Support Network
Chapter II, Section 4: Art. 19: EU Health Biotechnology Support
Network; Art. 20: European Health Biotechnology Steering Group
Chapter VII, Section 1: Art. 34: Support to biotechnology developers
Recitals (33)
X
4
Biosimilars
competitiveness
framework
Guidance on a
tailored
regulatory
approach for the
development of
biosimilars
Chapter V: Art. 28: Guidance by the Agency on biosimilars
Recitals (58)
X
Support package
for biotechnology
health strategic
projects for
biosimilars
Chapter V: Art. 29: Biotechnology health strategic projects for biosimilars
(specific criteria); Art. 30: International partnerships
Chapter II, Section 2 (Articles 11-14): Support measures apply
Recitals (59)-(60)
X
Time-to-market
5
Regulation of
novel health
biotechnology
products
Union regulatory
status repository
and time limits
Chapter VII, Section 1: Art. 35: Union regulatory status repository; Art.
36: Time limits in the regulatory status process
Recitals (72)-(74)
X
Foresight Panel
for Emerging
Health Innovation
Chapter VII, Section 2: Art. 37: Foresight Panel for Emerging Health
Innovation (establishment, tasks, composition); Art. 38: Support to the
Foresight Panel
Recitals (75)-(78)
X
103
Cross-framework
coordination for
regulatory
sandboxes
Chapter VII, Section 3: Art. 39(1): Member State-level sandbox
consultations; Art. 39(2): Union-level sandbox consultations; Art. 39(3):
Combination products considerations; Art. 39(4): Swift contribution
requirements
Art. 39(5): Cross-framework knowledge sharing and regulatory learning
Recitals (80)-(82)
X
Regulatory
sandboxes for
novel health
biotechnology
products
Chapter VII, Section 3: Art. 40(1): Scope and eligibility criteria; Art.
40(2): Time-limited framework for evidence generation; Art. 40(3):
Application requirements; Art. 40(4): Commission implementing act for
establishment; Art. 40(5): Sandbox plan requirements; Art. 40(6):
Consultations with Agency, SCB, Medical Devices Coordination Group,
Foresight Panel ; Art. 40(7): Participant liability; Art. 40(8)-(9):
Recommendations and lessons learned
Recitals (83)-(87)
X
6
Targeted
regulatory
reform of the
General Food
Law - (EC) No
178/2002
Streamlined
EFSA risk
assessment
processes
Chapter IX, Art. 56 (Amendments to Regulation (EC) No 178/2002): Art.
56(1): Art. 3 (new definitions – points 19-21); Art. 56(2): Art. 22(5)(a)
(EFSA nutrition mandate); Art. 56(3): Art. 28(3), (6), (9) (Scientific Panel
governance); Art. 56(4): Art. 32a(1) (enhanced pre-submission advice); Art.
56(5): Art. 32b(4), (5), (6) (shortened procedural timelines); Art. 56(6): Art.
32c(1) deletion (merger of consultation procedures)
Recitals (107)-(112)
X
Regulatory
sandboxes
framework for
food, feed and
GMOs
Chapter IX, Art. 56(7) (insertion of new Chapter IIIA in Regulation (EC)
No 178/2002): Art. 49a: General provisions on regulatory sandboxes; Art.
49b: Establishment of regulatory sandboxes; Art. 49c: Other
responsibilities, monitoring and reporting obligations;
Recitals (113)-(116)
X
104
7
Targeted
regulatory
reform of the
Advanced
Therapy
Medicinal
Products
(ATMPs)
framework -
(EC) No
1394/2007
Regulatory
simplification and
future-proofing of
ATMPs
Chapter IX, Article 57: Amendment to Art. 2(1): Addition of point (e);
Amendment to Art. 2: Addition of paragraph 6; New Art. 4a (paragraphs 1-
5); Replacement of Art. 25a (paragraphs 1-6)
Recitals (118)-(120)
X
8
Targeted
regulatory
reform of
clinical trials -
Regulation
(EU) No
536/2014
Accelerated and
streamlined
clinical trial
authorisation
procedures
Chapter IX, Art. 58: Art. 2: Definitions (points 3, 3a, 12, 13, 13a, 21, 36-
43, 47) ; Art. 3: General principles
Art. 4-5: Prior authorisation and submission ; Art. 5a-5b (new): RMS
appointment and validation ; Art. 6-8: Assessment reports and decision
(including translation adequacy assessment in Part II); Art. 14: Extension to
additional Member States ; Art. 14a (new): Appointment of new RMS ; Art.
14b (new): Accelerated procedure for public health emergencies ; Art. 17-
21: Substantial modifications ; Art. 25: Mandatory EU-templates for Part
II; Art. 63a (new): Harmonised GDP for investigational medicinal
products; Art. 28, 30-33, 41: Supporting provisions
Recitals (123)-(139)
X
Clinical trial
regulatory
sandboxes
Chapter IX, Art. 58: Art. 2(45) (new): Definition of regulatory sandbox;
Art. 27d (new): Clinical trial regulatory sandboxes; Art. 85(5)(i): CTAG
task to provide sandbox recommendations
Recital (149)
X
105
Digital innovation
and harmonised
data governance
for clinical trials
Chapter IX, Art. 58: Art. 2(44) (new): Definition of combined study ; Art.
2(46) (new): Definition of AI system
Art. 14c (new): Combined studies (coordinated assessment) ; Art. 27e
(new): Use of AI in clinical trials
Art. 29: Informed consent (electronic provisions) ; Art. 81: EU database
updates ; Art. 83a (new): Authority coordination ; Art. 85: CTAG
(expanded mandate) ; Art. 93 (new): Data protection (harmonised GDPR
basis)
Art. 98a (new): EU Portal development plan ; Annex I amendments
Recitals (140)-(148), (150)-(156)
X
Coordinated
assessment for
combined studies
Chapter IX, Art. 58: Art. 14c(1): Scope (clinical trials combined with IVD
performance studies or medical device clinical investigations) ; Art. 14c(2):
Single application submission; Art. 14c(3): EU Portal submission and
coordinating sponsor designation; Art. 14c(4): Coordinated assessment
under reporting Member State direction; Art. 14c(5): Assessment scope and
permitted considerations; Art. 14c(6)-(7): Mutual recognition and grounds
for disagreement; Art. 14c(8): Single decision by each Member State; Art.
14c(9)-(10): Commission delegated acts for streamlined procedures.
Recital (135)
X
Governance and
enforcement
framework
Chapter IX, Art. 58: Art. 78(1): National competent authority inspections
and supervision system; Art. 78(6): Inspection reports via EU Portal; Art.
78(8)-(9): Joint inspections and delegation of inspections; Art. 79:
Commission Union controls; Art. 79a: Member State obligations regarding
Union controls; Art. 83(1): National contact points for implementation; Art.
83(2): Powers, personnel, resources and expertise requirements; Art.
83a(1)-(2): Coordination between competent authorities and ethics
committees within Member States.
Recitals (147)-(148)
X
106
9
Targeted
regulatory
reform of
Veterinary
Medicinal
Products -
Regulation
(EU) 2019/6
GMO exemption
and single
regulatory
pathway for
veterinary
medicinal
products
Chapter IX, Art. 59: Recitals (161)-(164)
Amendments to Regulation 2019/6: Art. 3(3) (new): GMO exemption
('One-Stop-Shop'); Art. 4(46): Definitions (GMO VMPs); Art. 8(5):
Deletion; Art. 9(2a) (new), (3), (4): Clinical trials ERA; Art. 28(2): MA
examination consultations; Annex II: Technical amendments (as set out in
Annex III of BTA)
X
Reduction of
burden for the
handling of
variations not
requiring
assessment
(VNRAs)
Chapter IX, Art. 59
Recital (160)
Amendments to Regulation 2019/6: Art. 61: Variations procedure
(replacement with new paras 1-4)
X
Targeted SPC
extension for
zoonotic
biotechnology
veterinary
medicinal
products
Chapter IX, Art. 59
Recital (166)
Amendments to Regulation 2019/6: Art. 4(45): Definition; Art. 40a
(new): SPC extension for zoonotic biotech VMPs
X
Regulatory
sandbox for
innovative
technologies,
methods or
products related
to animal health
Chapter IX, Art. 59
Recitals (167)-(170):
Amendments to Regulation 2019/6: Art. 4(47): Definition (regulatory
sandbox); Art. 136a (new Chapter IX): Regulatory sandbox
X
107
10
Targeted
regulatory
reform of the
substances of
human origin
(SoHO)
framework -
Regulation
(EU) 2024/1938
SoHO regulatory
sandbox
framework
Chapter IX, Article 61: Art. 61(1): Amendment to Art. 3 – Addition of
definition (60) 'regulatory sandbox'
Art. 61(4): New Art. 39a – SoHO regulatory sandboxes (paras 1-13)
Recitals (171)-(173)
X
Streamlined
SoHO regulatory
status
consultation
procedures
Chapter IX, Article 61: Art. 61(2): New Art. 13(3a); Art. 61(3):
Amendment to Art. 69(2), first subparagraph
Recital (171)
X
11
Targeted
regulatory
reform of
Directive
2010/53/EU on
standards of
quality and
safety of
human organs
intended for
transplantation
Scope expansion
to include organ
processing
Amendment to Art. 2(1): Scope expansion; New Art. 3(ka): Definition of
'processing'; Amendment to Art. 3(q): Definition of 'transplantation'
X
Organ processing
authorisation
regime
New Art. 6a: Organ processing authorisation (paras 1-12)
Amendment to Annex Part B: 'Processing' data field
X
Cross-border and
cross-framework
regulatory
coherence
Art. 6a (4)-(8): Cross-framework coordination X
12
Regulatory
framework for
genetically
modified
micro-
organisms
(GMMs) in
non-food and
non-feed
Specific risk
assessment
criteria and
targeted
regulatory
requirements for
all GMMs
Amendments to Directive 2001/18/EC: Tailored GMM risk assessment
requirements; Detection method modalities; Unlimited validity of market
consents
X
Accelerated
market
authorisation
Amendments to Directive 2001/18/EC: Streamlined procedures for low-
risk GMMs (delegated act); Low-risk status demonstration requirements
(implementing act); PMEM exemption provisions
X
108
pathway for low-
risk GMMs
Access to capital
13
Financing
instruments for
biotech
companies and
projects
EU health
biotechnology
investment pilot
Chapter III: Art. 22: EU health biotechnology investment pilot
Recitals (44)-(49)
X
Support package
for an EU
biotechnology
late-stage capital
booster pilot
projects
Chapter III: Art. 23: EU biotechnology late-stage capital booster pilot;
Art. 24: Biotechnology as a strategic technology eligible for Union and
national financial support; Art. 25: Funding for high impact health
biotechnology strategic projects; Art. 26: Coordination of financing
Chapter II, Section 2 (Articles 11-14): Support measures apply via Article
4(1)(c)
Recitals (50)-(56)
X
Intellectual property
14
SPC extension
for
biotechnology
medicines
Extension of the
supplementary
protection
certificate
concerning best-
in-class
biotechnology
medicines
Chapter IV: Art. 27: Extension of the supplementary protection certificate
concerning best-in-class biotechnology medicines developed in the Union
Recital (57)
X
AI and data
15
AI and data
guidance
framework for
EMA guidance on
AI and advanced
technologies in
the medicinal
Chapter VI: Art. 31: Guidance on the deployment and use of systems
based on advanced technologies, including AI, in the lifecycle of medicinal
products
Recitals (64)-(68)
X
109
health
biotechnology
product lifecycle
(Article 31)
Biotechnology
testing
environments for
advanced
biotechnology
innovations
(Article 32)
Chapter VI: Art. 32: Biotechnology testing environments for advanced
biotechnology innovations
Chapter II: Art. 4(1)(d): High impact recognition criteria
Chapter II, Section 2 (Articles 11-14): Support measures apply
Recitals (69)-(70)
X
Biotechnology
data quality
accelerator
(Article 33)
Chapter VI: Art. 33: Biotechnology data quality accelerator
Chapter II: Art. 4(1)(d): High impact recognition criteria
Chapter II, Section 2 (Articles 11-14): Support measures apply
Recitals (69)-(71)
X
Biodefence and biosecurity
16
Control and
monitoring
framework for
biotechnology
products of
concern
Regulation of
biotechnology
products of
concern
Chapter VIII, Section 2: Art. 43: Biotechnology products of concern; Art.
44: Verification of legitimate need
Art. 45: Benchtop equipment; Art. 46: Prevention and reporting of
biotechnology misuse
Annex I: Biotechnology products of concern
Recitals (88)-(100)
X
Enforcement and
monitoring
mechanisms
Chapter VIII, Section 2: Art. 47: Training and awareness-raising ; Art. 48:
National inspection authorities
Art. 49: Commission enforcement support and monitoring; Art. 50: Audits;
Art. 51: Penalties ; Art. 52: Advisory group on biosecurity ; Art. 53:
Biological systemic risk ; Art. 54: Monitoring and guidance ; Art. 55:
Coordination on biosecurity and biosafety
Recitals (99)-(105)
X
110
17
Recognition
and support of
high impact
biodefence
projects
Support package
for EU biothreat
radar high impact
health
biotechnology
strategic projects
Chapter VIII, Section 1: Art. 41: EU Biothreat Radar
Chapter II: Art. 4(1)(e): High impact recognition criteria
Chapter II, Section 2 (Articles 11-14): Support measures apply
Recitals (86)-(87)
X
ANNEX 7: ADDITIONAL INFORMATION ON MEASURES AND
EXPECTED IMPACTS
This annex provides additional analytical detail supporting the assessment of expected
impacts of the interventions, drawing in particular on the Study to support the rapid
assessment of policy scenarios to strengthen innovation and competitiveness in the field of
biotechnology in the EU87. It complements the summary assessment in Section 5 of this
staff working document by further elaborating on the design of the measures, the baseline,
the impact transmission channels, the assumptions underpinning the assessment, potential
caveats and limitations – as appropriate for each intervention area. It further provides the
scientific and technical basis for the proposed measures in some areas.
More information is available in the support study (forthcoming), including the
assumptions made.
1 INTERVENTION N°2: TARGETED REGULATORY REFORM OF THE GENERAL FOOD
LAW
1.1 Baseline and counterfactual scenario
Conduct of business
Under the baseline, and in order to ensure a high level of protection of public health, animal
health, plant health and – where relevant – the environment, pre-market authorisations
for certain categories of food, feed and inputs to the food chain will continue to apply
with the specific procedural requirements set out in the sectoral legislations and read
together, where relevant, with the General Food Law. Authorisation procedures will
continue to be based on the principle that it is for the applicants to prove that the subject
matter of an application complies with EU requirements.88
In addition, EU authorisations will continue to act as a ‘regulatory passport’ to the
market of third countries, facilitating market access in many non-EU regions (e.g., Latin
America, Southeast Asia, Middle East). Third-country authorities often use the EU dossier
as a reference or starting point; as such, the studies performed for EU risk assessment
purposes and their stringent requirements are still considered by industry stakeholders as
an advantage for other markets.89
Nevertheless, under the baseline, it is expected that the uptake of pre-submission advice
mechanisms will remain limited and will thus not contribute to improve dossier quality.
87 Rapid Assessment Scenarios study, forthcoming. 88 That principle is based on the premise that human health, animal health, plant health and, where relevant, the
environment are better protected where the burden of proof is on the applicant since it has to prove that the subject matter
of its application is safe prior to its placing on the market, instead of the public authorities having to prove that the subject
matter is unsafe in order to be able to ban it from the market. Moreover, public money should not be used to commission
costly studies (several thousand to several million Euros) that will eventually help the industry to place a product on the
market. This principle remains valid. 89 The Commission’s 2024 evaluation of additives for use in animal nutrition indicates that third-country authorities in
Chile, Canada and China reportedly use EU data as a reference in their procedures, and EU authorisation is described as
helping to fast-track registrations in parts of Southeast Asia and Africa. See
https://food.ec.europa.eu/document/download/e2029994-aa27-49f0-9ab6-18cfa81e29fe_en?filename=animal-
feed_additives_eval-legis_reg-2003-429_swd_2024-46.pdf.
112
As a result, it is expected that delays linked with subsequent requests for additional data
and delays to ‘time to market’ will persist.
Administrative costs on businesses, including SMEs
Based on these characteristics of the existing regulation, the baseline assumes that in the
future businesses will still have to incur certain administrative burdens in order to
meet the regulatory requirements in the context of pre-market authorisations for
certain categories of food, feed and other inputs to the food chain. However, these
administrative costs could be reduced to some extent if businesses would take advantage
of the pre-submission advice mechanisms offered by EFSA under the existing legal
framework and the prescribed limitations in terms of scope. Especially, SMEs would
benefit from pre-submission advice as they would get a better understanding of the
concrete requirements of the authorisation process under the general pre-submission
advice. The exclusion of scientific matters from the scope of general pre-submission advice
is a structural gap that is expected to continue to result in the low uptake of such advice
and thus unnecessary administrative costs arising from poor quality application dossiers
on scientific aspects cannot be avoided/minimised. Although both EFSAs90 and the
European Commission91 has launched measures in recent years to support SMEs, SMEs
would continue to be constrained in their efforts to be fully in compliance without incurring
unnecessary administrative costs during the authorisation process. This might pose
substantial market entry hurdles and result in unexploited innovation potential92.
Competitiveness, trade and investment flows
Various studies that have been conducted in the past93 have confirmed that:
90 E.g. EFSA targeted calls for expressions of interest for SMEs seeking pre-submission advice in the area of novel foods
in 2024 and 2025 as well as fast tracking of general pre-submission advice for SMs. See also
https://www.efsa.europa.eu/en/applications/about/services/sme. 91 E.g. the Small Business Act for Europe (SBA) in 2008 or the Regulatory Fitness and Performance Programme
(REFIT). 92
See at: https://food.ec.europa.eu/document/download/fcfe7958-72ab-47b6-8b38-
0c5473bde0da_en?filename=gfl_fitc_comm_staff_work_doc_2018_part1_en.pdf. 93 In the context of the REFIT Evaluation of General Food Law (2018), it was found that the systematic application of
the risk analysis principle – with EFSA performing the EU risk assessment – across EU food law, provided a comparative
advantage for EU manufacturers. For example, foods accompanied by a health claim approved on scientific grounds
(EFSA’s positive assessment) provides a higher marketing value and create long term consumer trust on the food chain
vis-à-vis other unsubstantiated claims on foods in other markets that do not require scientific grounds for their
authorisation. See at: https://food.ec.europa.eu/document/download/fcfe7958-72ab-47b6-8b38-
0c5473bde0da_en?filename=gfl_fitc_comm_staff_work_doc_2018_part1_en.pdf. This was also confirmed in the 2016
Competitiveness Study performed by DG GROW, to be found
at:https://www.gpp.pt/images/Agricultura/Organizacao_da_Producao_e_Cadeia_Alimentar/CompetpositEuropfooddrin
kindustFR.pdf; These findings have also been reconfirmed by Intellera et al. (2025): Study supporting the Evaluation of
the European Food Safety Authority 2017-2024 (forthcoming).
Similarly, sectoral evaluations of EU legislation regarding pre-market authorisations have reached the same conclusion,
see https://food.ec.europa.eu/document/download/e2029994-aa27-49f0-9ab6-18cfa81e29fe_en?filename=animal-
feed_additives_eval-legis_reg-2003-429_swd_2024-46.pdf/.
.
113
- the high safety standards set at EU level have also provided incentives to develop
more innovative products that better protect public health and have equivalent or
better efficacy94;
- the ‘EU seal of approval’ (EU pre-market authorisations granted) renders business
operators competitive in the international field, as the relevant products are
perceived of ‘high quality’ allowing them to penetrate the market of third countries,
where third-country authorities increasingly use the EU dossier as a reference
point95.
It can therefore be assumed that in the upcoming future, the EU food law will continue
to support the European market position of the food chain industry, and especially the
food industry which is the largest manufacturing and employment sector in the EU.
Nevertheless, this competitive advantage is curtailed by the length of the risk analysis
process in certain sectors relating to innovative products due to delays that are often
observed during the risk assessment. These delays are caused by long stop-the-clock
procedures, which are mainly attributed to low quality dossiers (see dimension above:
administrative costs), and can increase administrative costs, resulting in lost revenues or
uncertainty of potential investors96.
Functioning of the internal market and competition
Under the baseline, it is assumed that the current EU food law legislation will continue to
contribute to the functioning of the internal market and competition. Compared with EU
legislation before 2002, when the EU food law was a patchwork of vertical legislation97,
the introduction of General Food Law and subsequent EU sectoral legislation provides a
common framework for the intended integrated approach and ensures that across all
Member States uniform food law definitions and principles are applied. This has been
confirmed by the 2018 Fitness Check on General Food Law Regulation.98 One main
finding was that the current legislative framework not only achieved its goals for a high
level of protection of public health and consumers’ interests in relation to food, but also
enhanced the functioning of the internal market in the EU by providing a level playing
field throughout the EU single market. Furthermore, the current regulation had led to
94 For example, the removal of plant protection products from the EU market which do not meet the safety criteria set
out in the EU legislation have provided incentives for the development of more innovative products that better protect
public health and have equivalent or better efficacy. See REFIT Evaluation of General Food Law (2018) at:
https://food.ec.europa.eu/document/download/fcfe7958-72ab-47b6-8b38-
0c5473bde0da_en?filename=gfl_fitc_comm_staff_work_doc_2018_part1_en.pdf. 95 Intellera et al. (2025): Study supporting the Evaluation of the European Food Safety Authority 2017-2024
(forthcoming) 96 REFIT Evaluation of GFL (2018). This finding was recently reconfirmed by Intellera et al. (2025): Study supporting
the Evaluation of the European Food Safety Authority 2017-2024 (forthcoming) 97 For the situation prior to 2002, see REFIT Evaluation of GFL (2018):https://food.ec.europa.eu/horizontal-
topics/general-food-law/fitness-check-general-food-law_en. 98 For more information see: REFIT Evaluation of GFL (2018): https://food.ec.europa.eu/horizontal-topics/general-food-
law/fitness-check-general-food-law_en. More specifically see at:
https://food.ec.europa.eu/document/download/fcfe7958-72ab-47b6-8b38-
0c5473bde0da_en?filename=gfl_fitc_comm_staff_work_doc_2018_part1_en.pdf.
114
greater harmonization across the EU compared to EU legislation before that was
characterized by complexity, duplication, overlaps and inconsistencies99.
For instance, the coherence of food law is particularly demonstrated by the systematic
application of the risk analysis principle – set out in the General Food Law – in all EU food
secondary food legislation (and not limited to food safety), where relevant. Moreover,
EFSA's input is not only required for legislation governing feed and food per se, but a more
holistic approach has been put in place covering all scientific issues pertinent for the food
chain, e.g. plant protection products and food contact materials, promoting coherence of
food law in general. At the same time, setting an acceptable level of risk at EU level
through a centralised science-based approach (EFSA) results in a higher level of scientific
expertise, while preventing the duplication of efforts in Member States in terms of risk
assessments and risk management decisions. Moreover, centralised authorisation
procedures have resulted in significant cost savings for Member States, especially for
the smaller Member States that cannot afford to invest in the required scientific capacity.
They have also resulted in cost savings for applicants as they only have to submit a
single application dossier instead of multiple national applications.100
Nevertheless, while the current framework ensures a high degree of harmonisation and a
level playing field in legal terms, its effectiveness in practice may be constrained by delays
in the risk analysis process in certain sectors relating to innovative products. These delays,
which are mainly attributed to low quality dossiers and the resulting stop-the-clock
procedures and additional requests for information, may slow down the placing of products
on the EU market and the speed at which operators can effectively access the internal
market. As a result, while the internal market framework is structurally well-functioning,
when authorised innovative products are placed on the market, the full benefits of the
internal market materialise in practice with certain delays impacting the return on
investment for innovative business operators.
Innovation and research
Under the baseline, the full potential of innovation and research in the food and feed
sector, especially regarding start-ups and SMEs, is generally hindered bythe often-
observed delays in risk assessment attributed to low quality of application dossiers; these
delays have been found to have a negative impact on innovation, in terms of expected
return on investment.101
This is further exacerbated by the current situation regarding regulatory sandboxes in the
EU food and feed area, which is marked by fragmentation and an underuse of their
potential in contributing to the development of innovative products and/or a faster
99https://food.ec.europa.eu/document/download/fcfe7958-72ab-47b6-8b38-
0c5473bde0da_en?filename=gfl_fitc_comm_staff_work_doc_2018_part1_en.pdf 100 REFIT Evaluation of GFL (2018), see https://food.ec.europa.eu/horizontal-topics/general-food-law/fitness-check-
general-food-law_en. This finding was recently reconfirmed by Intellera et al. (2025): Study supporting the Evaluation
of the European Food Safety Authority 2017-2024 (forthcoming). 101 REFIT Evaluation of GFL (2018), see https://food.ec.europa.eu/horizontal-topics/general-food-law/fitness-check-
general-food-law_en. This finding was recently reconfirmed by Intellera et al. (2025): Study supporting the Evaluation
of the European Food Safety Authority 2017-2024 (forthcoming).
115
adaptation of the regulatory framework to emerging needs. A few Member States have put
in place sandbox-type mechanisms, but these tend to be horizontal when connected to food
and feed law, and not anchored in a clear, harmonised EU framework under the General
Food Law.102 In the public consultation of the proposed European Biotech Act, it was also
claimed that the absence of regulatory sandboxes103 and limited opportunities for real-
world testing prevent innovators from gathering essential data and feedback, further
slowing the development and scaling of new solutions.104 Any existing regulatory
sandboxes are also not systematically linked to EFSA’s scientific work or meant to
contribute to an evidence-based proposal for a possible adaptation of regulatory
requirements. As a result, opportunities for structured, supervised experimentation in
real conditions that could facilitate innovation and inform future adaptations of EFSA’s
guidance (e.g., in relation to data requirements) and/or of regulatory requirements remain
largely missed or underused.
Public authorities
Under the baseline, it is assumed that EFSA’s general pre-submission advice continues to
exclude scientific matters such as study design and testing strategies and that there is a
separation between the EFSA staff that provide such advice and the EFSA staff that support
the Panels during the risk assessment.
EFSA’s Panels/Scientific Committees will continue to be chaired by experts while EFSA
staff will only be providing support to the Panels/Scientific Committees, by organising
their work, including preparatory work. Under the current regulatory framework, national
competent authorities do not have the opportunity to test data requirements or alternative
regulatory requirements in controlled environments under a clearly defined framework.
Under the baseline, the current structure of European Food Safety Authority’s pre-
submission advice regime is expected to persist, continuing to affect the quality and
efficiency of dossier preparation and assessment, by limiting applicants’ ability—
particularly SMEs and start-ups—to refine study designs and data-generation strategies in
line with EFSA’s latest scientific expectations and by increasing administrative effort for
EFSA staff at validation and during risk assessment through follow-up requests to address
gaps in dossiers, thereby contributing to lengthy risk assessment periods. With regard to
the governance of EFSA’s Panels, the current model – under which scientific experts chair
the Panels/Scientific Committee – has implications for steering, internal coherence across
assessments and the overall efficiency of the system. While expert chairs bring strong
scientific credibility and ownership of the assessments, their dual role may reduce the
scope for more centralised EFSA-level steering of priorities, methods and timelines. This
limited institutional steering may, at least indirectly, contribute to heterogeneity in
practices and, potentially, to longer or less predictable risk assessment processes. Another
102 E.g. In 2025, Spain launched a broad national innovation sandbox, the ‘Agrifoodtech Sandbox’, managed by CNTA
(EATEX Food Innovation Hub), covering agrifood and biotech. 103https://www.cambridge.org/core/journals/european-journal-of-risk-regulation/article/regulatory-sandboxes-for-
novel-foods/D8A2B8E29D2F32DE0334DBCE9AF27188 104 E.g., https://gfieurope.org/wp-content/uploads/2025/11/EU-Biotech-Act-Public-Consultation.pdf
116
issue is that under the current regulatory framework national competent authorities have
very limited scope to test data requirements or alternative regulatory approaches in
controlled environments under a clearly defined and commonly agreed framework. While
some Member States have started to experiment with regulatory sandboxes, these
initiatives tend to be ad hoc, unevenly structured and insufficiently embedded in a broader
EU-level governance architecture. As a result, their potential to generate robust evidence,
inform adjustments to data requirements, and support innovative risk assessment and risk
management approaches is not fully realised, and lessons learned remain fragmented rather
than systematically feeding back into the evolution of the EU food safety system.
Public health and safety
Under the baseline, the EU will continue to set high standards on food, feed and other food
chain inputs, especially for those subject to pre-market authorisations, and contribute to
sustainable development and food safety within and outside the EU, providing incentives
for the development of more innovative products that better protect public health and have
equivalent or better efficacy (as has been shown, for example, for plant protection
products105). However, these innovation opportunities cannot be fully exploited due to
lengthy risk assessment processes mainly attributed to low quality application dossiers.
The current legislation also faces limitations in addressing the scientific aspects that may
arise from the expected increase in the prevalence of diet related health issues in the
coming years due to the limited mandate of EFSA to deliver scientific advice in relation to
nutrition matters such as the nutritional properties of food products and practices derived
from advanced biotechnological processes.
1.2 Expected impacts
Conduct of business
The proposed scope extension of EFSA’s general pre-submission advice might help
businesses towards faster market authorisation by reducing delays during risk
assessment but also at the stage of validation of dossiers because of their low quality. The
inclusion of scientific aspects, such as study design and testing strategies, in the scope of
pre-submission advice may be particularly valuable for SMEs and start-ups, often first and
only time applicants, who often lack the understanding what type of requirements they
must provide within their dossiers106. This should also improve timeliness by facilitating
the reduction of deficiencies and data gaps in dossiers that currently trigger delays during
the validation process and/or “stop-the-clock” processes during risk assessment. The
proposed enhanced general pre-submission advice provided by EFSA, upon request, would
remain non-committal (as it is currently the case). It would also not undermine EFSA’s
independence and accountability since summaries of EFSA’s pre-submission advice would
105 REFIT Evaluation of General Food Law (2018). See https://food.ec.europa.eu/document/download/fcfe7958-72ab-
47b6-8b38-0c5473bde0da_en?filename=gfl_fitc_comm_staff_work_doc_2018_part1_en.pdf 106 https://foodhealthlegal.eu/?p=1380
117
continue to be published once a valid application is submitted, ensuring the transparency
of the process.
By shortening the procedural delays (penalty) for non-compliance with study notification
obligations from six to three months, the proposed measures could further contribute to
faster time-to-market as delays at pre-submission phase will be further reduced. While
keeping highest safety standards through elaborated risk assessments, the proposed
instruments may thus make the EU regulatory framework more innovation-friendly by
supporting businesses in preparing and submitting higher-quality dossiers107.
The proposed introduction of regulatory sandboxes may also have positive impacts for
businesses, by enabling them to test new products and processes in a safe, controlled
environment before market entry.
Innovation and research
The proposed measure of extending the scope of EFSA’s general pre-submission advice
might help businesses towards faster market authorisation by reducing delays during risk
assessment but also at the stage of validation of dossiers because of their low quality (see
dimension: conduct of business). This in turn could foster innovation due to an improved
expected return on investment.108
Moreover, introducing a regulatory framework for sandboxes would likely change how
companies, especially start-ups and SMEs, approach innovation. By allowing them to test
technologies, products and substances under controlled conditions at pre-market and pre-
authorisation stage, sandboxes would substantially reduce both research and development
(R&D) and regulatory risk. Within such sandboxes, real-world testing would also enable
much faster learning cycles. Firms could observe how their innovations perform in practice
– on safety, quality, usability and acceptance – and adapt their products and processes
accordingly. This would shorten development cycles and help viable innovations reach the
market more quickly.109 At the same time, formal sandbox participation, with visible
regulatory engagement, could serve as a strong positive signal to investors and industrial
partners making it easier for start-ups and SMEs to attract funding and strategic
collaborations to support their research and innovation activities.
Nevertheless, the European Biotech Act proposes the exclusion of novel foods from the
scope of regulatory sandboxes as such products involve complex scientific considerations,
which require thorough oversight. Moreover, experience has shown that certain types of
novel foods trigger ethical or cultural concerns among various consumer groups. As such,
novel foods were considered less suited to the flexible, experimental nature of sandboxes.
107 https://medfilesgroup.com/european-biotech-act/ 108 REFIT Evaluation of GFL (2018), see https://food.ec.europa.eu/horizontal-topics/general-food-law/fitness-check-
general-food-law_en. This finding was recently reconfirmed by Intellera et al. (2025): Study supporting the Evaluation
of the European Food Safety Authority 2017-2024 (forthcoming) 109 https://doi.org/10.1080/23311975.2025.2510555
118
Industry stakeholders consider this decision as a missed opportunity to form an open
dialogue that could enhance consumer confidence.110
Public authorities
The proposed amendment enlarging the scope of, and streamlining the pre-submission
advice mechanism could in this regard simplify administrative work at EFSA as applicants
are expected to increase the uptake of such advice and accordingly prepare better quality
dossiers and be better informed of the procedural requirements at pre-submission phase,
avoiding additional requests for information by EFSA to applicants that may have also a
resource cost of EFSA as public authority. This could result in a decrease of time between
the submission of an application dossier and its validity assessment as well as the time
between validated application dossiers and the delivery of EFSA’s scientific output.
Furthermore, such simplification could also lead to more compliance during the whole
process from application to authorisation and lead to a reduction of stop-the-clock
procedures. Hence, a possible impact could be the decrease in number of stop-the-clock
incidents, freeing EFSA’s resources that can be effectively focusing on supporting the
work of the Panels/Scientific Committee and their Working Groups, including the
preparation of scientific opinions and/or redeployed at pre-submission phase.
In addition, allowing experts but also EFSA staff supporting the Panels/Scientific
Committee and their Working Groups in the risk assessment phase to also be involved in
the provision of pre-submission advice will help to ensure alignment of that advice with
evolving scientific practice and thereby contribute to higher-quality, more targeted
application dossiers. The same effect is expected through the extension of the pre-
submission advice to scientific matters. It is also expected that through the expanded scope
of the pre-submission advice additional EFSA staff would be needed; in that respect,
additional resources are foreseen for supporting EFSA in this task. Finally, adjusting the
scientific panel governance has the potential to strengthen the coherence as EFSA staff
would chair these panels to ensure synergies related to the use of methodologies and risk
assessment approaches in a consistent and efficient manner.
Considering the introduction of regulatory sandboxes, it can be assumed that these
experimental environments could lead to the collection of evidence that could support a
faster adaptation of data requirements, especially when those are set out in EFSA guidances
without jeopardising a high level of protection of public health and while ensuring the
excellence of EFSA’s scientific outputs. That is all the more the case since EFSA can
participate in those regulatory sandboxes together with other agencies promoting also
further coherence and more on-spot outcomes. In addition to positive impacts for
businesses that have been described above, EFSA staff and public authorities in Member
States could benefit from structured regulatory learning through sandboxes (see next
impact dimension: public health and safety).
110 https://www.foodbev.com/news/eu-biotech-act-s-exclusion-of-novel-foods-from-regulatory-sandbox-is-a-missed-
opportunity-for-food
119
Public health and safety
The targeted amendments to improve timeliness and coherence of EFSA risk assessment
may foster the development and the placing on the EU market of innovative products that
not only meet the high food safety standards set out in EU food law, but it may also provide
additional positive health effects.
In the area of nutrition, biotechnology can enhance nutritional properties. The expanded
mandate of EFSA on nutrition matters, enabling EFSA to provide advice concerning
enhanced nutritional properties of food products and/or beneficial practices to nutrition
matters derived from advanced biotechnological processes, will further equip EU
regulators with the necessary scientific knowledge to address challenges relating with the
increasing prevalence of diet-related health issues.
Furthermore, the introduction of a harmonised regulatory framework for sandboxes
relating to the food chain in the EU could, in the long run, inform future adaptations of the
applicable framework in terms of alternative regulatory requirements to address
technological developments by harvesting evidence in controlled environments and under
the supervision of competent authorities and the possible participation of EU decentralised
agencies entrusted with risk assessment tasks, without jeopardising a high level of
protection of public health. Accordingly, regulatory sandboxes are considered to be a
“learning tool”111.
By allowing controlled, pre-market testing of innovative technologies, products and
substances, sandboxes could generate earlier and richer real-world data on hazards,
exposure and patterns of use. Authorities could see how products behave outside the
laboratory, detect risk factors, and identify vulnerable groups more accurately. If
sandboxes are also used to test and compare data requirements vis-à-vis the objectives
pursued, regulators can empirically determine the effectiveness and efficiency of
alternative data requirements and compare them with the existing ones in order to
determine the appropriate course of action in light of the objectives pursued by the sectoral
legislation (for instance the effectiveness of ‘new approach methodologies’ as opposed to
animal testing that is currently required by certain sectoral legislation in the context of pre-
market authorisations). This enables them to refine guidance and potentially even legal
requirements so that future applications contain the necessary data requirements. Similarly,
experimenting with alternative regulatory requirements (such as alternative means of
communicating food information to consumers such as digital labelling, conditions of use
or monitoring schemes) creates evidence on which risk-management options actually work
in practice, including how they influence consumer understanding and behavior.
For public authorities, these mechanisms could amount to structured regulatory
learning. They could help EFSA and national bodies to adapt methodologies and
frameworks to emerging technologies and to identify methodological and resource gaps
early on. A better, more targeted database gained through sandboxes would thus support
111 https://www.oecd.org/content/dam/oecd/en/publications/reports/2025/06/regulatory-sandbox-
toolkit_cc8d3e50/de36fa62-en.pdf
120
more accurate risk assessment and more effective, proportionate risk-management
measures. In the long run, this could translate into higher public health and safety: safety
issues are more likely to be detected at small scale in a controlled environment;
authorisation decisions can be better calibrated to real risks; and regulatory responses to
new technologies can be faster and more preventive.
However, these benefits depend on key design conditions: sandboxes must operate under
strict safeguards (limited scale, clear eligibility and stop-rules), data must be systematically
collected, standardized and fed into EU-level processes, and authorities must have enough
capacity to analyse and use the additional information. If these conditions are met,
sandbox-generated evidence is likely to strengthen the EU’s high level of health and
consumer protection.
2 INTERVENTION N°3: TARGETED REGULATORY REFORM OF THE ADVANCED
THERAPY MEDICINAL PRODUCTS (ATMPS) FRAMEWORK
2.1 Proposed measures
The measures are differentiated into two components: (1) ERA derogations for GMO-
containing investigational ATMPs and (2) update of tissue engineered products
(TEP)definition.
Regulatory simplification of environmental risk assessment (ERA) exemptions for
certain ATMPs containing or consisting of GMOs
The proposal amends Regulation (EC) No 1394/2007 to exempt clinical trial sponsors from
the obligation to submit an ERA for clearly delineated categories of investigational
ATMPs that consist of or contain GMOs presenting no or negligible risks to human health
and the environment (e.g., replication‑defective viral vectors).The aim is to reduce
administrative burden within the framework of Regulation (EU) No 536/2014,
Instead of an ERA, sponsors must submit, as part of the clinical trial application, a
declaration explaining why the investigational ATIMP falls into one or more of the
specified no or negligible‑risk categories. The CHMP will verify such declaration.
The same categories are proposed to be exempted from the GMO‑related manufacturing
and import requirements of Regulation (EU) No 536/2014. Annex I to Regulation (EU)
No 536/2014, corresponding amendments are proposed.
The rational of this measure, as provided in the recital of the Commission proposal is that
certain ATIMPs (for example, viral vectors rendered replication‑defective by removal of
wild‑type genome sequences) are described as presenting at most negligible risk to human
health and the environment, supporting a risk‑proportionate exemption approach.
Future‑proofing ATMP definitions via Delegated acts
To future- proof the ATMP-framework, the proposal empowers the Commission to adopt
delegated acts to amend the definition of a tissue engineered product (TEP) in Regulation
(EC) No 1394/2007, in light of technical and scientific advancements in the field of
121
ATMPs, provided such amendments do not extend the scope of those definitions. The
Commission will have to carry out appropriate consultations with the Agency (EMA) and
the Substances of Human Origin Coordination Board (SCB) when preparing such
delegated acts.
Summary of objectives
Together, these changes aim to:
• Simplify regulatory procedures by eliminating full ERA submissions for
negligible‑risk ATMPs.
• Future‑proof the ATMP framework through clarified and adaptable definitions that
account for scientific and technical advancements.
2.2 Baseline and counterfactual scenario
2025: Base year
Three structural problems characterise the baseline:
• GMO-related dual burden: All ATMP clinical trials involving ATMPs with a GMO
component require parallel GMO environmental risk assessments under national
legislation, resulting in duplicated procedures, variable timelines and additional
administrative burden.112
• TEP definition ambiguity: The definition present in the ATMP regulation of tissue
engineered products (TEPs) does not cover in vivo tissue generation, acellular
therapies, and bio-synthetic hybrids. This leads to case-by-case classification
disputes, forcing some developers to launch outside EU first. Other regulators,
notably FDA- approve products that fall outside EU categories, undermining EU
competitiveness.113-Other regulators, notably FDA- approve products that fall
outside EU categories, undermining EU competitiveness.114
Legislative Architecture: Three Relevant Instruments
The baseline must be understood against the legislative architecture governing GMO-
containing investigational medicinal products. Three instruments are relevant, with
different scopes and timelines.
112 Whomsley R, et al. Environmental risk assessment of advanced therapies containing genetically modified organisms
EU. Br J Clin Pharmacol. 2021 87, p. :2458 113 European Medicines Agency (2015) Reflection paper on classification of advanced therapy medicinal products.
EMA/CAT/600280/2010 Rev.1. [Online] London: European Medicines Agency. Available
at: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-classification-advanced-therapy-
medicinal-products_en.pdf 114 European Medicines Agency (2015) Reflection paper on classification of advanced therapy medicinal products.
EMA/CAT/600280/2010 Rev.1. [Online] London: European Medicines Agency. Available
at: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-classification-advanced-therapy-
medicinal-products_en.pdf
122
• Article 177 of the new Pharmaceutical Regulation (NPL), inserting Article 5a
into the Clinical Trials Regulation: applies to all GMO-containing
investigational medicinal products, regardless of product type. It introduces a
centralised, CHMP-led ERA assessment submitted through CTIS, replacing the
current fragmented system of parallel national ERA submissions. The political
agreement on the NPL has been reached in December 2025 and is expected to apply
from end of-2028.
• The delegated act under Article 5a(8) of the CTR: anchored in the NPL, not the
Biotech Act. It will specify the harmonised ERA procedure and content and must
take into account existing EMA Good Practice Documents. Critically, this
delegated act must be developed during the NPL implementation period and be
ready and in force before the NPL applies in mid-2028 — it is a prerequisite for
the Article 5a provisions to function operationally.
• Article 57 of the Biotech Act, amending Regulation (EC) No 1394/2007 and
inserting Article 4a: applies exclusively to ATMPs. Article 4a creates a derogation
from the Article 5a ERA requirement for the subset of ATMPs belonging to one of
the four defined categories presenting no or negligible risk. The two instruments
are complementary. Article 177 of the NPL delivers centralisation for all GMO-
containing IMPs; Article 4a of the proposed European Biotech Act delivers a full
ERA derogation for a defined subset of ATMPs.
2025–2028: Near-Term Projections (Pre-NPL Application)
• Until the NPL applies in mid-2028, the current fragmented system of parallel
national ERA submissions persists in full. Neither Regulation 1394/2007 nor
Regulation (EU) 536/2014 currently provides risk-based derogations for low-risk
ATMPs. All ATMP clinical trials involving a GMO component remain subject to
parallel ERA obligations under national legislation, with the procedural
complexity, timeline variability, and administrative burden this entails.
• Ambiguity of TEP definitions will remain.
From mid-2028: Post-NPL Baseline Without Biotech Act
• From mid-2028, Article 177 of the NPL will replace the fragmented national ERA
system with a centralised, CHMP-led ERA submitted through CTIS for all GMO-
containing IMPs. This delivers a significant structural improvement regardless of
the proposed European Biotech Act. The NPL amendments to Articles 61 and 91
of the CTR also remove parallel national contained-use authorisation requirements
under Directive 2009/41/EC for clinical trials within the scope of the CTR,
addressing one of the most practically significant comprehensiveness concerns.
Read together with Article 5a(3)’s disapplication of Articles 6 to 11 of Directive
2001/18/EC, the expected combined effect is to remove both the deliberate release
consent track and the contained-use track as parallel national requirements,
replacing them with the single centralised CTIS-based ERA procedure. Under the
baseline however, all ATMP clinical trials involving a GMO component —
including those with replication-defective viral vectors presenting negligible
environmental risk — would continue to undergo a full ERA under the centralised
Article 5a procedure.
123
• The TEP definition ambiguity would also remain unresolved under the baseline,
sustaining classification disputes and unpredictability for emerging ATMP
modalities such as in vivo genome editing, acellular therapies, and cell-device
combinations.
2.3 Expected impacts
Administrative costs on businesses, including SMEs
The proposed reform complements the ongoing revision of the EU pharmaceutical
legislation and aligns with the Pharmaceutical strategy for Europe, ensuring that regulatory
requirements for GMOs in medicines are fit for purpose.
The exemption from the ERA requirement for GMO-ATMPs falling within clearly defined
negligible-risk categories eliminates ERA preparation costs for qualifying products.
While no official EU estimate exists for these costs in the ATMP context, industry-
estimates suggest the reform primarily removes administrative and procedural
duplication rather than scientific work, with FTE savings concentrated in regulatory and
coordination activities.
For qualifying products, the current obligation to provide detailed environmental risk data
is replaced by a simplified declaration, in which the sponsor explains the applicable risk
categorisation and demonstrates compliance with predefined criteria. This mirrors the
tiered, risk-proportionate system used for contained use of GMOs.
Estimated FTE savings per CTA application:
lower bound: ~0.15 FTE-year
upper bound: ~0.3 FTE-years.
This corresponds to approximately 50–70% of the GMO-specific administrative
workload, while the underlying ERA data generation effort is retained.
Regulatory frameworks that introduce clear, risk-tiered criteria allow sponsors to self-
assess regulatory obligations and can reduce reliance on specialised consultancy services
for interpretation and compliance planning. This is widely recognised in regulatory policy
literature as a means to lower compliance costs and enhance predictability.
Importantly, safety oversight is maintained: the Committee for Medicinal Products for
Human Use (CHMP) will continue to verify all ERAs as part of the centralised marketing
authorisation procedure, ensuring ongoing safety verification for all GMO-ATMPs.
Competitiveness, trade and investment flows
The temporary COVID-19 derogation from GMO legislation granted by the European
Commission provided direct evidence of what a risk-proportionate exemption delivers in
practice: Pizevska et al. (Frontiers in Medicine, 2022) confirmed that the derogation had
documented timely and administrative benefits for sponsors and trial sites, demonstrating
that removing the ERA obligation for low-risk investigational products reduces procedural
124
delays without compromising safety oversight. ARM, EFPIA, and EuropaBio drew
explicitly on this precedent in calling for a permanent exemption, noting that without it,
GMO requirements would continue to threaten EU competitiveness in a sector where other
jurisdictions apply less cumbersome frameworks (EFPIA joint statement, May 2021). The
Article 4a derogation under the Biotech Act operationalises this evidence-based approach
on a durable legislative basis, for clearly defined negligible-risk ATMP categories. From
mid-2028, its interaction with the NPL’s centralised Article 5a ERA procedure — which
will itself replace the current fragmented national submission system for all GMO-
containing IMPs — further reduces the residual procedural burden for those ATMPs not
qualifying for the derogation.
On TEP definition ambiguity, the consequences of the static 2007 definition are
documented in the clinical trial data. TEPs represent fewer than 5% of ATMPs in EU
clinical trials and received only 5.1% of ATMP-designated trial funding in 2019. Of the
90 TEP-based EU trials undertaken since 2009, only four TEPs have ever received a
marketing authorisation, with two subsequently withdrawn (Joyce et al., Cell
Transplantation, 2022)115. As of February 2025, only three authorised ATMPs in the EU
are human cell and tissue products — two TEPs and one somatic cell therapy — with no
significant increase projected, in part reflecting the classification burden and regulatory
uncertainty the 2007 definition creates for developers of products that do not map cleanly
onto existing categories (Ongena et al., Wound Repair and Regeneration, 2025)116. EMA’s
own reflection paper on ATMP classification acknowledges that, due to the complex nature
of these products and the rapid evolution of science and technology, borderline
classification questions regularly arise and require case-by-case CAT assessment —
generating unpredictability that is itself a competitive disadvantage (EMA Reflection
Paper on Classification of ATMPs, 2015, updated). Empowering the Commission to adapt
the TEP definition via delegated acts, in light of scientific advances and following
consultation with EMA and the SCB, directly addresses this structural gap and reduces the
risk that emerging modalities — in vivo tissue generation, acellular therapies, bio-synthetic
hybrids — fall into regulatory grey zones requiring bespoke classification procedures.
Table 1. Indicators Competitiveness
Effect / impactIndicatorsExpected
change
Data source for baseline
Higher investment into
EU- based research and
innovation
EU Horizon investments
into regenerative
medicine
increase EU Horizon Europe programme: 20
ATMP projects with median funding
~ EUR 7.5 million117
115 Joyce K, Buljovcic Z, Rosic G, Kaszkin-Bettag M, Pandit A. Issues with Tissues: Trends in Tissue-Engineered
Products in Clinical Trials in the European Union. Tissue Eng Part B Rev. 2023 Feb;29(1):78-88. doi:
10.1089/ten.TEB.2022.0094. Epub 2022 Oct 21. PMID: 36062927; PMCID: PMC9940800. 116 Ancira J, Gabrilska R, Tipton C, Miller C, Stickley Z, Omeir K, Wakeman C, Little T, Wolcott J, Philips CD. A
structural equation model predicts chronic wound healing time using patient characteristics and wound microbiome
composition. Wound Repair Regen. 2025 Jan-Feb;33(1):e70004. doi: 10.1111/wrr.70004. PMID: 39959986; PMCID:
PMC11831583. 117 According to cordis: 20 projects funded on ATMPs in the Horizon Europe framework programme with a Median of
~ 7.500.000€ (ending between 2025 to 2031)
125
More favourable EU
innovation investment
location decision
Number of EU-
headquartered gene
therapy developers
increase Alliance for Regenerative Medicine
(2026), ARM Q4 2025 CGT Sector
Data" (396, incl. 145 private)118
Higher EU share of
global regenerative
medicine funding
EU share of global
funding
increase Europe Regenerative Medicine
Market Size & Outlook, 2025-
2033119
Innovation and research
Removing or reducing regulatory requirements- such as exempting qualified
GMO-containing ATMPs and broadening the TEP definition to a flexible, risk-based
umbrella would lower operational costs and speed up the transition from research to
clinical development. This particularly benefits smaller organizations and SMEs, which
represent over 60% of ATMP developers in Europe.
In some Member States, ATMP SMEs have reported workforce growth of over 180%- in
five years, indicating strong employment and innovation potential when regulatory barriers
are reduced.120 Simplifying requirements is expected to improve capital efficiency and
survival rates of SMEs in early clinical phases.121
Harmonizing and simplifying the Regulation (EU) No 536/2014 in combination with
harmonized ERA requirements and clearer ATMP classification is expected to improve
the feasibility of multinational trials, —particularly critical in rare disease indications
where patient populations are small and cross-border recruitment is essential.122 By
simplifying the regulatory environment, the EU would become more attractive for ATMP
research and investment, supporting the growth of over 580 ATMP companies across more
than 20 Member States123.
Faster Patient Access and Data Generation: Simplified pathways would accelerate
patient recruitment and data generation, reducing uncertainty for investors and developers.
For example, protocol amendments in Europe can currently take up to 90 days, compared
118 Alliance for Regenerative Medicine (2026) ARM Q4 2025 CGT Sector Data. [Online] Washington, DC: Alliance for
Regenerative Medicine. Available at: https://alliancerm.org/wp-content/uploads/2026/01/ARM-Q4-2025-CGT-Sector-
Data.pdf 119 Reed Intelligence (2025) Europe Regenerative Medicine Market Size & Share Report By 2033. [Online] Reed
Intelligence. Available at: https://reedintelligence.com/insights/regenerative-medicine-market/europe 120 ARM: Seizing Europe’s Opportunity for Transformative Medicine FINAL_ARM_Policy-Blueprint_Biotech-
Act_CEO-Letter.pdf 2025 121 Joyce, K., Buljovcic, S., Jerez, L., McCarthy, C. and Barry, F. 2023, ‘Issues with Tissues: Trends in Tissue-Engineered
Products in Clinical Trials in the European Union’, Tissue Engineering Part B: Reviews, 29(1), pp. 78–88. doi:
10.1089/ten.teb.2022.0094. 122 ATMP industry coalition, response to the Call for Evidence on the European Biotech Act, June 2025 123 AR Alliance for Regenerative Medicine (2026) ARM Q4 2025 CGT Sector Data. [Online] Washington, DC: Alliance
for Regenerative Medicine. Available at: https://alliancerm.org/wp-content/uploads/2026/01/ARM-Q4-2025-CGT-
Sector-Data.pdf
126
to around 30 days in other regions.124 Reducing these timelines would directly support both
faster innovation cycles and access to potentially curing treatments for patients.
Table 2. Indicators Innovation and research
Effect / impactIndicatorsExpected
change
Data source for baseline
Higher research
(and patenting)
activities
• Rate of In Vivo
Approvals
• Rate of Acellular
Therapy Approvals
• Number of Gene
Therapy Clinical
Trials initiated in EU
• Share of publications
and patents worldwide
Increase
Increase
Increase
increase
~15% cell-based therapies125
~70% acellular gene therapies126
Alliance for Regenerative Medicine
(2026), ARM Q4 2025 CGT Sector
Data" 127
Fraunhofer ISI / VFA (2023),
Technologische Souveränität
Pharma/Biotech
More investment in
Gene Therapy
Research in EU
Share of global market of EU
gene therapy
increase EU Horizon Europe programme: 20
ATMP projects with median funding
~EUR 7.5 million EUR million128
Public health and safety
Reducing avoidable regulatory steps at the clinical development stage could contribute to
earlier initiation of trials and earlier availability of innovative ATMPs for patients with
high unmet medical need. However, this effect would only apply to GMO -ATMPs falling
within the exempted categories. The ERA exemption is not a waiver of safety oversight;
rather, it replaces a full ERA dossier with a declaration verified by CHMP using existing
scientific knowledge., preserving the same level of safety assurance while eliminating
redundant procedural steps.
Clarifying the definition TEPs and modernising regulatory provisions to reflect modular
gene and cell technologies could reduce classification uncertainty and procedural delays.
Given that ATMP development often involves small patient populations, complex
manufacturing chains and iterative product modifications, greater procedural coordination
124 Alliance for Regenerative Medicine (2026) ARM Q4 2025 CGT Sector Data. [Online] Washington, DC: Alliance for
Regenerative Medicine. Available at: https://alliancerm.org/wp-content/uploads/2026/01/ARM-Q4-2025-CGT-Sector-
Data.pdf 125 ARM Q4 2025 data shows that of the global ATMP pipeline, approximately 15% are cell-based therapies and 70%
are gene therapies, with the remainder being tissue-engineered products. 126 Rapid Assessment Scenario Study (forthcoming), stakeholder consultation 127 Alliance for Regenerative Medicine (2026) ARM Q4 2025 CGT Sector Data. [Online] Washington, DC: Alliance for
Regenerative Medicine. Available at: https://alliancerm.org/wp-content/uploads/2026/01/ARM-Q4-2025-CGT-Sector-
Data.pdf 128 https://cordis.europa.eu/search?q=contenttype%3D%27project%27 AND
frameworkProgramme%3D%27HORIZON%27 AND
language%3D%27en%27%2C%27de%27%2C%27es%27%2C%27fr%27%2C%27it%27%2C%27pl%27 AND
(%27ATMP%27)&p=1&num=10&srt=Relevance:decreasing
127
between national competent authorities, ethics committees, and EMA structures could
reduce inconsistencies and improve predictability. .
Safety is specifically preserved through:
• CHMP verification of sponsor declarations regarding negligible-risk status.
• Comprehensive risk-benefit assessment as part of the clinical trial and marketing
authorisation processes.
• Existing pharmacovigilance mechanisms, including risk management plans and
long-term follow-up obligations.
Table 3. Public Health and Safety Indicators
Effect / impactIndicatorsExpected
change
Data source for baseline
Maintaining high
safety standards
ATMP withdrawals for
safety reasons
no change EMA annual reports no withdrawals
for safety reasons reported129
2.4 Summary of impacts:
Economic Impacts on Businesses
Exempting clearly delineated negligible‑risk categories of investigational
GMO‑containing ATMPs from the full Environmental Risk Assessment (ERA) eliminates
preparation costs and certain GMO‑related manufacturing and import requirements. While
this is expected to substantially reduce administrative costs for sponsors—particularly
small and medium‑sized enterprises (SMEs)—explicit quantifications could not be fully
estimated at this stage130.
A streamlined procedure requiring sponsors to submit a declaration justifying that the
product falls within predefined no‑risk or negligible‑risk categories, verified by the CHMP,
is expected to save considerable time and resources while increasing the predictability of
regulatory requirements.
Adapting the definition of tissue engineering products (TEPs) via delegated acts is
expected to future‑proof the regulatory framework by allowing products to be classified
according to their intended purpose and risk profile. Stakeholder interviews confirm the
need for this flexibility, emphasising that it enables greater regulatory adaptability to
scientific and technological advances.
129 https://www.ema.europa.eu/en/documents/report/annual-activity-report-2024_en.pdf 130 EFPIA, EUCOPE, EuropaBio. Industry survey on GMO-IMPs under the EU CTR. (Data referenced in the original
text and in Beattie et al., Cell & Gene Therapy Insights, 2024); ATMP2030 Annual Report 2024 (ATMP Sweden,
September 2024).
128
The combination of more predictable, internationally coherent definitions and robust EU
public health and safety standards is viewed by relevant stakeholders as a competitive asset
relative to jurisdictions such as the United States131.
Impact on Innovation, Competitiveness, and Patient Access
Exempting qualified GMO‑containing ATMPs from full ERA requirements, alongside
broadening the TEP definition into a flexible, risk‑based ATMP umbrella, is expected to
lower operational costs and accelerate the transition from research to clinical development.
This will particularly benefit smaller organisations and SMEs, which represent over 60%
of ATMP developers in Europe132.
Public Health and Safety
The reform targets procedural simplification rather than a substantive relaxation of safety
standards. ERA exemptions apply only to investigational ATMPs that fall into clearly
defined negligible-risk categories. By reducing unnecessary procedural delays, the
measures are expected to enable earlier initiation of trials and potentially earlier access to
safe, effective, and transformative ATMPs for EU patients — particularly in areas of high
unmet medical need.
The ability to adapt TEP definitions to scientific progress reduces the risk of regulatory
blind spots for emerging technologies, helping ensure that innovative ATMPs are brought
under appropriate oversight rather than remaining in a regulatory grey zone.
3 INTERVENTION N°4: TARGETED REGULATORY REFORM OF CLINICAL TRIALS
The following policy measures have been discarded133:
1. Consideration was given to establishing a centralised assessment body to
oversee the authorisation of the initial applications of multinational clinical
trials as well as applications for substantial modifications to such trials at the
EU level. This body was intended to manage the scientific, regulatory, and
ethical reviews of such trials. However, the proposal was discarded for the
following reasons. Firstly, approximately 60% of clinical trial applications are
mononational and do not require cross-border collaboration. Secondly,
national-specific aspects of the applications, detailed in Part II of the dossier,
would still need to be evaluated by the Member State concerned. Hence,
131 Bech‑Bruun. Analysis of the Biotech Act. March 2026. The EU Biotech Act: A targeted solution to Europe’s biotech
challenges. 132 EFPIA, EUCOPE, EuropaBio. Industry survey on GMO-IMPs under the EU CTR. (Data referenced in the original
text and in Beattie et al., Cell & Gene Therapy Insights, 2024); ATMP2030 Annual Report 2024 (ATMP Sweden,
September 2024). 133The Study Regulatory Framework Study (forthcoming) assesses the impact of four different sets of policy measures:
(i) Shortening timelines for the assessment procedures and improved coordination via a strengthened role of the reporting
Member States; (ii) the establishment of centralised assessment body for scientific and ethic review, (iii) the
establishment of a centralised assessment body limited to public health emergencies, and (iv) a shortening of the timelines
without procedural changes. For further details, please see the report.
129
creating this body would potentially result in two separate procedures, one for
mononational and one for multinational trials, ultimately leading to increased
fragmentation and retaining procedural complexity related to site and
investigator suitability, compensation, or insurance. Survey results134 indicate
that Member States consider the establishment of a centralised body,
particularly for the assessment of the ethical review, as a risk of further
fragmentations, while large enterprises rather favour a centralisation.
2. Reducing the timelines for clinical trial authorisation without altering the
authorisation procedure for clinical trials was also considered. However, this
would not address significant demands for reducing complexity through
simplification, such as e.g. the introduction of a single core dossier for trials
using the same IMPs, a single legal basis under the requirements of the GDPR
for processing of personal data and a single authorisation procedure for
combined studies. Moreover, shortening timelines without streamlining the
authorisation procedure would have placed additional pressure on already
strained national capacities and could have compromised both the quality and
safety of the authorisation process.
3. It was considered to apply the amendments to the Clinical Trial Regulation
under the proposed European Biotech Act specifically tobiological and not to
chemical products. However, implementing distinct authorisation procedures
or timelines might lead to fragmentation and increased complexity. Also, not
all the Member States would have the resources to accommodate two distinct
authorisation procedures which would have to create a potential discrimination
of access to clinical trials for EU patients depending on their country of
residence.
4 INTERVENTION N°5: TARGETED REGULATORY REFORM OF VMPS
4.1 Detailed description of the proposed measures
Measure 1: Exemption from GMO framework and single assessment under pharma
framework
The Act proposes to establish a 'One-Stop-Shop' principle, removing the dual-track
regulation and establishing Regulation 2019/6 as the specific and sole legal framework for
these products:
• For clinical trials: veterinary competent authorities assess environmental risks
within the clinical trial evaluation, with the possibility to consult with national
GMO bodies, particularly for novel questions or first-in-class products.
134 See Regulatory Framework Study (forthcoming)
130
• For marketing authorisation: the requirement to submit documentation as
required under the GMO Directive is removed. EMA may consult national GMO
authorities, in particular for first-in-class products or novel questions.
Furthermore, the proposed Act introduces a legal clarification regarding the
downstream status of animals treated with VMPs: the administration of VMPs does not
bring the treated animal or their derived products under the scope of Union GMO
legislation.
Measure 2: Targeted SPC extension for zoonotic biotech products
The proposed Act creates a 12-month extension of the SPC duration beyond the standard
maximum of 5 years, thus creating targeted an incentive for biotechnology-derived
veterinary products addressing zoonotic diseases. Eligibility requires satisfaction of five
cumulative conditions: (1) the product must be developed by means of a biotechnology
process as defined in Article 42(2)(a) of Regulation 2019/6; (2) it must be intended to
diagnose, treat, or prevent zoonotic diseases; (3) it must contain a new active substance
distinctly different from any authorised medicinal product in the Union; (4) it must have a
mechanism of action distinctly different from existing products for the same zoonotic
disease, with at least equivalent safety and efficacy; and (5) at least one manufacturing step
(excluding packaging, quality testing, and certification) must be performed in the Union.
EMA assesses compliance with these conditions as part of the marketing authorisation
procedure and issues a statement confirming eligibility, which is then included in the SPC
extension application to national patent offices.
Measure 3: Regulatory sandbox for animal health innovation
The proposed Act establishes a framework for regulatory sandboxes, specific to
innovations in animal health not regulated under other Union legislation. The Commission
may establish a sandbox where two conditions are satisfied: (a) the technology can be
expected to have a positive impact on animal health without unacceptable negative impacts
on human health or the environment; and (b) the development, placing on the market, or
use is hindered by the lack of a harmonised legal framework.
The process begins with an application to EMA from developers of eligible innovations.
EMA assesses applications and may submit a recommendation to the Commission
including justification, identification of regulatory challenges, estimation of benefits and
risks, mapping of available expertise, and a proposed duration. The Commission decides
by implementing act whether to establish the sandbox and specifies its duration.
Once established, EMA develops technical and scientific requirements, provides scientific
advice, and assesses benefits and risks of specific products, technologies or methods.
Products, technologies or methods developed under the sandbox cannot be placed on the
market or used in the Union until authorised by the Commission by an implementing act.
National competent authorities retain supervisory competences and are empowered to take
interim measures, including the suspension or recall, where serious risks are identified. In
such cases, an assessment by EMA takes place and eventually the Commission takes a
final decision by means of an implementing act. Two years before the end of an established
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sandbox period, EMA must submit an assessment report to the Commission including
recommendations for a regulatory framework after termination. The Commission may take
appropriate actions regarding permanent regulatory requirements, or extend the sandbox
duration where justified.
Measure 4: Reduction of burden for the handling of VNRAs
The proposed amendments introduce two significant modifications:
• First, the right to implement VNRAs is explicitly codified, strengthening legal
certainty for companies by removing the confirmation step by competent
authorities. Moreover, an anti-circumvention clause is added, balancing the
increased flexibility with enhanced enforcement capability during inspections.
• Second, for VNRA with no impact on product information, submissions can be
consolidated on a yearly basis. The 30-day deadline is only maintained for
variations affecting the summary of product characteristics, labelling, or package
leaflet; changes that veterinarians and users need to access immediately.
4.2 Baseline description (2025-2040)
Conduct of business
The dual-track regulatory system governing GMO-containing VMPs will persist through
2040, with no autonomous convergence expected between the veterinary and GMO
legislative frameworks. The clinical trial approval differential (currently estimated at 2–3
times longer for the GMO process compared to the standard CTA process), will remain.
As the number of GMO-based VMPs entering development grows steadily, the annual
volume of clinical trial applications subject to this duplicative burden will increase in
parallel. At an estimated rate of approximately 10 new GMO-containing VMPs
entering development per year with an 8–10 year development cycle, the throughput
of products requiring dual CTA submissions across fragmented national GMO authorities
will scale over the projection period.
At the marketing authorisation (MA) stage, the GMO consultation with national
competent authorities will continue to run in parallel to EMA's scientific assessment,
leading to a growing absolute number of GMO-containing products going through the
consultation process, with increasing resources being devoted to this process in the
rapporteur’s teams. Under accelerated or conditional assessment pathways (relevant for
emergency disease responses), the GMO consultation requirement will continue to
constitute a constraint on time-to-market.
Regarding commercial uptake of novel biotech VMPs in food-producing species, the
legal ambiguity concerning the GMO status of treated animals and their products will
persist. The risk that this impacts commercial uptake is projected to increase over the
baseline period as the number of GMO-based vaccines and therapies targeting food-
producing species increases.
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Administrative costs on businesses, including SMEs
For the GMO-related component, the burden of MA dual-dossier requirement is higher
than for non-GMO products. With an estimated pipeline of approximately 100 GMO-
containing VMPs up to 2040; the aggregate administrative cost of dual compliance will
scale. This burden is expected to intensify in relative terms as third-country jurisdictions
streamline their processes: the absolute per-product cost may remain broadly stable, but
the EU's comparative regulatory overhead grows, placing increasing competitive pressure
on companies operating in the single market.
For VNRAs, the Union Product Database (UPD) recorded 23,777 submissions
encompassing 185,662 individual VNRAs between 31 January 2022 and 12 December
2025. A survey by a trade association covering responses from holders of approximately
4000 marketing authorisations shows that the submissions of VNRAs has more than
doubled as compared with the number of submissions for Type IA variations under the
previous framework (from approximately 2,150 submissions of Type IA variation in 2021
to over 4,500 submissions of VNRAs in 2023). This confirms the growing increase of
administrative burden. As new MAs are awarded (according to UPD data, it is estimated
that there are currently 40,000-45,000 active MAs135, and this number is expected to grow)
the aggregate base of products requiring VNRA management expands. Assuming that
active portfolios generating 2-3 VNRAs per MA annually, and with each submission
requiring 2-5 or more hours of staff time, the aggregate annual FTE burden will grow
broadly in proportion to the expanding MA base. The uniform 30-day reporting
deadline will continue to force a reactive compliance pattern amplifying the per-unit cost
of each submission. As the 30-day uniform deadline persists, the aggregate VNRA volume
grows in rough proportion to the expanding MA base (a conservative compounding growth
rate of approximately 2-3% per year in active MAs). This brings the MA base to roughly
55,000-60,000 by 2040. In the absence of legal changes, the aggregate FTE burden, fees,
and compliance cost will scale proportionally. The aggregate VNRA fee burden,
currently estimated at approximately EUR 5 million per year sector-wide, is projected to
grow in proportion to the expanding MA base and maintained fee structures. Cross-country
variation in fees will persist, continuing to penalise companies with broad European
portfolios.
Competitiveness, trade and investment flows
The absence of SPC extensions for biotechnology-derived zoonotic VMPs will remain
unchanged. The rate of eligible products emerging will continue at the current pace of
approximately 1 potentially SPC-eligible biotech VMP for zoonotic diseases every 2 years.
In terms of competitiveness, although no veterinary biosimilars have been authorised in
the EU at T0, this is not likely to remain static through 2040. Technology maturation and
declining biologics manufacturing costs will progressively lower the entry threshold. Over
a 15-year horizon, it can be expected that originator companies developing biotechnology-
derived VMPs for zoonotic diseases will increasingly confront a competitive environment
135 The absolute number of products registered in UPD is close to 50.000 but it includes also authorisations which are
not relevant to the analysis, such as authorisations under Article 5(6) or authorisations for parallel trade.
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in which biosimilar entry, while structurally less aggressive than in human
pharmaceuticals, becomes a commercially relevant consideration.
Innovation and research
The GMO-containing VMP development pipeline is projected to grow steadily
throughout the baseline period. At T0, among the 8 vaccines authorised under exceptional
circumstances in 2024–2025, 5 employed biological recombinant approaches and 3 were
GMOs. All four vaccine platform technologies certified to date under Regulation 2019/6
are GMO-based. At an estimated entry rate of approximately 10 new GMO-containing
VMPs into development per year, with 8-10 years development timelines, the pipeline is
expected to encompass roughly 100 products in various stages of development by 2040.
While the persistence of the dual regulatory pathway is unlikely to prevent any GMO-
containing VMPs from ultimately reaching the market, the current system would lead to
higher-than-necessary costs and delays to market. The net effect on innovation is negative:
a systematic increment to development timelines, costs, and operational complexity that
reduces the efficiency of translating scientific opportunity into marketed products, without
a commensurate safety or environmental benefit.
Moreover, the current regulatory framework is a disadvantage for operators wanting to
conduct their innovation in the Union. Therefore, it can be expected that more operators
will move their activities to jurisdictions offering faster and more predictable pathways
and that emerging animal health innovation will progressively divert to third countries.
Thus, clinical trials, and over time the upstream R&D infrastructure that clusters around
trial activity, are likely to take place outside of the EU. Consequently, the EU is likely to
increasingly import the products of innovation conducted in third countries, deepening a
technological dependency that is difficult to reverse once the relevant expertise ecosystems
have relocated.
Under the baseline, there is no EU-level sandbox. Technological innovation is expected
to continue to outpace regulatory framework evolution, progressively widening the gap
between commercially deployable technologies and those with clear EU regulatory
pathways. Products that do not fall within the existing definition of a veterinary medicinal
product will continue to encounter regulatory limbo irrespective of their safety or efficacy
profile. Regulatory uncertainty is expected to extend throughout the baseline.
Public health and safety
Public health and safety are shaped by the downstream consequences of the regulatory
barriers that persist under the baseline. First, the legal ambiguity surrounding the GMO
status of animals treated with biotech-derived VMPs sustains a commercial risk under
which farmers and supply chain actors may prefer conventional treatments, including
antimicrobials, over novel biotech vaccines with potentially superior efficacy profiles in
food-producing species. While there is no evidence that this risk has materialised yet, the
conditions for such discrimination will become more pronounced over the projection
period as GMO-based vaccines increasingly target food-producing species. Second, the
absence of a regulatory sandbox mechanism and the expected impact on EU market
access to innovative technologies with potential public health benefits will remain. The
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gap between technological capability and regulatory accommodation is projected to widen
steadily, deferring potential public health gains from emerging approaches. In aggregate,
the baseline is characterised by a slower-than-achievable realisation of the public health
benefits that veterinary biotechnology innovation is technically capable of delivering.
4.3 Expected impacts
Conduct of business
On the average time for CTA, the reform eliminates the procedural duplication.
Under the current framework, the slower of the two authorisations required to conduct a
clinical trial determines the pace.
Further, at present, applicants must manage interactions with distinct authorities in every
Member State where they conduct a clinical trial. An EU level trade association estimated
that the one-stop shop approach would save approximately 3-6 months per CTA. This
estimate encompassing both the direct timeline reduction and the indirect reduction in
coordination-related delays and uncertainties.
Given the heterogeneity across Member States, a weighted approach is appropriate. Taking
data from an NCA on the well-synchronised end (0 to 30 days additional time) and
feedback from an EU-level trade association (90-180 day) time estimate as representative
of the poorly synchronised end, a conservative estimate for the average per-CTA
process timeline saving across the EU is 1-3 months, i.e. 30-90 days.
At an estimated throughput of 8-15 CTA applications per year subject to the dual-track
burden at baseline, rising to 12-20 per year by 2040 (reflecting pipeline growth), and
applying the central per-CTA saving of 30-90 days, the reform eliminates approximately
8-45 product-months of aggregate delay per year at current pipeline volumes, rising
to 12-60 product-months per year by 2040.
As regards marketing authorisation procedures, under standard evaluation timelines, the
reform will have no measurable impact on the average number of days. First, the GMO
consultation currently occupies a window within the first 90-100 days of the assessment
phase and runs concurrently with the CVMP's scientific evaluation. As the CVMP's
evaluation takes the full 198 days on average, the assessment phase remains unchanged.
Second, the reform converts the mandatory consultation into an optional one.
However, a positive impact of this measure on marketing authorisation timelines can
be identified in two specific scenarios:
• Accelerated assessment pathways, which are relevant for disease outbreaks,
the removal of the mandatory requirement provides regulatory authorities with
the procedural flexibility to consult with the GMO authorities solely when
additional expertise can add value. The frequency and circumstances of
accelerated assessments are inherently unpredictable, which is thus difficult to
quantify. However, between 2024-2025, 8 vaccines were authorised under
exceptional circumstances, of which 3 were GMOs. For these products, the
elimination of a mandatory parallel consultation could plausibly save 30-60
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days in the accelerated pathway. This saving applies to a small number of
products per year (estimated at 1-3 under emergency circumstances).
• With regards to the dossier preparation phase (upstream of the submission
of the marketing authorisation application),the elimination of the requirement
to compile Annex III documentation under Directive 2001/18/EC (in addition
to information requirements under the pharma framework that overlap) will
bring some administrative savings. Further savings can arise during the
assessment, insofar as companies require less time to prepare responses to
questions from national GMO bodies channelled through EMA. This effect is
captured under the indicators on administrative burden for marketing
authorisation dossier preparation, with an associated cost saving estimated at
approximately EUR 7,000 per marketing authorisation dossier.
Administrative costs on businesses, including SMEs
The proposed changes in the handling of VNRAs will lead to savings per-unit
administrative cost of the submissions related to variations that must be reported. The
impact manifests as a structural redistribution of the volume of notifications across
time, with cascading effects on staff effort, fees, and compliance cost.
It is estimated that 70-80% of VNRAs do not affect the SPC, labelling, or package leaflet.
Absent broader survey data, adopting a sector-wide estimate of 75% as a central
assumption is reasonable, with sensitivity bounds of 65-85% reflecting portfolio
heterogeneity. This means that, with a conservative baseline of 42,500 annual VNRAs per
year, , approximatively 10,625 VNRAs (25%) remain subject to the 30-day deadline
(SPC/labelling changes) and 31,875 VNRAs (75%) become eligible for annual reporting.
Thus, 75% of the volume migrates from continuous monthly submissions to
consolidated periodic filings.
The UPD data shows 23,777 submissions for 185,662 VNRAs, yielding an average of
approximately 7.8 VNRAs per submission. The batching enabled by the annual deadline
will increase this ratio substantially for the 75% of VNRAs that qualify. If companies
consolidate VNRAs with no impact on product information into 2 annual submission
windows rather than continuous 30-day filings (with required 10-12 filing cycles per year),
the number of discrete submission events for those VNRAs could fall by roughly 60-
70%.136 However, the 25% of VNRAs still under the 30-day deadline continue to
generate continuous submission events.
Indicatively, at sector level, the total number of submission events (currently
approximately 6,100 per year, derived from the 23,777 over 3.9 years) would
136 Moving from 10-12 cycles to 2 would yield an 80-83% reduction. The 60-70% figure is a downward adjustment
reflecting that not all companies currently file at full monthly frequency and some individual submission events contain
a mix of SPC-affecting and non-SPC VNRAs, meaning they cannot be cleanly separated into the two cohorts, and the
transition will not be perfectly clean, with some ad hoc submissions persisting outside the two main windows.
136
approximately be 1,525 events for the 30-day cohort and 4,575 for the annual
cohort137.
Thus, the total number of submission events could decline by an estimated 45-55%, to
approximately 2,900-3,400 per year. This reduction represents a meaningful decrease in
the frequency of UPD interactions.
Based on a survey from an EU level trade association, each VNRA is estimated to cost
for marketing authorisation holder between 2 and 5+ hours of staff time. The aggregate
per-MAH burden is estimated at 0.2 FTE per year (approximately 344 hours, assuming
1,722 hours per FTE138). Another EU level trade association estimated up to 20%
reduction in total man-hours through operational efficiencies gained from the
possibility to consolidate submissions of VNRAs over a period of time. While the
preparation work per VNRA persists, the consolidation would eliminate most of the
repetitive overhead of individual UPD submission events. Thus, a 10-20% range is
estimated for efficiency gain from consolidated workflows, even if the substantive
documentation effort is largely invariant. Based on a 15% reduction, EUR 1.46
million per year in staff cost savings are estimated.
Taking into account compounding growth drivers for 2025–2040 growth, the present-
value cumulative saving in real terms: EUR 15-30 million over 2025–2040, with a
central estimate of EUR 22.5 million.
Although the confirmatory assessment by competent authorities is the principal basis on
which several Member States charge per-VNRA fees, Member States can charge
administrative processing fees.139 It is thus assumed that Member States currently charging
explicit per-VNRA assessment-related fees will reduce or eliminate them, while those
already embedding VNRAs in annual maintenance fees will not make changes. Around
50% of the EUR 5 million in fees is estimated to be attributable to the confirmatory step,
thus the potential fee reduction is approximately EUR 2.5 million per year.
As the EMA will need to adapt the UPD system to accommodate the bifurcated deadline
and remove the approve/reject functionality for NCAs, the cost of the EMA is estimated
at EUR 150-300 thousand (3-6 months, 1 IT team), representing a one-off
implementation cost. No recurring operational cost increase was identified.
On the FTEs dedicated to the CTA process for GMO-VMPs, a standard CTA preparation
and management cycle (6-12 months, midpoint ~9 months) engages a small regulatory
affairs team. The GMO-specific FTE overhead is conservatively estimated at
approximately 0.3-0.5 FTE-years per CTA application, representing roughly 15–25%
of total CTA effort. This range accounts for the fact that the ERA data generation itself
137 Annual cohort at 60% reduction is 1,830 (total for both cohorts 3,355) and annual cohort at 70% reduction is
1,373 (total for both cohorts 2,898). 138 Eurofound. (2025). Balancing the clock: How Europe works and rests.
https://www.eurofound.europa.eu/en/publications/all/balancing-the-clock-how-europe-works-and-rests 139 An EU level trade association expressed that there is a risk that members expressed concerns that some Member
States may continue charging fees by invoking administrative handling in UPD or national systems/legislation, or,
alternatively, stop fees for VNRAs and instead shift costs by increasing annual licensing/maintenance fees.
137
(the most labour-intensive component) is retained, while the administrative duplication is
eliminated. By 2040, with an expanding pipeline and an estimated throughput of 12-20
GMO-related CTA applications per year (reflecting pipeline growth), the aggregate
annual GMO-specific FTE burden would rise to approximately 3.6-10 FTE/year, or EUR
403,000-1,119,000 per year. Thus, cumulative over the 15-year projection period,
assuming linear growth from current levels: approximately 45-130 FTE-years, or
approximately EUR 5-14.5 million in total GMO-specific CTA administrative costs
savings.
The GMO-specific increment at the MA stage is much smaller than at the CTA stage.
Based on the estimate that 1 full-time regulatory affairs specialist working for 3 weeks per
MA dossier, amounts to ~108 hours or ~0.06 FTE-year, leading to a cost saving of
approximately EUR 7,000 per MA dossier/application.
With an estimated 3-5 MA applications per year and assuming moderate growth
yielding approximately 5-8 GMO-containing MA applications per year by 2040, the
cumulative total of approximately 80 GMO-containing MA applications, corresponding
to a cumulative sector-wide saving of approximately EUR 560 thousand in eliminated
duplicative dossier preparation costs.
Competitiveness, trade and investment flows
On the biotechnology-derived VMPs awarded SPC extensions, a forward-looking estimate
is an average of 3 eligible products per year over 2026-2040. It is based on the
retrospective eligibility analysis (8 out of 28 over 16 years ≈ 2/year) and adjusted upward
modestly to reflect the growing share of biotech vaccines in the pipeline. The commercial
benefit of an additional 12 months of SPC duration depends on whether biosimilar
competition would otherwise materialise immediately upon expiry. At T0, no veterinary
biosimilars have been authorized. Therefore, the marginal revenue preserved by the
extension is, for all practical purposes, close to zero in the short to medium term.
Under the forward-looking scenario in which veterinary biosimilar competition begins to
materialise by the mid-2030s, the narrow pool of eligible products and the fact that data
protection typically outlasts patent/SPC terms mean the number of cases where the 12-
month extension is the binding margin of protection would be very small.
In terms of costs,the measure creates a modest new tasks for EMA (eligibility statements
assessment as part of the MA procedure) and for national patent offices (processing the
extended SPC applications). Given the very low volume, these costs are negligible in
aggregate.
Therefore, the impact of this measure is not appropriately captured through quantification
of direct commercial or cost effects, because the primary function of the SPC extension is
not to deliver measurable near-term revenue protection but to serve three signalling and
future-proofing purposes. First, the measure serves as a signal on the EU institutional
commitment to veterinary biotechnology innovation addressing zoonotic diseases,
potentially influencing long-term R&D allocation decisions at the margin. Second, the
measure is expected to make the legislation future-proof. Should veterinary biosimilar
competition eventually materialise, the mechanism would already be in place. Third, the
requirement that at least one manufacturing step be performed in the Union introduces an
138
explicit industrial policy lever. However, stakeholders indicated that manufacturing
location decisions are dominated by existing capacity, and the marginal influence of an
additional 12 months of SPC on site selection is very limited.
As a conclusion, Measure 2 is a very low-cost, low to medium impact instrument whose
principal value lies in its signalling and institutional-readiness functions (medium- to long-
term) rather than in any quantifiable near-term economic effect.
Innovation and research
Although measure 1 is not expected to increase the number of GMO-containing VMPs
marketed in the EU, it is expected to lead to benefits in terms of research activities
conducted in the Union.
Stakeholder consultations indicate that no additional GMO-containing VMPs are likely to
reach the market over the next 15 years as a direct result of this change, because the current
authorisation pathway does not prevent authorisation outcomes. The dual-track system has
never generated a negative opinion on the GMO component of any VMP. Furthermore, the
pipeline growth rate is primarily driven by scientific and technological imperatives and by
market demand, which are exogenous drivers to the reform. Some indirect benefits are
nevertheless expected. First, for smaller developers with constrained budgets, the
cumulative effect of reduced procedural costs and improved timeline predictability
could tip individual investment decisions. This effect cannot be quantified as it concerns
projects that do not yet exist and whose existence would depend on firm-specific financial
conditions. Second, the reform may lead products already in the pipeline to progress faster
(captured under Indicators 1 and 4).
Moreover, the key expected benefit is to incentivise research activities in the Union,
avoiding that the conduct of clinical trials with GMO VMPs is moved to outside the Union
to avoid the heavy regulatory framework. This is not a hypothetical risk but an observed
pattern: regulatory complexity does not suppress innovation globally; it displaces it
geographically. This risk would lead the Union to become a recipient rather than an
originator of next-generation veterinary biotechnology. Products developed under non-
EU regulatory frameworks are typically launched first in the jurisdictions where they
were developed and trialled, meaning that EU farmers and veterinarians gain access to
critically needed innovations, particularly during zoonotic disease outbreaks, later than
their counterparts in competing markets, with direct implications for outbreak response
capacity and One Health preparedness.
On the impact of the sandbox mechanism, stakeholder consultations indicate an average
of one sandbox per five years, since the mechanism operates per technology area rather
than per product. Each sandbox requires a Commission implementing act, which also
involves institutional effort.
On this basis, for the 2026–2040 period, 3-4 sandbox applications are estimated, of
which potentially 2-3 result in established sandboxes. This is estimated based on the 15-
year projection window divided by the estimated 5-year cycle per sandbox; the time for
EMA to develop application procedures and assessment criteria (i.e. application is unlikely
before 2028); and the narrow eligibility scope of the sandboxes.
139
With regards to the effects of the sandboxes on innovation, it is likely that each
established sandbox provides a time-limited pathway for specific innovations to be
developed, tested, and potentially authorised under regulatory supervision which could
lead to several products or technologies that would otherwise have no EU market
pathway. In addition, the two-year reporting requirement before sandbox expiry
means each sandbox generates structured evidence to inform permanent regulatory
framework development. Thus, each sandbox effectively conducts a regulatory pilot that
would otherwise require years of legislative deliberation. Furthermore, stakeholders
consulted noted that the sandbox is likely to have a broader signalling function,
demonstrating that a regulatory pathway exists, potentially unlocking investment currently
stalled by regulatory uncertainty.
In terms of quantitative impacts140, costs are likely modest and fall primarily on public
authorities. Each sandbox requires EMA resources for application assessment, technical
requirement development, scientific advice, risk-benefit assessment, and the two-year
assessment report plus Commission resources for the implementing act.
Public health and safety
With regards to the uptake of GMO-containing VMPs in food-producing species, the
impact of the legal clarification should be understood as the averted cost of a
counterfactual scenario in which, absent the firewall, the legal ambiguity eventually
crystallises into a concrete market disruption. The measure eliminates a tail risk whose
expected cost, while difficult to quantify precisely, is potentially very large given the
economic and health stakes involved.
It is estimated141 that even a modest suppression of farmer uptake of next-generation
biotech vaccines (e.g., a 5–10% avoidance rate in food-producing species), would translate
into foregone disease prevention benefits worth potentially hundreds of millions of euros
annually across the Union, when accounting for both on-farm productivity losses and
downstream public health costs.
The legal clarification does not impose compliance costs on any actor. There is no
implementation cost for Member States, EMA, or industry.
As a conclusion, Measure 1 delivers a high-value, zero-cost legal clarification which is
characterised as insurance against a growing and potentially costly downside risk.
5 INTERVENTION N°7: TARGETED REGULATORY REFORM OF THE DIRECTIVE ON THE
DELIBERATE RELEASE INTO THE ENVIRONMENT OF GMOS
This Annex summarises the key statements of the scientific and technical reports of the
European Food Safety Authority (EFSA) (section 5.1.1) and the European Network of
GMO Laboratories (ENGL) (section 5.1.3) that provide scientific justification to various
140 Based on the 3-4 applications (yielding 2-3 established sandboxes), the first established sandbox plausibly operational
by 2029 and 1-3 possible products/technologies per sandbox (yielding a cumulative total of around 2-9 innovations with
EU market access) 141 See the Rapid assessment scenario study for more details
140
elements of the legislative proposal to amend Directive 2001/18/EC as regards genetically
modified micro-organisms (GMMs). In addition, it explains the development and
application of the Qualified Presumption of Safety (QPS) approach in the context of EFSA
risk assessments (section 5.1.3), a concept relied on for certain provisions of the proposal.
Section 5.2 provides an overview of the applications of GMMs in the areas in the scope of
the proposal.
5.1 Scientific Context
5.1.1 EFSA scientific opinions and guidance on GMMs
At the request of the Council, the Commission published in 2021 a study on new genomic
techniques (NGTs) applied to plants, animals and micro-organisms142, which identified
significant developments in all three areas. NGTs are techniques that are capable of altering
the genetic material of an organism and that have emerged or have been developed since
2001, when the current legislation on genetically modified organisms (GMOs) – namely
Directive 2001/18/EC - was adopted. Following up on this report, the Commission adopted
a legislative proposal for a Regulation on plants developed with certain NGTs143. In the
area of micro-organisms, the study, however, concluded that data, especially as regards
safety aspects, were still limited and did not provide an adequate basis for taking any policy
action in this area. The Commission indicated it intended to continue building up the
required scientific knowledge, in view of possible further policy actions.
As a follow-up, the Commission mandated EFSA to prepare a scientific opinion on new
developments in biotechnology applied to micro-organisms144 that covered products
containing or consisting of GMMs for environmental release as well as food and feed
products containing, consisting of or produced from such GMMs. EFSA adopted the
opinion in 2024. While the focus of this opinion is on new developments in biotechnology,
notably NGTs, EFSA also draws conclusions that are relevant for GMMs or micro-
organisms in general. EFSA considers that any new possible hazard relates to genotypic
and phenotypic changes introduced in the micro-organism and not to the method used for
the modification. In other words, this means that any new potential hazards of a GMM
compared to the parental organism are related to new properties conferred to the micro-
organism regardless of the method used to give rise to these changed properties. For this
reason, EFSA recommends that “the risk assessment approach of micro-organisms should
be based on the strain/product itself, independently of the method used to alter the
genotypic or phenotypic characteristics”, i.e. NGT, established genomic technique (i.e.
genetic modification techniques developed before 2001) or conventional (random)
mutagenesis (i.e. the application of chemical or physical mutagens).
142 Study on the status of new genomic techniques under Union law and in light of the Court of Justice ruling in Case C-
528/16, SWD(2021) 92 final. https://food.ec.europa.eu/system/files/2021-04/gmo_mod-bio_ngt_eu-study.pdf 143 COM(2023) 411 final – COD 0226/2023. A provisional political agreement was reached on 3 December 2025. 144 EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), Mullins, E., Bresson, J.-L., Dewhurst, I. C.,
Epstein, M. M., Firbank, L. G., Guerche, P., Hejatko, J., Moreno, F. J., Naegeli, H., Nogué, F., Rostoks, N., Sánchez
Serrano, J. J., Savoini, G., Veromann, E., Veronesi, F., Cocconcelli, P. S., Glandorf, D., Herman, L., Jimenez Saiz,
R., Ruiz Garcia, L., Aguilera Entrena, J., Gennaro, A., Schoonjans, R., Kagkli, D. M., Dalmay, T. (2024). New
developments in biotechnology applied to microorganisms. EFSA Journal, 22(7), e8895.
https://doi.org/10.2903/j.efsa.2024.8895
141
Furthermore, the scientific opinion formulates some concrete recommendations for the risk
assessment of GMMs and related products. In particular, EFSA asserts that, on a case-by-
case basis, some data requirements may not be needed to assess the safety of the micro-
organism or its products for humans, animals and the environment and gives concrete
examples of some areas. Toxicology studies may not be necessary for certain GMMs, for
example if the GMM qualifies for the Qualified Presumption of Safety (QPS) status (for a
detailed explanation of QPS see below). The assessment of the possibility of horizontal
gene transfer may be waived, on a case-by-case basis, depending on the nature of the
modification and the resulting new trait of the GMM, for example in cases where the GMM
was only modified by introducing genes of the same or closely related species (so-called
self-cloning) or site-specific changes (or edits) in the DNA sequence, or by introducing
deletions of sequences to remove or inactivate genes. Likewise, post-market environmental
monitoring may not be needed for certain GMMs, especially those modified by self-
cloning, by introducing deletions or by introducing edits.
In addition, EFSA published in 2025 a new guidance on the characterisation of micro-
organisms145 in support of the risk assessment of micro-organisms in products under the
remit of EFSA. It addresses both genetically modified as well as not genetically modified
micro-organisms, reflecting the key recommendation of the above scientific opinion that
the approach to risk assessment for micro-organisms should be governed by the properties
of the micro-organism or product irrespective of the technique used for its modification.
In this respect, wherever product-specific legal obligations allow, the guidance provides a
uniform approach to risk assessment of micro-organisms regardless of any potential use of
genetic modification techniques.
The micro-organisms covered are bacteria, yeasts, filamentous fungi, microalgae and other
protists, and viruses, including bacteriophages. The guidance addresses aspects regarding
the taxonomic identification of a micro-organism, particularly in view of fulfilling the
requirements originating from the assignments of a potential QPS status, the presence of
genes of concern in the micro-organism’s genome, the presence of viable cells, genetic
material or substances of concern in the final product, and the possible impacts of products
containing living micro-organisms on the environment.
As the above-mentioned opinion, this guidance asserts that, in principle, for micro-
organisms belonging to taxonomic units listed in the QPS list, information regarding
toxigenicity, pathogenicity, infectivity and history of use does not need to be provided by
the applicant for the purpose of risk assessment. Similarly, for micro-organisms having
obtained the QPS status no further assessment of environmental safety is required unless
genetic modifications have been introduced, which may lead to potential adverse
environmental effects.
145 EFSA Scientific Committee, Bennekou, S. H., Allende, A., Bearth, A., Casacuberta, J., Castle, L., Coja, T., Crépet,
A., Halldorsson, T. I., Hoogenboom, R., Jokelainen, P., Knutsen, H. K., Lambré, C., Nielsen, S. S., Turck, D., Civera,
A. V., Villa, R. E., Zorn, H., Gómez, M. A., … Brétagne, S., Christensen, H., Cocconcelli, P.S., Herman, L., Prieto-
Maradona, M., Mayo, B., Peláez, C., Saarela, M., Sánchez Serrano, J., Vernis, L., Yurkov, A., Aguilera, J., Anguita, M.,
Bozzi Cionci, N., Brozzi, R., Correia, S., García-Cazorla, Y., Istace F., Pettenati, E., Revez, E., Schoonjans, R., Valeri,
P., Glandorf, B. (2025). Guidance on the characterisation of microorganisms in support of the risk assessment of products
used in the food chain. EFSA Journal, 23(11), e9705. https://doi.org/10.2903/j.efsa.2025.9705
142
Concretely, for the areas of risk that must be addressed in an environmental risk assessment
of a GMM in accordance with Annex II to Directive 2001/18/EC, EFSA indicates some
possible simplifications and flexibility in data requirements. Persistence, invasiveness and
selective advantage may not need to be assessed if the GMM qualifies for QPS or belongs
to a species commonly found in the microbiome of the receiving environment and its
genetic modification leads to a trait known to be present in the microbiome of the receiving
environment. Horizontal gene transfer may not need to be assessed if the genetic
modification only results in deletions or insertions of sequences conferring traits that are
already present in the microbiome of the receiving environment. Effects on non-target
organisms, including on humans or animals may not need to be assessed if the GMM
cannot produce new compounds or metabolites or higher quantities of endogenous
compounds or metabolites compared to the unmodified parental strain or if the non-target
organisms, including humans or animals would already naturally be exposed to those
compounds or metabolites. Similarly, the effect on geochemical processes should only be
assessed if the genetic modification may cause higher expression of endogenous
compounds or metabolites of concern, may lead to the expression of new compounds or
metabolites not known to be naturally present in the microbiome of the receiving
environment, or introduces metabolic pathways that would be new to the microbiome of
the receiving environment.
The above findings and conclusions of EFSA’s 2024 scientific opinion on new
developments in biotechnology applied to micro-organisms and its 2025 new guidance on
the characterisation of micro-organisms have been relied on to propose the adaptation of
the data requirements for the environmental risk assessment of GMMs (new Article 24b in
Directive 2001/18/EC), to propose the use of the QPS status as one criterion to determine
GMMs which could profit from a streamlined consent procedure (new Article 24e in
Directive 2001/18/EC) and, finally, to propose greater flexibility in the requirement of
post-market environmental monitoring for certain GMMs (new Article 24f in Directive
2001/18/EC). In addition, EFSA’s conclusion that risks of a GMM relate to the properties
introduced rather than the method used for the genetic modification inform the choice to
adapt current rules to the specificity of GMMs regardless of the (new or established)
technique used for their modification.
5.1.2 The QPS approach
To provide background to and further rationale for the use of the QPS approach in the
proposal (new Article 24e in Directive 2001/18/EC), this section summarises how the
approach was developed, its evolution and implications as well as the use in the context of
risk assessments.
In 2002, a working group consisting of members of the Scientific Committee on Animal
Nutrition, the Scientific Committee on Food and the Scientific Committee on Plants of the
European Commission (predecessors of EFSA) started developing a working paper on a
generic approach for the safety assessment of micro-organisms used in food and feed or in
their production. In this Commission working paper146, a process was initially envisaged
146 European Commission working paper, On a generic approach to the safety assessment of micro-organisms used in
feed/food and feed/food production; 2003. https://food.ec.europa.eu/system/files/2020-12/sci-com_scf_out178_en.pdf
143
that should, similarly to the concept and purpose of the Generally Recognised As Safe
(GRAS) approach of the USA147, allow for a generic pre-assessment of the safety of micro-
organisms used in food and feed and the wider food and feed chain, including plant
protection products. The core of this system was the assignment of the status of so-called
Qualified Presumption of Safety (QPS) to defined groups (taxonomic units, usually a
species) of micro-organisms on the basis of available evidence on the safety (body of
knowledge) of and familiarity (history of use) with the micro-organism. The goal was to
make the safety assessment of micro-organisms across the food and feed chain more
consistent and make better use of resources without compromising safety. For taxonomic
units of micro-organisms with QPS status, a complementary case-by-case risk assessment
was then to focus on specific aspects relevant to the particular micro-organism or product
type.
This initial work was, after a public consultation on the concept, advanced by EFSA, who
in 2007 published the first list of micro-organisms with QPS status and formally integrated
it into its risk assessment procedures, initially only for products directly consumed as or in
food or feed148. In 2009, the approach was extended to micro-organisms used as active
substances in plant protection products. As in the initial Commission working paper149
referred to above, EFSA sees the QPS approach as a practical tool for building on available
knowledge and experience, avoiding the reassessment of aspects known not to cause
concern in relation to the specific micro-organism (at taxonomic unit level, usually the
species) and to concentrate the assessment where there is still uncertainty about potential
risks150.
Today, QPS assessments are conducted by the EFSA Biological Hazards (BIOHAZ) Panel
with support of the QPS working group and EFSA staff when EFSA receives an application
for authorisation of a regulated product or active substance under their remit that entails a
micro-organism not yet granted QPS status. Micro-organisms previously excluded from
the QPS process or that have recently been assessed are not subject to a renewed QPS
assessment151. The QPS assessment is made independently of the legal framework under
which the application for authorisation was made and the data contained in that application
and without prejudice to further assessment that might be needed under that framework.
The QPS approach is based on four pillars:
147 https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras 148 Opinion of the Scientific Committee on a request from EFSA on the introduction of a Qualified Presumption of Safety
(QPS) approach for assessment of selected microorganisms referred to EFSA. The EFSA Journal (2007) 587, 1-16;
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2007.587 149 European Commission working paper, On a generic approach to the safety assessment of micro-organisms used in
feed/food and feed/food production; 2023.
https://food.ec.europa.eu/system/files/2020-12/sci-com_scf_out178_en.pdf 150 Opinion of the Scientific Committee on a request from EFSA on the introduction of a Qualified Presumption of Safety
(QPS) approach for assessment of selected microorganisms referred to EFSA. The EFSA Journal (2007) 587, 1-16;
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2007.587 151 EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), Allende, A., Alvarez-Ordóñez, A., Bortolaia, V., Bover-
Cid, S., De Cesare, A., Dohmen, W., Guillier, L., Jacxsens, L., Nauta, M., Mughini-Gras, L., Ottoson, J., Peixe, L.,
Perez-Rodriguez, F., Skandamis, P., Suffredini, E., Chemaly, M., Cocconcelli, P. S., Fernández Escámez, P. S.,
Herman, L. (2026). Update of the list of QPS-recommended biological agents intentionally added to food or feeds as
notified to EFSA. EFSA Journal, 24(1), e9823. https://doi.org/10.2903/j.efsa.2026.9823
144
1. establishing the taxonomic identity of the micro-organism under assessment;
2. identifying the existing body of knowledge about the micro-organism, including
any history of use;
3. identifying any known safety concerns for humans, animals and the environment,
primarily linked to pathogenicity and similar aspects;
4. establishing the intended form of use of the micro-organism in products or in their
manufacturing, i.e. as living micro-organism, as biomass or as production strain152.
The maintenance of the QPS list is based on extensive literature searches (ELS). To
accommodate any advancement in knowledge, in particular any arising safety concerns,
this literature review is updated every 6 months. Any new additions to the QPS list153 and
micro-organisms notified for QPS assessment154 are published every 6 months by EFSA,
together with the detailed protocol for the literature review155 and used search terms156. In
addition, every 3 years EFSA publishes a scientific opinion summarising the evolution of
the list over the last 3-year period and announcing any updates to the approach considering
developments regarding established methodologies in microbiology, new scientific
insights and new applications of micro-organisms in the food and feed chain157. Micro-
organisms having obtained QPS status are listed in a public database158.
When assigning QPS status to a certain taxonomic unit, EFSA is satisfied that the available
knowledge documented in the literature, expert knowledge and the experience from
previous use are sufficient to exclude certain potential adverse effects on human and
animal health and the environment and that the same degree of confidence is achieved as
would be the case with a case-by-case assessment. In this evaluation, the available
scientific evidence indicating an exposure of humans and animals through food and feed,
the distribution of the micro-organism in natural environments and their routes of dispersal,
as well as the history of use in agricultural and food manufacturing systems and for
biotechnological and medical purposes are considered. In addition, with increasing
availability of whole genome sequencing data the screening for the presence of any
virulence factors and other genes of concern has been incorporated159.
If a specific safety concern is identified that is applicable to a defined sub-group of the
species or specific uses, a condition to applying the QPS status, a so-called ”qualification“,
is formulated to exclude the identified safety concern. In that case, the QPS status is only
152 See footnote 170 153 https://doi.org/10.2903/j.efsa.2026.9824https://zenodo.org/records/15827398 154 https://zenodo.org/records/18335928 155 https://zenodo.org/records/18336181 156 https://zenodo.org/records/18336241 157 EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), Allende, A., Alvarez-Ordóñez, A., Bortolaia, V., Bover-
Cid, S., De Cesare, A., Dohmen, W., Guillier, L., Jacxsens, L., Nauta, M., Mughini-Gras, L., Ottoson, J., Peixe, L.,
Perez-Rodriguez, F., Skandamis, P., Suffredini, E., Chemaly, M., Cocconcelli, P. S., Fernández Escámez, P. S.,
Herman, L. (2026). Update of the list of QPS-recommended biological agents intentionally added to food or feeds as
notified to EFSA. EFSA Journal, 24(1), e9823. https://doi.org/10.2903/j.efsa.2026.9823 158 https://zenodo.org/records/18329226 159 EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), Allende, A., Alvarez-Ordóñez, A., Bortolaia, V., Bover-
Cid, S., De Cesare, A., Dohmen, W., Guillier, L., Jacxsens, L., Nauta, M., Mughini-Gras, L., Ottoson, J., Peixe, L., Perez-
Rodriguez, F., Skandamis, P., Suffredini, E., Chemaly, M., Cocconcelli, P. S., Fernández Escámez, P. S., Herman, L.
(2026). Update of the list of QPS-recommended biological agents intentionally added to food or feeds as notified to
EFSA. EFSA Journal, 24(1), e9823. https://doi.org/10.2903/j.efsa.2026.9823.
145
valid if the specific microbial strain used in a product or in its manufacturing fulfils the
qualification. Currently established qualifications are, e.g. the “absence of acquired
resistance genes to therapeutic antimicrobials”, the “absence of toxigenic activity”and “for
production purposes only”. Any micro-organism requiring assessment by EFSA that can
be unambiguously assigned to a taxonomic unit with QPS status and that fulfils any
potential qualifications linked with this status does not require assessment of certain
aspects of safety already addressed in the QPS assessment160.
As indicated above, the main focus of the QPS assessment is to identify possible safety
concerns linked to pathogenicity, virulence and toxigenicity for humans and animals,
which will need to be excluded for all regulated products assessed by EFSA, including for
GMMs. To some degree these aspects are also addressed in respect to plant health161. A
taxonomic unit is included in the QPS list when certain risks for human and animal health
have been excluded allowing for a simplified assessment of a product containing a specific
strain of this taxonomic unit. Therefore, for strains belonging to that taxonomic unit and
complying with the existing qualifications, specific data, e.g. on antimicrobial production,
toxigenicity and pathogenicity, are generally not required162.
At the same time, the QPS approach does not cover the entire spectrum of potential safety
concerns that may arise in relation to microbial products. For this reason, the QPS approach
was from its conception envisaged as a tool to simplify the assessment of certain recurring
safety concerns, while being complemented by a product-specific risk assessment to
address remaining specific safety concerns. As a consequence, safety concerns that are
relevant only for specific regulated products under EFSA remit, for example those
regarding the wider environment in case of plant protection products or GMMs, will not
be fully addressed by the generic QPS assessment but require a product-specific risk
assessment on a case-by-case basis.
The concept of QPS is now relied upon in several areas of EU legislation. In the areas of
plant protection products163 and food enzymes164, applicants can refer to the QPS status of
the micro-organism in the product to justify not providing certain data during the respective
160 Opinion of the Scientific Committee on a request from EFSA on the introduction of a Qualified Presumption of Safety
(QPS) approach for assessment of selected microorganisms referred to EFSA. The EFSA Journal (2007) 587, 1-16;
https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2007.587. 161 EFSA BIOHAZ Panel, Allende, A., Alvarez-Ordóñez, A., Bortolaia, V., Bover-Cid, S., De Cesare, A., Dohmen, W.,
Guillier, L., jacxsens, . liesbeth ., Nauta, M., Mughini-Gras, L., Ottoson, J., Peixe, L., Perez-Rodriguez, F., Skandamis,
P., Suffredini, E., Cocconcelli, P. S., Fernández Escámez, P. S., Maradona, M. P., … Correia, S. (2026). Protocol for
Extensive literature search (ELS) for the maintenance and update of list of QPS-recommended biological agents. Zenodo.
https://doi.org/10.5281/zenodo.18336181. 162 EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), Allende, A., Alvarez-Ordóñez, A., Bortolaia, V., Bover-
Cid, S., De Cesare, A., Dohmen, W., Guillier, L., Jacxsens, L., Nauta, M., Mughini-Gras, L., Ottoson, J., Peixe, L., Perez-
Rodriguez, F., Skandamis, P., Suffredini, E., Chemaly, M., Cocconcelli, P. S., Fernández Escámez, P. S., Herman, L.
(2026). Update of the list of QPS-recommended biological agents intentionally added to food or feeds as notified to
EFSA. EFSA Journal, 24(1), e9823. https://doi.org/10.2903/j.efsa.2026.9823. 163 Commission Regulation (EU) 2022/1439 of 31 August 2022 amending Regulation (EU) No 283/2013 as regards the
information to be submitted for active substances and the specific data requirements for micro-organisms; see Annex II,
Part B, Section 2, points 2.1.3. and 5.2. 164 Commission Implementing Regulation (EU) No 562/2012 of 27 June 2012 amending Commission Regulation (EU)
No 234/2011 with regard to specific data required for risk assessment of food enzymes Text with EEA relevance; see
Article 1a and Article 8(3) and (5) of Commission Regulation (EU) No 234/2011; see also recital (6) of Commission
Implementing Regulation (EU) No 562/2012.
146
authorisation procedures. In the area of fertilising products165, having QPS status is used
as one criterion on the basis of which a microbial species may be allowed as a component
of fertilising products. QPS is also a determining criterion for assigning the Ecolabel166 to
detergents containing a micro-organism.
5.1.3 ENGL report on detection of micro-organisms obtained with NGTs
The provision in the proposal that the modalities to comply with analytical method
requirements may be adapted if compliance may otherwise not be feasible (new Article
24d in Directive 2001/18/EC) takes into account the work of the ENGL on detection
methods for GMMs.
To implement and enforce traceability and labelling requirements in accordance with
Directive 2001/18/EC, notifiers under Part C of that Directive need, as part of the
information required for notifications defined in its Annex III, to present a detection
method that is suitable to detect (i.e. prove the presence of a known genetic modification),
identify (i.e. prove that the detected genetic modification is attributable to the presence of
a particular regulated GMO or its product) and quantify (i.e. measure the relative quantity
of the identified GMO or its product in a given sample). Providing such a detection method
is a mandatory prerequisite for the granting of consent for placing on the market of a GMO,
including GMMs, as or in products in the EU.
The Commission requested from the European Network of GMO laboratories (ENGL) a
technical report on the detection of micro-organisms obtained by NGTs in food and
feed products167 to address knowledge gaps regarding GMMs identified in the 2021
Commission study on NGTs applied to plants, animals and micro-organisms168. A similar
report was previously published on plant-based food and feed in 2019169 and updated in
2023170.
The ENGL’s report on GMMs published in 2025 investigates the analytical possibilities
and challenges linked to the detection of micro-organisms obtained with NGTs that do not
entail the insertion of foreign genetic material. It concludes that detecting certain GMMs
obtained with NGTs poses considerable analytical challenges as certain genetic
modifications obtained with NGTs may be indistinguishable from those that can arise in
165 Regulation (EU) 2019/1009 of the European Parliament and of the Council of 5 June 2019 laying down rules on the
making available on the market of EU fertilising products and amending Regulations (EC) No 1069/2009 and (EC) No
1107/2009 and repealing Regulation (EC) No 2003/2003; see Article 42(4). 166 Commission Decision (EU) 2017/1217 of 23 June 2017 establishing the EU Ecolabel criteria for hard surface cleaning
products (notified under document C (2017) 4241). https://eur-lex.europa.eu/eli/dec/2017/1217/oj; see in Annex,
criterion 4, lett. (h), point (ii).. 167 Sowa, S., Broothaerts, W., Burns, M., De Loose, M., Debode, F. et al., Detection of microorganisms, obtained by
new genomic techniques, in food and feed products, Publications Office of the European Union, Luxembourg, 2025,
JRC143597. https://publications.jrc.ec.europa.eu/repository/handle/JRC143597 168 Study on the status of new genomic techniques under Union law and in light of the Court of Justice ruling in Case C-
528/16, SWD (2021) 92 final. https://food.ec.europa.eu/system/files/2021-04/gmo_mod-bio_ngt_eu-study.pdf 169 European Network of GMO Laboratories (ENGL), Detection of food and feed plant products obtained by new
mutagenesis techniques, 26 March 2019 (JRC116289). https://gmo-crl.jrc.ec.europa.eu/doc/JRC116289-GE-report-
ENGL.pdf 170 European Network of GMO Laboratories, Detection of food and feed plant products obtained by targeted mutagenesis
and cisgenesis, Publications Office of the European Union, Luxembourg, 2023, doi:10.2760/007925, JRC133689.
https://publications.jrc.ec.europa.eu/repository/handle/JRC133689
147
nature or by using conventional mutagenesis techniques. This problem may be
exacerbated, compared to plants, by the high genetic diversity of micro-organisms. Tracing
back such modifications to the use of NGTs for genetic modification of a GMM or its
product will not be possible through analytical means, i.e. identification and quantification
may not be possible in those cases. According to the ENGL, technical advancement, such
as high-throughput sequencing technologies, may further support enforcement in the future
but will be unlikely to resolve the particular problem of identification.
5.2 Applications of GMMs As or In Products
5.2.1 Overview of Applications
The Commission’s Joint Research Centre (JRC) has conducted in 2026 an up-to-date
analysis of GMM products for environmental release in development around the world to
supplement this staff working document171. It complements previous work by the JRC on
current and future market applications of NGTs, including when applied to micro-
organisms, which supported the Commission’s 2021 NGT study172. An external study on
the assessment of policy scenarios in the area of biotechnology conducted to support this
staff working document provided in addition estimates on the global market sizes for some
areas of microbial products173.
The JRC report on current and future applications of GMMs for environmental
releases174 referenced above found that there is a growing interest to leverage GMMs for
applications involving environmental releases. These applications span a wide variety of
product types and sectors. The following product types and applications (for uses other
than food and feed which are outside the scope of this proposal) have been identified in
the JRC report. Where available, the sections below also include data on market sizes from
the mentioned external study.
Agriculture
The use of microbial solutions is not new in the agricultural sector to maintain or increase
productivity, while reducing environmental impact. However, conventional microbial
strains do not always provide equally efficient alternatives to the wide range of applications
for chemical agricultural inputs. GMMs as biofertilisers, biopesticides and biostimulants
can provide improved functionality and reliability compared to conventional microbial and
chemical products. The first GM biofertilisers and GM biopesticides are already on the
market in the U.S.
The external study referred to above reported one estimate of the global biofertilisers sector
at EUR 1.18 billion in 2024 with a projection to reach EUR 2.42 billion by 2030, growing
171 Lowe, C.R., Ponferrada, V., Ruiz Aquino, C., Compaño, R., Nanda, A.K. (2026). Current and future market
applications of genetically modified microorganisms (GMMs) to be placed on the market or for environmental release.
JRC Technical Report, Publications Office of the European Union, Luxembourg (publication forthcoming). 172 Parisi, C. and Rodriguez Cerezo, E. (2021) Current and future market applications of new genomic techniques,
Publications Office of the European Union, Luxembourg, https://data.europa.eu/doi/10.2760/02472, JRC123830. 173 Rapid assessment scenario study - forthcoming. 174 Lowe, C.R., Ponferrada, V., Ruiz Aquino, C., Compaño, R., Nanda, A.K. (2026). Current and future market
applications of genetically modified microorganisms (GMMs) to be placed on the market or for environmental release.
JRC Technical Report, Publications Office of the European Union, Luxembourg (publication forthcoming)
148
at a Compound Annual Growth Rate (CAGR) of 12.8% from 2025 to 2030175. Another
estimate from this study reported the global market size even at EUR 2.65 billion in 2023,
projected to reach EUR 4.45 billion by 2028 with a CAGR of 10.9%176. However, both
these estimates relate to microbial fertilisers in general and only a part will be attributable
to GMMs. So far, commercial biofertiliser products are mostly not genetically modified,
yet various GMMs are in a research and development phase. For commercially available
GMM biofertiliser products, see the case study below in section 3.
With regard to the microbial biocontrol sector, including microbial biopesticides, the
above-mentioned study reports an estimated market size of EUR 5.56 billion in the year
2025, which is expected to increase to EUR 14.2 billion by 2032, growing at a CAGR of
14.3%177. In 2024, microbial solutions (bacteria, fungi, viruses) comprised over 58% of all
biocontrol agent units globally178. However, the study reports that there are no estimates
available specifically for GMMs and of the part of the market that will be attributable to
GMM-based products.
Bioremediation
Bioremediation is the use of living organisms, such as bacteria, fungi, or plants, to remove,
neutralise, or degrade pollutants (e.g., heavy metals, oil, pesticides) from contaminated
soil, water, or air.
GMMs can improve bioremediation by providing enhanced functionalities compared to
non-genetically modified microbes. They can be used to degrade pollutants such as oil,
plastics, heavy metals and persistent chemicals (e.g. per- and polyfluoroalkyl compounds
(PFAS)). So far, many genetically modified strains have been developed for
bioremediation purposes, and further progress promises to enable wider deployment
beyond field trials179.
One U.S. start-up, for example, offers tailored genetically modified micro-organisms to
address chemical pollution of industrial sites. The GMMs are engineered to improve and
combine natural abilities of certain micro-organisms to degrade chemicals, for example
PFAS, into less or non-toxic compounds180.
The above-mentioned external study reports that the global bioremediation market size
was valued at EUR 14.1 billion in 2024 and is projected to grow from EUR 15.5 billion in
2025 to EUR 32.9 billion by 2033, growing at a CAGR of 9.93% during the forecast period
175 Grand View Research. Biofertilizers Market (2025 - 2030). https://www.grandviewresearch.com/industry-
analysis/biofertilizers-industry. 176 Markets and Markets. Global Biofertilizers Market Size, Trends, Growth Forecast (2023–2028). 13 November 2025.
https://www.marketsandmarkets.com/blog/FB/biofertilizers-market. 177 ReAnIn. Biocontrol Agents Market Size & Share Analysis - Growth Trends and Forecast (2025 - 2032). March 2026.
https://www.reanin.com/reports/biocontrol-agents-market 178 Industry Research Biz. Biocontrol Market Size, Share, Growth, and Industry Analysis, By Type (Microbials,
Macrobials, Biochemicals), By Application (Grains and Cereals, Oilseeds and Pulses, Fruits and Vegetables, Other Crop
Applications), Regional Insights and Forecast to 2035. January 2026. https://www.industryresearch.biz/market-
reports/biocontrol-market-113645 179 Singh JS, Abhilish PC, Singh HB, Singh RP & Singh DP (2011) Genetically engineered bacteria: An emerging tool
for environmental remediation and future research perspectives. Gene 480, 1-9. 180 Paliwoda Group. Lysosome Resources. January 2026. https://www.paliwoda.com/lysosomeresources.php
149
(2026 – 2033)181. Other estimates even expect a CAGR of 13.0% from 2025 to 2034182.
Although there are no specific data for a GMM bioremediation market available, the use
of GMMs is marked as a “key market trend”183.
Wastewater treatment & pollution control
Water pollution through industrial releases such as agricultural, mining and industrial
wastes and domestic effluents and its subsequent treatments have become major global
concerns. GMMs can offer tailored solutions for wastewater treatment by enhancing the
removal of a multitude of pollutants and making treatment more efficient, cost-effective
and eco-friendly. Large scale release of these solutions is so far limited although they are
frequently used in contained settings184.
Biomining, bioleaching and bioaccumulation
Biomining uses micro-organisms to extract metals from ores, while bioleaching
specifically employs bacteria to dissolve metals via acidic solutions, and bioaccumulation
describes how micro-organisms absorb and concentrate substances (e.g. metals) from their
environment.
At present, there are no GMMs used in global commercial scale biomining operations, but
this is an active area of research to enhance the efficiency, speed and environmental
sustainability of metal recovery via bioleaching, bio-oxidation and bioaccumulation185,186.
Bioleaching is employed in two separate scenarios which differ in scale: urban waste
streams containing critical metals, which is mostly done in contained environments but
may also be used in environmental release scenarios; and natural ore processing at scale
using environmental releases directly within the geographical locations. Conventional
microbes have been used in ore bioleaching. However, GMMs are now being developed
to overcome limitations of conventional microbes, such as slow process times and
sensitivity to fluctuating site conditions like temperature, pH and metal concentrations.
GMMs provide, for example, unique opportunities for biomining rare earth elements,
181 SkyQuest Technology Consulting Pvt. Ltd. Bioremediation Market Size, Share, and Growth Analysis. Bioremediation
Market By Type (Situ Bioremediation, And Ex Situ Bioremediation), By Technology (Biostimulation,
Phytoremediation), By Service (Soil Remediation, Oilfield Remediation), By Region - Industry Forecast 2026-2033.
November 2024. https://www.skyquestt.com/report/bioremediation-market 182 Dimension Market Research. Bioremediation Market. Bioremediation Market By Type (In Situ Bioremediation, Ex
Situ Bioremediation), By Technology, By Service - Global Industry Outlook, Key Trends and Forecast 2025-2034.
November 2024. https://dimensionmarketresearch.com/report/bioremediation-market/ 183 SkyQuest Technology Consulting Pvt. Ltd. Bioremediation Market Size, Share, and Growth Analysis. Bioremediation
Market By Type (Situ Bioremediation, And Ex Situ Bioremediation), By Technology (Biostimulation,
Phytoremediation), By Service (Soil Remediation, Oilfield Remediation), By Region - Industry Forecast 2026-2033.
November 2024. https://www.skyquestt.com/report/bioremediation-market 184 Gaurav Pant, Deviram Garlapati, Urvashi Agrawal, R. Gyana Prasuna, Thangavel Mathimani, Arivalagan
Pugazhendhi, Biological approaches practised using genetically engineered microbes for a sustainable environment: A
review, Journal of Hazardous Materials, Volume 405, 2021, 124631, ISSN 0304-3894,
https://doi.org/10.1016/j.jhazmat.2020.124631.
185 Chen J, Liu Y, Diep P & Mahadevan R (2022) Harnessing synthetic biology for sustainable biomining with Fe/S-
oxidising microbes. Front Bioeng Biotech 10, 920639 186 Gumulya Y, Boxall, NJ, Khaleque HN, Santala V, Carlsson RP & Kallsonen AH (2018) In a quest for engineering
acidophiles for biomining applications: Challenges and opportunities. Genes 9, 116.
https://doi.org/10.3390/genes9020116
150
which are critical elements for renewable energy, military equipment, electric vehicles and
other products of advanced engineering.
One concrete example comes from a U.S. start-up developing a genetically modified yeast
that binds cobalt in wastewater streams from mining operations. This approach aims, on
the one hand, to prevent ecological damages stemming from heavy metal contamination
of water sources and, on the other hand, to retain the valuable metal, while being more cost
effective than the conventional method of membrane filtration and avoiding the use of
chemicals for precipitation. The company claims that their use of the GMM enables the
recovery of 97% of the cobalt contained, also cleaning the wastewater to fulfil the U.S.
Environmental Protection Agency’s wastewater standards, and that it can save 50% of
energy compared to conventional methods187.
The above-named external study reports the market size estimate at EUR 8.70 billion in
2024, with a projection to reach EUR 18.3 billion by 2033, growing at a CAGR of 8.9%
from 2025 to 2033188. Another reported estimate values the market size at EUR 9.58 billion
in 2025 and projects it to grow from EUR 10.4 billion in 2026 to EUR 20.9 billion by 2034,
exhibiting a CAGR of 9.06% during the forecast period189. Specific GMM-related data are
not available, but GMMs are mentioned as future opportunity and potential field of
innovation190.
Construction materials
Biomaterials have been proposed as a sustainable alternative to e.g., plastics and concrete
in the construction and infrastructure sectors. Engineered Living Materials (ELMs)191
applied to the construction industry provide a new class of sustainable biomaterials that
can be grown from living organisms or incorporate living cells to furnish entirely unique
capabilities such as self-healing and carbon sequestration. Their deployment requires
environmental release of the GMM. The leading-edge of construction biotechnology could
leverage GMMs as biosensors i.e., to detect environmental cues, such as moisture, pH
shifts or mechanical stress. The GMMs can then initiate selective responses, including
carbonate precipitation, polymer secretion or the release of “healing compounds”. Such
ELMs could lead to the development of adaptive, intelligent self-regulating infrastructure
capable of sensing environmental changes via real-time monitoring and stress-responsive
functions.
187 MIT Solve. 2025 Global Climate Challenge. Aquasaic: Bioengineered yeast for eco cobalt recovery. August 2025.
https://solve.mit.edu/solutions/102928 188 Grand View Research. Bioleaching Market (2025 - 2033) Size, Share & Trends Analysis Report By Metal (Copper,
Gold, Zinc & Nickel), By Source (Primary Ores, Mine Tailings), By Region (North America, Europe, Asia Pacific), And
Segment Forecasts. https://www.grandviewresearch.com/industry-analysis/bioleaching-market-report 189 Fortune Business Insights. Bioleaching Market Size, Share, and Industry Analysis By Metal Type (Gold, Copper,
Nickel, Cobalt, and Others), By Microorganism Type (Bacteria, Fungi, and Others), By Application (Mining, E-Waste
Recycling, Industrial Waste Treatment, Agriculture, and Others), and Regional Forecast, 2026-2034. March 2026.
https://www.fortunebusinessinsights.com/bioleaching-market-110894 190 Grand View Research. Bioleaching Market (2025 - 2033) Size, Share & Trends Analysis Report By Metal (Copper,
Gold, Zinc & Nickel), By Source (Primary Ores, Mine Tailings), By Region (North America, Europe, Asia Pacific), And
Segment Forecasts. https://www.grandviewresearch.com/industry-analysis/bioleaching-market-report 191 Gilbert C and Ellis T (2019) Biological Engineered Living Materials: Growing Functional Materials with Genetically
Programmable Properties. ACS Synthetic Biology 2019 8 (1), 1-15 https://doi.org/10.1021/acssynbio.8b00423
151
Cutting edge research and development on ELMs is funded by the European Innovation
Council192. One of the funded projects, the REMEDY Consortium entailing partners from
Austria, the Netherlands, Slovakia and Slovenia, aims to develop substances containing
mixtures of micro-organisms that can be printed onto surfaces of buildings. This
“microbial ink” is intended to improve local air quality in built-up areas by producing
oxygen, sequestering carbon dioxide and degrading pollutants193.
Defence
Recent developments in genetic engineering are creating new paradigms for biodefense,
national security, medical countermeasures and advanced materials. Examples of key
defence applications of GMMs in research and development include submarine detection
with marine bacteria that react to emissions from submarines, GMMs able to detect
explosives in e.g., landmines, advanced protective and responsive garments and self-
healing ELMs for camouflage, construction, ships and aircraft (also see “construction
materials” above)194. Most of these applications would entail the environmental release of
the GMM.
Carbon capture
Advances in biotech now enable the optimisation of carbon capture with more precision
by tailoring GMMs to boost their photosynthetic capacity and absorb greater amounts of
CO2 from the atmosphere. In addition, GMMs are being used to sequester carbon in a stable
form that prevents its release into the atmosphere, whilst the stable carbon-rich compounds
can either be stored long-term195 or used to generate renewable energy196 or act as
substrates for biomanufacturing of higher value products in contained systems197. While
most of the applications are currently limited to contained use, the scale of what is needed
to effectively capture and store enough carbon to mitigate climate change would require
strategies including environmental releases in order to be viable198.
Cosmetic products and personal care
Currently, the use of GMMs in the cosmetics and personal care industry is mostly limited
to contained use, through the production of key compounds and ingredients through
industrial fermentation. However, they are also increasingly being developed for direct use
192 European Commission: European Innovation Council and SMEs Executive Agency, EIC pathfinder portfolio –
Engineered living materials – Strategic plan – Brussels, November 2023, Publications Office of the European Union,
2023, https://data.europa.eu/doi/10.2826/260175 193 Remedy Consortium. https://eic-remedy.eu/consortium/?lang=en 194 Lowe, C.R., Ponferrada, V., Ruiz Aquino C., Compaño, R., Nanda, A.K. (2026). Current and future market
applications of genetically modified microorganisms (GMMs) to be placed on the market or for environmental release.
JRC Technical Report, Publications Office of the European Union, Luxembourg (publication forthcoming). 195 Onyeaka H & Ekwebelem OC (2023) A review of recent advances in engineering bacteria for enhanced CO2 capture
and utilisation. Intl J Environ Sci & Tech 20, 4635-4648. https://doi.org/10.1007/s13762-022-04303-8 196 Priyadharshini K & Niju S (2025) Current advances in microbial carbon capture cells – a unique bioelectrochemical
system for sustainable future. Sust Chem Environ 10, 100244. https://doi.org/10.1016/j.scenv.2025.100244 197 Hoque M, Iannelli V, Padula F, Radice RP, Saha BK, Martelli G, Scopa A & Drosos M (2025) Microalgae: green
engines for achieving carbon sequestration, circular economy and environmental sustainability – a review based on last
ten years of research. Bioengineering 12, 909. https://doi.org/10.3390/bioengineering12090909 198 https://luminaprobiotic.com/
152
in cosmetic products and personal care products199,200. Currently, one GMM probiotic,
developed to improve dental health by reducing the build-up of lactic acid, is commercially
available in the USA since 2023201.
Table 4. Examples of GMM products202 for environmental release in various stages
of development
Micro-organism Application Trait Issue addressed Development
stage Country Reference
Bacteria
(Klebsiella
variicola and
Kosakonia
sacchari)
Agriculture -
biofertiliser
Nitrogen
fixation in
soil/rhizosphere
Dependency on
synthetic fertiliser;
Negative
environmental
impacts of
excessive fertiliser
use
Commercial;
Pre-
commercial
USA;
Brazil
203, 204, 205,
206
Bacteria
(Paenibacillus
polymyxa,
P. odorifer)
Agriculture -
biofertiliser
Nitrogen
fixation in
soil/rhizosphere
Dependency on
synthetic fertiliser
Negative
environmental
impacts of
excessive fertiliser
use
Pre-
commercial
Brazil
USA
207, 208, 209,
210, 211, 212,
213
Bacteria
(Pseudomonas
species)
Agriculture -
food safety
Removal of
arsenic from
the
environment
Arsenic
accumulation in
agricultural produce
for human
consumption
R&D stage India 214, 215
199 Atallah, C.; El Abiad, A.; El Abiad, M.; Nakad, M.; Assaf, J.C. Bioengineered Skin Microbiome: The Next Frontier
in Personalized Cosmetics. Cosmetics 2025, 12, 205. https://doi.org/10.3390/cosmetics12050205 200 Chinjoo N & Golzary A (2025) Microalgae: revolutionising skin repair and enhancement. Biotechnol Rep 47, e00911.
https://doi.org/10.1016/j.btre.2025.e00911 201 https://luminaprobiotic.com/ 202 Based on the description of the micro-organism and in accordance with the EU GMO definition. Products may be
classified as non-genetically modified in the respective 3rd country. 203 https://www.pivotbio.com/press-releases/peer-reviewed-study-validates-pivot-bios-gene-edited-microbes-as-a-third-
source-of-nitrogen-delivery 204 https://www.pivotbio.com/product-proven40-corn 205 https://worldwide.espacenet.com/patent/search/family/070918989/publication/WO2021221690A1
206 https://www.prnewswire.com/news-releases/pivot-bio-readies-brazilian-operation-with-expanded-team-
302265792.html 207 https://one.oecd.org/document/ENV/CBC/MONO(2024)22/en/pdf 208 https://www.aphis.usda.gov/sites/default/files/25-007-02air-response.pdf 209 https://www.aphis.usda.gov/sites/default/files/25-007-02air-cbidel-a1.pdf 210 https://www.aphis.usda.gov/sites/default/files/25-007-01air-cbidel-a1.pdf
211 https://www.aphis.usda.gov/sites/default/files/25-007-01air-response.pdf 212 https://www.aphis.usda.gov/sites/default/files/25-182-02air-response.pdf 213 https://www.aphis.usda.gov/sites/default/files/25-182-02air-cbidel-a2.pdf
214 https://microbiologyjournal.org/role-of-pseudomonas-putida-ckvf1-in-alleviating-arsenic-induced-stress-in-vicia-
faba-l/ 215 https://pubmed.ncbi.nlm.nih.gov/39999859/
153
Bacteria
(Acetobacter,
Sarcina
ventriculi and Agrobacterium)
Agriculture -
drought
resilience
Excretion of
water-retaining
compounds
Drought resilience R&D stage UK 216, 217
Bacterium
(Bacillus
thuringiensis)
(multiple strains)
Agriculture -
biopesticide
Expression of
toxins active
against
lepidopterous
larvae
Economic losses
due to various plant
pests
Commercial;
Pre-
commercial
China
USA;
Brazil
218, 219, 220
Bacterium
(Agrobacterium
radiobacter/
Rhizobium
rhizogenes)
Agriculture -
biopesticide
Production of
antibiotic
compound
Economic losses
due to crown gall
disease
Commercial
Australia
Türkiye
USA
221, 222, 223
Bacteria, Fungi Bio-
remediation
Degradation of
harmful
chemicals
Chemical pollution
of industrial sites R&D stage USA 224
Bacterium
(Shewanella
oneidensis)
Bio-
remediation
Degradation of
DNA
conferring
antibiotic
resistance
Antibiotic resistance
gene reservoirs in
wastewater
R&D stage China
USA 225
Yeast
(Saccharomyces
cerevisiae)
Biomining -
wastewater
treatment
Binding of
cobalt
Cobalt
contamination in
wastewater from
mining operations
R&D stage USA 226
Microbial
consortia
Construction
materials –
ink
Sequestration
of carbon,
production of
oxygen or
degradation of
pollutants
Poor air quality in
built areas R&D stage EU 227, 228
Bacteria
(Streptococcus
mutans)
Cosmetics –
dental care
Conversion of
sugar into
alcohol instead
of lactic acid
Tooth decay Commercial USA 229, 230, 231
216 https://www.crobio.com/technology
217 https://patents.justia.com/patent/20230034438 218 https://www.certisbio.com/products/bt-biolarvicides/crymax 219 https://pmc.ncbi.nlm.nih.gov/articles/PMC12665435/ 220 https://one.oecd.org/document/ENV/CBC/MONO(2024)22/en/pdf 221 https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/related_PC-006474_1-Sep-99.pdf 222 https://bio-caretechnology.com/ 223 https://www.mdpi.com/2073-4395/10/8/1126 224 https://www.paliwoda.com/lysosomeresources 225 https://www.nature.com/articles/s44221-024-00289-4 226 https://solve.mit.edu/solutions/102928
227 https://www.innovationnewsnetwork.com/remedy-redefining-architecture-through-engineered-living-
materials/62541/ 228 https://eic-remedy.eu/research-results 229 https://luminaprobiotic.com/ 230 https://www.scientificamerican.com/article/this-start-up-wants-you-to-put-custom-bacteria-on-your-teeth/ 231 https://sfstandard.com/2025/02/22/lumina-probiotic-cavity-bioengineered-toothpaste/
154
In addition, the Commission asked EFSA, in the context of its scientific opinion on new
developments in biotechnology applied to micro-organisms232, to produce a horizon scan
on micro-organisms and their products obtained by new developments in biotechnology233.
The EFSA horizon scan found that there is significant activity in the development of
innovative GMMs by both private and public/academic entities but noted that the majority
of the identified GMMs originated from the USA or China, while only a limited number
were developed within the EU. EFSA identified 35 products making use of GMMs
obtained by NGTs, which was the focus of the horizon scan, and primarily in the food and
feed area, that are currently on the market in third countries or expected to come to the
market within the next 10 years. About half of these products would contain the living
micro-organism (and would therefore fall in the scope of Directive 2001/18/EC), while the
other half would be derived from the GMM without containing living cells. The used
micro-organisms included yeasts, bacteria, fungi and microalgae. About a quarter of the
identified products were developed using a combination of NGTs and established genomic
techniques.
To complement this horizon scan, EFSA conducted an online call for data in March/April
2023. The results of this call are presented in the above-named scientific opinion. This call
largely confirmed the trends identified in the horizon scan, while a higher proportion (75%)
of the reported products in development made use of a combination of NGTs and
established genomic techniques.
5.2.2 Case Study: GMMs for Biological Nitrogen Fixation
The most advanced application of GMMs for environmental release are biofertilisers. A
practical approach to reducing dependency on synthetic fertilisers is through biological
nitrogen fixation (BNF) by genetically modifying nitrogen-fixing bacteria to enhance their
ability to supply crops with sufficient nitrogen. This specific use is investigated by the JRC
with a case study explained below234.
While synthetic fertilisers have driven unprecedented increases in crop yields, the
dependence on them raises farmers’ production costs, increases energy demand, and harms
the environment, contributing to greenhouse gas emissions and water contamination. A
key solution to mitigate these economic and ecological impacts is replacing synthetic
nitrogen inputs with nitrogen from BNF, a natural process in which soil micro-organisms
convert atmospheric nitrogen into plant-available ammonia. One approach to reducing
fertiliser dependency through BNF is by genetically modifying nitrogen-fixing bacteria to
232 EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), Mullins, E., Bresson, J.-L., Dewhurst, I. C.,
Epstein, M. M., Firbank, L. G., Guerche, P., Hejatko, J., Moreno, F. J., Naegeli, H., Nogué, F., Rostoks, N., Sánchez
Serrano, J. J., Savoini, G., Veromann, E., Veronesi, F., Cocconcelli, P. S., Glandorf, D., Herman, L., Jimenez Saiz, R.,
Ruiz Garcia, L., Aguilera Entrena, J., Gennaro, A., Schoonjans, R., Kagkli, D. M., Dalmay, T. (2024). New
developments in biotechnology applied to microorganisms. EFSA Journal, 22(7), e8895.
https://doi.org/10.2903/j.efsa.2024.8895 233 Ballester, A.R., Roqué, M., Ricci-Cabello, I., Rotger, A., Malih, N. 2023. Horizon scanning on microorganisms and
their products obtained by new developments in biotechnology. EFSA supporting publication 2023:EN-8503, 65 pp.
doi:10.2903/sp.efsa.2023.EN-8503 234 Burren, S., Palacios, J., Areal, F.J., Rodriguez-Cerezo, E., Barreiro-Hurle, J. (2026). The potential of genetically
modified microorganisms to reduce nitrogen loads in the EU agricultural sector. JRC Technical Report, Publications
Office of the European Union, Luxembourg
155
enhance their ability to supply crops with sufficient nitrogen while ensuring the GMMs
remain competitive and thrive in soil conditions.
At present, at least four companies are developing GMM products to address BNF in
crops. The most advanced of these companies in terms of market readiness recently
launched their third generation of a GMM-based nitrogen-fixation solution in the USA,
building on their first- and second-generation products introduced to the U.S. market in
2019 and 2021, respectively. In addition, this company is preparing the market entry in
Brazil awaiting the approval of their commercial registration of their products. The
products are designed to enhance BNF in nitrogen-rich agricultural soils – a situation
typical for European agriculture. The GMMs are modified through targeted mutagenesis
to convert nitrogen to ammonia, which in turn can readily be taken up and used by plants.
Beyond the most used products to support the cultivation of maize, related formulations
are marketed for cotton, sorghum and millet, and for small grains and oilseeds including
wheat, oats, barley, rye, and sunflower. After commercial launch of the first-generation
GMM in 2019, the products have been used on at least 2 million hectares of maize across
the U.S.
The GMM products have been tested in multiple academic trials, third-party substitution
trials, and more than 3,000 commercial farm fields, primarily in maize under U.S.
agronomic conditions. Across different sources (peer-reviewed studies, commercial
on-farm trials, university field trials, company reports and independent research
organisations) the reported nitrogen (N) replacement values ranged from roughly
10 kg N/ha up to 50 kg N/ha. Corresponding yield increases over the use of traditional
fertilisers varied between 0.10 and 0.80 t/ha resulting in income gains for farmers of
typically between €20 and €60/ha per harvest. Disregarding any potential yield gains and
considering the price of the product calculated by the company, traditional nitrogen sources
can be replaced by the biofertiliser at no greater costs for farmers if nitrogen costs range
between €0.94 per kg N (assuming 50 kg N/ha replacement) and €4.70 per kg N (assuming
10 kg N/ha replacement). Lower product costs, higher nitrogen prices or greater nitrogen
placement would render the biofertiliser more cost effective than traditional solutions.
Based on the recorded prices of nitrogen, having fluctuated between €0.53 and
€1.73 per kg N over the past five years and given that the latest geopolitical disruptions
signal towards higher fertilizer prices in the short to midterm, using the biofertiliser appears
to be economically viable in the majority of use scenarios and in some situations would be
economically beneficial for farmers in comparison to the use of traditional nitrogen
sources. The latter is further supported when taking into account the modest yield increases
the GMM product can deliver over the use of traditional fertilisers.
In addition, this economic evaluation is not considering environmental benefits that may
be considerable when broader adoption of biofertilisers occurs. For example, according to
company estimates, widespread adoption across the U.S. maize cultivation area could
reduce synthetic nitrogen fertilizer use by approximately 12%, with associated reductions
in greenhouse gas emissions and nitrate losses. One study demonstrated that use of the
GMM product reduced the average amount of nitrate washed out from soil into ground and
surface water (so-called nitrate leaching) by approximately 10 kg/ha relative to untreated
controls and so addresses one major concern arising from the use of synthetic nitrogen
156
fertilisers. Taken together, the evidence suggests that BNF technologies can provide these
environmental benefits at no additional costs for farmers compared to synthetic fertilisers
and, if larger nitrogen-replacement rates are achieved, the price for nitrogen increases or
any yield increases are realised, would lead to economic advantages to farmers over
traditional nitrogen sources.
Figure 1: case study: GMMs for biological nitrogen fixation
6 INTERVENTION N°8: TARGETED LEGISLATIVE REFORM OF THE DIRECTIVE ON
HUMAN ORGANS INTENDED FOR TRANSPLANTATION
6.1 Detailed description of the proposed measures
Measure 1: Scope expansion
The first measure amends Article 2(1) of the Directive to insert “processing” (replacing
“preservation”) into the list of activities to which the Directive applies, alongside donation,
testing, characterisation, procurement, transport, and transplantation. Thus, preservation
becomes legally subsumed as a specific type of processing, as established in the new
definition of “processing” under Article 3(ka). This change establishes the prerequisite for
the entire revision by bringing organ processing activities within the material scope of the
Directive’s quality and safety framework.
The measure also introduces a new definition of “processing”, defined as any operation
involving the handling of organs, including but not limited to preservation, application of
chemotherapy, and surgery, performed to maintain or improve the functional status of an
organ prior to transplantation. Although the definition is deliberately broad, it draws three
exclusions. First, it excludes the preparatory handling of the organ during the surgical
157
transplantation intervention itself, as routine surgical preparation in the operating room
falls within Member State competence. Second, it excludes the repurposing of organs into
tissues or cells, which falls under the SoHO Regulation (EU) 2024/1938. Third, it excludes
the use of pharmacologically active substances where the primary aim is to treat or prevent
a disease in the recipient rather than to process the organ, drawing a functional boundary
between treating the organ (regulated under the new processing regime) and treating the
patient (regulated under the standard medicinal products framework).
The definition of “transplantation” in Article 3(q) is also adjusted by removing “from a
donor”, so that transplantation is now defined as a process intended to restore certain
functions of the human body by transferring an organ to a recipient covering the case where
the recipient and the donor are the same person.
Measure 2: Organ processing authorisation regime
The proposed new Article 6a aims to establish a comprehensive regulatory regime for
organ processing. The foundational rule (Article 6a (1)) prohibits transplantation centres
from applying a processed organ to a recipient without prior authorisation of this specific
processing technology/technique from the competent authority. The authorisation
requirement applies per processing technology and per transplantation centre. This prior
authorisation requirement shifts organ processing from an unregulated clinical activity to
one that requires formal approval of the applied processing technology from the oversight
authority before clinical application.
The transplantation centre must conduct an upfront benefit–risk assessment of the
processing technique, taking into account the intended clinical indication (Article 6a (2)).
Based on this assessment, the competent authority grants an authorisation (implementing
rules referred to in Article 6a (12)), considering the adequacy of the evidence base and
whether the benefit–risk profile is favourable. Where the available evidence is insufficient
to support a benefit–risk assessment or where that assessment identifies a significant risk
(Article 6a(3)), the transplantation centre must submit a proposal for a clinical-outcome
monitoring plan for approval by the competent authority. The extent of the clinical
outcome monitoring plan will be defined by the identified risk and the availability of data.
This functions as a tailored approval pathway: initial clinical use of novel or higher-risk
processing techniques will be permitted in a controlled setting.
Article 6a (9) introduces change control, prohibiting transplantation centres from making
significant changes to authorised processing steps without prior written agreement from
the competent authority. Competent authorities can suspend authorisations where there is
reasonable ground to suspect non-compliance (Article 6a (10)). The Commission will
publish a list of authorised organ processing operations/techniques, including any
associated medicinal products, medical devices, or SoHO preparations (Article 6a (11)).
This mechanism serves a dual function: it provides a reference point for transplantation
centres across the EU regarding the state of the art, and it creates the informational basis
for a de facto convergence of practice that could facilitate cross-border organ exchange.
The Commission can also adopt implementing acts laying down detailed rules for the
authorisation of organ processing techniques (Article 6a (12)).
158
The complementary data set in Part B of the Annex is amended to add “Processing” as an
information field covering processing steps applied to the organ with the aim of improving
its functional status, with a potential impact on its quality and safety. This creates the data
collection mechanism that will enable competent authorities, transplant registries, and the
Commission to track which organs have been processed, by what method, and, when linked
to outcome data, with what clinical result. The placement in Part B (complementary data)
means that reporting is not strictly mandatory in all circumstances.
Measure 3: Cross-border and cross-framework coherence
A defining feature of the regime is its cross-framework coordination mechanism (Articles
6a (4)– (8)), requiring competent authorities to verify that any such product or substance
used in processing is duly authorised or certified under its respective EU legislative
framework.235 Competent authorities under the organ Directive and those under the
pharmaceutical, medical device, and SoHO frameworks collaborate in order to exchange
clinical outcome data. To facilitate implementation, Article 6a (5) lays down provisions on
guidelines regarding the benefit risk-assessment and the management of the organ after the
administration of a medicinal product.
6.2 Baseline description
Conduct of business
The total volume of organ transplants in the EU-27 is projected to continue growing at the
structural CAGR of 1.54% per million population (pmp), the rate observed over the full
post-transposition period of 2012–2024 following the implementation of Directive
2010/53/EU236. Applying this rate forward from the 2024 observed anchor of 72.0 pmp237,
the baseline projects approximately 78.9 pmp (~35,350 transplants) by 2030, 85.2 pmp
(~38,200 transplants) by 2035, and 92.0 pmp (~41,200 transplants) by 2040.
Transplantation centres will continue to adopt machine perfusion and associated
processing technologies through organic, centre-driven clinical channels, but at a limited
pace. At T0, approximately 27% of the EU’s 717 organ transplantation programmes (~195
programmes across an estimated 120–160 unique centres) have active organ processing
capability, with adoption concentrated in 7 Member States. Finding from a national survey
shows that 85% of machine perfusion programmes were established between 2020 and
2024. Without regulatory clarity and a harmonised authorisation pathway, diffusion
to the remaining 73% of programmes, smaller multi-organ programmes, and centres
in Member States with less developed regulatory infrastructure, is expected to
proceed slowly and unevenly.
The share of EU transplantation programmes with active processing capability will rise to
approximately 35–38% by 2030 and 42-48% by 2035, before plateauing at approximately
48–55% by 2040. This plateau effect reflects the structural barrier that legal uncertainty
235Article 6a(4)–(5): medicinal products under Directive 2001/83/EC or Regulation (EC) No 726/2004; Article 6a(6):
medical devices under Regulation (EU) 2017/745; Article 6a(7): SoHO preparations under Regulation (EU) 2024/1938. 236 The use of this full twelve-year period, which spans pre-pandemic expansion, pandemic disruption, and recovery,
provides a more statistically robust and conservative estimate of the structural growth rate than any shorter sub-period 237 32,222 transplants across a population of approximately 448 million.
159
discourages investment in new programmes, particularly in jurisdictions that have not
developed national oversight arrangements. Transplantation centres in the EU will
increasingly bifurcate into two tiers: a first tier of large, well-resourced centres
performing routine advanced processing across multiple organ types (concentrated in
approximately 6–8 Member States), and a second tier relying predominantly on SCS or
basic hypothermic preservation. This bifurcation will be the defining feature of the
conduct-of-business landscape under the baseline.
Administrative costs on businesses, including SMEs
No EU-level organ processing authorisation regime exists, and no formal, processing-
specific administrative obligations stem from Union law. The average cost per organ
processing authorisation application stemming from EU level legislation remains at zero
throughout the assessment period.
However, those Member States that have developed or are developing national oversight
arrangements will impose jurisdiction-specific documentation, reporting, and approval
requirements on transplantation centres. Centres operating in these jurisdictions will bear
the costs of preparing internal benefit-risk documentation, maintaining processing-specific
quality records, and engaging with their national competent authority on an ad hoc basis.
This fragmentation generates duplicative effort and prevents the economies of
standardisation that a harmonised framework would deliver.
Conversely, transplantation centres in Member States that have not established any
national processing oversight regime will face no formal administrative cost related to
processing but will instead bear the hidden costs of legal uncertainty (e.g., ad hoc costs
of seeking legal advice on the permissibility of specific processing operations). Over
the assessment period, the administrative cost landscape under the baseline is therefore
expected to become progressively more heterogeneous, with total national-level
compliance costs rising in aggregate as more Member States develop national
arrangements but remaining inefficient.
Functioning of the internal market and competition
Based on Eurotransplant data, over the last three years, the cross-border exchange rate
fluctuated between 22.2% in 2023, 22.5% in 2024, and 20.5% in 2025.
Cross-border exchange rates within the major European organ exchange organisations
are expected to remain stable throughout the assessment period, continuing to fluctuate
within the range of approximately 20–23%. In addition, bilateral exchanges and surplus-
organ platforms will likewise remain at volumes comparable to current levels. The
competitive landscape for manufacturers of perfusion devices, perfusates, and
therapeutic agents will remain fragmented, as companies continue to face a patchwork
of national regulatory environments with no harmonised EU authorisation pathway for
organ processing technologies, impacting market predictability and scale.
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Innovation and research
Established technologies, particularly hypothermic machine perfusion for livers and
kidneys, and Ex Vivo Lung Perfusion (EVLP), will likely continue to diffuse to additional
centres, driven by the growing clinical evidence base, declining equipment costs as the
market matures, and peer-to-peer knowledge transfer within professional networks. The
aggregate share of programmes with active processing capability is expected to rise
from approximately 27% at T0 to approximately 42–48% by 2035, with the most
pronounced gains in liver perfusion (potentially reaching 70–75% of programmes)
and EVLP (60–65%). Kidney perfusion uptake will remain structurally limited by the fact
that kidney-only centres, which account for a significant proportion of the 260 kidney
programmes, typically lack the institutional infrastructure, volume, and capital to sustain
a perfusion programme: 0 of 7 kidney-only centres had adopted machine perfusion is
likely to persist as a structural feature.
The unfavourable environment for next-generation and experimental processing
technologies will remain. Without an EU-level authorisation framework that provides both
legal certainty and a structured route from conditional (monitored) use to full clinical
deployment, developers of technologies will face an uncertain and fragmented market.
The clinical evidence base for organ processing will also remain nationally siloed and
methodologically inconsistent.
Public authorities
Since no EU-level organ processing authorisation regime exists, the number of organ
processing authorisations granted remains at zero throughout the assessment period under
the baseline.
A subset of Member States with well-resourced transplant authorities will expectedly
develop national oversight arrangements, ranging from informal guidance issued by the
competent authority to more structured approval procedures embedded within existing
national transplant legislation. This process will be incremental and uncoordinated,
producing a growing patchwork of national approaches with no common benchmark for
the stringency, scope, or procedural requirements of processing oversight. The remaining
Member States, particularly those with smaller transplant systems (fewer than 3–5
transplantation centres), are unlikely to develop dedicated processing oversight.
Competent authorities will continue to lack any structured mechanism for cross-
framework coordination with pharmaceutical, medical device, and SoHO authorities
regarding the use of regulated products in the context of organ processing. The
clinical outcome data generated when a medicinal product is administered to an organ
during perfusion, or when a medical device is used in a novel ex-vivo application, will
remain trapped within the organ transplant reporting system (to the extent it is captured at
all) and will not be systematically shared with the relevant product-sector authorities. This
regulatory silo effect represents a persistent information loss that impedes both patient
safety oversight and evidence-based product regulation.
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Public health and safety
The public health and safety baseline encompasses the largest cluster of indicators and
represents the domain in which the consequences of inaction are most directly measurable
in-patient terms.
Organ supply: discard rate, donor utilisation, and organ yield: The EU-27 proxy organ
discard rate at T0 stands at approximately 12–13% across all organ types combined, with
substantial organ-specific variation (kidney ~10%, liver ~18%, pancreas ~49%, heart ~2%,
lung ~6%). Thus, the continued organic adoption of machine perfusion in leading
centres is expected to produce a modest, uneven decline in the discard rate. A
reduction to approximately 11–12% by 2030, 10–11% by 2035, and 9–10.5% by 2040 is
projected. The gains will be concentrated in liver and lung, where machine perfusion is
most clinically mature, and will be minimal for pancreas and heart. The deceased donor
utilisation rate (94.8% at T0) is expected to improve marginally to approximately 95.5–
96% by 2035 and 96–96.5% by 2040, with the most significant improvements among DCD
donors (whose utilisation rate of 85.2% globally at T0 has the greatest room for
improvement). The organ yield per utilised deceased donor (2.77 at T0) is projected to rise
modestly to approximately 2.85–2.90 by 2035 and 2.90–2.95 by 2040, driven primarily by
the rehabilitation of individual organs within multi-organ donors. These projections are
below the gains achievable with wider processing adoption: a national survey’s finding of
a ~10% increase in organ utilisation attributable to machine perfusion, applied across all
EU programmes, would imply substantially larger improvements.
Patient safety: SAE/SAR rate: The proxy EU-27 SAE/SAR rate at T0 is approximately
4 per 1,000 organ recipients per year (plausible range: 3-6), corresponding to an estimated
130 SAE/SAR cases annually, with approximately 17 proven or probable disease
transmission events and 3-4 associated deaths. Under the baseline, this rate is expected to
remain broadly stable or may trend modestly upward over the assessment period. The
critical dynamic is that the expansion of processing, which involves the introduction of
new pharmacological, surgical, and biological interventions on the organ, creates new risk
categories that the existing SAE/SAR reporting system was not designed to capture.
Without a mandatory benefit-risk assessment requirement, a structured clinical-outcome
monitoring obligation, or an EU-level mechanism for disaggregating adverse events
attributable to processing from those attributable to other causes, the safety profile of organ
processing techniques will depend entirely on the internal governance standards of
individual transplantation centres and, where they exist, national oversight frameworks.
As processing volumes grow, the absolute number of processing-related adverse events is
likely to increase, but many of these events may go undetected or unreported because the
existing reporting taxonomy does not include processing as a distinct cause category.
Waiting time and waiting-list mortality: The aggregate EU-27 waiting-list turnover ratio
at T0 is approximately 19.5 months, overwhelmingly driven by the kidney waiting list
(42,855 patients, turnover ratio of ~26.8 months). Under the baseline transplant growth
trajectory of 1.54% CAGR, annual transplant volumes will rise from 32,222 (2024) to
approximately 38,200 by 2035 and 41,200 by 2040. However, on the demand side, waiting
lists are expected to grow in parallel, driven by demographic ageing (which increases the
incidence of end-stage organ failure, particularly for kidneys), the progressive expansion
of transplant listing criteria, and improvements in dialysis and bridge therapies that keep
162
patients alive and on the list for longer. It is assumed that the EU-27 waiting list grows at
approximately 0.5% per year (plausible range of 0.35-0.65%), reflecting the net balance
between rising incidence of end-stage organ failure on the demand side and the absorptive
effect of growing transplant volumes on the supply side. This rate is broadly consistent
with the Eurotransplant experience, where the active waiting list has remained
approximately stable in recent years despite concurrent growth in transplant activity, and
is conservative relative to the demand-side pressures described above.238 Applied to the T0
waiting list of 52,488, this projects approximately 55,000-56,500 active patients by 2035
and 57,000-58,000 by 2040. The net effect is that waiting times are projected to decline
only modestly: the aggregate turnover ratio may fall from ~19.5 months to approximately
17-18 months by 2035 and 16-17 months by 2040, with kidney remaining above 22-24
months throughout. Waiting-list mortality, currently estimated at approximately 3,366
deaths per year (an average of 9 patients per day in the EU-27), is projected to decline
marginally to approximately 3,100-3,200 per year by 2035 and approximately 2,900-
3,100 by 2040, representing a persistently high and only slowly diminishing toll.
Burden of kidney disease and dialysis dependence: The EU’s dialysis-dependent
population (approximately 310,000 at T0, out of an estimated 511,549 on kidney
replacement therapy) is expected to grow over the assessment period, driven by the rising
incidence of chronic kidney disease associated with population ageing, the increasing
prevalence of diabetes and hypertension, and the widening of dialysis initiation criteria.
Under the baseline, the dialysis-dependent population is projected to rise to approximately
330,000-340,000 by 2035 and 350,000-365,000 by 2040. While the transplant rate will
also grow (kidney transplants are projected to rise from 19,170 in 2024 to approximately
22,700 by 2035 under the 1.54% CAGR), the demand-side growth will outpace the supply-
side gains, meaning the proportion of kidney replacement therapy patients living with a
functioning transplant rather than on dialysis will, at best, remain stable and may
marginally decline. This represents a structural constraint: absent a step-change in the
transplantable kidney supply, the kind of step-change that wider adoption of kidney
processing technologies could deliver, the baseline trajectory is one of growing, not
shrinking, unmet transplantation needs.
6.3 Expected impacts
The estimated impact on the adoption of organ processing technologies is based the
triangulation of three elements. First, the growth regimes in EU transplant activity
(0.59% pmp (2005–2012) and 1.54% pmp (2012–2024), yields an incremental
acceleration effect of +0.95 percentage points per annum since the transposition of
the Directive in 2012. Second, the expected programme-level adoption rises from 27%
of EU programmes at T0 to 42-48% by 2035, plateauing at 48-55% by 2040. The clinical
ceiling is estimated at 65-80% of programmes across all organ types. The gap between the
baseline plateau and the clinical ceiling (approximately 15-25 pp) represents the adoption
headroom that the regulatory intervention can unlock. Three scenarios assume that the
238 The 0.5% annual growth rate implies that the EU-27 waiting list grows from 52,488 (end-2024) to approximately
55,400 by 2035 and 56,800 by 2040. Combined with the baseline transplant projection (1.54% CAGR), this yields
aggregate turnover ratios of approximately 17.5 months (2035) and 16.6 months (2040). The plausible range of 0.35–
0.65% is determined by the joint constraint that the turnover ratio falls within 17-18 months by 2035 and 16-17 months
by 2040; a waiting-list growth rate below 0.28% or above 0.66% would violate one or both of these constraints.
163
framework closes 25%, 50%, and 100% of this headroom, respectively. Third, on organ-
level processing intensity, the proposed framework is expected to shift from “selective
use” toward “systematic use” by standardising benefit–risk assessment and generating
structured outcome data that strengthen the evidence case for routine application.
Table 5. Pillar 1: Programme-level adoption of organ processing
Indicator / horizon T0 (2024) 2030 2035 2040 Δ vs baseline (2035)
Baseline (no policy change) 27% 35–38% 42–48% 48–55% —
Conservative (25%) 27% 38–42% 50–55% 55–62% +5-8 pp
Moderate (50%) 27% 42–48% 55–63% 62–70% +10-15 pp
Optimistic (100%) 27% 48–55% 63–72% 70–78% +15-22 pp
Clinical ceiling (benchmark) — — 65–80% 65–80% —
Source: Estimates based on EDQM data, German national survey (Ibrahim et al., 2025), Italian national survey (Trapani
et al., 2022), and ONT (2025). The clinical ceiling is derived from Spanish (49% of transplanted organs processed) and
Italian data (62-70% of centres with MP experience by 2021), adjusted for EU-27 heterogeneity. Scaling factors represent
the assumed proportion of the 15-25 pp adoption headroom closed by the framework.
Under the moderate scenario, approximately 70-110 additional programmes adopt
active processing capability by 2035 that would not have done so under the baseline. The
incremental effect is concentrated in two categories: a) “second-tier” centres in advanced
Member States that have clinical capacity but currently lack institutional confidence
without regulatory validation; and b) centres in Member States with less developed
oversight infrastructure where an EU-level pathway substitutes for absent national
arrangements.
Table 6. Pillar 2: Organ-level processing intensity
Scenario T0 (2024) 2030 2035 2040 Δ vs baseline (2035)
Baseline 10–15% 14–18% 18–22% 20–25% —
Conservative (25%) 10–15% 16–20% 22–26% 25–30% +3-5 pp
Moderate (50%) 10–15% 18–23% 25–30% 30–36% +6-10 pp
Optimistic (100%) 10–15% 22–28% 30–38% 36–45% +10-16 pp
Source: T0 value derived from the German organ-level data (~20% of DBD livers, ~0.6% of DBD kidneys perfused),
weighted by EU-27 transplant volumes and adjusted upward to account for Spanish and Italian processing rates. The
moderate scenario assumes the framework shifts the centre-level equilibrium from selective to more systematic
application of processing, consistent with the transition from the German model (~20% of livers perfused selectively)
toward the Spanish model (~49% processed systematically).
Table 7. Pillar 3: Downstream transplant volume effect
Scenario Additional CAGR
increment
Additional
transplants/year
by 2035
Cumulative
additional (2028–
2035)
Transplant rate 2035
(pmp)
Baseline — — — 85.2
Conservative (25%) +0.24 pp/year ~730 ~3,150 86.8
Moderate (50%) +0.47 pp/year ~1,435 ~6,205 88.4
Optimistic (100%) +0.95 pp/year ~2,950 ~12,685 91.8
164
Source: The baseline CAGR of 1.54% pmp is applied forward from the 2024 anchor of 72.0 pmp; scenario CAGRs add the scaled
Directive effect (+0.95 pp × 25%/50%/100%) to the baseline rate from 2027 onwards. Cumulative figures cover 2028–2035 (eight full
years), as the 2027 start year marks entry into force of the authorisation regime, with the first full-year effect materialising in 2028.
Additional transplants/year by 2035 and pmp values are computed from year-by-year compound growth. Assumes a stable EU-27
population of ~448 million and no major external shocks.
Table 8. Consolidated estimate and central scenario
Impact dimension Conservative Moderate (central) Optimistic
Programme adoption (Δ by
2035)
+35–55 programmes (+5–8
pp)
+70–110 programmes (+10–
15 pp)
+110–160 programmes (+15–
22 pp)
Organ-level processing (Δ
by 2035)
+3–5 pp +6–10 pp +10–16 pp
Additional transplants/year
by 2035
~730 ~1,435 ~2,950
Cumulative add.
transplants (2028–35)
~3,150 ~6,205 ~12,685
Discard rate reduction (Δ
by 2035)
Additional −1–1.5 pp vs
baseline
Additional −1.5–2.5 pp vs
baseline
Additional −2.5–4 pp vs
baseline
The three pillars converge on the moderate scenario as the most defensible central
estimate. Four factors support a scaling factor closer to 50% than to 25%. First, the
technology is at an inflection point on its adoption S-curve (85% of German MP
programmes established 2020–2024), the moment at which a regulatory framework has its
greatest catalytic effect on fast followers. Second, the proposed model is an adaptation of
the tested SoHO Preparation Authorisation framework under Regulation (EU) 2024/1938,
reducing implementation risk. Third, 73% of EU programmes currently lack processing
capability, representing a large untapped adoption pool concentrated precisely in settings
where an EU harmonisation instrument has the greatest marginal impact. Fourth, the
framework’s primary function is to remove institutional and legal friction that slows
translation of existing evidence into practice.
Two countervailing factors constrain the estimate below. First, many national transplant
authorities will need to build multi-disciplinary assessment capabilities. Second, costs of
processing equipment (EUR 150,000–300,000 per perfusion device, plus recurrent
perfusate costs) will remain a barrier for less-resourced centres.
The estimated impact of MP on organ discard rate allows to estimate additional
transplants attributable to wider processing adoption. The EU-27 proxy baseline discard
rate is approximately 12-13% across all organs combined, implying approximately 4,110
organs discarded annually out of estimated 32,766 procured (deceased donors).
165
Liver
Table 9. Liver
Source Design Key Finding
Nasralla et al., 2018239 RCT (n = 220) ~50% lower liver discard rate with NMP vs. SCS (P = 0.008)
Mergental et al. (VITTAL),
2020240
Prospective
single-arm trial
71% of discarded livers passed NMP viability criteria; 22
transplanted, all functioning at 90 days
Hospital HTA review, BMC,
2022241
HTA meta-
review
Up to 50% lower graft discard; comparable/improved 1-year
survival
A conservative range (discounted for real-world selection effects) of 30–50% reduction
in liver discard rate where NMP is applied.
Lung
Table 10. Lung
Source Design Key Finding
Keshavjee et al. (2025)242 Single-centre retrospective
(n = 1,000)
65% of EVLP-assessed marginal lungs accepted for
transplant, representing 29% of all transplants performed
during the study period.
Tian et al. (2019)243 EVLP systematic review and
meta-analysis (8 studies, n =
1,191)
Successful transplantation of lungs with significantly worse
donor baselines (lower PaO2/FiO2, more abnormal CXR,
higher smoking rates) compared to non-EVLP standard
grafts, resulting in similar post-transplant outcome.
Chakos et al. (2020)244 Meta-analysis / 13 studies,
407 EVLP lung transplants
and 1,765 as per standard
protocol.
EVLP and standard protocol lungs show no significant
survival difference, despite EVLP lungs having significantly
worse PaO2/FiO2 ratios and a higher rate of abnormal
chest X-rays. EVLP expands the transplantable donor pool.
EVLP enables a 20-29% increase in programme transplant volume by rescuing
marginal donor lungs.
239 Nasralla, D., Coussios, C. C., Mergental, H., et al. (2018). A randomized trial of normothermic preservation in liver
transplantation. Nature, 557(7703), 50–56. https://doi.org/10.1038/s41586-018-0047-9 240 Mergental, H., Laing, R. W., Kirkham, A. J., Perera, M. T. P. R., Boteon, Y. L., Attard, J., Barton, D., Curbishley, S.,
Wilkhu, M., Neil, D. A. H., Hübscher, S. G., Muiesan, P., Isaac, J. R., Roberts, K. J., Abradelo, M., Schlegel, A.,
Ferguson, J., Cilliers, H., Bion, J., Adams, D. H., … Mirza, D. F. (2020). Transplantation of discarded livers following
viability testing with normothermic machine perfusion. Nature communications, 11(1), 2939.
https://doi.org/10.1038/s41467-020-16251-3 241 De Simone, P., & Ghinolfi, D. (2022). Hospital-Based Health Technology Assessment of Machine Perfusion Systems
for Human Liver Transplantation. Transplant international : official journal of the European Society for Organ
Transplantation, 35, 10405. https://doi.org/10.3389/ti.2022.10405 242 Keshavjee, S., Sage, A. T., Borrillo, T., Yeung, J. C., Piyasena, D., Wakeam, E., Donahoe, L., Waddell, T. K., De
Perrot, M., Pierre, A., Balachandran, S., Ghany, R., Ali, A., Yasufuku, K., & Cypel, M. (2025). One thousand cases of
ex vivo lung perfusion for lung transplantation: A single-center experience. Journal of Thoracic and Cardiovascular
Surgery, 171(2), 540-550.e2. https://doi.org/10.1016/j.jtcvs.2025.08.036 243 Tian, D., Wang, Y., Shiiya, H., Sun, C., Uemura, Y., Sato, M., & Nakajima, J. (2019). Outcomes of marginal donors
for lung transplantation after ex vivo lung perfusion: A systematic review and meta-analysis. Journal of Thoracic and
Cardiovascular Surgery, 159(2), 720-730.e6. https://doi.org/10.1016/j.jtcvs.2019.07.087 244 Chakos, A., Ferret, P., Muston, B., Yan, T. D., & Tian, D. H. (2020). Ex-vivo lung perfusion versus standard protocol
lung transplantation-mid-term survival and meta-analysis. Annals of cardiothoracic surgery, 9(1), 1–9.
https://doi.org/10.21037/acs.2020.01.02
166
Kidney
HPM primarily mitigates discard driven by extended cold ischaemia time (CIT). A large
OPTN population cohort study (n = 137,835) demonstrates that end-ischaemic HMP is
frequently deployed to rescue kidneys with significantly longer CITs (median 23.0 hours
versus 17.3 hours for the general pool), thereby preventing discard of organs delayed by
logistical or geographic barriers.245 The Cochrane kidney review further confirms that
HMP improves one-year graft survival to 94% compared to 90% for SCS.246 In the UK,
‘poor perfusion’ accounts for nearly 20% of the roughly 350 annual kidney organ discards
after retrieval.247
HMP/NMP could reduce kidney discards by 10-20% (reflecting indirect mechanism via
DGF prevention rather than direct viability assessment).
Conduct of business
Number and proportion of transplanted organs
The reform introduces a prior authorisation obligation that fundamentally restructures this
conduct of business. The new obligations impose operational requirements that centres
must integrate into their workflows, including documentation, data collection, and
engagement with the competent authority. The establishment of a clear regulatory pathway
resolves the legal ambiguity that, under the baseline, operates as a structural drag on
institutional decision-making.
The conduct-of-business impact is assessed along two dimensions: the change in the
operational model of transplantation centres (qualitative) and the change in transplant
output attributable to the policy-induced shift in processing adoption (quantitative).
Under the moderate policy scenario, the authorisation framework is projected to close
approximately 50% of the adoption headroom between the baseline plateau and the clinical
ceiling (estimated at 65-80% of programmes). This implies that programme-level adoption
reaches 55-63% by 2035, representing approximately 70-110 additional programmes
with active processing capability beyond the baseline. This means 70-110 programmes
(residing in an estimated 50-80 additional unique centres) transition from the second tier
to the first, adopting structured processing workflows under the Article 6a regime. These
centres will need to invest in processing equipment (MP device, recurrent perfusate and
disposable costs, etc.), train clinical and technical staff, and integrate the authorisation
process into their institutional governance.
245 Amarnath, D. R., Kourounis, G., Massie, A., Segev, D., Jochmans, I., Wilson, C. H., & Tingle, S. J. (2026). Machine
perfusion modulates cold preservation injury in kidney transplantation: IDEAL Stage 4 OPTN Population Cohort study.
American Journal of Transplantation. https://doi.org/10.1016/j.ajt.2026.02.025 246 Tingle, S. J., Figueiredo, R. S., Moir, J. A., Goodfellow, M., Talbot, D., & Wilson, C. H. (2019). Machine perfusion
preservation versus static cold storage for deceased donor kidney transplantation. The Cochrane database of systematic
reviews, 3(3), CD011671. https://doi.org/10.1002/14651858.CD011671.pub2 247 Fallon, J., Sagar, A., Elzawahry, M., Sadik, H., Gyoten, K., Abbas, S. H., Dumbill, R., & Friend, P. (2025). The
Hitchhiker's guide to isolated organ perfusion: a journey to 2040. Frontiers in transplantation, 4, 1642724.
https://doi.org/10.3389/frtra.2025.1642724
167
The operational model of existing first-tier centres also changes under the policy: centres
that currently process organs on an ad-hoc, selective basis are expected to shift toward
more systematic application. Organ-level processing intensity rises from a baseline of
18-22% by 2035 to 25-30% under the moderate scenario, a gain of 7-8 percentage
points. This shift is partially driven by the evidence-validation mechanism embedded in
the authorisation regime: the structured clinical-outcome data generated under Article 6a
(3) monitoring plans progressively strengthens the evidence base for routine (as opposed
to selective) processing.
The downstream transplant volume effect of this conduct-of-business transformation is
estimated at approximately 1,435 additional transplants per year by 2035 under the
moderate scenario, cumulating to approximately 6,205 additional transplants over the
2028-2035 period. This increment is composed of two channels: additional transplants in
centres that newly adopt processing capability and additional transplants in existing
processing centres that deepen their organ-level application rate.
As ~70-110 newly processing programmes represent roughly 10-15% of all EU
programmes, and assuming that these operate at the processing intensity of a centre in its
first 3-5 years of adoption (~10-15% of organs processed, below the EU-wide average
intensity of 25-30%), and that each programme performs, on average, approximately 55
transplants per year (derived from the EU aggregate of ~38,200 transplants across ~717
programmes under the 2035 baseline), the newly processing programmes contribute
approximately 385-905 additional organs processed annually. Applying an estimated
additional-transplant yield of approximately 15-20% of processed organs (reflecting
the combined effect of discard reduction, expanded acceptance of marginal donors, and
improved preservation enabling transplantation of organs that would otherwise have been
declined), this implies approximately 60-180 additional transplants per year from the
extensive margin. The remainder of the ~1,435 total (approximately 1,255-1,375 per year)
is attributable to deeper processing within existing first-tier centres and the compound
growth effect captured by the CAGR-proxy model.
The primary operational cost borne by transplantation centres under the policy, is the
administrative cost of the authorisation process itself. The equipment costs are not
attributable to the regulatory changes, since centres would face these costs under the
baseline if they chose to adopt processing on their own initiative. The framework's
marginal contribution to equipment expenditure is indirect (i.e., accelerating adoption
in 70-110 additional programmes, residing in an estimated 50-80 additional unique centres,
that would not have adopted under the baseline).
The authorisation regime imposes proportionate operational requirements on
transplantation centres while simultaneously removing the legal uncertainty that has
functioned as an institutional barrier to processing adoption.
Public health and safety
Organ discard rate
The authorisation regime accelerates the adoption and deepens the application of machine
perfusion and associated reconditioning technologies.
168
Drawing on the assumptions applied at the moderate-scenario organ-level processing
intensity of 25-30% by 2035, the organ-specific additional transplants attributable to
discard reduction are estimated as follows:248
• Liver Applying the 30-50% rescue rate yields approximately 120-265
additional livers transplanted per year by 2035 beyond the baseline. The liver
accounts for the single largest absolute discard reduction.
• Lung Applying a conservative EVLP rescue rate of 50-65% to the
approximately 70-125 would-be discarded within the processed pool, this
implies approximately 35-80 additional lungs transplanted per year by 2035.
• Kidney Applying the 10-20% rescue rate yields approximately 45-110
additional kidneys transplanted per year by 2035. The kidney estimate is the
most conservative of the three quantified organs, reflecting the indirect
mechanism of action (HMP primarily prevents delayed graft function and
thereby avoids secondary discard, rather than directly rehabilitating already-
compromised organs as with NMP for livers).
• Heart and pancreas: As DCD heart transplantation using normothermic
regional perfusion is at an early stage in the EU, and pancreas discard is driven
primarily by anatomical fragility during procurement rather than by
preservation-related deterioration, a negligible marginal discard reduction for
these organs in the assessment period is therefore assumed.
The organ-specific estimates sum to approximately 200-455 additional transplants per
year by 2035 attributable to the discard-reduction channel alone. This is substantially
below the central estimate of ~1,435 additional transplants per year, which is derived from
the top-down CAGR-proxy model.
Each additional organ transplanted represents a high-value therapeutic intervention.
While the economic value of a transplant varies by organ type and Member State, an
indicative estimate can be constructed for kidneys, which dominate the additional
transplant pool. Evidence suggests a median annual cost of in-centre haemodialysis at
approximately EUR 18,000-43,000 per patient (with wide cross-country variation)249,
while the annual maintenance/care cost of a kidney transplant recipient is approximately
EUR 10,000-30,000 per year on average during the first three years post-
transplantation.250 Adopting a mid-range estimate of EUR 20,000 in net annual savings
per kidney transplant (dialysis costs avoided minus transplant maintenance), the ~847
additional kidney transplants per year by 2035 imply recurrent annual savings of approx.
EUR 17 million per year from each annual cohort of additional transplants (of which
approximately 45-110 stem from the reduction in organ discard rate, accounting for EUR
248 For each organ, the number of procured organs at 2035 is derived by dividing the projected baseline deceased-donor
transplant volume (T0 deceased-donor transplants × the 1.1855 baseline growth factor) by (1 − baseline 2035 discard
rate). The additional transplants are then computed as: procured organs × processing intensity × baseline discard rate ×
evidence-based discard reduction rate. 249 ERA. (2025). Chronic Kidney Disease in Europe: The Missing Link in Cardiovascular Risk Assessment.
https://www.era-online.org/publications/chronic-kidney-disease-in-europe-the-missing-link-in-cardiovascular-risk-
assessment/ 250 Chamberlain, George & Baboolal, Keshwar & Pockett, Rhys & Mcewan, Phil & Sabater, Javier & Sennfält, Karin.
(2014). The Economic Burden of Posttransplant Events in Renal Transplant Recipients in Europe. Transplantation. 97.
854-61. 10.1097/01.TP.0000438205.04348.69
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0.9-2.2 million/year). This estimate excludes the substantial additional savings from
avoided dialysis among patients who receive additional liver, lung, and other organ
transplants (who would otherwise face end-stage organ failure with its associated intensive
care and palliative costs), and it does not account for the productivity gains from returning
transplant recipients to an active life.
Deceased donor utilisation rate
The deceased donor utilisation rate measures whether a donor from whom organs are
procured ultimately yields at least one transplant.
Under the moderate scenario, the accelerated adoption of processing technologies is
expected to yield an additional 0.5-1.0 percentage point improvement, reaching
approximately 96-97% by 2035. Applied to the projected number of actual deceased
donors (~12,000-12,500 by 2035, assuming modest growth in the donor pool), this implies
that an additional 60-125 donors would proceed to at least one transplant annually
compared with the baseline. The gains are expected to be concentrated among DCD
donors, where the policy-induced improvement may be as large as 2-3 percentage points
(from a baseline-projected ~88% to ~90-91%), reflecting the particular clinical value of
machine perfusion in managing the ischaemic injury inherent in circulatory-death
donation.
This indicator measures donor-level salvage rather than organ-level salvage. A donor who,
under the baseline, would have been abandoned entirely because all procured organs were
deemed unviable may, with processing, yield one or more transplantable organs. The
combined effect of the above indicators is therefore larger than either alone.
Organ yield per utilised deceased donor
Processing technologies rehabilitate individual organs within multi-organ donors that
would otherwise be discarded, thereby increasing the per-donor transplant count.
Under the moderate scenario, the broader adoption of processing is expected to increase
organ yield by an additional 0.05-0.15 per utilised donor beyond the baseline, reaching
approximately 2.90-3.05 by 2035. Applied to approximately 11,663-11,868 utilised donors
projected by 2035251, this translates to approximately 583-1,780 additional organs per
year, a range that brackets central estimate of ~1,435 additional transplants per year,
providing internal consistency.
While the discard rate captures whether a specific procured organ is transplanted, the
organ yield captures the aggregate recovery per donor. A centre that begins processing
livers may simultaneously discover that viability assessment enables it to accept additional
kidneys from the same donor, a synergistic “technology spillover” effect that is well-
documented in the clinical literature.
251 The baseline projects total transplants at ~38,200 by 2035. Living-donor transplants at T0 are ~3,691 (11.5% of
32,222). Deceased-donor transplants by 2035: 38,200 × (1 – 0.115) = ~33,824. Dividing by the baseline organ yield of
2.85-2.90 gives: 33,824 / 2.90 = 11,663 to 33,824 / 2.85 = 11,868 utilised donors.
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Rate of serious adverse events and reactions (SAE/SAR)
The proposed authorisation regime introduces three safety-relevant mechanisms that are
absent under the baseline: a) mandatory benefit–risk assessment prior to the clinical
application of any processing technique; b) mandatory clinical-outcome monitoring plans
for novel or higher-risk processing techniques, which generate structured evidence on
processing-related adverse events; and c) the addition of “Processing” as a data field in the
complementary data set, which creates the taxonomic infrastructure to disaggregate
processing-attributable events from those attributable to other causes.
The impact of the authorisation regime on SAE/SAR rates could not be quantified. First,
the available evidence does not disaggregate processing-attributable adverse events, thus
there is no baseline against which to measure a processing-specific safety improvement.
Second, the initial effect of improved reporting infrastructure is likely to increase recorded
SAE/SARs, an artefact of better detection rather than worse safety. Third, the adverse
events prevented by the ex-ante safety filter (i.e., processing techniques that are not
authorised because they fail the benefit–risk assessment) are counterfactual events.
A first qualitative conclusion is that the authorisation regime will create a systematic
capacity to detect and attribute processing-related adverse events at the EU level.
This is a significant safety improvement over the baseline, where processing-related harms
may be occurring but going unrecorded because the existing vigilance taxonomy does not
include processing as a cause category. A second qualitative conclusion is that each organ
lost to an unregulated, ineffective processing attempt represents both a direct patient-
safety failure (potential harm to the intended recipient) and an indirect harm (denial of
a viable organ to another patient on the waiting list).
Over the medium term (post-2035), the accumulation of structured clinical-outcome data
from monitoring plans under Article 6a (3) will enable evidence-based refinement of
processing protocols, progressively improving the safety profile of the field.
Average waiting time to transplantation
Additional transplants generated by the policy reduce the backlog of patients on the waiting
list, shortening the average time to transplantation. The effect is organ-specific and is most
consequential for kidneys (42,855 of 52,488 active patients at end-2024, i.e. 82%).
Under the moderate scenario, the ~1,435 additional transplants per year by 2035 would
further reduce the turnover ratio. Under the baseline, 2035 transplant volumes are projected
at ~38,200 against a waiting list of approximately 55,000-56,500 (derived from the T0
waiting list of 52,488 growing at the assumed 0.5% per year). This yields a baseline
turnover ratio of approximately 17.2-17.8 months. With the additional ~1,435 transplants,
the denominator rises to ~39,635, producing a turnover ratio of approximately 16.5-17.1
months; a reduction of approximately 0.6 months (roughly 2.5 weeks) relative to the
baseline. For kidney specifically,where ~847 additional transplants (59% of 1,435) are
projected, and applying the same demand-side growth rate to the kidney waiting list (from
42,855 at T0 to approximately 44,500-46,000 by 2035), the kidney turnover ratio
declines from a baseline of approximately 23.5-24.5 months to approximately 22.5-
23.5 months, a reduction of approximately 1 month. This aggregate effect is modest, as
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the demand side (driven by demographic ageing and the rising prevalence of chronic
kidney disease) is growing in parallel with the supply side, and the ~1,435 additional
transplants per year represent a ~3.8% increment over the baseline transplant volume of
~38,200. A step-change in waiting times would require a substantially larger supply
expansion than the processing amendments alone can deliver. Stakeholders
representing European societies of relevant healthcare professionals identified domestic
donation infrastructure (consent laws, transplant coordinators, elimination of conflicts of
interest) rather than processing technology as the primary variable affecting system
performance. However, the modest aggregate conceals a more meaningful effect for
specific patient populations. Additional liver transplants (estimated 120-265/year)
against a liver waiting list of ~4,500 by 2035 would reduce the liver turnover ratio by
approximately 0.1-0.2 months.252 For lung, additional transplants (35-80/year)
against a smaller waiting list (1,600) would reduce the turnover ratio by
approximately 0.1-0.2 months.253 While organ-specific discard-reduction channel
alone produces small waiting-time effects, but that the total policy effect (captured by
the aggregate ~1,435 figure) delivers the approximately 0.5-0.7-month aggregate
reduction.
Burden of kidney disease and dialysis dependence
Each additional kidney transplant removes one patient from chronic dialysis. Under the
moderate scenario, approximately 847 additional kidney transplants per year by 2035 (59%
of the total ~1,435 additional transplants) would be performed. Cumulated over the 2028-
2035 period, this yields approximately 3,660 additional kidney transplants beyond the
baseline. Assuming an average five-year kidney graft survival rate of approximately 90%
(consistent with European registry data), approximately 3,295 additional patients would be
living with a functioning transplant rather than on dialysis by 2035. Against a projected
dialysis-dependent population of ~335,000 under the baseline, this represents a reduction
of approximately 1.0%. The proportion of KRT patients on dialysis would decline from
approximately 60.6% (baseline) to approximately 60.0% (policy scenario), a
measurable but structurally modest shift. The policy only slows the growth of the dialysis-
dependent population: the additional ~847 kidney transplants per year represent a ~3.7%
increment over baseline kidney transplant volumes, while the dialysis-dependent
population is growing by approximately 1–1.5% per year (roughly 3,000-5,000 additional
dialysis patients annually).
Using the conservative estimate of EUR 20,000 in net annual savings per kidney transplant
patient (dialysis avoided minus transplant maintenance), the approximately 3,295
additional patients living with a functioning transplant by 2035 (representing the decrease
252 Baseline liver transplants 2035 (total, including living donor at 3% share): 8,015 × 1.1855 growth factor = ~9,502.
Baseline liver turnover: (4,500 / 9,502) × 12 = 5.68 months.
• With +120 additional: (4,500 / 9,662) × 12 = 5.61 months → reduction = 0.07 months (approx. 0.1)
• With +265 additional: (4,500 / 9,752) × 12 = 5.53 months → reduction = 0.15 months (approx. 0.2)
The aggregate growth factor of 1.1855 is the ratio of projected baseline total transplants in 2035 to total transplants at
T0 (38,200 / 32,222). 253 Baseline lung transplants 2035: 2,221 × 1.1855 = ~2,633.
Baseline lung turnover: (1,600 / 2,633) × 12 = 7.29 months.
• With +35: (1,600 / 2,668) × 12 = 7.20 months → reduction = 0.10 months (approx. 0.1)
• With +80: (1,600 / 2,713) × 12 = 7.08 months → reduction = 0.22 months (approx. 0.2)
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in dialysis-dependent population by 2035) would generate recurrent annual healthcare
savings of approximately EUR 66 million per year from 2035 onwards. The
cumulative dialysis cost avoidance over the 2028–2035 period is estimated at
approximately EUR 158 million.254 This estimate applies the lower bound of the net
savings range derivable from European health-economic literature, and excludes the
broader economic benefits of reduced hospitalisation, improved quality of life, and
restored workforce participation among transplant recipients.
Waiting-list mortality
Each additional transplant removes a patient from the waiting list and eliminates their
exposure to waiting-list mortality risk.
To estimate the policy impact, the annual waiting-list mortality rate to the patient-years
of waiting-list exposure averted by additional transplants is applied. The annual
waiting-list mortality rate at T0 is approximately 6.4% (3,366 deaths / 52,488 patients). By
2035, this rate may decline modestly to approximately 5.5-6.0% as transplant volumes
grow. The ~1,435 additional transplants per year by 2035 each remove one patient from
the waiting-list mortality risk pool. Not all additional transplants avert a death: many
patients on the waiting list, particularly those with less urgent need, would survive to
receive a transplant under the baseline regardless. The marginal mortality-prevention effect
of an additional transplant depends on the urgency profile of the patients reached.
If the annual waiting-list mortality rate among the marginal patient population (those who
receive an additional transplant earlier than they would have under the baseline) is
approximately 4-5% (lower than the average, reflecting that the most urgent patients are
already prioritised under existing allocation systems), ~1,435 additional transplants per
year would prevent approximately 57-72 waiting-list deaths per year by 2035. Over
the cumulative period 2028–2035, with a progressive ramp-up of additional transplant
volumes, the total number of waiting-list deaths averted is estimated at 248-311.
This estimate can be cross-validated against organ-specific waiting-list mortality data. The
~1,435 additional transplants per year by 2035 are allocated across organ types using the
T0 EU-27 transplant distribution, yielding approximately 847 additional kidney transplants
(~59%), 357 liver transplants (24.9%), and 99 lung transplants (6.9%). Applying the organ-
specific annual waiting-list mortality rates: kidney: 4.2% (1,797 deaths / 42,855 active
254 Assumption: Net savings begin the year after transplant (year 1 is absorbed by surgery costs), with 2% annual graft
attrition.
Each cohort generates savings only in subsequent years within the period, discounted by graft loss:
• 2028 cohort (94 patients): savings in 2029–2035 = 94 × (0.98 + 0.98² + … + 0.98⁷) = 94 × 6.48 = 609
patient-years
• 2029 cohort (191): savings in 2030–2035 = 191 × 5.60 = 1,070
• 2030 cohort (291): savings in 2031–2035 = 291 × 4.71 = 1,371
• 2031 cohort (395): savings in 2032–2035 = 395 × 3.81 = 1,504
• 2032 cohort (502): savings in 2033–2035 = 502 × 2.88 = 1,446
• 2033 cohort (614): savings in 2034–2035 = 614 × 1.94 = 1,191
• 2034 cohort (729): savings in 2035 only = 729 × 0.98 = 714
• 2035 cohort (847): no savings within period (surgery year) = 0
Total: 7,905 patient-years × EUR 20,000 = ~ EUR 158 million
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patients); liver: 21.9% (934 / 4,270); lung: 14.7% (221 / 1,500), the following averted
deaths per year by 2035 are estimated: kidney ~36; liver ~78; lung ~15; summing to
approximately 129 averted deaths per year.
This estimate substantially exceeds the aggregate estimate of 57–72 derived above. The
divergence is a direct consequence of the methodological difference between the two
approaches. The aggregate estimate applies a flat marginal mortality rate of 4–5%,
deliberately calibrated below the overall waiting-list average of 6.4% to reflect the
assumption that marginal transplants disproportionately benefit less-urgent patients. The
organ-specific approach applies actual waiting-list mortality rates and reveals that the
additional transplant pool includes approximately 25% liver, an organ type whose waiting-
list mortality (21.9%) is more than five times the flat rate assumed. The organ-weighted
average mortality rate across the additional transplant pool is approximately 9.8%, roughly
double the flat-rate assumption.
The conservative aggregate estimate of 57–72 averted deaths per year is adopted. Each
averted waiting-list death represents a life prolonged by transplantation. While assigning
a monetary value to prevented premature death is methodologically and ethically
contested, the European Commission reference value of a statistical life year (VOLY) (~
EUR 115,000)255 provides a reference frame. If the average additional life expectancy
conferred by transplantation is approximately 10-15 years, the cumulative value of 248-
311 averted deaths over the 2028–2035 period256 is in the range of EUR 285–537
million.
Administrative costs on businesses, including SMEs
Cost of organ processing authorisation application
Transplantation centres that perform processing must submit either a benefit–risk
assessment (Article 6a(2)) or a clinical-outcome monitoring plan (Track 2, Article 6a(3))
to the competent authority, verify the regulatory status of any products used in processing
across the pharmaceutical, medical device, and SoHO frameworks (Articles 6a(4)–(7)),
manage the ongoing authorisation relationship (Article 6a(9)), and collect and report
processing-specific data under the amended Annex (Part B).
The administrative cost falls on transplantation centres as the applicants, while the
competent authorities bear a corresponding assessment cost. The proposal does not
introduce a fee mechanism.
One national transplant authority estimates that the assessment of a single processing
authorisation application requires approximately 15 working days for one person on the
competent authority side, excluding external expert consultations. On the applicant
(transplantation centre) side, the preparation effort is expected to be of a higher magnitude,
as the centre must compile the clinical evidence, perform or commission the benefit–risk
255 European Commission. (2024). Commission staff working document: impact assessment report. SWD(2024) 63 final. 256 At 4%: Σ(year-by-year additional transplants × 0.04) = 248; At 5%: Σ(year-by-year additional transplants × 0.05) =
311.
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assessment, document the processing protocol, and assemble the cross-framework
verification dossier. This effort can be differentiated as follows:
• Track 1 (full authorisation, Article 6a (2)): applicable to well-established
processing techniques with a robust evidence base. Estimated effort is 15
working days of senior clinical/scientific staff, 10 working days of
regulatory/quality staff, and 5 working days of administrative support. This
leads to approximately EUR 11,500.
• Track 2 (conditional authorisation with clinical-outcome monitoring,
Article 6a (3)): applicable to novel or higher-risk techniques where the evidence
base is insufficient for a full benefit–risk assessment. Estimated effort is 20
working days of senior clinical/scientific staff, 15 working days of
regulatory/quality staff, and 10 working days of administrative support. This
leads to approximately EUR 16,750.
These estimates are based on EU-level loaded labour costs for healthcare professionals
(Eurostat, NACE Rev.2 Section Q), which incorporate gross wages, employer social
contributions, and institutional overhead: senior clinical/scientific staff at EUR 350-450
per working day; regulatory/quality officers at EUR 250-350 per working day; and
administrative support at EUR 150-250 per working day.
Furthermore, centres authorised under Track 2 bear recurrent data collection,
analysis, and reporting obligations for the duration of the monitoring period. These
are estimated at approximately 5 working days per quarter (20 days per year) of
clinical/quality staff time, amounting to EUR 9,000 per year per active monitoring plan.
The weighted average per-application cost depends on the expected distribution between
Track 1 and Track 2 applications. In the initial transition phase (years 1-3 post-
transposition), the majority of applications will concern established techniques for which
substantial clinical evidence already exists: we estimate approximately 70-80% Track 1
and 20-30% Track 2. Over time, as the field shifts toward more novel processing
modalities, the Track 2 share will rise progressively. For the initial transition phase, the
weighted average cost per application is approximately EUR 12,800.
The total EU-27 administrative burden depends on the volume of authorisation
applications. This is estimated as follows, anchored in stakeholder consultations:
1. Initial transition phase (years 1-3 post-transposition, approximately 2029-
2031): The entry into force of the regime will generate a transitional surge of
applications as centres seek to regularise processing techniques already in
clinical use. At T0, approximately 195 programmes across an estimated 120-
160 centres have active processing capability. Each centre will need to secure
authorisation for each distinct processing technique it employs. The number of
distinct techniques requiring separate authorisation per centre is estimated at 1-
3. However, a competent authority's assessment of a given technique may apply
to multiple centres within the same jurisdiction. Therefore, the total initial
application volume at the Member State level is estimated at: approximately 15-
18 Member States with active processing centres, each processing 4-8 distinct
technique-level applications during the transition, yielding approximately 60-
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145 applications across the EU-27 during the transition period (central
estimate: ~100). At a weighted average cost of ~EUR 12,800 per application,
the total transition-phase administrative cost for transplantation centres is
approximately EUR 768,000-1,856,000, spread over three years.
For Track 2 authorisations, the ongoing monitoring obligation generates a persistent annual
cost. If approximately 25% of all authorisations issued are Track 2, and at and additional
EUR 9,000 per monitoring plan per year (EUR 27,000 over three years), the aggregate
recurrent monitoring cost over the three years is approximately EUR 405,000-980,000.
This brings the total to EUR 1,173,000-2,836,000 (central estimate per year: ~EUR
670,000).
2. Steady-state phase (from approximately 2032 onwards): One national
transplant authority consulted estimate of 2-3 applications per year for its
Member State provides the anchor. Assuming 2 applications per Member State
and extrapolating to the EU-27 by scaling for the number of active processing
centres relative to this same Member State, the steady-state flow is estimated at
approximately 7-10 applications per year across the EU-27. The annual
steady-state administrative cost on transplantation centres is therefore
approximately EUR 90,000-128,000 per year. An additional EUR 16,000-
22,500 in recurrent monitoring costs can be expected, bringing the total to
approximately EUR 106,000-150,500 (central estimate: ~EUR 130,000).
Over the 2029-2035 assessment period, the cumulative administrative cost on
transplantation centres is estimated at approximately EUR 2.5 million.
This estimated gross administrative cost must be assessed against the counterfactual
baseline costs. Under the baseline, transplantation centres in Member States that develop
national oversight arrangements bear jurisdiction-specific documentation, reporting, and
approval costs that are fragmented, duplicative, and non-standardised. The harmonised EU
framework replaces this patchwork with a standardised administrative process that delivers
two efficiency gains: a) centres can use common templates and evidentiary standards,
reducing duplicative preparation effort; and b) the published list of authorised processing
operations (Article 6a(11)) means that a technique authorised in one Member State
generates transferable evidence for formal authorisation at the national level. The net
incremental administrative cost of the policy, relative to the baseline, is therefore lower
than the gross estimates above.
Functioning of the internal market and competition
Cross-border organ exchange
By establishing common EU-level quality and safety standards for organ processing, the
framework enables competent authorities in receiving Member States to accept processed
organs originating elsewhere on the basis of a recognised authorisation rather than ad hoc
bilateral assessment. MP also extends the viable preservation time of organs, thereby
widening the geographic catchment area within which an organ can be allocated.
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The policy is expected to generate a modest but real upward shift in cross-border
exchange, operating primarily through the trust channel rather than through an increase in
the absolute number of organs available for export. Based on stakeholder consultations,
the magnitude of this effect is expected to be limited by the fact that domestic demand
absorbs the large majority of processing-enabled additional organs; by the cumbersome
logistical burden of cross-border transport of organs on perfusion devices; and by the fact
that cross-border kidney exchange programmes primarily serve hyperimmunised patients
(approximately 5% of kidney waiting lists).
The harmonisation effect is important for two reasons. First, within existing exchange
organisations, the proportion of exchanged organs that have undergone processing is
expected to rise materially over the assessment period. If the share of transplanted organs
that undergo processing rises to 25-30 % by 2035 under the moderate scenario, then
approximately one in four cross-border organs would be a processed organ, a
proportion at which the absence of harmonised standards would constitute a material
barrier. Second, the extension of viable preservation time enabled by wider perfusion
adoption enlarges the effective catchment area for organ allocation within existing
exchange systems.
Under the moderate policy scenario, total EU-27 transplant volumes are projected at
approximately 39,635 by 2035 (38,200 baseline + ~1,435 additional). Within
Eurotransplant, which performs over 22% of EU transplants (7,160/32,222), this implies
approximately 9,100 allocated organs by 2035. If the harmonised framework enables an
increase in the cross-border exchange rate of 1-2 percentage points (from the baseline ~20-
23% to ~22-25%), this would correspond to approximately 90-180 additional cross-border
organ exchanges per year within the Eurotransplant system alone. Extrapolating
proportionally to the full EU-27, the total increment is estimated at approximately 120-250
additional cross-border organ exchanges per year by 2035. The effect is concentrated
in hearts and lungs, where cross-border exchange rates are already highest (31.8% and
28.9% respectively within Eurotransplant at T0) and where MP most directly extends the
allocation radius. This estimate reflects both the stakeholder views on the structural
constraints described above and the observation that Eurotransplant's cross-border
exchange rate has remained stable at 20-23% over recent years despite concurrent
processing adoption.
Innovation and research
Transplantation centres actively performing advanced organ processing
First, the establishment of a defined EU-level pathway for organ processing removes the
legal uncertainty that, under the baseline, functions as a structural deterrent to institutional
investment in processing capability. Second, the mandatory clinical-outcome monitoring
plans generate structured, standardised outcome data that do not currently exist at the EU
level. This data infrastructure enables cross-centre and cross-country comparison of
processing outcomes, supports the progressive strengthening of the evidence base for
specific techniques, and provides the empirical foundation for future evidence-based
regulatory refinement. Third, the dual-track authorisation model seeks to accommodate
next-generation processing technologies that are at earlier stages of clinical development.
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The quantitative impact of the policy on the rate of processing technology adoption can
be summarised as follows. Under the baseline, the share of EU-27 programmes with active
processing capability is projected to rise from approximately 27% at T0 to 42-48% by
2035, plateauing at 48-55% by 2040. The clinical ceiling, derived from benchmarking
against Spain, Germany, and Italy, is estimated at 65-80% of programmes. Under the
moderate policy scenario, adoption reaches 55-63% by 2035, representing
approximately 70-110 additional programmes (residing in an estimated 50-80
additional unique centres) transitioning to active processing capability beyond the baseline.
With regards to the clinical evidence base for organ processing, the policy transforms the
nationally siloed environment as the clinical-outcome monitoring plans generate
structured, prospective outcome data for novel or higher-risk processing techniques.
Assuming that approximately 25% of authorisations issued during the transition phase are
Track 2, this implies approximately 15-36 active monitoring plans across the EU-27
during the transition period, each generating structured data on processing-specific
outcomes. Moreover, the addition of "Processing" as a data field in the
complementary data set (Part B of the Annex) creates the taxonomic infrastructure to
disaggregate processing-attributable outcomes from those attributable to other causes.
The most consequential long-term innovation effect may be the framework's impact on
next-generation processing technologies. Under the baseline, these technologies face an
uncertain and fragmented regulatory environment that could deter the private investment
necessary for clinical translation. The conditional-authorisation pathway under Article 6a
(3) is specifically designed to address this. The absence of such a pathway risks either
driving innovation outside the EU or allowing unregulated experimentation that could
compromise patient safety and undermine public trust in the technology.
Public authorities
Organ processing authorisations granted
The proposed Article 6a regime introduces a new supervisory mandate for national
competent authorities, requiring them to receive, assess, and determine applications for
organ processing authorization.
During the transition phase (approximately 2029–2031), the authorisation regime's entry
into force generates a transitional surge of applications as centres regularise processing
techniques already in clinical use. The total initial application volume is estimated at
approximately 60-145 applications across the EU-27 over this three-year period (central
estimate: ~100). Each application requires competent-authority assessment. The national
transplant authority consulted estimated the processing time per assessment at
approximately 15 working days for one person, excluding external expert consultations.
Applying this estimate, and incorporating the cost of external expert consultations
(estimated at 3-5 days per assessment at approximately EUR 400-500 per day for clinical
and pharmacological specialists), the per-assessment cost on the competent authority side
is estimated as follows:
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• Internal assessment staff: 15 working days × EUR 350-450 per day (loaded
labour cost for senior health-authority officials, Eurostat NACE Q) = EUR
5,250-6,750
• External expert consultation: 3-5 days × EUR 400-500 per day = EUR 1,200-
2,500
• Administrative overhead (documentation, correspondence, cross-framework
verification under Articles 6a (4)– (7)): estimated at approximately EUR 500-
750 per assessment
• Total per-assessment cost on the competent authority side: approximately
EUR 7,000-10,000 (central estimate: ~EUR 8,500)
For the transition phase, the aggregate competent-authority cost is therefore approximately
EUR 420,000-1,450,000 over three years (central estimate: ~EUR 850,000, or ~EUR
280,000 per year). Distributed across 15-18 Member States with active processing centres,
this equates to approximately EUR 28,000-96,000 per Member State over the full
transition period.
During the steady-state phase (from approximately 2032 onwards), the steady-state
application flow is estimated at approximately 7-10 applications per year across the EU-
27. At the per-assessment cost of ~EUR 8,500, the annual steady-state competent-authority
assessment cost is approximately EUR 60,000-85,000 per year across the EU-27. This is
a modest recurrent cost in absolute terms, but it is unevenly distributed: larger Member
States with multiple active processing centres (Germany, France, Italy, Spain) will handle
the majority of applications, while smaller Member States may process one application
every several years or none at all.
In addition, for processing techniques authorised under Track 2 (conditional authorisation
with clinical-outcome monitoring), competent authorities must review periodic monitoring
reports, assessed whether the evidence supports transition to full authorisation or warrants
withdrawal, and coordinate data interpretation with the centres. This recurrent
monitoring oversight is estimated at approximately 3-5 working days per active
monitoring plan per reporting cycle (assumed quarterly), equating to approximately 12-20
days per year per active Track 2 authorisation. If approximately 15–36 monitoring plans
are active during the transition phase (25% of ~60–145 authorisations), the aggregate
monitoring oversight cost is approximately EUR 63,000-216,000 per year during the
transition phase (declining in the steady state as monitoring plans convert to full
authorisations or are withdrawn).
Furthermore, the upfront institutional investment required to establish the assessment
capability (capacity-building cost) encompasses recruitment or training of staff with
multidisciplinary assessment expertise; establishment of formal cooperation channels with
pharmaceutical, medical device, and SoHO authorities (as mandated by Articles 6a (4)–
(8)); and development of internal procedures and assessment templates. Quantification of
these one-time institutional costs is not possible with precision from the available
evidence.
Moreover, the proposal formalises and mandates coordination with pharmaceutical,
medical device, and SoHO authorities regarding the regulatory status and clinical outcome
data of products used in organ processing. The recurrent cost of this coordination is
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difficult to isolate from the per-assessment cost estimated above (which already includes
cross-framework verification time), but it represents a qualitative expansion of the
competent authority's relational network that, over time, will require established
inter-authority communication protocols and possibly joint assessment procedures.
It is worth noting that cooperation with the medicines agency in the SoHO context is
already smooth and operational in some Member States; the marginal effort to extend this
model to the organ processing context is expected to be limited in Member States with
existing cooperation infrastructure but more substantial in those without.
The proposal also generates administrative costs at the EU level. The Commission is
tasked with: adopting implementing acts to establish the detailed authorisation procedure
(Article 6a(12)); maintaining and updating the publicly accessible list of authorised
processing operations (Article 6a(11)); and facilitating the exchange of clinical outcome
data between competent authorities (Article 8, as amended). The magnitude of the
Commission-level investment is not quantifiable from the available evidence, but the
SoHO Regulation (2024/1938), which establishes a comparable framework for SoHO
preparation authorisation, provides an indicative precedent.
Overall, the marginal cost per assessment should decline over time as the body of
authorised techniques grows. The net incremental cost of the policy on public authorities,
relative to the baseline, is therefore lower than the gross estimates above, and the
qualitative benefits (systematic oversight capability, cross-framework coordination, EU-
level evidence infrastructure) represent a structural improvement in the public-
authority governance of organ transplantation that cannot be replicated by
fragmented national action.
7 INTERVENTION N°9: RECOGNITION AND SUPPORT OF STRATEGIC HEALTH
BIOTECHNOLOGY PROJECTS
7.1 Detailed description of the proposed measures
The measure establishes a framework for the recognition and support of health
biotechnology strategic projects within the Union, with the objective to address bottlenecks
in project execution and scale-up by reducing regulatory fragmentation, shortening
permitting timelines, improving administrative coordination, and facilitating access to
funding and investment.
Under this framework, Member States designate, by reasoned decision, projects located in
the Union that make a substantial contribution to the objectives of strengthening industrial
capacity, securing value chains, and accelerating the development and deployment of
biotechnology products. Recognised projects are then granted access to a coordinated
package of regulatory, administrative and financial support measures:
• Access to single points of contact (SPOCs) to coordinate the permit-granting
process and provide information on administrative, technical and financial
support.
• Administrative support, including: (a) assistance to ensure compliance with
administrative, regulatory and reporting obligations; (b) support and facilitation
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of permitting and authorisation procedures; and (c) assistance to inform the
public and those in the vicinity of the project.
• Permit-granting deadlines - 10 months from acknowledgement that the
application is complete, with a possible extension of up to 3 months in duly
justified complex cases.
• Priority status / public interest: considered as contributing to strengthening
biomanufacturing capacity and supply resilience of biotechnology products in
the Union and therefore considered in the public interest.
• Accelerated procedures.
• Highest national significance status available in national law and ensure the
most rapid permit-granting and licensing procedures possible, including
environmental and spatial-planning procedures.
• Urgent treatment for dispute resolution and judicial remedies relating to such
projects, to the extent national law allows.
• National support eligibility: Member States may use relevant frameworks for
providing public support, including national promotional banks and other public
support instruments, in line with State aid rules, to support health biotechnology
strategic projects.
• Union-level financial support: Projects can be supported under Union
programmes, funds and financial instruments, but without an explicit priority
label.
• Access to EU Health Biotechnology Support Network and related services:
project promoters receive support for identifying Union-level funding
opportunities, liaison with investors. They are also directed by SPOCs to
national and regional antennas of the Network.
7.2 Baseline and counterfactual scenario
Under the baseline, the following conditions are expected to persist:
- project delivery in health biotechnology remains characterised by slow and fragmented
administrative pathways, with complex procedures and uncertain timelines. The burden is
expected to be disproportionate for SMEs, start-ups and scale-ups, with barriers to scaling
up production linked to complex and fragmented permitting, overlapping legislative
requirements and uneven implementation across Member States.
- no dedicated EU-level priority-project recognition or fast-track governance track exists
under the baseline, meaning there is no recognised strategic project pipeline and no project-
specific signal or coordinated “front door” for investors and public financiers to identify,
diligence and prioritise strategic-scale projects.
- structural finance constraints at scale-up and industrial deployment stages persist,
reflecting fragmented capital markets and limited depth of pan-European late-stage funds,
while access to public and private investment instruments (including debt and equity)
remains difficult and is often perceived as not worth applying for.
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- biotechnology ecosystems remain fragmented, with clusters, infrastructures and support
schemes often operating in isolation, limiting critical mass, cross-border collaboration and
EU-scale value chain formation.
- investment decisions for strategic-scale deployments remain constrained by a
combination of the wider financing environment and project-level execution risk,
including permitting uncertainty and time-to-revenue risk.
2025 baseline (status quo)
In 2025, the baseline issue was that health biotechnology projects were materially affected
by fragmented administrative pathways and limited predictability. Stakeholder inputs
pointed to duplication and uncertainty, with repeated calls for a one-stop shop for
regulation and permitting and for maximum timelines and accelerated approval concepts
to reduce friction, particularly for SMEs and start-ups. Public consultation257 results
reinforced the salience of permitting as a bottleneck: 61.6% (286 out of 464) agreed or
strongly agreed that the length and or complexity of permitting processes for new facilities
is a challenge for biotechnology manufacturing in the EU, rising to 75.4% (153 out of 203)
among industry respondents.
The core conduct-of-business baseline metric concerned permit-granting duration and
predictability, measured from acknowledgement of completeness to the final decision,
including the share completed within a 10-month benchmark and the use of extensions.
Health-biotechnology-specific permitting duration statistics are not available, but
comparable strategic industrial project evidence indicated that permitting timelines can
vary from months to multiple years, with substantial outliers and with environmental
assessment durations ranging widely across Member States.
Competitiveness and investment conditions reflected a pronounced scale gap. As
background context on the wider financing environment. Over the last 10 years, US
biopharma start-ups received around nine times more late-stage funding than EU
biopharma start-ups, with around EUR 219 billion of venture capital focused on health
biotechnology invested in the US compared to EUR 25 billion in the EU between 2015
and June 2025258. At project level, the baseline constraint for strategic-scale deployments
was not only the general funding gap, but also the absence of a recognised project pipeline
and associated project-specific signal for investors and public financiers, with projects
remaining exposed to permitting uncertainty and execution risk, delaying financing
decisions and extending time-to-close.
Public consultation259 evidence further indicated persistent hurdles in accessing finance.
Only 18.8% (87 out of 464) agreed or strongly agreed that it is easy to access EU grants
and subsidies such as Horizon or EU4Health, while 45.9% (213 out of 464) disagreed or
strongly disagreed. For debt and equity instruments such as the EIC, EIB or STEP, only
257 European Commission ‘Have Your Say’, European Commission website, https://ec.europa.eu/info/law/better-
regulation/have-your-say/initiatives/14627-Biotech-Act/public-consultation_en. 258 Landscape analysis study 259 European Commission ‘Have Your Say’, European Commission website, https://ec.europa.eu/info/law/better-
regulation/have-your-say/initiatives/14627-Biotech-Act/public-consultation_en.
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5.2% (24 out of 464) agreed or strongly agreed that access is easy, compared with 46.3%
(215 out of 464) who disagreed or strongly disagreed, while neutral and not applicable or
I do not know responses together accounted for 48.5% (225 out of 464). This reinforced
the perception that companies do not see a clear, coordinated pathway to identify and
access relevant instruments and that the expected costs of applying can outweigh perceived
benefits.
Innovation performance combined strong science with weaker translation. The EU
produced more biotechnology publications than the US, yet the US consistently filed more
IP5 biotechnology patent families since the mid-1980s and China had almost reached EU
patenting levels by 2020. Over the last decade, US biotech companies raised around 870%
more Series C capital and around 945% more in IPO proceeds (EUR 45.4 billion versus
EUR 4.28 billion). US business sector biotech R&D intensity rose to over 0.4% of GDP
compared to 0.04-0.12% in the EU260. This translation gap was reinforced by perceived
ecosystem fragmentation, including reported barriers linked to insufficient collaboration
among clusters (45.9% agreement) and incapacity to reach a critical mass of stakeholders
(46.3% agreement).
Baseline evolution 2025-2030 (near term)
Over 2025-2030, baseline evolution implies continuity of regulatory and administrative
complexity, with limited automatic compression of permitting durations in the absence of
sector-specific streamlining. Any improvements in permitting predictability are expected
to be gradual and uneven, driven mainly by horizontal measures such as administrative
digitalisation and modernisation rather than a step-change in governance. Under this
trajectory, the distribution of permit durations is expected to remain wide, with only limited
improvement in the share of complex projects permitted in under one year.
Administrative costs for promoters are expected to remain case-specific and potentially
significant, particularly where technology novelty increases interpretative uncertainty and
reliance on external consultants and legal support.
On finance and competitiveness, near-term evolution implies continued policy attention
but persistent structural constraints in late-stage capital availability. Time-to-financial-
close for capital-intensive projects is expected to remain constrained and sensitive to
bankability and execution risk, with continued dispersion across Member States and
project types. Aggregate mobilisation through transversal instruments is expected to
continue, but without generating a traceable cohort of projects benefiting from a common
governance track and without creating a project-specific signal or coordinated pathway
that could systematically accelerate investment decisions. Ecosystem fragmentation and
limited inter-cluster collaboration are expected to continue to constrain EU-scale
collaboration and diffusion effects.
Baseline evolution 2030-2038 (medium term)
Over 2030-2038, baseline evolution implies gradual modernisation and some learning
effects from parallel strategic-project approaches in other sectors, but not systematic
260 Bridging the Gap – Transforming EU Biotech Policy, ADC, DANSK BIOTEK, 2025.
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convergence towards predictable, capped permitting timelines for health biotechnology. In
comparable strategic-project settings, the impact of introducing permitting provisions has
been framed as potentially reducing average permitting duration materially, for example
using a one-third reduction assumption derived from other infrastructure contexts. Under
baseline conditions, such a structural reduction would not be expected to materialise at
scale, meaning permitting uncertainty would continue to weigh on bankability and time-
to-revenue, especially for multi-site and multi-purpose industrial projects.
Administrative uncertainty is expected to sustain material economic exposure for large
strategic deployments. Delay and uncertainty remain economically material for capital-
intensive investments, with an indicative benchmark suggesting that regulatory delays of
more than 12 months beyond initial projections have been associated with an average 34%
increase in total development costs, alongside a high incidence of additional funding
rounds and some programme abandonment, highlighting the potential magnitude of delay-
related economic exposure for capital-intensive, timeline-sensitive innovation investments
261.
In the medium term, competitiveness and investment flows are expected to improve only
gradually and unevenly, with continued sensitivity of investment timing and location
decisions to execution risks and persistent late-stage funding asymmetries. The baseline
continues to lack a recognised project pipeline, a project-specific signal and a coordinated
support pathway that would, in itself, reduce time-to-close for large strategic projects or
produce a traceable uplift in public-private co-investment and leverage associated with a
recognised portfolio. In parallel, ecosystem fragmentation and uneven collaboration across
clusters are expected to remain a structural constraint on EU-scale value chain
development and on stronger links between innovation outputs and industrial deployment
decisions.
7.3 Expected impacts
Conduct of business
The strongest effects are expected to arise at project level through a reduction in
administrative uncertainty and execution risk. More specifically, the framework changes
the operational conditions under which project promoters organise permitting and project
preparation. Instead of dealing with multiple, partly sequential interfaces, promoters would
benefit from coordinated case management through single points of contact, combined
with a legally anchored maximum permit-granting timeline and associated facilitation
measures. The practical importance of this change lies not only in the potential shortening
of average timelines, but in the reduction of variability and unpredictability across cases.
This distinction is important. For strategic industrial projects, the main business effect of
administrative streamlining is often a reduction in the volatility of project schedules rather
than a uniform shortening of every phase. Lower volatility improves planning horizons,
contracting and procurement sequencing, and the alignment of financing drawdowns with
261 https://www.boyle-associates.com/the-hidden-costs-of-regulatory-delays
184
project milestones. In other words, the effect is not limited to “faster permitting” in a
narrow sense, but extends to more reliable project execution.
A key caveat is that the size of the benefit remains sensitive to project complexity and to
the use of justified extensions. In practice, more complex projects, especially those
involving multiple sites or interfaces with environmental procedures, are likely to continue
to require more intensive handling. The expected gain is therefore best understood as a
structured reduction in uncertainty and schedule risk, not as the elimination of all timing
frictions.
Administrative costs on businesses, including SMEs
Reduced transaction costs and avoided delay costs are the core administrative-cost effects
that are expected, based on several mechanisms:
First, the framework creates a predictable recognition stage. This is analytically relevant
because, under business-as-usual, there is no equivalent standardised entry point. A
recognition decision within a defined period provides earlier certainty for promoters on
whether a project qualifies for the support architecture and can therefore benefit from the
related facilitation measures. This reduces the search and coordination costs associated
with navigating fragmented support arrangements.
Second, administrative burden is expected to fall through fewer parallel interfaces, lower
duplication of exchanges and reduced reliance on external consultants and legal support.
This is expected to matter in particular for SMEs, start-ups and scale-ups, which tend to
have a more limited internal regulatory capacity. This is confirmed by stakeholder
consultation responses calling for one-stop-shop arrangements, simplified evidence
requirements and dedicated channels for smaller operators.
Third, the regulatory design contains specific features that support lower compliance costs
over time. These include electronic submission and the possibility to reuse existing data,
studies and authorisations where the evidence remains applicable and up to date. This is
important because, for complex projects, repeated preparation of similar documentation
across procedures is a significant source of administrative burden.
The monetisation of avoided delay costs can be illustrated on the basis of indicative project
values, for which a range of EUR 60–200 million is considered reasonable, noting that the
strategic-project portfolio is expected to be heterogeneous and may include smaller-scale
deployments. On the basis of indications from a closely regulated medical technology
context that regulatory delays of more than 12 months beyond initial projections may be
associated with an average increase in total development costs of 34%262, the implied cost
exposure in the event of a major delay would be roughly EUR 20.4–68.0 million per
project. Assuming, for illustration, that the framework reduces the probability of such a
delay by 25%, the expected avoided delay cost is estimated at around EUR 5.1–17.0
million per mature project. Combined with the assumption that roughly 70–80% of
262 https://www.boyle-associates.com/the-hidden-costs-of-regulatory-delays/
185
recognised projects reach sufficient maturity for this exposure to be economically material,
this underpins the cumulative ranges reported in the main text.
The main caveat is that these values are illustrative and highly sensitive to project size,
maturity and implementation conditions. They should therefore be interpreted as showing
the scale of the mechanism, not as a fixed per-project saving. The largest gains can be
expected to be concentrated in the most capital-intensive projects, where schedule
adherence lies on the critical path.
Competitiveness, trade and investment flows
The central impact channel for competitiveness is the creation of a more “investable”
project pipeline. Recognition as a strategic project matters not only because it is linked to
administrative streamlining, but because it provides a structured signal to investors and
public financiers that a project is strategic, publicly relevant and embedded in a coordinated
support architecture. This signalling effect is expected to interact with lower execution risk
resulting from more predictable permitting and support services.
The framework for strategic biotechnology projects is expected to affect both the speed
from recognition to funding decision and financial close and the amount of total investment
mobilised. In practical terms, the reduction in permitting uncertainty is expected to lower
risk premia and reduce the probability that financing is delayed pending administrative
milestones. This supports shorter time-to-close and improves the likelihood that large-scale
industrial deployment takes place in the Union rather than being relocated elsewhere.
To give substance to the mobilisation estimates, indicative capital values for biopharma
manufacturing and related infrastructure can be used as a proxy for the investment
envelope of relevant industrial deployments. Evidence from recent investments suggests
that large-scale manufacturing facilities typically fall in the range of approximately EUR
316–428 million263, while smaller-scale or modular facilities and specialised production
units may require lower investment levels, for example in the range of EUR 60–200 million
as used elsewhere in this analysis.
Taken together, this supports the use of a broad investment envelope spanning medium to
large-scale deployments. Combined with the assumption that approximately 70–80% of
recognised projects would reach financial close (the point at which a project’s financing is
fully secured, contractually committed, and ready for disbursement) under standard
project-development conditions, this provides a plausible basis for the mobilisation ranges
set out in Section 5.
The main caveat is that competitiveness impacts are especially sensitive to uptake and
project maturity. Under low uptake, the effects may be economically meaningful but
remain localised to a relatively small portfolio. Under medium and high uptake, the project
pipeline becomes more visible and more likely to generate crowding-in effects. The
263 Based on reported values for a syringe manufacturing facility and a vaccine manufacturing facility transaction:
https://apnews.com/article/north-carolina-syringes-plant-jobs-5a69d78d39973fb59eaf6e4da167bc2c;
https://www.wsj.com/business/wuxi-biologics-to-sell-irish-vaccine-facility-to-merck-for-500-million-4d6684dc
186
measure therefore improves the conditions for investment but does not remove broader
structural financing constraints in the Union.
Functioning of the internal market and competition
The key effect is not harmonisation of national permitting systems as such, but the creation
of a more visible, comparable and coordinated pipeline of strategic projects. In that sense,
the measure reduces information asymmetries and lowers dispersion in execution risk
across Member States.
A particularly important operational feature is cross-border recognition for projects located
in two or more Member States. Where one designated authority issues a recognition
decision, that recognition is then to be acknowledged by the designated authorities of the
other Member States concerned. This does not eliminate differences in national
procedures, but it does reduce duplicative recognition steps and supports greater
consistency of treatment for genuinely cross-border projects.
The report also provides a plausibility benchmark by referring to other EU priority-project
mechanisms operating across many jurisdictions, including the first Union list of Projects
of Common Interest and Projects of Mutual Interest, which comprised 166 projects264.
While health biotechnology is narrower in scope, the comparison is used to support the
proposition that a sufficiently large recognised pipeline could, over time, begin to reduce
perceived fragmentation and strengthen contestability of investment across the internal
market.
The corresponding caveat is that the effect should not be read as implying uniform
convergence of national permitting outcomes. The relevant signal is improved
transparency and comparability, particularly for multi-country projects, rather than
complete alignment of administrative regimes. The size of the effect remains dependent
on uptake, cross-border footprint and implementation capacity.
Innovation and research
The measure is expected to support faster translation of scientific and technological
capabilities into industrial deployment by facilitating projects that strengthen industrial
capacity, scale up or upgrade research and technology infrastructures, and support
collaboration across actors.
As a rough comparator for portfolio effects, benchmarks from other sectors can be
considered, such as the microelectronics IPCEIs, which comprise 100 projects across 14
Member States265. The point of the comparison is not to equate the sectors, but to support
the logic that a sufficiently large portfolio of recognised projects can generate visible
infrastructure and collaboration outputs over time.
264 https://cinea.ec.europa.eu/news-events/news/first-pcispmis-list-data-available-transparency-platform-managed-
cinea-2024-05-14_en 265 https://competition-policy.ec.europa.eu/state-aid/ipcei/approved-ipceis/microelectronics-value-chain_en
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The main caveat is that innovation impacts are expected to be strongly dependent on
project composition. If the recognised portfolio contains relatively few projects with
material research and innovation, pilot or testing components, the effect on this category
will remain limited. The framework therefore contributes incrementally to innovation and
research by strengthening late-stage translation conditions, rather than by directly altering
the broader research system.
Public authorities
Impacts for public authorities are expected to be front-loaded because implementation
requires the establishment or designation of single points of contact, the operation of
recognition processes and the provision of structured support services. However, this
should not be interpreted as requiring entirely new administrative bodies in all Member
States, given that such bodies have already been set up in other frameworks for EU
strategic-project regimes, including the Net-Zero Industry Act, the Critical Raw Materials
Act and the European Chips Act, all of which allow Member States to designate or adapt
existing authorities and coordination mechanisms rather than build new institutions from
scratch. This supports the conclusion that the main public authority cost is likely to arise
from process design, workload reallocation and service standards rather than from the
creation of wholly new structures.
As regards workload implications, it should be underlined that impact can be expected to
scale with uptake because recognition decisions, coordination and support functions are
workload-driven. Using illustrative assumptions on project activity and active case
management over a 2–3 year period, and assuming that one FTE can manage around 10–
15 active cases per year, indicative capacity ranges can be calculated as indicated in section
5. These ranges should only be considered as indicative illustrations of scale rather than
staffing forecasts.
The key caveat is that implementation effects are highly context-dependent. Where
Member States already have strong coordination structures, incremental resource needs
may be relatively modest. Where baseline coordination is more fragmented,
implementation may be more demanding. Over time, however, routinised handling, digital
tools and reduced duplication are expected to improve efficiency per case.
Public health and safety
The key impact mechanism is that faster and more predictable project delivery enables
earlier commissioning of EU-based capacity for selected strategic biotechnology products,
which can then contribute to supply resilience.
At the same time, public health and resilience outcomes depend on wider market and
system conditions and cannot be inferred mechanically from project recognition alone. For
that reason, the scenario logic remains outcome-oriented and attribution-aware: uptake and
earlier capacity commissioning may be linked to observable resilience proxies, but the
effect on realised health outcomes will still depend on product mix, external shocks and
broader supply conditions.
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This means that the value of the measure in this category is best understood as improving
the conditions under which resilience-enhancing capacity can materialise earlier, rather
than as guaranteeing a given health-system result.
Cross-cutting drivers, caveats and limitations
Across all categories, the magnitude of impacts depends primarily on uptake, project
maturity and implementation capacity. Uptake matters because the framework is voluntary
and the aggregate effect is proportional to the number of projects entering the recognised
pipeline. Project maturity matters because the most material business, administrative-cost
and investment effects are concentrated in projects that are sufficiently advanced to face
economically relevant delay exposure and to reach financial close. Implementation
capacity matters because the effectiveness of single points of contact and coordinated
support will vary across Member States.
In terms of limitations of the analysis, it should be noted that quantified effects rely on
illustrative assumptions rather than observed implementation data, because the framework
does not yet exist. Comparisons with other EU strategic-project regimes and other
industrial sectors are analytically useful, but they are not one-to-one proxies for health
biotechnology. Finally, some categories, in particular innovation and public health, are
inherently more difficult to quantify.
For these reasons, the quantified results in section 5 of the SWD should be interpreted as
orders of magnitude that support the plausibility and direction of impacts, rather than as
precise forecasts.
8 INTERVENTION N°10: RECOGNITION AND SUPPORT OF HIGH IMPACT STRATEGIC
HEALTH BIOTECHNOLOGY PROJECTS
8.1 Detailed description of the proposed measures
The measure establishes a framework for the recognition and support of high impact
strategic health biotechnology projects, i.e. projects with the potential to contribute to the
Union’s biotechnology objectives in a systemic manner and to generate catalytic effects
across the Union biotechnology ecosystem. High-impact projects may cover different
types of interventions defined in the Regulation, including biotechnology development
accelerators, centres of excellence for advanced therapies, projects linked to late-stage
financing, AI-enabled innovation infrastructures and biodefence capabilities.
For the purpose of this analysis, the measure focuses on two categories of high-impact
projects: biotechnology development accelerators and centres of excellence for advanced
therapies (as impacts expected from projects linked to late-stage financing, AI-enabled
innovation infrastructures and biodefence capabilities are assessed in the respective
sections). Biotechnology development accelerators are shared infrastructures providing
trusted testing and demonstration facilities that replicate real-world biomanufacturing
conditions, including GMP-compliant processes, and support process testing, validation
and small-batch manufacturing, including for investigational medicinal products. They
combine state-of-the-art equipment, applied research, training activities and partnerships
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between industry, academia and public authorities to integrate research, innovation and
skills development.
Centres of excellence for advanced therapies are specialised infrastructures aimed at
strengthening the Union’s capabilities in advanced therapies, including cell and gene
therapies. They provide or coordinate advanced manufacturing and downstream
processing infrastructures, integrate regulatory science, quality and safety functions, and
support the transition from laboratory research to commercial manufacturing. They offer
services such as acceleration and incubation programmes, access to GMP facilities,
partnership facilitation and connections to clinical and hospital settings for testing and
validation. A key feature is cross-border accessibility, enabling users from all Member
States to access their services and supporting Union-wide development and deployment of
advanced therapies.
As regards the general support architecture, high impact strategic health biotechnology
projects benefit from the same package of regulatory, administrative and financial support
measures as strategic health biotechnology projects, as described under Intervention n°9.
This includes, in particular, access to single points of contact, administrative support,
priority treatment in relevant procedures, access to the EU Health Biotechnology Support
Network and eligibility for national and Union support instruments.
In addition, high impact projects benefit from enhanced treatment reflecting their systemic
relevance and expected multiplier effects. In particular:
• they are recognised at Union level, either at the request of Member States or
following dedicated calls for proposals;
• they benefit from priority access across procedures, in the context of the
administrative support measures that strategic projects benefit from;
• they are subject to a shorter permit-granting timeline of 8 months, instead of 10
months for strategic projects, with a possible extension of up to 3 months in duly
justified complex cases;
• they are given particular consideration for Union financial support, including
where relevant in the form of blended financing.
8.2 Baseline and counterfactual scenario
Key assumptions:
• Late-stage translation in health biotechnology remains constrained by limited
availability and uneven distribution of advanced testing, validation and scale-up
infrastructures, particularly for complex modalities such as advanced therapies.
Existing infrastructures are fragmented, vary in capability and scale, and are not
organised as a visible or coordinated Union-level portfolio.
• No dedicated EU-level framework exists to identify, recognise and support a
limited number of catalytic, system-relevant infrastructures with cross-border
accessibility, resulting in weak signalling to investors and users and limited
ability to prioritise or coordinate support for such projects.
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• Project development for capital-intensive infrastructures remains exposed to
administrative complexity and permitting uncertainty, with no differentiated
fast-track or priority handling for projects with systemic relevance.
• Investment mobilisation for large, shared infrastructures remains constrained by
execution risk, time-to-revenue uncertainty and the absence of a clearly
identifiable pipeline of investable flagship projects, limiting the speed and scale
of financing decisions.
• Cross-border access to late-stage translation and manufacturing capabilities
remains uneven and largely dependent on geographical proximity to established
clusters, with limited transparency on available services and access conditions.
• The translation of research into clinical development and scalable
manufacturing remains constrained by bottlenecks in late-stage testing,
validation, GMP capacity and regulatory integration, particularly for advanced
therapies.
2025 baseline (status quo)
In 2025, the baseline is characterised by the presence of relevant infrastructures and
initiatives across Member States, including pilot facilities, testing platforms and
specialised centres, but without a coordinated Union-level framework to identify and
support a limited portfolio of high-impact, system-relevant projects. As a result, the key
baseline issue is not the absence of capacity as such, but its fragmentation, uneven
accessibility and limited visibility at Union level.
From a conduct-of-business perspective, access to late-stage capabilities remains case-
specific and often dependent on informal networks or bilateral arrangements. While some
infrastructures operate at high technical standards, access conditions, service scope and
pricing structures vary significantly, and utilisation is not systematically optimised at
Union level. Metrics such as number of firms served, service engagements or utilisation
rates are not consolidated across facilities, limiting transparency over bottlenecks and
capacity gaps.
From an administrative perspective, project promoters of capital-intensive infrastructures
face standard permitting and authorisation pathways, without systematic priority treatment
or capped timelines linked to the systemic relevance of the project. Permit-granting
duration remains variable across Member States and project types, and compliance costs
remain case-specific, with particular challenges for smaller operators lacking internal
regulatory capacity.
From a competitiveness and investment perspective, the baseline is characterised by the
absence of a clearly identifiable pipeline of flagship projects. While financing instruments
exist at Union and national level, projects are not systematically packaged or signalled as
strategic investment opportunities. This contributes to longer time-to-financial-close,
fragmented financing structures and continued exposure to execution risk. Public
consultation evidence points to persistent perceived difficulties in accessing support for
capacity expansion and scaling.
For the internal market, cross-border access to specialised infrastructures remains uneven
and largely driven by proximity to established ecosystems, with limited comparability of
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access conditions and limited data on cross-border usage. For innovation and research,
strong upstream scientific performance is not consistently matched by efficient late-stage
translation into clinical development and manufacturing, particularly for advanced
therapies. For public authorities, administrative handling remains dispersed across
authorities and projects, with no dedicated framework for the selection, monitoring and
coordination of a limited flagship portfolio.
Baseline evolution 2025–2030 (near term)
Over 2025–2030, the baseline implies gradual expansion of late-stage infrastructures
through existing national initiatives, Union programmes and private investment, but
without structural coordination at Union level. Improvements in access and capacity are
expected to remain uneven and cluster-driven, with limited convergence in access
conditions or service availability across Member States.
Administrative processes may benefit from incremental digitalisation and learning effects,
but no systematic reduction in permitting timelines for catalytic infrastructures is expected
in the absence of a differentiated high-impact track. Investment mobilisation is expected
to continue through existing channels, but remains opportunistic rather than pipeline-
driven, with time-to-close continuing to depend on project-specific risk profiles and
administrative readiness.
Cross-border collaboration and usage of infrastructures may increase gradually, but
without a coordinated framework, barriers related to information asymmetries, access
conditions and fragmentation are expected to persist. Innovation outcomes are expected to
improve incrementally, but bottlenecks in late-stage translation and scale-up remain a
structural constraint.
Baseline evolution 2030–2038 (medium term)
Over 2030–2038, the baseline implies continued maturation of the EU biotechnology
ecosystem, with incremental improvements in infrastructure capacity, skills and
collaboration. However, in the absence of a mechanism to identify and support a limited
number of high-impact, system-relevant projects, fragmentation is expected to persist and
convergence towards a coherent, Union-wide late-stage translation layer is not expected to
materialise.
Conduct-of-business conditions for users of advanced infrastructures remain
heterogeneous, with continued variability in access, cost and service scope. Administrative
uncertainty for large, capital-intensive infrastructures remains economically relevant, with
delays and coordination challenges continuing to affect project timelines and investment
decisions.
Competitiveness and investment flows are expected to improve gradually but remain
constrained by the absence of a visible flagship project pipeline capable of generating
strong signalling and crowding-in effects. Internal market integration remains partial, with
continued uneven access to specialised capabilities. Innovation performance continues to
be shaped by strong upstream research but constrained by persistent bottlenecks in late-
stage development and industrial deployment, particularly for advanced therapies.
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8.3 Expected impacts
Conduct of business
The high-impact designation is expected to facilitate development and use of specialised
testing, validation and small-batch GMP services and related scale-up support for a wider
set of firms than the project promoters themselves, thereby reducing coordination frictions
and dependence on bespoke, network-based sourcing. The incremental effect relative to
strategic projects is that high-impact projects are expected to generate benefits that extend
beyond the project boundary, through a structured service offer with cross-border
accessibility, clear access conditions and a deliberate orientation towards broader
ecosystem users, including SMEs, start-ups and scale-ups.
These impacts are expected to be most observable through increased utilisation of the
supported infrastructures and services, measured through the number of firms served
(including SMEs), the number of service engagements delivered (such as testing,
validation and small-batch GMP runs) and the utilisation rate of relevant facilities. The
expected direction of change is an increase in both breadth of access and intensity of such
service provision, reflecting reduced entry barriers, clearer access conditions and stronger
coordination of demand for late-stage translation services at Union level. For recognised
projects taking the form of biotechnology development accelerators and centres of
excellence for advanced therapies, conduct-of-business effects are expected to concentrate
on improved planning horizons for development and scale-up activities, with less time
spent on searching for suitable capacity, negotiating bespoke arrangements and managing
discontinuities between development stages.
Under a low uptake scenario (around 6-8 recognised projects by 2038), the portfolio would
plausibly include around 2 promoter-led shared translation infrastructures with a service
offer aimed at broader ecosystem users. On an illustrative utilisation assumption of around
30-60 firms served per year per infrastructure, with around 2-4 service engagements per
firm266, the order of magnitude would be around 60-120 firms served per year and roughly
120-480 service engagements per year once facilities are operational and demand
stabilises. Under medium uptake (around 12-15 projects), assuming around 4-6 such
infrastructures, the corresponding order of magnitude would increase to around 120-360
firms served per year and around 240-1,440 engagements per year. Under high uptake
(around 20-25 projects), assuming around 8-10 infrastructures, the order of magnitude
would rise to around 240-600 firms served per year and around 480-2,400 engagements
per year.
266 The utilisation assumptions are calibrated using observed throughput of comparable late-stage translation and
biomanufacturing support infrastructures. For example, the Cell and Gene Therapy Catapult reports collaborating with
70 companies in a single year and delivering 127 collaborative projects (https://ct.catapult.org.uk/about/annual-
review/annual-review-2025), implying close to two projects per company per year. In addition, a bioprocessing research,
development and demonstration facility (Verschuren Centre, https://www.canada.ca/en/atlantic-canada-
opportunities/news/2022/06/verschuren-centre-expansion-will-help-cleantech-entrepreneurs-find-solutions-to-
environmental-challenges.html) reports working with more than 40 companies. Against these benchmarks, an illustrative
range of 30-60 firms served per year per infrastructure is conservative, but suitable for a specialised, high-impact facility,
while 2-4 service engagements per firm reflects that firms typically interact through more than one structured work
package (such as testing, validation, GMP-mirroring runs and associated quality control activities) rather than a single
one-off interaction.
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These ranges should be interpreted as project-level throughput rather than market-wide
effects. The incremental impact of the high-impact designation would be evidenced by the
extent to which utilisation is cross-border, repeat usage is sustained and service offers
reduce reliance on bespoke sourcing, relative to a baseline where comparable capacity,
where it exists, is less visible and less structured as a Union-facing service layer.
Administrative costs on businesses, including SMEs
The key additionality in terms of administrative cost impacts attributable to the high-
impact designation stems from the tighter time cap for permit granting and prioritised
access to facilitation support for the recognised project cohort. This is expected to reduce
schedule uncertainty for a small number of capital-intensive catalytic projects, which is
economically material given their exposure to delay-related costs and knock-on effects on
financing and procurement sequencing.
The principal quantification and monetisation route remains avoided delay costs for
capital-intensive investments, as the high-impact designation reduces time-to-decision
relative to what would otherwise be achieved.
For SMEs, the expected incremental benefit is concentrated in reduced indirect transaction
costs, including fewer iterations and lower reliance on external advisory support when
interacting with a prioritised facilitation pathway for the small cohort of recognised high-
impact projects, rather than a general reduction of administrative burden across the sector.
With an illustrative project value range of EUR 60-200 million for capital-intensive
catalytic projects, calibrated against biotechnology-relevant infrastructure proxies267,
combined with the assumption that regulatory delays of more than 12 months beyond
initial projections can be associated with an average 34%268 increase in total development
costs, delay-related economic exposure can be material even for a small flagship portfolio.
Under low uptake (6-8 projects), assuming around 4-5 projects reach sufficient maturity
for delay-related exposure to be economically material, the order of magnitude effect is
that a small subset of projects would benefit from reduced probability and duration of
material delays. In this scenario, the implied cost exposure per project is EUR 20.4-68.0
million. If it is assumed, for illustration, that the high-impact pathway reduces the
probability of such a >12-month delay by 25%, the resulting expected avoided delay costs
are around EUR 20.4-85.0 million cumulatively for the low uptake case.
267 The lower bound is anchored in published orders of magnitude for bioprocessing translation and training
infrastructures. For example, the NIBRT facility in Ireland was reported as a EUR 57 million build
(https://www.rte.ie/news/business/2011/0609/302171-research-business/) and NIBRT’s 2022 annual report states that
IDA Ireland has invested over EUR 80 million in NIBRT since 2011, with a further EUR 21 million cell and gene therapy
related investment referenced (https://www.nibrt.ie/wp-content/uploads/2023/01/NIBRT-Annual-Report-2022.pdf). The
upper bound reflects that more GMP-intensive advanced-therapy capability and manufacturing facilities can move into
the low hundreds of millions, depending on scope and industrial intensity, for example UCB announced an investment
of more than EUR 200 million in a gene therapy development and clinical manufacturing facility
(https://www.ucb.com/newsroom/press-releases/article/ucb-expands-innovation-footprint-with-new-state-of-the-art-
gene-therapy-facility). Additional reference points indicating variation in scale include a EUR 14 million hospital-linked
ATMP facility investment (https://www.uzleuven.be/en/news/uz-leuven-and-ku-leuven-invest-14-million-euros-new-
cell-and-gene-therapy-facility) and public investments in ATMP ecosystem capability at regional level
(https://www.wallonia.be/en/news/advanced-therapy-wallonia-invests-eu81-million-atmp). 268 See footnote 279.
194
Under medium uptake (12-15 projects), assuming around 10-12 projects reach this
maturity, the expected avoided delay costs scale proportionately to around EUR 51.0-204.0
million cumulatively under the same assumptions. Under high uptake (20-25 projects),
assuming around 18-20 projects reach maturity, the expected avoided delay costs increase
to around EUR 91.8-340.0 million cumulatively, with the largest benefits concentrated in
the most capital-intensive projects where schedule adherence is on the critical path and
financing resilience is most sensitive to delay risk. Any reductions in routine administrative
compliance costs (staff time and external advisory costs) are expected to be smaller than
this delay-exposure channel and concentrated in the recognised project cohort, with
proportionately larger relative benefits for SMEs where reduced iteration and clearer
process milestones reduce reliance on external support.
Competitiveness, trade and investment flows
The high-impact designation is expected to increase the probability that a small portfolio
of flagship projects reaches financial close and proceeds to implementation in the Union
by strengthening the credibility of delivery plans, improving comparability of project
propositions and reducing perceived execution risk for investors and public financiers.
Relevant indicators to assess this include the volume of public financing mobilised for
recognised high-impact projects and time to disbursement, including the share delivered
as blended finance and the time profile from recognition to first disbursement,
complemented by private capital mobilised alongside public support and the associated
leverage ratio. The expected direction of change is faster progression from recognition to
first disbursement and stronger mobilisation and leverage for sufficiently mature projects,
reflecting improved signalling effects and a more “investable” project narrative.
Evidence from cross-border flagship initiatives indicates that EU-level co-financing can
be catalytic in expanding the scale of financing packages even where it does not determine
initial participation decisions, and may encourage participation by Member States with
limited prior engagement in such initiatives269. This supports the expectation that high-
impact designation, and in particular the particular consideration for Union financial
support that high impact projects would be given, can help unlock larger financing
packages for a small number of capital-intensive projects with multiplier effects.
Public consultation evidence further indicates that access to public support for capacity
expansion is widely perceived as difficult, particularly among industry respondents,
reinforcing the relevance of mechanisms that improve packaging and “investability” for a
targeted flagship portfolio rather than dispersing support thinly across many initiatives.
Comparator evidence from strategic-tech infrastructure programmes also supports the
plausibility that concentrating resources into a small number of shared, state-of-the-art
infrastructures can strengthen visibility and perceived credibility of flagship assets and
269 Case study on cross-border and multi-country projects, with specific focus on Important Projects of Common
European Interest (IPCEIs), https://commission.europa.eu/document/download/30a28e5a-a052-4f49-9c79-
f5ec35f10527_en?filename=case-study-on-cross-border-and-multi-country-projects.pdf
195
support investment mobilisation, without implying an economy-wide solution to structural
financing constraints270.
Under low uptake (6-8 projects), the expected incremental competitiveness effect would
be concentrated in a small flagship portfolio. For scenario purposes, if recognised projects
mobilise total investment (public and private) of around EUR 300-800 million per project
once they reach financial close271, the implied order of magnitude would be around EUR
2-6 billion of total investment mobilised over the period, with the public component and
leverage ratio dependent on the instrument mix and project risk profile.
Under medium uptake (12-15 projects), the order of magnitude would rise to around EUR
4-12 billion. Under high uptake (20-25 projects), the order of magnitude would rise to
around EUR 6-20 billion.
Functioning of the internal market and competition
Internal market and competition effects attributable to the high-impact designation are
expected to arise from improved transparency and comparability of a limited flagship
project pipeline and from strengthened cross-border accessibility of the services and
capabilities delivered by recognised projects. The key element is the explicit systemic
orientation of the high-impact cohort, which is expected to be selected and supported on
the basis of Union-level added value, including cross-border relevance and broader
ecosystem benefits, rather than on purely local or national considerations. This is expected
to reduce information asymmetries for promoters, users and investors regarding where
relevant capacity exists, what services are available and under what conditions access can
be obtained.
Relevant indicators to assess progress in this area include take-up of the high-impact
recognition framework, alongside cross-border usage patterns, including the share of users
accessing supported services from a different Member State than the service location and
the share of supported projects implemented across two or more Member States. The
expected direction of change is increased cross-border usage and multi-country
implementation for the recognised high-impact cohort, reflecting more contestable access
conditions and reduced dependence on informal networks or proximity to established
clusters.
Experience from cross-border initiatives in the medical device domain suggests that such
initiatives can help address fragmentation and support investment mobilisation, including
for SMEs, by creating cross-border synergies, strengthening the internal market and
building a structured ecosystem around priority innovation areas. This supports the logic
that a small number of catalytic flagship initiatives can function as a practical lever to
270 https://digital-strategy.ec.europa.eu/en/policies/european-chips-act 271 The assumed investment range per project is based on indicative evidence from comparable large-scale
biopharmaceutical research and manufacturing investments, as analysed in the Rapid Assessment Scenario Study
(forthcoming), where examples of such investments are featured.
196
reduce fragmentation and generate observable cross-border ecosystem integration
effects272.
Under low uptake (6-8 projects), assuming for scenario purposes that around 2-3 projects
are implemented across two or more Member States and the subset of shared-capability
projects supports cross-border users at a rate of around 20-40% of total users273, the order
of magnitude of cross-border users supported would be around 12-48 firms per year once
services are operational, based on the low-uptake throughput assumptions in conduct of
business.
Under medium uptake (12-15 projects), assuming around 4-6 multi-country projects and
20-40% cross-border usage, the order of magnitude would increase to around 24-144 cross-
border users per year. Under high uptake (20-25 projects), assuming around 7-10 multi-
country projects and a similar cross-border share, the order of magnitude would increase
to around 48-240 cross-border users per year.
Innovation and research
The high-impact designation is not expected to improve the innovation system in general.
Rather, it is expected to generate systemic translation effects by supporting promoter-led
projects that provide shared infrastructures and services that directly de-risk and accelerate
late-stage development steps, including specialised testing, validation and small-batch
GMP activities, and, where relevant, integration with regulatory science and early
engagement pathways.
The materialisation of such effects could be observable through proxies linked to the
recognised project portfolio, including clinical pipeline activity (applications and
authorisations and median time from submission to authorisation decision) and knowledge
creation and transfer outputs (patent families, licences and spin-offs attributable to
supported projects and associated capabilities). The expected direction of change is
improved throughput and timeliness for development and translation activities linked to
the recognised portfolio, with the strongest effects expected where the supported assets
address known late-stage bottlenecks and operate with broad user access.
The materiality of this translation focus is reinforced by the structural characteristics of
advanced biomedical innovation, where development cycles are cited at 10-15 years and
investment needs at EUR 1.28-1.71 billion to bring a new drug to market, with around half
272 Decision for the Important Project of Common European Interest (IPCEI) – Innovative medical devices and support
software (Tech4Cure). 273 The 20-40% range is a conservative proxy for the share of users expected to originate from a different Member State
than the service location once EU-wide access is operational, recognising that facility-type infrastructures will typically
continue to serve a material domestic user base alongside cross-border users. The calibration draws on established
practice in EU-funded Transnational Access schemes, where access is explicitly reserved for external user groups and
eligibility commonly requires that the user group leader and the majority of users work in a country other than the country
where the installation is located (for example ChETEC-INFRA eligibility criteria: https://www.chetec-
infra.eu/ta/application/; JERICO access rules referencing the EC grant agreement: https://www.jerico-ri.eu/ta/access-
rules/; SERA-TA transnational access conditions: https://sera-ta.eucentre.it/transnational-access/). Given that such
“transnational-only” access rules imply a much higher cross-border share within the funded access stream, applying 20-
40% as the cross-border share of total users is intended as an order-of-magnitude assumption that allows for continued
national usage alongside a substantial but not dominant cross-border component.
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of time and investment occurring in clinical trial phases. In this context, catalytic late-stage
assets can be expected to generate disproportionate value by reducing iteration cycles,
improving readiness and shortening time-to-clinic and time-to-scale for a subset of high-
potential programmes, even if broader innovation system dynamics remain unchanged274.
Under low uptake (6-8 projects), if for scenario purposes it is assumed each such capability
project supports around 10-20 development programmes per year with de-risking steps that
shorten iteration cycles and improve readiness, and if around 2-4 programmes per
infrastructure per year translate into clinical trial applications attributable to the supported
capability, the order of magnitude would be around 4-8 clinical trial applications per year
linked to the capability layer in steady state.
Under medium uptake, assuming 4-6 capability projects, the order of magnitude would be
around 8-24 such applications per year and under high uptake, assuming 8-10 capability
projects, around 16-40 per year. Knowledge creation and transfer effects would be
expected to scale in a broadly similar way, with the most policy-relevant signal being
improved throughput and timeliness in late-stage translation steps rather than system-wide
shifts in patenting or publication trends.
Public authorities
Impacts for public authorities attributable specifically to the high-impact designation are
expected to be limited and not driven by more demanding selection and monitoring
requirements for the high-impact cohort, to ensure that the designation is reserved for
projects with credible Union-level added value and measurable multiplier effects. Cost
drivers associated with general project delivery facilitation, including standard
administrative support arrangements and routine permitting operations, should not be
attributed to the high-impact category again.
Experience from multi-country flagship initiatives underlines the importance of early,
inclusive Member State engagement, a designated coordinator with sufficient
administrative capacity and a jointly managed timeline and workplan to maintain
manageability. It also highlights that overly large project portfolios are harder to
coordinate, design and assess, supporting an approach that concentrates effort on a limited
number of high-leverage projects. These lessons are directly relevant to the design and
implementation of the high-impact designation and the associated governance model275.
Under low uptake (6-8 projects), impacts for public authorities would imply a small steady-
state workload for processing applications, documenting decisions and collecting
performance information, with the incremental burden broadly scaling with the number of
recognised projects and the share that are multi-country.
Under medium uptake (12-15 projects) and high uptake (20-25 projects), incremental
workload would rise proportionately, but the scale would remain bounded by design, since
274 Decision for Important Project of Common European Interest (IPCEI) on health (Med4Cure). 275 DG COMP Code of good practices for a transparent, inclusive, faster design and assessment of IPCEIs,
https://competition-policy.ec.europa.eu/system/files/2023-05/IPCEIs_DG_COMP_code_of_good_practices.pdf. See
also Joint European Forum (JEF-IPCEI) workstreams and related guidance, including IPCEI factsheets, templates and
the IPCEI Design Support Hub: https://competition-policy.ec.europa.eu/state-aid/ipcei_en
198
the high-impact category is intended to remain a limited portfolio. The relevant
quantification would therefore depend on the number of applications processed per year,
the number of monitoring cycles completed, and the intensity of cross-border coordination
required, rather than on general costs related to permitting and single point of contact
operations that are not specific to the high-impact designation.
Public health and safety
Public health and safety impacts, expected to be positive but indirect and in the medium
term, would be driven by the potential of the high-impact project framework to facilitate
the development and operation of shared capabilities that enable faster, safer and more
efficient development of innovative therapies, in particular advanced therapies, through
improved access to specialised testing, validation, small-batch GMP and quality-control
services. This is expected to reduce late-stage bottlenecks and iteration cycles, support
earlier identification and mitigation of quality and safety risks and improve readiness for
clinical development and scale-up.
In addition, where recognised high-impact projects are connected to relevant data and
digital infrastructures, the framework can contribute to improved patient access across the
Union by supporting more efficient development pathways and, indirectly, more consistent
cross-border availability of innovative therapies.
Under low uptake (6-8 projects), if for scenario purposes it is assumed each capability
project supports around 1-2 high-potential therapy programmes per year to progress more
rapidly and with stronger quality assurance through specialised testing, validation, small-
batch GMP and quality control, the order of magnitude would be around 2-4 programmes
per year experiencing improved development pathways under low uptake, rising to around
4-12 under medium uptake and around 8-20 under high uptake.
These figures should be interpreted as indicative throughput effects rather than direct
health outcomes, since patient access depends on downstream regulatory, reimbursement
and health system conditions.
9 INTERVENTION N°11: HEALTH BIOTECHNOLOGY ECOSYSTEM SUPPORT
FRAMEWORK
9.1 Detailed description of the proposed measures
This intervention includes four mutually reinforcing components: (i) strategic mapping of
the Union’s biotechnology ecosystem; (ii) networks of health biotechnology clusters; (iii)
an EU Health Biotechnology Support Network; and (iv) a European Health Biotechnology
Steering Group. Together, these measures aim to reduce information asymmetries,
improve coordination across Member States, facilitate access to regulatory support and
funding, and strengthen ecosystem connectivity around strategic and high-impact strategic
projects.
First, the proposal provides for a strategic mapping of the Union’s biotechnology
ecosystem, to be carried out by the Commission in cooperation with Member States and
maintained over time. The mapping is intended to deliver a comprehensive and up-to-date
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overview of capacities, infrastructures, dependencies, gaps and investment needs across
biotechnology value chains. It covers in particular industrial and research infrastructures,
access to risk-tolerant capital, clusters and ecosystems, skills needs, and the availability
and use of data and AI infrastructures. The mapping serves as the evidence base for the
identification and prioritisation of strategic and high-impact projects and informs Union
and national policy and funding decisions, as well as the work of the Steering Group.
Second, the proposal promotes the development of networks of health biotechnology
clusters, facilitated by the Commission and Member States. These networks are intended
to provide the structural connectivity layer of the ecosystem by linking regional and
national clusters and supporting cross-border collaboration. Their activities may include
facilitating interregional value chains, pooling resources and infrastructures across
Member States, enabling cross-border access to research and biomanufacturing facilities,
supporting scale-up from research to industrial deployment, and promoting knowledge
transfer, standardisation and inter-cluster cooperation. Where appropriate, such networks
may adopt dedicated governance structures or legal entities to implement joint actions and
investments.
Third, the proposal establishes an EU Health Biotechnology Support Network, coordinated
by the Commission and composed of national and regional antennas. The Network
provides a single entry point for biotechnology developers and project promoters—
particularly SMEs, start-ups and scale-ups—to navigate the Union’s regulatory and
funding landscape. Its functions include providing information on applicable Union and
national rules and authorisation procedures, supporting access to relevant regulatory
pathways and support mechanisms, and facilitating identification of funding, scaling-up
and collaboration opportunities. The Network is designed to build on and complement
existing structures and may be supported by digital tools to enhance accessibility and
efficiency.
Fourth, the proposal creates a European Health Biotechnology Steering Group, composed
of Member State representatives and the Commission, to provide the governance and
coordination layer of the framework. The Steering Group facilitates the exchange of
information and best practices, supports the effective recognition and implementation of
strategic projects, and provides advice on ecosystem development, including cluster
networking and funding coordination. It also contributes to identifying and addressing
systemic challenges faced by biotechnology projects and supports broader coordination
across Member States.
Taken together, these components form an integrated support architecture: the mapping
provides the analytical foundation; the Steering Group ensures coordination and strategic
guidance; the Support Network delivers operational support to firms and project
promoters; and cluster networks strengthen cross-border linkages and access to
infrastructures. The intervention therefore complements the strategic project framework
by improving the functioning of the broader ecosystem in which such projects are
developed and scaled.
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9.2 Baseline and counterfactual scenario
Core baseline assumptions (counterfactual without the ecosystem support measures)
• No single-entry point exists for health biotechnology innovators to navigate the
EU regulatory and funding landscape; developers must independently engage
multiple national and EU-level bodies without coordinated guidance.
• General support networks (EEN, national innovation agencies) lack health
biotechnology-specific expertise and are not positioned to develop such
specialisation without dedicated investment.
• No structured investor-innovator matchmaking mechanism exists at EU level
for health biotechnology; connections remain ad hoc, network-dependent, and
geographically concentrated in a few leading ecosystems.
• Support conditions for health biotechnology innovators vary significantly across
Member States, creating an uneven playing field where a company's prospects
depend substantially on location.
• Cross-border access to biomanufacturing facilities and research infrastructure is
not systematically available; cluster cooperation remains fragmented with
limited inter-cluster collaboration.
• No structured EU-level governance mechanism exists for coordinating health
biotechnology ecosystem development; Member States set priorities
independently without standardised mechanisms for discussing
complementarity or identifying dependencies.
2025 baseline (status quo)
Health biotechnology SMEs and start-ups face substantial transaction costs when
identifying applicable regulatory pathways, funding instruments, potential investors, and
available infrastructure across the EU's multi-framework landscape. Companies seeking to
scale across borders face engagement with national innovation agencies, regulatory
authorities, funding bodies, and cluster organisations in each Member State, compounded
by divergent national interpretations of EU frameworks276. SMEs struggle to identify
available R&D capacity, testing facilities, GMP manufacturing slots, and scale-up
infrastructure due to fragmented information and poor visibility of clusters and support
services across the EU277. These burdens fall disproportionately on SMEs and start-ups
lacking in-house regulatory affairs capacity.
Investor perception of the EU biotechnology ecosystem remains shaped by fragmentation,
poor navigability, and absence of a transparent overview of EU capabilities and investment
opportunities.
276 EuropaBio (2024). Joint Statement on the EC Initiative: Boosting Biotechnology and Biomanufacturing in the EU.
Available at: https://www.europabio.org/joint-statement-on-the-ec-initiative-boosting-biotechnology-and-
biomanufacturing-in-the-eu/. 277 European Commission (2024). Communication from the Commission to the European Parliament, the Council, the
European Economic and Social Committee and The Committee of the Regions: Building the future with nature: Boosting
Biotechnology and Biomanufacturing in the EU, COM(2024) 137 final.
201
Regional disparities in support availability persist, with biotechnology SMEs' ability to
navigate the system depending heavily on which Member State they are located in. Cross-
border access to pilot plants, testing facilities, and GMP capacity is not systematically
available. Cluster cooperation remains fragmented, with health biotech clusters poorly
integrated and lacking strong cross-border collaboration.
The EU's strong basic research output does not translate proportionally into commercial
innovation. OECD analysis confirms that structural ecosystem weaknesses, not scientific
capability, are the primary cause of the EU's underperformance in translating research into
innovation278. Weak academic-industry linkages persist279, knowledge transfer between
clusters remains ad hoc and project-dependent, and no systematic mechanisms exist to
identify R&D capability gaps at EU level.
At public authority level, no structured EU-level governance mechanism exists specifically
for coordinating health biotechnology ecosystem development.
Baseline evolution (medium to long term)
Without ecosystem support measures, current conditions are expected to persist or
deteriorate. The navigational burden for SMEs is expected to increase as additional
regulatory and policy frameworks become relevant, adding procedural steps and
institutional contact points without corresponding enhancement in support capacity.
General support networks will continue providing cross-sectoral SME services but are not
positioned to develop health biotechnology-specific expertise given their mandate.
The competitive disadvantage relative to the other jurisdictions is expected to persist, as
global competitors continue strengthening their positions: the US Biotechnology and
Biomanufacturing Initiative provides coordinated federal support, while China deploys
state-directed cluster development with substantial infrastructure investment280. The
cumulative effect is continued high attrition in the EU health biotechnology pipeline, with
projects failing not due to inadequate science but because developers cannot efficiently
access the support, funding, and infrastructure needed to progress.
The intra-EU innovation divide is expected to persist, with leading ecosystems
(Netherlands, Denmark, Germany, France) continuing to benefit from established clusters,
stronger investor networks, and more developed support structures, while less developed
ecosystems in Central and Eastern Europe and Southern Europe lack these foundations.
Incompatible national frameworks will continue to limit cross-border value chain
development.
278 OECD (2026). A comparison of the innovation and regulatory environments for biotechnology and biosolutions
across the EU and the United States. Available at: https://www.oecd.org/en/publications/a-comparison-of-the-
innovation-and-regulatory-environments-for-biotechnology-and-biosolutions-across-the-european-union-and-the-
united-states_1ec20342-en.html. 279 European Commission (2024). Communication from the Commission to the European Parliament, the Council, the
European Economic and Social Committee and The Committee of the Regions: Building the future with nature: Boosting
Biotechnology and Biomanufacturing in the EU, COM(2024) 137 final. 280 See https://www.bridgecross.bio/mapping-chinas-biotech-hubs-where-policy-capital-and-competition-collide/;
https://merics.org/en/report/lab-leader-market-ascender-chinas-rise-biotechnology.
202
The translation gap between EU research output and commercialisation is expected to
persist or grow. The pipeline of frontier biotechnologies continues to expand (AI-enabled
drug discovery, advanced therapies, precision medicine, synthetic biology), requiring
increasingly sophisticated translation infrastructure that the current fragmented ecosystem
is not positioned to deliver. EU-funded research projects will continue to produce high-
quality science, but commercialisation will increasingly occur outside the EU.
Without a Steering Group or equivalent coordination mechanism, the risk of duplicative
national investments will persist. As EU-level biotechnology investment grows,
particularly under the European Competitiveness Fund, the coordination gap becomes
increasingly costly, with larger volumes of funding channelled through fragmented
national systems increasing the probability of duplication and suboptimal resource
allocation.
9.3 Expected impacts
Conduct of business
The ecosystem support measures assessed may indirectly influence companies’ conduct of
business, but these effects are difficult to isolate, as changes in companies’ behaviour are
likely to result from the combined effect of several measures under the European Biotech
Act as well as other factors. The relevant pathways through which the intervention may
affect conduct of business are captured under other impact areas. Given the difficulty of
attributing conduct of business effects specifically to the ecosystem support measures,
impacts on this category are considered neutral in the multi-criteria analysis scoring.
Administrative costs on businesses, including SMEs
The EU Health Biotechnology Support Network, acting as a single entry point with health
biotechnology-specific support and navigation capacity, is expected to reduce the
transaction costs currently borne by businesses and SMEs in particular. The proposal
envisages that national and regional antennas may build on existing structures such as the
European Enterprise Network (EEN) where appropriate.
Evidence from comparable support networks indicates the potential scale of impact. The
EEN impact evaluation shows that supported businesses report substantially higher
knowledge levels across relevant areas compared to unsupported businesses: how to access
funding and finance (57% vs 40%); the market in which they operate (88% vs 78%);
regulation and standards (78% vs 72%)281. Among EEN-supported businesses reporting
positive impacts, improved knowledge was cited by 57% regarding finance access, 50%
for market knowledge, and 35% for regulations and standards. Similarly, evidence from
the EMA SME office survey found over 80% of respondents rated assistance services as
281 Innovate UK (2023). Enterprise Europe Network impact evaluation. Available at:
https://www.ukri.org/publications/enterprise-europe-network-impact-evaluation/.
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relevant to their needs – suggesting that the Support Network's advisory functions would
be utilised and deliver value to the target population282.
Together, accessible single entry points and health biotechnology-specific advisory
capacity are assumed to reduce FTE days spent on identifying applicable regulatory
pathways, funding instruments, and scaling-up opportunities.
Competitiveness, trade and investment flows
The competitiveness effect of the intervention is expected to operate primarily through the
EU Health Biotechnology Support Network's matchmaking function. In addition, better
ecosystem navigation, targeted support, and improved infrastructure access are expected
to contribute to reduced time-to-market for health biotechnology products.
Evidence from existing EU-level networks indicates the potential scale of impact on
investor access and matchmaking. The EEN impact evaluation shows that supported
businesses report higher capability in investment-related areas compared to unsupported
businesses: investment readiness (57% vs 42%) and ability to access funding or finance
(52% vs 44%)283. The Single Market Programme evaluation found that over 84% of SMEs
using EEN services reported either strong or reasonable impact on access to finance and
funding opportunities – the strongest impact areas among all assessed284. This
demonstrates that network antennas with matchmaking functions can result in improved
access to investors and capital for developers. The European Innovation Council (EIC)
provides further evidence that structured matchmaking can increase innovator-investor
connections that translate into measurable funds raised. Since 2021, through its Business
Acceleration Services, the EIC has facilitated over 20 000 one-on-one meetings between
EIC awardees and corporates, procurers, and investors, resulting in 595 deals and EUR
350 million raised through investor outreach285.
On time-to-market effects, several sources support the proposition that structured
navigation and support in retrieving information systematically can reduce development
timelines. EMA analysis of initial marketing authorisation applications indicates that
applicant-side "clock-stops" represent a substantial portion of total procedure time, and in
2023, the average duration of clock-stops (198 days) was comparable to the assessment
time itself (204 days)286. EMA reports that 42% of applicants requested extended clock-
stops because their data was not mature enough at submission, suggesting that
interventions improving submission readiness could reduce elapsed time. Evidence from
the EMA SME Office indicates persisting demand for support services that help SMEs
prepare for regulatory interactions. Surveys show high satisfaction with existing services
(80-90% depending on the specific service), but also consistent calls from SMEs to expand
282 European Medicines Agency (2025). Outcome of SME office survey on the implementation of the SME regulation -
Commission Regulation (EC) No 2049/2005. Available at: https://www.ema.europa.eu/en/about-us/support-smes/sme-
regulation-reports. 283 Innovate UK (2023). Enterprise Europe Network impact evaluation. Available at:
https://www.ukri.org/publications/enterprise-europe-network-impact-evaluation/. 284 European Commission (2025). Single market programme mid-term evaluation – Supporting study – Final report.
Available at: https://data.europa.eu/doi/10.2873/1307895. 285 See https://eic.ec.europa.eu/eic-funding-opportunities/bas_en. 286 See https://www.ema.europa.eu/en/news/improving-efficiency-approval-process-new-medicines-eu.
204
regulatory assistance, training, and pre-submission support287. The Support Network
would not itself provide regulatory advice. However, by helping SMEs navigate the
complex landscape of documentation, requirements, and available pathways upstream of
regulatory engagement, it could ensure that developers come better informed and prepared
to their interactions with the EMA SME Office and, where eligible, with schemes such as
PRIME288. This improved preparedness would address the submission readiness gaps that
contribute to extended clock-stops, thereby contributing to reduced overall time-to-market.
The UK Regulatory Advice Service for Regenerative Medicine (RASRM) further offers a
comparator to the proposed Support Network. RASRM operates as a "one-stop shop"
providing a single point of access to coordinated expert responses, aiming to reduce the
burden of navigating required standards and legislation for complex therapies289. The UK
Government response notes that the service resolved concerns regarding the complexity of
the regulatory environment and provides an early opportunity to help speed access290.
Taken together, this evidence supports the expectation that the Support Network's function
of helping navigate the system and retrieve relevant and timely information would
contribute to reduced time-to-market.
Functioning of the internal market and competition
The EU Health Biotechnology Support Network is expected to reduce the effect of varying
national support structures by providing comparable advisory services through antennas
across all Member States. By establishing health biotechnology-specific antennas based
on common criteria across the EU291, the intervention would reduce the current dependence
on national support structures that vary significantly in scope and capacity. This addresses
the baseline condition where a health biotechnology SME's ability to navigate the system
and access support depends on which Member State it is located in. Stakeholder
consultations validated this approach, emphasising the importance of building on existing
structures and instruments. Workshop participants noted that clusters already maintain
connections across multiple levels, including innovation agencies, the ECCP, European
Clusters Alliance, and industry associations, providing an established foundation for the
proposed networks292.
The cluster networks are intended to improve cross-border access to biomanufacturing
facilities and research infrastructure. Although outcome-level data on facility access is
limited, evidence on existing cluster initiatives supports the potential impact of this
287 EMA 2020 and 2025 SME Office surveys. Available at https://www.ema.europa.eu/en/about-us/support-smes/sme-
regulation-reports. See also https://somerville-partners.com/how-successful-are-the-emas-sme-initiatives/. 288 PRIME is a scheme run by EMA to enhance support for the development of medicines that target an unmet medical
need. This voluntary scheme is based on enhanced interaction and early dialogue with developers of promising
medicines, to optimise development plans and speed up evaluation so these medicines can reach patients earlier. 289 See https://www.hta.gov.uk/guidance-professionals/guidance-sector/human-application/regulatory-advice-service-
regenerative. 290 See
https://assets.publishing.service.gov.uk/media/5a81f4bced915d74e3400f57/Government_Response_to__Inquiry_into_
Regenerative_MedicineCm_9491.pdf. 291 As per the Proposal for the European Biotech Act (Section 4, Article 19(5)) “The Commission shall select the
members of the Network based on criteria made public pertaining to the expertise and capabilities required to fulfil the
missions referred to in paragraph 3”. 292 Workshop on strengthening biotechnology clusters: current landscape and potential impacts of the European Biotech
Act proposal.
205
mechanism. The ECCP Cluster Panorama underlines the role of cluster networks as
facilitating economic resilience and market integration by enabling firms to pool
infrastructure and operate shared resources including testbeds, GMP facilities, and data
spaces, and can arrange access to pilot lines and form cross-border consortia from
demonstration to manufacturing293. The importance of cluster collaboration for
infrastructure access is recognised in other strategic sectors. For example, the Silicon
Europe cluster alliance, connecting over 2 500 companies and research institutions in the
electronics sector, acts as a single entry point with aligned shared infrastructures.
Innovation and research
The cluster networks and Support Network measures are expected to contribute to
innovation and research through complementary functions. The cluster networks bring
together projects, research organisations, and market actors in cross-border collaborations,
pooling resources and strengthening research-industry linkages that support the translation
of research into market applications. The Support Network helps individual actors navigate
the ecosystem and connect with relevant cluster networks and cooperation opportunities,
thereby increasing the uptake of research collaboration.
Cluster networks: Evidence from other EU initiatives demonstrates that cluster-based
approaches can generate measurable partnership activity and research-market connections.
The 2021 evaluation of EU cluster initiatives under COSME and Horizon 2020 found that
INNOSUP-1 supported 1,687 SMEs, bringing together companies and research
organisations in cross-border consortia; ESCP-4i facilitated 64 partnerships across 32
countries; and ESCP-S3 strengthened interregional collaboration with 57 partners from 19
countries294. Stakeholder consultations confirm that cluster organisations possess deep
ecosystem knowledge developed over many years of close interaction with industry and
research actors, positioning them to identify bottlenecks and facilitate targeted
connections295.
Support Network: The Support Network is expected to contribute to innovation capacity
at firm level by helping developers identify relevant research partnerships and access
cluster networks. The EEN impact evaluation shows that firms receiving network support
report higher capability across innovation-related areas compared to unsupported firms:
knowledge sharing and collaboration (69% vs 55%), management of innovation (79% vs
66%), and culture of innovation (84% vs 74%)296. Among supported businesses, 55%
reported positive impact on knowledge sharing and collaboration, 52% on management of
innovation, and 43% on R&D spend. Workshop participants noted that current EU cluster
instruments primarily attract early-stage start-ups, while mature scale-ups, whose priorities
centre on industrialisation, regulatory acceleration, and market access, engage less
293 European Cluster Collaboration Platform (2025). Clusters and Europe’s Competitiveness ECCP Summary Report
2025. Available at: https://www.clustercollaboration.eu/sites/default/files/document-
store/ECCP_SummaryReport_2025.pdf. 294 Prognos, CSES, Idea Consult (2021). Evaluation Study of and Potential Follow-Up to Cluster Initiatives under
COSME, H2020 and FPI. Available at: https://data.europa.eu/doi/10.2873/977418. 295 Workshop on strengthening biotechnology clusters: current landscape and potential impacts of the European Biotech
Act proposal. 296 Innovate UK (2023). Enterprise Europe Network impact evaluation. Available at:
https://www.ukri.org/publications/enterprise-europe-network-impact-evaluation/.
206
frequently297. The Support Network's functions are expected to help these actors identify
and access relevant cluster networks, extending ecosystem support for research
collaboration and innovation across the full development lifecycle.
Public authorities
The intervention introduces several obligations for Member State authorities:
participation in the European Health Biotechnology Steering Group (Article 20), data
provision for strategic mapping upon Commission request (Article 17), facilitation of the
Support Network's tasks (Article 19(7)), and designation of single points of contact for
strategic projects (Article 11).
Comparable strategic project initiatives provide indicative benchmarks. The Net-Zero
Industry Act estimates 1–2 FTEs for Member States to operationalise permitting one-stop
shop functions, with potentially higher requirements depending on project volume and
federal structures, and a maximum of 1 FTE per Member State for administrative support
to strategic projects298. The Critical Raw Materials Act estimates 0.25 FTE per year for
reporting on the state of strategic projects and 2 FTEs per year for participation in the
governance structure299. Given that one-stop shop architectures will have already been
established under these initiatives, Member States will have developed points of contact,
coordination channels, and workflows, resulting in marginally lower set-up costs.
Remaining incremental cost would primarily relate to scope extension – integrating health
biotechnology strategic projects into existing workflows and developing sector-specific
expertise. The costs associated with Steering Group participation, national coordination,
and data submissions for strategic mapping will depend on the frequency of mapping
requests and the intensity of Steering Group activity.
These initial obligations are expected to yield efficiency gains over time. Member States
gain access to a systematic evidence base (strategic mapping) and a coordination forum
(Steering Group) that do not currently exist for biotechnology specifically, improving
national decision-making and reducing duplicative investments by providing comparable
information on capacities, gaps, and funding priorities across the Union. The Support
Network would also alleviate the burden on national administrations that bear the full load
of guiding health biotechnology applicants through complex EU funding and regulatory
landscapes (see section on competitiveness, trade and investment flows).
At EU level, administrative costs arise from operating the Steering Group secretariat,
conducting and maintaining the strategic mapping, and coordinating the Support Network.
297 Workshop on strengthening biotechnology clusters: current landscape and potential impacts of the European Biotech
Act proposal. 298 European Commission (2023). Commission Staff Working Document for a Regulation of the European Parliament
and of the Council on establishing a framework of measures for strengthening Europe’s net-zero technology products
manufacturing ecosystem (Net Zero Industry Act). Available at
https://www.europarl.europa.eu/RegData/docs_autres_institutions/commission_europeenne/swd/2023/0219/COM_SW
D(2023)0219_EN.pdf. 299 European Commission (2023). Commission Staff Working Document Impact Assessment Report accompanying the
document Proposal for a Regulation of the European Parliament and of the Council establishing a framework for
ensuring a secure and sustainable supply of critical raw materials and amending Regulations (EU) 168/2013, (EU)
2018/858, 2018/1724 and (EU)
2019/1020. Available at: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:52023SC0161.
207
The proposed act identifies relevant tasks including administrative and logistic support to
Steering Group meetings, drafting calls for proposals for the Support Network, project
selection and assessment for strategic projects, workflow management of Support Network
queries, and promoting networking and cooperation among projects. Technical assistance
appropriations of approximately EUR 2.6 million annually (EUR 18.4 million over the
MFF period) include, among other tasks, financing the contract agents implementing these
functions on the Commission side. The Critical Raw Materials Act estimates 2 FTEs for
the governance structure secretariat plus EUR 75,000 per year in organisational costs, and
1 FTE for supporting strategic project selection. As with other EU-coordinated support
structures, the long-term sustainability of the Support Network and its antennas will
depend on the development of sustainability strategies and funding diversification
approaches.
Public health and safety
The ecosystem support measures do not directly affect public health and safety outcomes.
Given the absence of a direct transmission mechanism and the difficulty of isolating any
indirect effects, impacts on this category are considered neutral.
10 INTERVENTION N°12: BIOSIMILARS COMPETITIVENESS FRAMEWORK
10.1 Detailed description of the proposed measures
The proposal includes the update and development of EMA guidelines on tailored and
risk-proportionate regulatory approaches for biosimilar development, reflecting
manufacturing and analytical testing advances. Guidance will consider potential reduction
of clinical data requirements for biosimilar development and approval without affecting
quality, safety and efficacy. They will aim at shortening the development and facilitating
the authorisation of biosimilar medicinal products.
The proposal also includes the establishment of a framework for the recognition and the
support health biotechnology strategic projects focused on biosimilar research,
development, manufacturing and marketing authorisation. The support package includes
administrative, regulatory and financial and technical support at Member State level, also
promoting international cooperation between economic operators and biotechnology
clusters in this area.
10.2 Baseline and counterfactual scenario
Non-binding guidance by the European Medicines Agency for a tailored regulatory
approach for biosimilar development, reflecting advances in analytical science and
considering potential reductions in clinical data requirements (Article 28):
Biosimilar development currently entails costs of approximately EUR 85.6–257 million
and timelines of 6–9 years300. A major cost and time driver is the comparative efficacy
study (CES), which accounts for 20–50% of total development costs (approximately EUR
300 McKinsey & Company. (2022, August 19). Three imperatives for R&D in biosimilars.
https://www.mckinsey.com/industries/life-sciences/our-insights/three-imperatives-for-r-and-d-in-biosimilars
208
14–46 million) and extends development timelines by 12–24 months301,302. Europe is the
leading region for biosimilar clinical trials with 83 trials conducted between 2020–2025
and roughly EUR 4.9 billion biosimilar trials investments, 71% of which dedicated to
CES.
Regulatory practice has already begun to evolve toward a risk-based approach. For well-
characterised, simpler products with accepted pharmacodynamic biomarkers the EMA has
accepted PK/PD-based clinical packages without Phase III CES for many years. From the
EMA Medicines Database, 41 of 151 authorised biosimilars (27.2%) are simple biologics
in this category303. For monoclonal antibodies and fusion proteins, Phase III CES with
clinical efficacy endpoints was included in 100% of the 36 MAAs evaluated by EMA
between July 2012 and November 2022304. However, evidence shows that negative
regulatory outcomes were linked to quality deficiencies rather than clinical efficacy results,
indicating that CES has had limited regulatory impact in determining approval
outcomes305.
The European Medicines Agency draft Reflection Paper on a Tailored Clinical Approach
in Biosimilar Development (2024) proposes formalised criteria for waiving CES
requirements, marking a shift from case-by-case flexibility to a generalised scientific
principle306. This approach aligns with international regulatory convergence. The U.S.
Food and Drug Administration has removed switching study requirements and expanded
flexibility in clinical evidence (2024–2025)307, while Canada is consulting on CES
elimination for most biosimilars308. South Korea already applies CES waivers in
practice309, and Japan is expected to adopt similar flexibility by 2028.
Under the baseline, the EMA continues a gradual shift toward tailored, risk-based
approaches through non-binding guidance, without changes to formal regulatory standards
for safety, quality, or efficacy. At the same time, global competitors streamline evidentiary
requirements more rapidly. As a result, EU competitiveness in biosimilar development is
301 Moore, T. J., Mouslim, M. C., Blunt, J. L., Alexander, G. C., & Shermock, K. M. (2020). Assessment of availability,
clinical testing, and US Food and Drug Administration review of biosimilar biologic products. JAMA Internal Medicine,
181(1), 52–60. https://doi.org/10.1001/jamainternmed.2020.3997 302 IQVIA, The Impact of Biosimilar Competition in Europe, January 26, 2026, iqvia-the-impact-of-biosimilar-
competition-in-europe-2026-01-26-forweb.pdf 303 European Medicines Agency. (2026). Medicines output report [dataset]. Retrieved 2 March 2026 from
https://www.ema.europa.eu/en/medicines/download-medicine-data 304 Kirsch-Stefan, N., Guillen, E., Ekman, N., Barry, S., Knippel, V., Killalea, S., Weise, M., & Wolff-Holz, E. (2023).
Do the outcomes of clinical efficacy trials matter in regulatory decision-making for biosimilars? BioDrugs, 37(6), 855–
871. https://doi.org/10.1007/s40259-023-00631-4 305 Kirsch-Stefan, N., Guillen, E., Ekman, N., Barry, S., Knippel, V., Killalea, S., Weise, M., & Wolff-Holz, E. (2023).
Do the outcomes of clinical efficacy trials matter in regulatory decision-making for biosimilars? BioDrugs, 37(6), 855–
871. https://doi.org/10.1007/s40259-023-00631-4 306 European Medicines Agency. (2024). Reflection paper on a tailored clinical approach in biosimilar development (draft
for consultation). Amsterdam: EMA. 307 U.S. Food and Drug Administration. (2024). Considerations in demonstrating interchangeability with a reference
product: Update (draft guidance). Silver Spring, MD: FDA. 308 Smart & Biggar. (2025, July 4). Update on biosimilars in Canada – June 2025.
https://www.smartbiggar.ca/insights/publication/update-on-biosimilars-in-canada-june-2025 309 Kang, H. N., Thorpe, R., Knezevic, I., et al. (2020). The regulatory landscape of biosimilars: WHO efforts and
progress made from 2009 to 2019. Biologicals, 65, 1–9. https://doi.org/10.1016/j.biologicals.2020.02.005
209
expected to weaken, with developers prioritising earlier submissions in jurisdictions with
lighter requirements, potentially delaying EU market entry.
Europe and the United States combined hold over 80% of the global biosimilar market by
revenue. However, the EU’s relative share is declining as the US market expands rapidly.
The US biosimilar market grew from EUR 6.1 billion in 2020 to an estimated EUR 10.1
billion in 2024, while the Asia-Pacific region - driven primarily by China - grew from EUR
1.5 billion to approximately EUR 4.5 billion over the same period310. The EU biosimilar
market projected to grow at a compound annual growth rate (CAGR) of approximately
17%, increasing from EUR 13.2 billion in 2025 to EUR 62.9 billion by 2035311 driven
primarily by patent expiries and expanding therapeutic applications. The estimated
cumulative savings of EUR 75 billion from biosimilar competition since 2006 with EUR
13 billion in 2024 continues to grow.
Advances in analytical sciences are expected to further strengthen the scientific consensus
that Phase III CES provides limited additional value for well-characterised biosimilars.
However, as development shifts toward more complex products (e.g. monoclonal
antibodies, bispecific antibodies, antibody–drug conjugates), a proportion of applications
will continue to require clinical data, particularly for immunogenicity assessment.
Biosimilar strategic projects recognition and support (Article 29 -30)
Conduct of business
Assumption
The Chapter II strategic project support infrastructure (Articles 3–14) is operational for
general health biotechnology projects, providing single points of contact (Art. 11), priority
permit-granting (Art. 12), compliance assistance (Art. 13), and pathways for financial and
technical support (Art. 14). However, biosimilar-specific eligibility criteria under Article
29 do not exist in the baseline. Biosimilar companies may compete for general industrial
support but lack dedicated recognition.
Administrative costs on businesses, including SMEs
Assumption
Chapter II administrative support infrastructure (single points of contact, compliance
assistance, priority permitting under Articles 11–14) is operational for general health
biotechnology projects but not accessible to biosimilar-specific projects absent Article 29
recognition.
Competitiveness, trade and investment flows
310 Precedence Research. (2025, August 13). Biosimilars market size to hit USD 175.99 billion by 2034.
https://www.precedenceresearch.com/biosimilars-market 311 Precedence Research. (11 Mar 2026). Biosimilars Market Size, Share and Trends 2026 to 2035.
https://www.precedenceresearch.com/biosimilars-market
210
Biosimilar-specific investment data (venture capital, FDI) disaggregated from the broader
health biotechnology sector is not publicly available. However, what can be stated with
biosimilar-specific evidence is:
• The EU retains significant biosimilar manufacturing capacity. Of the top five
global biosimilar companies by revenue in 2024, two are EU-based (Sandoz,
Austria/Germany; Fresenius Kabi, Germany) and two operate major EU
manufacturing facilities despite non-EU headquarters (Samsung Bioepis,
Netherlands operations; Celltrion, Hungarian operations).312
• Despite 77% of innovative biologic active ingredients being sourced within
Europe313, dedicated biosimilar manufacturing is increasingly migrating to Asia,
particularly South Korea and India.314
• Recent studies identified an increasing number of partnerships involving ex-EU
biosimilar companies that collaborate with European manufacturers to launch
products in Europe. Historically, these partnerships were relatively uncommon, but
their prevalence has increased. Between 2006 and 2013, ex-EU partnerships
represented 30% of all approvals, but more recently this figure increased to 45%
(2014–2024).
Assumption
EU-based companies hold approximately 49% of EU biosimilar authorisations, with South
Korean companies (Samsung Bioepis, Celltrion) at 16% and US/global pharma at 17%.
While international cooperation among biosimilar economic actors is an increasing trend,
there is increasing competitive pressure from developers from India, China, and Korea that
expand their EU market presence.315
Functioning of the internal market and competition
Assumption
Biosimilar strategic project measure’s implementation depends on Member State
establishment of Chapter II infrastructure. Differences in administrative capacity across
Member States can be a potential implementation uncertainty for strategic projects, as with
other EU industrial support frameworks. This risk is mitigated by the European Biotech
Act's institutional design: the European Health Biotechnology Steering Group provides
implementation guidance and facilitates best-practice exchange (Article 20); the
Commission's strategic mapping identifies capacity gaps and investment needs (Article
22); and Member States may designate or adapt existing coordination mechanisms as
single points of contact rather than creating new structures.
312 Alira Health. (2025, November 6). Key players in the biosimilars market 2025. https://alirahealth.com/key-players-
biosimilars-market-2025/ 313 Why Europe is Becoming a Global Hub for Biologics Manufacturing. Mabion Science Hub:
https://www.mabion.eu/science-hub/articles/why-europe-is-becoming-a-global-hub-for-biologics-manufacturing/ 314 Cohen, H. P., Turner, M., McCabe, D., & Woollett, G. R. (2023). Future evolution of biosimilar development by
application of current science and available evidence: The developer’s perspective. BioDrugs, 37(5), 583–593.. 315 European Medicines Agency. (2026). Medicines output report [dataset]. Retrieved 2 March 2026 from
https://www.ema.europa.eu/en/medicines/download-medicine-data
211
Innovation and research
Assumption
Innovation in analytical science continues to advance, enabling increasingly precise
characterisation of biosimilar products. Modern mass spectrometry, high-resolution
chromatography, and functional assays can now characterise protein structures with
extraordinary precision316.In absence of biosimilar strategic project recognition these
advancements continue but are not candidates for potential support under Article 29’s
measure.
Public authorities
Assumption
Chapter II infrastructure (single points of contact, priority permitting, compliance
assistance under Articles 11–14) is operational for general health biotechnology projects
but not accessible to biosimilar-specific projects absent Article 29 recognition.
10.3 Expected impacts
Non-binding guidance by the European Medicines Agency for a tailored regulatory
approach for biosimilar development, reflecting advances in analytical science and
considering potential reductions in clinical data requirements (Article 28)
Administrative burden
The administrative burden and associated costs of preparing marketing authorisation
applications (MAAs) for biosimilars, with or without a Phase III comparative efficacy
study (CES) follows the methodology follows the Standard Cost Model (SCM) from the
Better Regulation Toolbox, where administrative cost is calculated as person-days
multiplied by labour rate and quantity. Labour rates are based on two Eurostat scenarios:
€400 per person-day as a baseline and EUR 600 per person-day for specialised regulatory
affairs or external consultancy. Task decomposition draws on common technical
documentation (CTD) structure requirements, industry benchmarks for MAA team size
and timeline (typically 20–30 people over 18–24 months), and EMA biosimilar-specific
guidance on clinical data requirements.
The administrative burden differs depending on whether a CES is included. Category A,
representing a tailored clinical package (PK/PD plus immunogenicity, no CES), requires
approximately 253 person-days, whereas Category B, representing a full Phase III CES
316 Guillen, E., et al. (2023). A data driven approach to support tailored clinical programs for biosimilar mAbs. Clinical
Pharmacology & Therapeutics, 113(1), 108–123. https://doi.org/10.1002/cpt.2785
212
package, requires approximately 328 person-days, giving a difference of 75 person-days
(range: 50–100). This difference arises from three main workstreams:
• First, CES-specific clinical modules—including clinical study report drafting,
efficacy analysis, and extended safety narratives—account for 40–80 person-days.
These modules exist only in Category B, so if CES is eliminated, these sections are
no longer required.
• Second, immunogenicity assessment contributes 5–10 person-days of additional
effort. While both categories require immunogenicity data, Category A generates
it within a combined PK/immunogenicity study (~100–400 subjects), whereas
Category B generates it within the Phase III CES (~500–1,500 patients), producing
a larger dataset requiring more documentation.
• Third, eCTD publishing and submission accounts for 5–10 person-days difference.
Without CES modules, the electronic common technical documentation is smaller,
reducing formatting, cross-referencing, and quality control efforts. All other
workstreams—including regulatory strategy,
quality/chemistry/manufacturing/control (CMC) comparability, non-clinical
comparability, and PK/PD modules—are identical between Categories A and B.
Applying the SCM formula, the 75 person-day difference translates into an administrative
cost saving of EUR 30,000–45,000 per MAA (75 PD × EUR 400–600/PD). This saving
applies only to dossier preparation labour and is deliberately separate from, and much
smaller than, the CES trial execution cost saving, estimated at EUR 19–26 million per
product. Both savings are additive but operate at very different scales.
Table 11. Cost and efficiency impacts of CES implementation (2025–2038)
INDICATOR 2025 (BASE) 2025–2030 2030–2038 EMA
GUIDELINES
FOR CES
WAIVERS
BIOSIMILAR
STRATEGIC
PROJECTS
SUPPORT
CES execution
cost saved per
product
EUR 19–26
million (USD
20–28
million) per
CES
EUR 222–467
million/year
(aggregate, 12–
18 MAAs)
EUR 463
million–1.0
billion per
year (25–40
MAAs)
Direct: full trial
elimination for
qualifying
products
—
Development
timeline saving
0 ~24 months per
product
~24 months
per product
Direct: shorter
pipeline, later
start, reduced
commercial risk
—
MAA dossier
preparation
(person-days
per MAA)
253–328 253 for 50–
75% of mAb
MAAs
253 for 70–
80% of all
MAAs
~75 person-days
saved per
transitioning
MAA; EUR 30–
45 thousand
—
Aggregate
annual dossier
saving (EUR)
— EUR 0.4–0.8
million/year
EUR 1.0–2.5
million/year
12–18 MAAs
near-term; 25–
—
213
40 medium-
term
Sources: Annex I (dossier preparation, Nevens et al., 2019); Annex II (CES execution, Ranbhor & Kulkarni,
2026); Cakić (2026);
Biosimilar strategic projects recognition and support (Article 29 -30)
Table 12 presents the illustrative order-of-magnitude impacts for biosimilar strategic
projects under Article 29, derived by proportional scaling from the Strategic Projects of
chapter II (intervention No 9)
Table 12. Overall strategic project impact adapted for the biosimilar case
Impact category Low uptake (3–5
projects)
Medium uptake
(8–12 projects)
High uptake (15–20
projects)
Conduct of business
Projects completing permit-
granting within 10 months (Article
12)
~2–4
~6–10
~11–17
Administrative costs on
businesses, including SMEs
Avoided delay costs (cumulative,
EUR million)
~EUR 13–60 million
~EUR 33–147
million
~EUR 57–260 million
Competitiveness, trade and
investment flows
Total investment mobilised
(cumulative, EUR billion)
~EUR 0.9–1.7 billion
~EUR 2.3–4.3
billion
~EUR 4.0–7.6 billion
Functioning of the internal
market and competition
Cross-border projects (≥2 Member
States)
~0–1
~1–2
~2–4
Innovation and research
Projects with material R&I or
analytical innovation outputs
(Article 29(1)(b))
~1–2
~2–4
~3–6
Public authorities
Biosimilar recognition decisions
per year; incremental single point
of contact capacity
~0.3/year; negligible
incremental FTE
(absorbed within
Chapter II SPoC)
~1/year; ~0.1–0.2
incremental FTE
~1.5/year; ~0.2–0.3
incremental FTE
Public health and safety
Capacity-relevant biosimilar
manufacturing deployments
~1–2
~3–5
~5–10
Source: Derived by proportional scaling from the Strategic Projects IA (Cakić, 2026), applying biosimilar-
specific uptake scenarios to the same per-project impact parameters. Scaling ratios: Low = 4/27.5 (0.145);
Medium = 10/65 (0.154); High = 17.5/110 (0.159). Figures rounded to reflect order-of-magnitude precision.
214
Expected impact of both biosimilar measures (Article 28-30)
Competitiveness, Trade and Investment Flows
By adopting CES waiver guidelines, the EU aligns itself with leading global jurisdictions
and strengthens its regulatory appeal, ensuring it remains a premier destination for
developer investment, not losing terrain to the US and Asia-Pacific markets. The medium-
term effect of biosimilar strategic projects support on EU-based MAH share depends on
whether Article 29 provides sufficient incentive to offset lower manufacturing costs in
other regions e.g., Korea, India, and China. The total investment mobilised by Article 29
varies by uptake hypothesis, ranging from EUR 0.9–1.7 billion in the low uptake scenario
(3–5 projects) to EUR 4.0–7.6 billion in the high uptake scenario (15–20 projects) [see
Table 12 above “overall strategic project impact adapted for the biosimilar case”].
Table 13. Global competitiveness and market position of the EU biosimilar sector
(2025–2038)
INDICATOR 2025 (BASE) 2025–2030 2030–2038 EMA
GUIDELINES
FOR CES
WAIVERS
BIOSIMILAR
STRATEGIC
PROJECTS
SUPPORT
EU share of global
biosimilar market
(revenue)
~43–55% (~USD
13–18B depending
on scope and methodology
38–43% (US
growth erodes
share; EU grows
in absolute terms)
35–40% (global
market reaches
USD 150–175B;
EU grows to USD 55–65B)
Indirect: faster
entry maintains EU as preferred
launch territory
Direct:
manufacturing capacity retention in
EU
EU-based MAH
share of EU
authorisations
49% 45–50% (Korean
+ Indian competition
continues)
40–50% without
strategic projects; 45–55% with
strategic projects
— Direct: Art. 29
support retains EU-
based developers
Jurisdictions with
CES waiver 2 (South Korea,
UK)
4–5 (US,
Canada, Japan
formalise by 2028)
6–8 (global
convergence
toward tailored approach)
Direct: CES
waiver ensures EU is in the
leading group,
not lagging
—
Sources: Alira Health (2025) for market size; EMA Medicines Database for MAH analysis; Precedence
Research (2025) for market projections; Smart & Biggar (2025) and FDA (2024–2025) for jurisdiction CES
status317,318.
Functioning of the Internal Market and Competition
The EMA guidance is expected to contribute to the increase of biosimilar competition in
the EU market by reducing barriers to entry and accelerating time-to-market. Recent
industry reports document that biosimilar competition typically drives prices down by 20–
50% or more following market entry, with cumulative savings of approximately EUR 75
billion and roughly EUR 13 billion in 2024319. Faster and cheaper biosimilar development
is expected to increase the number of competitors per reference product and reduce the
time from patent expiry to first biosimilar entry, strengthening competition and price
pressure. Biosimilar strategic projects support can also boost faster and cheaper biosimilar
317 Alira Health. (2025). 2025 global biosimilars report. https://alirahealth.com/biosimilars-market-2025-market-size-
growth-drivers-regional-dynamics/ 318 Precedence Research. (2025). Biosimilars market size to hit USD 175.99 billion by 2034.
https://www.precedenceresearch.com/biosimilars-market 319 Medicines for Europe. (2024). The impact of biosimilar medicines in Europe. Brussels.
215
development, the impact on internal market functioning will depend on how many member
states will prioritise strategic projects in this domain.
Table 14. Impact of EMA guidelines for CES waivers and biosimilar strategic
projects: health savings, price reduction and operational infrastructures
INDICATOR 2025 (BASE) 2025–2030 2030–2038 EMA GUIDELINES
FOR CES WAIVERS
BIOSIMILAR
STRATEGIC
PROJECTS SUPPORT
Cumulative EU
biosimilar savings
(EUR)
~EUR 75
billion (since
2006); ~EUR 13 billion in
2024
EUR 130–160
billion
cumulative by 2030; EUR
16–22
billion/year
EUR 300–450
billion
cumulative by 2038; EUR 22–
35 billion/year
Indirect: faster entry +
more competitors =
greater savings
Indirect: EU supply
security supports access
continuity
Average price
reduction post-entry 20–50% 25–60% (more
competitors
per molecule)
30–70% (mature
competition +
next-generation
procurement)
Indirect: more entrants =
deeper competition
—
MS with operational
Ch. II single points of
contact
0 (not yet
operational)
15–20 MS (larger MS
first)
22–27 MS (full
rollout)
— Direct: depends on how
many member states take
up the measure
Sources: IQVIA (2025) for baseline savings; Medicines for Europe (2024) for price reduction range. Savings
projections assume 17% CAGR in biosimilar market + CES waiver acceleration
Public Health and Safety
The upper bounds of the therapeutic area and authorisation projections are constrained by
the 'biosimilar void': of approximately 100 biologics expected to lose exclusivity by 2032,
79% have no biosimilars in development and only 10% are likely to face biosimilar
competition in Europe (IQVIA, 2026). The EMA guidance and the biosimilar strategic
project support are designed to address this gap:
• the first by reducing per-product development costs (EUR 19–26 million for CES
elimination), making lower-value biologics commercially viable for biosimilar
development;
• and the second by providing investment support through the Chapter II strategic
project framework (see table 13 above “overall strategic project impact adapted for
the biosimilar case”).
The principal risk is to perceived safety, not actual safety. If prescribers or Health
Technology Assessment bodies lose confidence in biosimilars approved with less clinical
data, uptake could decrease, offsetting the access benefits of faster entry. Effective
communication strategies and transparent post-marketing monitoring are prerequisites.
The 2030–2038 projection assumes that the first decade of tailored-approach approvals
(2025–2035) generates sufficient pharmacovigilance evidence to confirm that the safety
profile is equivalent regardless of the clinical data package at authorisation.
Table 15. Impact of EMA guideline for CES waivers and biosimilar strategic projects
on public health and safety
INDICATOR 2025 (BASE) 2025–2030 2030–2038 EMA GUIDELINES
FOR CES
WAIVERS
BIOSIMILAR
STRATEGIC
PROJECTS
SUPPORT
216
Biosimilars authorised
(cumulative) 151 250–350 450–650 Indirect: accelerated
authorisations —
Therapeutic areas
covered ~27 reference
products ~35–45 reference
products ~55–75 reference
products Indirect: lower
barriers open new
areas
—
Annual healthcare
system savings (EUR) ~EUR 13 billion
(2024)
EUR 16–22
billion/year by
2030
EUR 22–35
billion/year by
2035–2038
Indirect: more
biosimilars = deeper
competition = greater
savings
Indirect: EU supply
security supports
access continuity
Safety: biosimilars
withdrawn on safety
grounds
0 (in 19 years) 0 expected 0 expected No change: CES
waiver modifies
evidence type, not
safety standard
—
EudraVigilance
identifiability rate 91.5% (2011–
2019;
downward
trend)
Requires
monitoring —
CES waiver must
not exacerbate
decline
Target: >90%
maintained through
strengthened
traceability policies
Risk: more
biosimilars may dilute
identifiability if not
managed
—
11 INTERVENTION N°13: SPC EXTENSION FOR BIOTECHNOLOGY MEDICINES
11.1 Additional information on baseline and assumptions
Conduct of business
Baseline
Market authorisation holders in the EU benefit from several layers of protection from
generic and biosimilar competition. Regulatory data and market protection lasts ten years
from the date of market authorisation (MA) in the current system. This will however
change when the revision of the pharmaceutical legislation will come into
force, introducing a modular system of market protection that will allow to obtain an extra
year of market protection in certain cases. Application is foreseen by the second half of
2028 at the earliest.
Patents last twenty years from filing and therefore may expire before or after the end of
the regulatory protection (RP) depending on the time it took to bring the product to market.
SPCs currently provide up to five and a half years (the additional half year being
conditional on a paediatric investigation plan (PIP)) of protection beyond the expiry of the
primary patent lasting a maximum of fifteen and a half years beyond the market
authorisation date. The actual length of the SPC is conditional to the time lasted from the
patent filing to the marketing authorisation of the product.
The evaluation of the pharmaceutical legislation found that on average medicines for which
SPC is the last protection to expire (around 30-35% of the medicinal products) have higher
revenues and longer lifecycles than RP-reliant medicines and shorter lifecycles than patent-
reliant medicines. The modular length of market protection that will apply when the
pharmaceutical reform comes into force might affect the pool of products for which SPC
is the last protection to expire. However, while it is impossible to estimate in advance the
impact of the changes of the regulatory protection, it is expected that there will not be an
impactful change in the overall duration of RP. Most of the newly authorised products will
be expected to reach the maximum of 10 years RP bringing consequently also benefits to
the patients and the society. Consequently, it is not expected that the modular system of
217
market protection introduced in the pharma reform will have a significant impact on which
is the last protection to expire.
The economic importance of SPCs is reflected in the revenue profiles of protected
products. Looking at the cohort of 198 products analysed for this assessment, we see
confirmed the trend observed in previous literature and studies, i.e. that SPC reliant
medicines generate substantially higher revenues in the final year before expiry compared
to products relying on regulatory data protection or patents.
Table 16. Average protection duration and pre-expiry revenues by last line of
protection (all products, n=198)
Source: author analysis based on IQVIA MIDAS and IQVIA Patent Intelligence 320
When focusing specifically on the subset of biological medicines in our 198-product
cohort, the difference becomes even more pronounced, with SPC-reliant products
exhibiting significantly higher pre-expiry sales.
Table 17. Average protection duration and pre-expiry revenues by last line of
protection (biological products, n=31)
Last line of protection Number of products Avg. protection duration Avg sales in year before expiry
Regulatory protection 10 10.1 EUR 83 m
Market Exclusivity 6 10.7 EUR 42 m
SPC 12 14.8 EUR 743 m
Patent 3 16.7 EUR 395 m
Grand Total 31 12.7 EUR 361 m
Source: Author analysis based on IQVIA MIDAS and IQVIA Patent Intelligence
Key Assumptions
• Protection profiles remain decisive: differences in revenue outcomes across
products continue to reflect the last layer of protection and the associated
effective regulatory protection period.
320 Analysis using IQVIA MIDAS® quarterly sales data 2008-2024. Geographical coverage: EU27 without Cyprus,
Malta and Denmark which were obtained under license from IQVIA and reflect estimates of real world activity.
Copyright IQVIA. All rights reserved. Last layer of protection was determined through analysis of IQVIA Patent
Intelligence.
Last line of
protection
Number of
products
Avg. protection
duration
Avg sales in year before expiry
Regulatory
protection
68 10.1 EUR 151 m
Market
Exclusivity
12 10.7 EUR 36 m
SPC 96 14.4 EUR 320 m
Patent 22 16.9 EUR 173 m
Grand Total 198 13.0 EUR 227 m
218
• Lifecycle management unchanged: originator firms continue to concentrate
commercial strategies on the final years of effective regulatory protection,
reflecting persistent expectations of steep post-expiry revenue losses. This
includes a continued focus on pricing, contracting and market coverage during
the remaining period of regulatory protection.
• ATMPs follow distinct dynamics: commercial performance remains primarily
driven by clinical adoption, reimbursement and manufacturing scale-up. Given
their technical complexity and the current lack of established follow-on
competition, ATMPs have, in practice, faced limited exposure to post-expiry
competitive erosion to date. Accordingly, commercial outcomes are less
strongly linked to predictable post-expiry dynamics under the baseline.
Nevertheless, we include ATMPs in our assessment of eligible products for SPC
extension not to exclude that in the future biosimilar versions of these products
might be approved.
Functioning of the internal market and competition
Key assumptions
• Biosimilar entry remains legally constrained by the expiry of the last applicable
protection instrument. Although the revised pharmaceutical legislation is expected
to enter into force from mid-2028 at the earliest, no systematic acceleration or delay
of entry is assumed within the baseline, given long development timelines.
• Following expiry, biosimilar authorisations occur shortly thereafter, subject to
standard regulatory procedures and Member State–level market access processes.
• Post-entry price erosion remains broadly consistent with historical EU patterns and
continues to vary by product class, with faster erosion for small molecules and more
heterogeneous outcomes for biologics and complex therapies.
Innovation and research
Key assumptions:
• Patent data as innovation proxy: patent-family counts are used as an indicator of
innovation output, reflecting firms’ expectations about the commercial value and
appropriability of biotech inventions.
• Geographic anchoring: the earliest filing jurisdiction is used as a proxy for early
protection and location preferences, recognising that it does not necessarily reflect
the physical location of R&D or later commercialisation.
• Multi-jurisdiction filings: simultaneous filings are analysed separately,
distinguishing between filings that include and exclude the EU, to capture the EU’s
relative prioritisation in global protection strategies.
• Cross-country comparability: patent volumes are interpreted cautiously, as filing
behaviour is influenced by national policy and institutional factors; high patent
counts do not translate one-to-one into globally oriented innovation.
Competitiveness, trade and investment flows
Key assumptions
219
• Business as usual behaviour: Absent policy change, firms’ decisions on the location
of clinical development and manufacturing activities continue to reflect expected
lifecycle revenues under protection, alongside market size, access conditions,
regulatory predictability and operational considerations.
• Gradual evolution of EU activity: The presence and geographical distribution of
EU-based clinical trials and manufacturing activity are assumed to evolve
gradually over time, reflecting changes in technology and industrial conditions.
Administrative costs on businesses, including SMEs
Key assumptions:
• Under the baseline, administrative costs for businesses remain broadly stable over
time, reflecting existing SPC procedures and routine IP management practices. No
additional costs arise in the absence of an SPC extension.
• Firms continue to apply for SPC only where commercially justified, with no change
in the frequency or scope of applications attributable to policy developments.
• Biotech SMEs continue to rely heavily on external legal and regulatory advisors
due to limited in-house capacity, as under current practice.
Public authorities
Key assumptions:
• National authorities continue to process SPC applications under existing
procedures, with assessment workload driven by case complexity rather than an
increase in application volumes.
• Coordination between patent offices, medicines regulators and other bodies remain
a structural feature of the SPC system, reflecting fragmented institutional
responsibilities rather than inefficiencies.
• Administrative and legal costs borne by public authorities under the SPC system
remain broadly in line with historical patterns, with year-to-year variation driven
by individual cases.
• The baseline assumes no impact from the proposed unitary SPC system, which
remains under discussion and is not affected by the proposed SPC extension under
the European Biotech Act; national SPC procedures therefore continue to apply
unchanged.
Public health
Key assumptions:
• Affordability outcomes are assumed to change primarily in response to the expiry
of effective regulatory protection and the ensuing entry of biosimilar competition.
• Other determinants, including demand trends, prescribing behaviour and regulatory
requirements, are assumed to evolve gradually and therefore do not generate
discrete affordability effects over the period considered.
220
11.2 Additional information on measures and expected impacts
The proposed measure introduces a 12-month extension of SPC protection for a limited
subset of biotechnology-derived medicinal products and advanced therapy medicinal
products that meet specific eligibility criteria. Eligible medicinal products will have to
contain a new active substance which is effective via a mechanism of action distinctly
different to that of any other product already authorised in the EU for prevention or
treatment the same disease. The clinical trials supporting their marketing authorisation will
need to have been conducted in more than two Member States and at least one
manufacturing step, excluding packaging, quality and testing certification, will need to be
performed in the Union.
Conduct of business, functioning of the internal market and competition
The proposed 12-month SPC extension is expected to entail limited short-term
affordability and access pressures by delaying the entry of biosimilar competitors relative
to the baseline. For biotechnology-derived medicines, biosimilar entry does not typically
result in sharp reductions in average treatment prices; consequently, the difference in
average prices between the extension scenario and the baseline is expected to be modest.
Instead, the main effect of the extension relative to the baseline is the temporary
postponement of additional product entry, implying fewer available treatment options and
delayed expansion of supply for patients during the extension period.
By postponing competitive entry, the extension maintains higher average prices for an
additional year and delays the expansion of supply associated with follow-on products.
Our model estimate that an additional year of protection results in an additional direct cost
to public payers of approximately EUR 70 million per product in the central case,
corresponding to approximately EUR 210 million annually at aggregate level based on an
average of three qualifying medicines per year. The aggregated cost in our model provides
an approximation of the average annual EU wide impact on payers based on list prices
from the IQVIA MIDAS321 (see table 18).
Table 18. Impact of change of +1 SPC extension for biotechnology medicines
Source: Author analysis based on IQVIA MIDAS data322
321 Geographical coverage: EU27 without Cyprus, Malta and Denmark. 322 Internal analysis by the authors using IQVIA MIDAS® quarterly sales data 2008-2024. Geographical coverage: EU27
without Cyprus, Malta and Denmark. which were obtained under license from IQVIA and reflect estimates of real world
activity. Copyright IQVIA. All rights reserved
1 year increase in SPC Per med Annual (3 meds)
Originator gross profit 230 m 690 m
Biosimilar gross profit -80 m -240 m
Cost to public payer 70 m 210 m
Patients monetised gains/losses 135 m 405 m
Patients + payer monetised gain/loss 205 m 615 m
221
Sensitivity analysis, applying stricter sample filters and modified parameters323, yields a
range of EUR 5 million to EUR 80 million per medicine (see table 19). The relatively
contained magnitude of the payer cost impact reflects the shallow post-expiry revenue
decline characteristic of SPC-reliant biologicals: unlike the sharp price erosion observed
for small-molecule medicines upon generic entry, biosimilar competition produces more
gradual and moderate price reductions, limiting the price differential between the extension
scenario and the baseline.
Table 19. Sensitivity analysis on impact of change of +1 SPC extension for
biotechnology medicines
1 year increase in SPC Min per medicine Max per medicine
Originator gross profit 140 m 290 m
Biosimilar gross profit -60 m -110 m
Cost to public payer 5 m 80 m
Patients monetised gains/losses 135 m 180 m
Patients + payer monetised gain/loss 170 m260 m Source: Author analysis based on IQVIA MIDAS data. NB. Because the maximum/minimum has been taken
for each line, the combined cost will not equal the sum of the two components.
Further distributional analysis of the SPC cost-benefit results
In this section, we argue that the total of the monetised cost to patients and the additional
cost to payers can be interpreted as an approximation of the transfer of surplus from payers
and patients to companies. In our analysis, we calculate the following costs:
Table 20. Patients + payer monetised loss of +1 SPC extension for biotechnology
medicines
SPC+1 Per medicine
(1) Cost to public payer 70 m
(2) Patients monetised gains/losses 135 m
(3) Patients + payer monetised gain/loss 205 m Source: Author analysis based on IQVIA MIDAS data
For the purposes of this analysis, focussing on the distributional impacts as between
patients/payers/society on the one hand and companies on the other hand, we will not
distinguish between originators and biosimilars. In the diagram below, QB refers to the
baseline quantity, PB to the baseline price etc. Manufacturing, marketing and distribution
costs are assumed to be constant and less than PB (not shown on the diagram). For both
scenarios, PB/PSPC+1 can be thought of as the average price over the reference period. The
willingness to pay (WTP) curve is depicted as steep, but not vertical, indicating a certain
degree of price-sensitivity on the part of payers. This is confirmed empirically by the
323 Namely removing products with lower than €50m revenue in the year before expiry and removing non-biotech
products as well as including products with much shorter protection periods that are nonetheless SPC-reliant, and
modified parameters for calculating profits
222
trajectory of the total volume as can be seen in Figure 1 of Annex 4, with a marked uptick
in growth coinciding with the decline in price that occurs upon loss of protection.
Figure 2. Illustrating the derivation of costs from prices and quantities in the model
Note that in the model, we calculate the price and quantity in both scenarios, so we are
able to calculate:
(A) Baseline quantity at baseline prices = QB x PB = G+O
(B) Baseline quantity at scenario prices = QB x PSPC+1 = R+G+O+Y+P
(C) Scenario quantity at scenario prices = QSPC+1 x PSPC+1 = G
(D) Scenario quantity at baseline prices = QSPC+1 x PB = G+R
Using the initials R(ed), G(reen), O(range), Y(ellow), P(urple), we find that:
(1) is given by C - A = (R+G) – (G+O) = R-O
(2) is given by B - C = (R+G+O+Y+P) – (R+G) = O+Y+P
(3) is given by (2)+(1) = R+Y+P
In addition, assuming linear WTP with Y=P, we have B-A-C+D = (R+G+O+Y+P) – (R+G)
– (G+O) + G = Y+P = 2Y, allowing Y+P to be estimated at EUR 10 million and Y at EUR
5 million.
(1) has clear policy relevance, being the change in spending by payers. As for (2),
calculated at EUR 135 million, it has a common-sense interpretation – the amount we
would have to pay to restore baseline coverage at policy scenario prices. The objective
here is to argue that the combined amount (3) is also of economic significance, since it can
be interpreted as an approximation of the transfer of surplus from payers/patients to
companies (i.e. R, the red rectangle on the diagram). To give a more precise figure, we
223
would subtract Y+P, which can be estimated from the model at around EUR 10 million,
giving EUR 195 million for the transfer of surplus. However, given that the difference is
small, (3) remains a good approximation.
Impact on public health
As outlined in the previous section, delayed entry is associated with a reduction of
coverage relative to the baseline, combining direct payer expenditure with the monetised
cost of delayed patient access. Our model estimates this combined cost at approximately
EUR 205 million per medicine in the central case (sensitivity range: EUR 170 million to
EUR 260 million), corresponding to approximately EUR 615 million annually at aggregate
level based on an average of three qualifying medicines per year. The cost is driven
primarily by the delay in the expansion of patient coverage rather than by direct price
effects: the modelling shows that coverage expands rapidly upon loss of protection, and
the main social cost of the extension therefore consists in the temporary postponement of
this expansion. The monetised cost of delayed patient access, estimated at approximately
EUR 135 million per medicine (EUR 405 million annually based on an average of three
qualifying medicines per year), substantially exceeds the direct payer cost, reflecting the
fact that for SPC-reliant biologicals the volume effects of competition are at least as
significant as the price effects.
To illustrate how this impact may translate across Member States, the EU total was
allocated according to national shares of the EU pharmaceutical market (EFPIA 2023).
This assumes that additional expenditure from delayed biosimilar entry broadly follows
the existing geographic distribution of pharmaceutical consumption. Large pharmaceutical
markets are therefore expected to account for the majority of the aggregate cost. Germany,
France, Italy and Spain together represent around 65% of the EU pharmaceutical market,
implying that they would bear a similar share of the additional expenditure. At the same
time, these countries also exhibit relatively high healthcare spending capacity, with total
health expenditure exceeding the EU average of around 9% of GDP324. This suggests that,
while the absolute budgetary impact would be concentrated in these large markets, their
health systems may be better positioned to absorb the additional costs compared with
Member States with lower health spending levels.
Innovation output and geographic anchoring of biotech R&D
The extension of SPC protection is expected to improve the EU’s relative attractiveness
for SPC-eligible biotech innovation at the margin, by increasing the expected duration and
predictability of post-authorisation exclusivity for highly innovative products.
In practical terms, the impact is expected to materialise mainly through early patenting and
protection strategies, as these are among the first observable decisions influenced by
changes in expected protection. Relative to the baseline, the SPC extension is expected to
marginally increase the likelihood that the EU is included as an early filing jurisdiction for
SPC-eligible biotech inventions, either as a first filing location or as part of simultaneous
multi-jurisdiction filings. Effects are expected to be more pronounced for EU-based firms,
324 European Federation of Pharmaceutical Industries and Associations. (2025). The pharmaceutical industry in figures
2025. https://www.efpia.eu/media/uj0popel/the-pharmaceutical-industry-in-figures-2025.pdf
224
for which EU protection conditions directly affect portfolio and sequencing decisions,
while impacts on non-EU firms are likely to be limited to a subset of globally oriented,
high-value biotech projects.
Given the multiplicity of factors influencing innovation location decisions, the SPC
extension is expected to contribute as one among several factors including national
policies, tax regimes and regulatory procedures.
Competitiveness, trade and investment flows
The EU faces increasing global competition in the field of biotechnology. The problem
drivers outlined in paragraph 2.2 - including in subparagraph 2.2.6 on SPCs -underscore
the need for policy action to foster investment in clinical trials and biomanufacturing in
the EU.
If we analyse the products authorised in the EU that would have been eligible for the SPC
extension between 2016 and 2025, according to EMA data, almost half of those that met
the “innovation” criteria (i.e. new active substance and mechanism of action) also
conducted clinical trials in more than two member states and a part of their manufacturing
in Europe. This means that on average, there were five medicines approved per year that
meet all the criteria between 2016 and 2025. A further five meet the “innovation” criteria
but fail on one or both of the geographical criteria (i.e. clinical trials supporting their
marketing authorisation conducted in more than two Member States and at least one
manufacturing step, excluding packaging, quality and testing certification conducted in the
EU). The table below summarises this dynamic.
Table 21. ATMP and biotechnology product eligibility for 1+ SPC extension (2016-
2025)325
2016-25 Annual
a. Meeting all criteria 49 5
With distinct and different new active substance and mechanism of action and either:
b. one manufacturing step in the EU other than packaging, labelling
and testing (manufacturing criterion), but no Clinical Trials (CTs)
in more than 2 Member States (MS)
14 1
c. CT in more than 2 MS, but manufacturing criterion not met 24 2
d. Neither b nor c met 13 1
Subtotal 51 5
Total 100 10
Source: author own calculation based on EMA data between 2016-2025
325 Annual values represent the average number of medicines per year over the 2016–2025 period (10 years), calculated
as the total divided by 10 and rounded to the nearest whole number. As medicinal products cannot be meaningfully
expressed in fractional units, results are presented in whole numbers. Minor discrepancies in totals may arise due to
rounding.
225
Out of the 31 biologics we analysed for assessing the cost of the SPC extension, 40% relied
on SPC as their last effective protection. Assuming the proportion of products relying on
SPC remains constant, the SPC extension would have an economic impact on 2-3 products
per year. These products represent marginal cases for which trial design and/or
manufacturing decisions could plausibly be adjusted in response to the additional
incentives.
Public Authorities
The proposed SPC extension would not materially increase administrative workload for
national patent offices. Eligibility conditions would be assessed by the European
Medicines Agency (EMA), with national authorities mainly verifying documentation
rather than performing additional substantive assessment.
The measure introduces a new eligibility verification task for EMA, which would confirm
whether applicants fulfil the conditions for the extension. The assessment would rely
largely on regulatory information already available to the Agency, including clinical trial
data, marketing authorisation documentation and manufacturing information. Based on
comparable regulatory verification tasks, and consistent with the paediatric SPC
experience at national patent offices, the assessment is estimated to require approximately
one full-time equivalent working day per application.
Given the limited number of products expected to qualify, the resulting annual workload
for EMA is expected to remain small. Between 2020 and 2025, EMA granted
authorisations to between 15 and 28 biotech products annually. While not all of these
would be eligible under the proposed European Biotech Act, they represent the total
population of products potentially subject to assessment, implying a maximum workload
of up to 28-30 working days per year.
Administrative costs on businesses, including SMEs
Under the current regulatory framework, companies applying for SPCs incur
administrative costs associated with preparing and submitting applications, assessing
eligibility, and interacting with patent and regulatory authorities. SPC applications require
legal interpretation of patent scope, marketing authorisation timelines and regulatory
status. They require internal legal and regulatory staff time and, in many cases, recourse to
external legal advisors. For SMEs, SPC-related administrative and advisory costs can
weigh more heavily, given their more limited in-house legal and regulatory resources and
greater dependence on outsourced expertise.326 Evidence from the impact assessment of
the Commission proposals for a unitary SPC327 shows that that overall administrative and
326 European Commission (2023), Commission Staff Working Document – Impact Assessment accompanying the
proposals on supplementary protection certificates, SWD(2023) 118 final, Brussels, 27 April 2023, Section 2.3.2 and
Annex 6 (SME Test). 327 European Commission (2023), Commission Staff Working Document – Impact Assessment accompanying the
Proposal for a Regulation of the European Parliament and of the Council on the supplementary protection certificate for
medicinal products (recast) and the Proposal for a Regulation on the unitary supplementary protection certificate for
medicinal products, SWD(2023) 118 final, Brussels, 27 April 2023, Section 2.3.2 and Annex 5B.
226
advisory costs for filing SPC extensions across multiple Member States typically range
between approximately EUR 80,000 and EUR 150,000 per product.
Compared with the additional revenues linked to obtaining the SPC extension, the
administrative costs associated with preparing and filing SPC applications represent a
negligible fraction of the economic value generated by the extension. Even under the most
conservative assumptions (maximum administrative cost of EUR 150,000 against the
lower-bound profit estimate of EUR 203 million), administrative costs remain below
0.08% of additional gross profits.
The SPC system is subject to disputes over eligibility, duration and scope, which
generate administrative and legal costs for companies, public authorities and courts185. The
proposed SPC extension, by introducing novel eligibility criteria, could increase litigation
risk and consequently administrative costs and burdens.
Conclusion
Overall, the SPC extension constitutes a targeted policy instrument that seeks to strengthen
incentives for high-value biotechnology innovation while generating limited and time-
bound costs for healthcare systems. Its impact is expected to be moderate in scale but
strategically relevant in the context of broader efforts to enhance the competitiveness of
the EU biotechnology sector.
Table 22. Summary assessment of the effects due to the policy measure
Policy
interventions
COB Admin CTI Int Mar I&R PA H&S
MCA score ++ 0/- + - + 0 -
Justification for
each category
Improved
business
certainty,
reduced late-
stage commercial
risk, and
enhanced
predictability of
returns for a
limited but
clearly defined
subset of biotech
and ATMP
products
No new
standalone
administrative
obligations
introduced by
the SPC
extension
itself. Possible
minor
adjustment
costs
Incremental
influence on:
clinical trials
location, late-
stage
manufacturing
decisions,
scale-up in the
EU, inclusion
of EU in global
value chains
Competition
is postponed
but not
distorted
structurally
Operates
mainly
through:
expectations of
protection,
early patenting
and portfolio
decisions,
anchoring
high-value
biotech
projects
No new
standalone
administrative
obligations
introduced by
the SPC
extension itself.
Possible minor
adjustment
costs
fewer
available
products
during
extension
period,
prices
remain
somewhat
higher for
longer
12 INTERVENTION N°15: USE OF ARTIFICIAL INTELLIGENCE AND DATA
12.1 Detailed description of the proposed measures
The proposal establishes a framework to facilitate the safe, effective and scalable
deployment of AI across the lifecycle of medicinal products, addressing regulatory
uncertainty, infrastructure gaps and data limitations that currently constrain uptake.
First, the proposal introduces non-binding guidance to be developed and regularly updated
by the European Medicines Agency (EMA), in agreement with the Commission, including
the AI Office. This guidance covers the full lifecycle of medicinal products, including pre-
227
clinical research, clinical development and trials, manufacturing, regulatory evaluation and
approval, and post-authorisation monitoring. It aims to provide clarity on the development,
deployment and validation of AI-enabled methodologies, including general-purpose AI
models, while ensuring full coherence with the requirements of the AI Act and relevant
sectoral legislation.
Second, the proposal provides for the recognition of high-impact health biotechnology
strategic projects in the form of trusted AI-enabled biotechnology testing environments.
These environments are designed to bridge the gap between research and market
deployment by providing integrated infrastructures combining wet-lab, computational and
data-driven capabilities. Operating under “trusted conditions” that ensure compliance with
Union and national legislation, they aim to complement existing AI regulatory sandboxes
and testing facilities established under the AI Act, while avoiding duplication.
These testing environments are intended to support experimentation, development and
translational validation of AI-enabled biotechnology innovations, particularly in areas
where AI can have a transformative impact, such as advanced therapies (e.g. ATMPs),
immunology, and the development of new approach methodologies (NAMs). By enabling
the joint use of advanced experimental systems and computational tools, they aim to
optimise workflows, reduce development risks and accelerate validation processes.
Third, the proposal establishes a framework for biotechnology data quality accelerators as
a distinct category of high-impact strategic projects, addressing a critical bottleneck for AI
deployment in biotechnology: the limited availability of high-quality, interoperable and
AI-ready datasets. These accelerators aim to support the curation, standardisation,
annotation and provenance verification of datasets used for training, testing and validation
of AI systems and models in health biotechnology applications.
12.2 Baseline and counterfactual scenario
In the absence of the enabling measures on AI and data, the EU biotechnology sector is
expected to face a widening capability gap relative to global competitors, such as US or
China. While the Union possesses strong fundamental research, the lack of integrated
infrastructure and lifecycle guidance specifically for bio-AI creates a bottleneck that
constrains the translation of into scalable industrial value. According to industry surveys,
82% of biopharmaceutical executives believe AI will fundamentally transform research
and development within five years, and 63% consider that organisations failing to scale AI
will fall behind in market relevance.328 However, the Union is losing ground to faster-
moving competitors in North America and Asia, who are scaling up through targeted policy
interventions.329
Regulatory clarity
328 Capgemini Research Institute. (2026). Smart bet, only option, or both?: Biopharma R&D turns to AI. Capgemini.
https://www.capgemini.com/wp-content/uploads/2026/01/120126CRI_Gen-AI-in-Lifesciences-_Final-interactive.pdf 329 Lowe, C. R., Minssen, T., & Skentelbery, C. (2024). Emerging biotechnologies in Europe: Foresight for policy (P.-
M. Pélissier, Ed.). Publications Office of the European Union. https://doi.org/10.2760/4814109
228
AI-based methods are already widely used in pharmaceutical and biotechnology
development, primarily to optimise processes, with outputs validated through conventional
scientific methods330. However, the emergence of AI uses in the lifecycle of medicines is
creating uncertainty regarding how AI-enabled approaches may be applied within existing
regulatory processes. This uncertainty largely reflects the absence of specific guidance or
established practice for the development, validation and acceptance of AI-enabled
methodologies in across the medicines lifecycle. Developers must rely primarily on case-
by-case regulatory interactions to obtain feedback on whether specific AI applications may
be considered acceptable in regulatory submissions, in order to obtain clarity on whether
internal governance and validation procedures will satisfy regulatory authorities331.
The principal formal mechanism for obtaining regulatory clarity is EMA's Qualification
Procedure for Novel Methodologies, costing EUR 89,000 per request (90% reduction for
SMEs; no reduction for academic or non-profit developers) and taking 160–250 days332.
Firms also use other forms of regulatory interaction, including scientific advice procedures,
Innovation Task Force meetings, and other early-stage regulatory discussions, which serve
distinct purposes within the regulatory framework, with AI-related interactions growing
and concentrated at the pre-authorisation stage333,334,335,336. Crucially, all outcomes are
confidential and non-reusable — each company must fund its own interaction, producing
no cumulative public knowledge base337.
These timelines capture only the duration of the EMA Qualification Procedure for Novel
Methodologies described above. The upstream period during which firms assess whether
AI-enabled approaches are regulatorily viable before engaging EMA is unquantified but
acknowledged as significant338. Workshop participants confirmed that R&D teams delay
commitment to AI-enabled approaches pending regulatory clarity, particularly for patient-
facing applications such as AI-driven clinical trial site selection and patient selection,
where validation standards remain unclear (workshop). No regulatory standard, guidance,
or accepted practice currently exists for validation of AI-generated evidence, generative
330 Discussed during the stakeholder workshop on Data and AI – Rapid Assessment Scenario Study - forthcoming. 331 Discussed during the stakeholder workshop on Data and AI – Rapid Assessment Scenario Study - forthcoming. 332 European Medicines Agency. (2023). Qualification of novel methodologies for drug development: Guidance to
applicants (EMEA/CHMP/SAWP/72894/2008 Rev. 5). https://www.ema.europa.eu/en/documents/regulatory-
procedural-guideline/qualification-novel-methodologies-drug-development-guidance-applicants_en.pdf 333 European Federation of Pharmaceutical Industries and Associations. (2024). EFPIA position on the use of artificial
intelligence in the medicinal product lifecycle. https://www.efpia.eu/media/tzeavw1t/efpia-position-on-the-use-of-
artificial-intelligence-in-the-medicinal-product-lifecycle.pdf 334 European Medicines Agency. (2025). 2024 AI observatory report (EMA/76534/2025).
https://www.ema.europa.eu/en/documents/report/2024-ai-observatory-report_en.pdf 335 European Medicines Agency. (2025). 2024 AI observatory: Compilation of 2024 experience (EMA/154528/2025).
https://bluepharm.fr/wp-content/uploads/2025/11/2024-ai-observatory-report-compilation-2024-experience_en.pdf 336 European Medicines Agency. (2025). New approach methodologies EU-Innovation Network horizon scanning report
(EMA/56850/2025 Rev. 1). https://www.ema.europa.eu/en/documents/report/new-approach-methodologies-eu-horizon-
scanning-report_en.pdf 337 European Medicines Agency. (2023). Qualification of novel methodologies for drug development: Guidance to
applicants (EMEA/CHMP/SAWP/72894/2008 Rev. 5). https://www.ema.europa.eu/en/documents/regulatory-
procedural-guideline/qualification-novel-methodologies-drug-development-guidance-applicants_en.pdf 338 Lowe, C. R., Minssen, T., & Skentelbery, C. (2024). Emerging biotechnologies in Europe: Foresight for policy (P.-
M. Pélissier, Ed.). Publications Office of the European Union. https://doi.org/10.2760/4814109
229
AI outputs, internal AI governance frameworks, or AI applications in clinical trials339
(sentiment was also expressed in stakeholder workshop).
The measurable baseline is therefore EUR 89,000 and 160–250 days per formal
interaction, with total pathway identification time substantially longer due to upstream
deliberation340,341.
Once developers have identified the applicable regulatory pathway, additional clarification
and documentation efforts may arise when AI-enabled methodologies are used, due to the
absence of specific guidance on their regulatory acceptance. The absence of codified
evidence standards for AI-derived data342 forces developers into repeated clarification
requests and additional regulator engagement to confirm the acceptability of their
approaches. Stakeholders note that without fit-for-purpose frameworks, developers cannot
align with regulatory expectations early in the process343, and the EMA's AI Workplan
acknowledges that gaps in guidance require ongoing stakeholder engagement to prevent
frameworks from lagging behind technological advances344.
No specific guidance is yet available for lifecycle management of AI-based tools, including
model retraining and updates, leaving "model change management" unresolved345 and
imposing ongoing post-approval costs as developers design and justify their own
procedures without regulatory reference points. Public consultations confirm that a
substantial share of administrative costs arises from the need to interpret how different
regulatory frameworks interact when applied to emerging AI-enabled methodologies346.
AI tools could accelerate regulatory submissions by approximately 19% through
automation and predictive modelling347. However, this potential is limited by uncertainty
regarding how systems based on advanced technologies, including AI, can be deployed
and used within existing regulatory frameworks for medicinal products across the
medicines lifecycle.
339 European Medicines Agency. (2024). Reflection paper on the use of artificial intelligence (AI) in the medicinal
product lifecycle (EMA/CHMP/CVMP/83833/2023). https://www.ema.europa.eu/en/documents/scientific-
guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf 340 European Medicines Agency. (2023). Qualification of novel methodologies for drug development: Guidance to
applicants (EMEA/CHMP/SAWP/72894/2008 Rev. 5). https://www.ema.europa.eu/en/documents/regulatory-
procedural-guideline/qualification-novel-methodologies-drug-development-guidance-applicants_en.pdf 341 Lowe, C. R., Minssen, T., & Skentelbery, C. (2024). Emerging biotechnologies in Europe: Foresight for policy (P.-
M. Pélissier, Ed.). Publications Office of the European Union. https://doi.org/10.2760/4814109 342 Lowe, C. R., Minssen, T., & Skentelbery, C. (2024). Emerging biotechnologies in Europe: Foresight for policy (P.-
M. Pélissier, Ed.). Publications Office of the European Union. https://doi.org/10.2760/4814109 343 “EFPIA Position on the Use of Artificial Intelligence in the Medicinal Product Lifecycle,” EFPIA, 2024,
https://efpia.eu/media/tzeavw1t/efpia-position-on-the-use-of-artificial-intelligence-in-the-medicinal-product-
lifecycle.pdf. 344 European Medicines Agency, “Multi - Annual AI Workplan 2023 - 2028,” European Medicines Agency, 2023,
https://www.ema.europa.eu/en/documents/work-programme/multi-annual-artificial-intelligence-workplan-2023-2028-
hma-ema-joint-big-data-steering-group_en.pdf. 345 European Medicines Agency, “Qualification Opinion for Artificial Intelligence-Based Measurement of Non-
Alcoholic Steatohepatitis Histology in Liver Biopsies to Determine Disease Activity in NASH/MASH Clinical Trials,”
European Medicines Agency, 2025. 346 Aggregated findings from the Public Consultation and Call for Evidence. 347 Capgemini Research Institute. (2026). Smart bet, only option, or both?: Biopharma R&D turns to AI. Capgemini.
https://www.capgemini.com/wp-content/uploads/2026/01/120126CRI_Gen-AI-in-Lifesciences-_Final-interactive.pdf
230
Under the business-as-usual scenario, these conditions are expected to worsen. AI-related
regulatory queries are already increasing348 and will accelerate as AI integration deepens.
Each new entrant will face the same navigation costs, the confidential nature of outcomes
will prevent any cumulative learning, and the growing complexity of the regulatory
environment applicable to AI-enabled approaches will lengthen upstream deliberation
further. For SMEs and academic developers, the barrier will become progressively more
prohibitive, increasing the risk of project deferral, relocation outside the Union, or
discontinuation.
Use of data for AI
In terms of data use, European AI models frequently rely on datasets originating from outside
the Union, in particular for reference genetic sequences and multi-omics data.349 The European
Health Data Space will provide diverse health data for AI training, testing and validation. At the
same time, datasets relevant for biotechnology innovation often lack the annotation,
interoperability, metadata, and provenance needed to support the training of regulatory-
grade AI models.350 Health and genomic datasets remain siloed under incompatible
formats.351 Fewer than 20% of Union life-science firms possess the in-house AI expertise
to curate high-quality datasets.352 Industry surveys reveal that for eight out of eleven key
data elements needed for AI in research and development, fewer than half of biopharma
executives believe their companies are adequately prepared.353
The biotechnology sector faces challenges with both data quantity and quality; without
standardising curation processes, the Union cannot leverage its data assets to compete with
the massive, integrated datasets available to competitors in North America and Asia.354
Fragmented metadata standards and inconsistent provenance documentation reduce
interoperability across Member States, limiting the formation of large, regulatory-grade
training datasets.
Databases with errors or incomplete data continue to result in imprecise outcomes.355 AI
models require large, high-quality, annotated datasets. Absent stronger initiatives for data
curation processes, validation criteria and interoperability standards, high-value datasets
are likely to remain dispersed across incompatible environments. This may limit the
development of foundational biological AI models trained on European data and slow the
emergence of shared reference datasets for regulatory use. Over time, the interaction
between fragmented standards, delayed guidance and uneven data quality risks reinforcing
a cycle in which innovation advances faster than harmonised oversight frameworks,
constraining the effective functioning of the internal market.
348 European Medicines Agency. (2025). 2024 AI observatory report (EMA/76534/2025).
https://www.ema.europa.eu/en/documents/report/2024-ai-observatory-report_en.pdf 349 Submission to the Public Consultation by an European trade association. 350 Submissions to the Call for Evidence. 351 Submissions to the Call for Evidence. 352 Submissions to the Call for Evidence 353 Capgemini Research Institute. (2026). Smart bet, only option, or both?: Biopharma R&D turns to AI. Capgemini.
https://www.capgemini.com/wp-content/uploads/2026/01/120126CRI_Gen-AI-in-Lifesciences-_Final-interactive.pdf 354 Submissions to the Call for Evidence and Public Consultation. 355 Submissions to the Call for Evidence and Public Consultation.
231
Under the baseline, data fragmentation, uneven standard adoption and regulatory
variability are expected to persist. Their interaction increases cumulative compliance and
integration costs for cross-border operations, effectively raising the marginal cost of
scaling AI-enabled biotechnology within the Union. Over time, this dynamic may
discourage multi-country deployment strategies, slow Union-wide diffusion of AI-enabled
innovations and reduce the effective functioning of the internal market for advanced
biotechnology.
Without the intervention of data quality accelerators, the lack of clear standards means that
the uptake of enhanced datasets is expected to remain low, and the volume of data available
for secondary use is not expected to increase significantly.356
Access to shared infrastructure and cross-border scale-up capacity
Under current conditions, severe capacity constraints limit scale-up opportunities for the
wider ecosystem. Facilities such as the Bio Base Europe Pilot Plant report performing
scale-up work for over 280 different companies, including large enterprises. However,
public authorities note that most European fermentation and production capacity is already
fully utilised.357 The lack of available capacity creates a bottleneck for the entire sector.
When pilot and demonstration facilities operate at or near full capacity, project timelines
lengthen and firms must queue for access, increasing opportunity costs and delaying
commercial translation. While SMEs are financially excluded from access to industrial-
grade infrastructure, larger firms also face delays due to the scarcity of open-access
demonstration facilities required to generate scalable data.358 This scarcity affects both
entry and expansion, limiting the ability of smaller firms to transition from laboratory
validation to industrial deployment.
Several examples of cross-border bio-AI scale-ups exist, including Biohm, MICROBS,
and Kantify. Pilot facilities such as the Bio Base Europe Pilot Plant, Utrecht Science Park,
and Estonia's Biobank facilitate effective scaling across borders.359 In the medium and long
term, capacity constraints are expected to persist. This may reinforce geographic
concentration of industrial biotechnology in a limited number of hubs and reduce the
ability of firms to scale operations across multiple Member States. Over time, constrained
access to industrial-grade infrastructure risks slowing the translation of AI-enabled
research into market-ready production within the Union.
The lack of investment in AI testbeds and innovation sandboxes limits opportunities for
experimentation in realistic settings. Stakeholders stress that voluntary risk assessments
are inadequate and call for mandatory safety evaluations for high-risk biological AI
tools.360 Workshop participants also emphasised that uncertainty regarding validation
standards and lifecycle management increases the difficulty of designing effective test
environments, as developers lack clarity on what constitutes acceptable regulatory-grade
356 Submissions to the Call for Evidence and Public Consultation. 357 Public authority submissions to the Call for Evidence and Public Consultation 358 Submissions to the Call for Evidence and Public Consultation 359 Submissions to the Call for Evidence and Public Consultation 360 Submissions to the Call for Evidence and Public Consultation.
232
evidence. An international regulatory stakeholder notes that innovation is hampered by the
lack of structured, validated evidence from real-world testing environments. Without
access to dedicated validation infrastructures, AI models cannot be effectively trained or
tested against biological ground truth, limiting the accumulation of evidence that regulators
need to issue fit-for-purpose guidance.361
Under the baseline, the transition from proof-of-concept to validation is expected to remain
slow. Multiple digital policy frameworks addressing different aspects of AI and data and
the lack of accessible validation infrastructure, including biobanks and high-performance
computing, extend timelines. Regulatory requirements for rigorous validation are resource-
intensive, and SMEs in particular face uncertainty about the level of proof required, leading
to delays. Workshop stakeholders confirmed that ambiguity regarding evidentiary
standards contributes to iterative clarification processes, increasing time-to-validation. The
absence of integrated testing environments means that flaws in biological AI models are
often detected only after significant investment, rather than during early-stage iterative
testing. The research and development process remains linear and risk-heavy rather than
iterative and agile. Public authorities are unable to accumulate the structured evidence
needed to issue rapid, fit-for-purpose guidance.362
In the baseline, the Union's biotechnology sector faces a significant capability gap in AI
expertise. Fewer than 20% of Union life-science firms possess in-house AI expertise,
compared to 45% in the United States.363 Industry surveys reveal that for eight out of
eleven key data elements needed for AI in research and development, fewer than half of
biopharma executives believe their companies are adequately prepared.364
This capability gap limits firms’ ability not only to develop AI tools internally but also to
critically assess, validate and integrate externally developed models into regulated
workflows. In controlled tasks, AI demonstrates exceptional capability. The EMA's
Scientific Explorer achieved F1 scores of 0.89 to 0.94 in information retrieval365, and
OpenAI's o1-preview model achieved 96% accuracy on medical licensing datasets366.
However, a systematic review reveals a knowledge-practice gap: while models score high
on knowledge benchmarks (61 to 79%), their performance drops in practice-based
scenarios (45 to 69%)367.
This knowledge–practice gap underscores the difference between benchmark performance
and deployment readiness. Without integrated testing environments and clear validation
361 Submissions to the Call for Evidence; with references to ICMRA PQ KMS and Collaborative Hybrid Inspection
Pilots. 362 Submissions to the Call for Evidence and Public Consultation. 363 Submissions to the Call for Evidence and Public Consultation. 364 Capgemini Research Institute. (2026). Smart bet, only option, or both?: Biopharma R&D turns to AI. Capgemini.
https://www.capgemini.com/wp-content/uploads/2026/01/120126CRI_Gen-AI-in-Lifesciences-_Final-interactive.pdf 365 EMA, Scientific Explorer performance data 366 Gong EJ, Bang CS, Lee JJ, Baik GH. Knowledge-Practice Performance Gap in Clinical Large Language Models:
Systematic Review of 39 Benchmarks. J Med Internet Res. 2025 Dec 1;27:e84120. doi: 10.2196/84120. PMID:
41325597; PMCID: PMC12706444. 367 Gong EJ, Bang CS, Lee JJ, Baik GH. Knowledge-Practice Performance Gap in Clinical Large Language Models:
Systematic Review of 39 Benchmarks. J Med Internet Res. 2025 Dec 1;27:e84120. doi: 10.2196/84120. PMID:
41325597; PMCID: PMC12706444.
233
standards, high-performing models are expected to struggle to translate into reliable,
regulatory-grade tools.
Workshop participants emphasised that uncertainty regarding evidentiary requirements
and lifecycle management further complicates internal capability development, as firms
lack clarity on the level of proof and documentation required for regulatory acceptance.
This increases reliance on external consultants and technology providers, reinforcing
capability asymmetries between large firms and SMEs.
Under the baseline, limited in-house expertise, ambiguous validation expectations and
insufficient integrated experimentation environments are expected to reinforce each other.
Firms with constrained AI capability may underinvest in lifecycle integration, while
regulatory uncertainty discourages ambitious internal scaling strategies. Over time, these
dynamic risks widening the capability gap between Union firms and global competitors
with more mature AI integration ecosystems.
12.3 Expected impacts
Conduct of business
The non-binding guidance is expected to help reduce costly, one-off bilateral interactions
by having a single publicly available reference point, reducing per-company transaction
costs and enabling firms, to make development decisions with greater confidence368. The
guidance would also reduce internal deliberation time within companies, where R&D
teams currently delay commitment to AI-enabled approaches pending clarity on regulatory
acceptability.
The guidance would disproportionately benefit SMEs, start-ups, and scale-ups by
democratising access to regulatory intelligence that is currently available only through
expensive formal procedures or informal networks with EMA. The potential cost relief is
concrete. EMA's qualification procedure costs EUR 89,000 reduced by 90% for SMEs but
not for academic or non-profit developers369. Even with the reduction, the procedure
demands 160–250 days and produces confidential, non-reusable outcomes. Published
guidance could help replace at least part of these procedures this with a free, publicly
accessible reference point.
It is important to note, however, that the costs will not be fully eliminated. While the
guidance is not binding, once EMA publishes this guidance it will become a de facto
standard that assessors reference, so companies that deviate will bear the burden of
justifying alternative approaches.
The testing environments are expected to generate significant structural impacts by
addressing the current deficit of shared GMP-compliant pilot and scale-up infrastructure
368 European Medicines Agency. (2023). Qualification of novel methodologies for drug development: Guidance to
applicants (EMEA/CHMP/SAWP/72894/2008 Rev. 5). https://www.ema.europa.eu/en/documents/regulatory-
procedural-guideline/qualification-novel-methodologies-drug-development-guidance-applicants_en.pdf 369 European Medicines Agency. (2023). Qualification of novel methodologies for drug development: Guidance to
applicants (EMEA/CHMP/SAWP/72894/2008 Rev. 5). https://www.ema.europa.eu/en/documents/regulatory-
procedural-guideline/qualification-novel-methodologies-drug-development-guidance-applicants_en.pdf
234
in the Union. They would convert some firm-level fixed capital expenditure into pooled
infrastructure accessible to multiple users. This is expected to reduce per-firm investment
requirements for AI-enabled validation and scale-up activities. Where supported by
predictable funding, comparable shared infrastructure models have demonstrated the
capacity to crowd in private investment and accelerate the commercial translation of
research outputs.
Time-to-access effects are likely to be material. SMEs may face delays of up to 18–24
months in securing pilot-GMP capacity under current conditions. Such delays reduce the
effective duration of intellectual property protection and weaken competitiveness. Criteria-
based access to shared facilities would reduce these delays by removing the need for
individual firms to establish or negotiate bespoke infrastructure arrangements.
For SMEs and start-ups in particular, the expected impact extends beyond cost reduction.
Limited access to pilot-scale infrastructure constrains the practical deployment of AI-
enabled biotechnology and increases the risk that projects are delayed, outsourced outside
the Union, or discontinued. Shared testing environments are therefore expected to function
as an enabling condition for commercialisation, rather than merely as a cost-efficiency
measure.
Administrative costs on businesses, including SMEs
Detailed guidance may function as a de facto standard, which means that if guidance is
overly prescriptive or diverges from emerging international approaches, EU-based
developers may face higher compliance burdens in global development programmes.
As regards testing environments and data quality accelerators, their recognition as high
impact health biotechnology strategic projects entails that promoters must prepare
applications, demonstrate eligibility against defined criteria, and operate under trusted
conditions with ongoing reporting and knowledge-sharing obligations. This creates
material implementation costs at firm level, the scale of which depends on the governance
route chosen by Member States. For the recognition-and-coordination pathway the
proposal establishes, cost estimates can be drawn from Horizon Europe experiences, where
beneficiary administrative effort typically runs at 6–10% of project budgets, corresponding
to approximately 0.5–1 FTE per project per year370. Scaled to reflect the additional
requirements of a strategic project recognition framework, including dual reporting to
national and EU authorities and longer monitoring periods, a reasonable central estimate
is 1–2 FTE per project per year, corresponding to approximately 1–2% of total project
value. Evidence from comparable EU funding instruments indicates that beneficiary
administrative burden can absorb around 11% of eligible funding compared with 4% for
370 The administrative burden observed in Horizon Europe projects (typically estimated at 6–10% of project budgets) is
used as a reference point, corresponding to approximately 0.5–1 FTE of administrative effort per project per year. IPCEI
reporting and compliance obligations are assumed to require approximately two to three times higher effort, reflecting
additional State aid requirements, dual reporting to national and EU authorities, and longer monitoring periods. This
implies an estimated administrative effort of 1–3 FTE per year per participant. When scaled to the larger investment
volumes of IPCEI projects, this corresponds to approximately 1–2% of total project value. These figures should be
interpreted as indicative orders of magnitude.
235
managing authorities371; given the lighter governance structure of the Act's recognition
pathway, this figure should be treated as an upper bound rather than a central estimate.
Where Member States choose to route funding under State aid rules, they are obliged to
notify the envisaged aid to the Commission (for assessment and decision) before the public
funding is granted. This should be factored in the overall procedure, while however it is
not necessarily representative of the Act's default recognition-and-coordination pathway.
Competitiveness, trade and investment flows
OECD analysis confirms that investment increasingly concentrates in jurisdictions with
specialised infrastructure: regions possessing advanced clusters and pilot facilities capture
78% of R&D-related FDI projects372, and capital sorts towards jurisdictions with mature
digital ecosystems373. These patterns underpin the rationale for trusted biotechnology
testing environments and data quality accelerators as competitiveness-enhancing
instruments.
Expected benefits of the testing environments that could be developed as high-impact
strategic projects under the framework set out in the European Biotech Act proposal
include:
• Addressing the principal R&D bottleneck. Firm-level evidence indicates that the
most significant bottleneck for AI-biotech innovation lies in the validation
phase, where computational models must be tested against biological data in
regulated environments. The main causes of AI pilot failure are data quality and
availability (55%) and IP, data security and compliance friction (50%)374. Firms
with integrated "wet-dry" research environments are nearly twice as likely to
attract investment (30% vs 18%)375.
• Reducing offshore relocation of validation activity. By offering shared,
regulatory-proximate validation capacity, Article 32 reduces the need for firms,
particularly SMEs and startups, to build proprietary infrastructure or relocate
validation activities to competing jurisdictions. The greatest expected impact is
on the validation and translational stages of R&D, increasing the likelihood that
AI-generated assets are developed within the Union rather than relocated to
competing ecosystems.
371 European Commission, Spatial Foresight, & t33. (2018). New assessment of ESIF administrative costs and burden:
Final report. European Commission, Directorate-General for Regional and Urban Policy.
https://ec.europa.eu/regional_policy/sources/studies/assess_admin_costs.pdf 372 Montegu, J., Saporito, N. F., & Polakiewicz, Z. (2026). The evolution of the biotechnology sector: Implications for
FDI and SME linkages across Europe (OECD SME and Entrepreneurship Papers No. 75). OECD Publishing.
https://doi.org/10.1787/420bb546-en 373 Organisation for Economic Co-operation and Development. (2026). Connecting FDI and SMEs for productivity and
innovation in Europe. OECD Publishing. https://doi.org/10.1787/9848e952-en 374 Benchling. (2026). The 2026 biotech AI report: Breakthroughs, bottlenecks, and the power shift shaping biotech’s AI
future. Benchling.
https://downloads.ctfassets.net/kzeezny59h5p/YpQPwDughrM22nvqp8pxl/ac49d590d9c9c74400dde6e6bf0657ea/202
6-Biotech-AI-Report.pdf 375 Benchling. (2026). The 2026 biotech AI report: Breakthroughs, bottlenecks, and the power shift shaping biotech’s AI
future. Benchling.
https://downloads.ctfassets.net/kzeezny59h5p/YpQPwDughrM22nvqp8pxl/ac49d590d9c9c74400dde6e6bf0657ea/202
6-Biotech-AI-Report.pdf
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If access procedures are complex or facilities remain insufficiently integrated with
regulatory pathways, the expected investment-attraction effect may be reduced despite
public expenditure.
As regards data quality accelerator projects, expected benefits include:
• Reducing "data friction" as a driver of R&D relocation. The binding constraint
for AI-biotech is often not compute or algorithms but the availability of "AI-
ready" datasets: 48% of healthcare respondents identify data quality and
integration as the main barrier to AI adoption376, and the OECD identifies access
to large, high-quality datasets as a "key competitive differentiator" that
effectively subsidises R&D costs in data-rich jurisdictions377.
• Lowering material cost penalties from fragmented data. The Commission
estimates the absence of FAIR data costs the EU economy at least EUR 10.2
billion annually in lost productivity and innovation spillovers378. Data
engineering consumes 25–40% of total AI spend, with integration complexity
adding a 2–3× labour-cost premium379. Jurisdictions that reduce these burdens
improve their attractiveness for inward AI-biotech investment.
• Converting the EHDS into a distinctive competitiveness asset. Article 33
enables the EU to position EHDS secondary use across a 450-million population
as an industrial competitiveness instrument. The Data Union Strategy projects
EUR 11 billion in economic value over ten years from secondary use380,381. The
phased implementation timetable provides a planning horizon for investment
decisions, while Health Data Access Bodies as "one-stop shops" are intended to
reduce fragmentation-related "push factors." The expected benefit is therefore
not only increased data volume but improved data usability and predictability
for cross-border, data-intensive R&D.
Both policy measures require non-trivial public CAPEX and sustained OPEX. Their
intended functions are comparable to EU "meaningful scale" technology infrastructure
interventions rather than small grants. The following EU instruments provide financial
proxies for the order of magnitude required to make such environments globally credible:
376 IntuitionLabs. (2026). AI for biotech: A build vs. buy decision framework. IntuitionLabs.
https://intuitionlabs.ai/articles/build-vs-buy-ai-biotech 377 Montegu, J., Saporito, N. F., & Polakiewicz, Z. (2026). The evolution of the biotechnology sector: Implications for
FDI and SME linkages across Europe (OECD SME and Entrepreneurship Papers No. 75). OECD Publishing.
https://doi.org/10.1787/420bb546-en 378 European Commission, Directorate-General for Research and Innovation, & PwC EU Services. (2018). Cost-benefit
analysis for FAIR research data: Cost of not having FAIR research data. Publications Office of the European Union.
https://doi.org/10.2777/02999 379 IntuitionLabs. (2026). AI for biotech: A build vs. buy decision framework. IntuitionLabs.
https://intuitionlabs.ai/articles/build-vs-buy-ai-biotech 380 European Commission. (2025). Communication from the Commission to the European Parliament and the Council:
Data Union strategy – Unlocking data for artificial intelligence (COM(2025) 835 final). European Commission.
http://publications.europa.eu/resource/celex/52025DC0835 381 European Commission. (n.d.). European Health Data Space regulation (EHDS). European Commission.
https://health.ec.europa.eu/ehealth-digital-health-and-care/european-health-data-space-regulation-ehds_en
237
Table 23. EU instruments providing financial proxies for the order of magnitude of
investment in testing environments/data quality accelerators Proxy instrument Scale Relevance to testing environments/data quality
accelerators
IPCEI European
Battery Innovation
EUR 2.9 billion public
funding, unlocking EUR 9
billion private (≈1:3 leverage)
Upper bound; Act anticipates large-scale public-private
investment for high-impact projects
Microelectronics IPCEI ~EUR 63 million per partner
(2018) → ~EUR 145 million
per partner (2021)
Illustrative proxy for the order of magnitude of support
observed in selected strategic technology projects
developed under the IPCEI framework,
Horizon Europe Large-
Scale Service Pilot
EUR 35 million per pilot Mid-scale proxy for individual Art. 32 nodes or Art. 33
accelerator configurations
Graphene Flagship ~EUR 1 billion over 10 years Long-running network model illustrating OPEX
exposure
IMI2 life-science PPP EUR 3.276 billion (≈50/50
public-industry)
PPP proxy where Art. 32/33 projects pool public and
private expertise
If implemented at the scale implied by their intended functions, budget impacts will
materialise primarily through (i) prioritisation and mobilisation of existing Union
programmes and (ii) Member State co-financing and/or State-aid compatible funding,
rather than negligible incremental spending.
Infrastructure evidence suggests stable operation typically requires core funding covering
60–70% of operational costs as a "healthy" baseline, with user-fee-only models often
unrealistic for research-grade infrastructures382. This is directly relevant because the Act's
policy intent is to provide shared capability, particularly supporting SMEs and cross-
ecosystem networking, rather than purely commercial facilities financed by full cost
recovery.
A risk common to both articles is the potential for an "operation gap": facilities and data
services are launched but cannot be sustained at the utilisation and quality level required
to deliver the Act's competitiveness objectives. Unless long-term funding and governance
arrangements are secured through Union programmes, Member State co-financing, and/or
PPP co-investment significant public CAPEX may be deployed without the ongoing OPEX
needed for credible, high-utilisation operation. This would reduce both the direct benefits
(validation capacity, data quality uplift) and the indirect competitiveness signal to global
investors.
Functioning of the internal market and competition
Impacts in this category are expected to be driven primarily by the measure on data quality
accelerators.
The current EU health data landscape is characterised by heterogeneity in readiness. While
the EU-27 composite eHealth maturity score stands at 83%, this aggregate masks a stark
divide: "trendsetters" such as Belgium (100%), Estonia (100%) and Denmark (98%)
operate near-universal digital coverage, while Romania (46%) and Ireland (44%) lag
382 Organisation for Economic Co-operation and Development. (2017). Strengthening the effectiveness and sustainability
of international research infrastructures (OECD Science, Technology and Industry Policy Papers No. 48). OECD
Publishing. https://doi.org/10.1787/fa11a0e0-en
238
significantly383,384. The divide is most acute in data depth: only 26% of Member States
provide access to medical imaging through national infrastructures. The "meaningful use"
of EHRs varies from 73% in Finland to 5% in Germany385, and private provider
connectivity lags at 59% versus 79% for public providers386. The data quality uplift that
data quality accelerators would bring is therefore expected to expand the number of
Member States where legally compliant AI development is practically feasible, enlarging
the effective Single Market for data-driven biotech products.
These infrastructure disparities currently drive measurable innovation concentration.
Medicon Valley (Eastern Denmark and Southern Sweden) alone attracted over EUR 2.5
billion in financing between 2023–2024, while for example, Romania's digital
infrastructure contributes to "negligible" clinical trial activity387. In addition, industry
stakeholders report that pharmaceutical companies "mainly use data from outside the EU,
primarily from the US," because US datasets are larger, more streamlined and easier to
access at scale388. Data quality accelerators are expected to reduce these location-based
asymmetries and support a broader geographic distribution of AI-biotech activity, rather
than further concentration in existing hubs.
On the risk side, three structural dynamics could partially offset these gains:
- The absorptive capacity gap (80% of large firms vs under 30% of SMEs using advanced
analytics389) means data quality improvements may disproportionately benefit incumbents.
- Gatekeeping by data holders (52% of user obstacles linked to legal fragmentation390) may
persist where the framework does not enforce transparent, non-discretionary access.
- The length of the implementation timeline may entail a prolonged transition during which
the digital divide may widen before it narrows.
Innovation and research
Overall, the net R&I impact of the policy measures is expected to be positive:
- Testing environments have the potential to address the validation bottleneck that
hampers SMEs from the AI-biotech pipeline, accelerating time-to-validation,
regulatory submissions and boosting firm growth;
383 European Court of Auditors. (2024). Special report 25/2024: Digitalisation of healthcare.
https://www.eca.europa.eu/ECAPublications/SR-2024-25/SR-2024-25_EN.pdf 384 Capgemini Invent. (2025). 2025 Digital Decade eHealth indicator study: Final report. European Commission.
http://espanadigital.gob.es/sites/espanadigital/files/2025-
12/Estudio%20de%20Indicadores%20de%20eHealth%20de%20la%20D%C3%A9cada%20Digital%202025.pdf 385 Organisation for Economic Co-operation and Development, & European Observatory on Health Systems and Policies.
(2025). Synthesis report 2025: Health policy reform trends in the EU. OECD Publishing.
https://doi.org/10.1787/1f6a8e9a-en 386 Capgemini Invent. (2025). 2025 Digital Decade eHealth indicator study: Final report. European Commission.
http://espanadigital.gob.es/sites/espanadigital/files/2025-
12/Estudio%20de%20Indicadores%20de%20eHealth%20de%20la%20D%C3%A9cada%20Digital%202025.pdf 387 Organisation for Economic Co-operation and Development, & European Observatory on Health Systems and Policies.
(2025). Romania: Country health profile 2025. OECD Publishing.
https://www.oecd.org/content/dam/oecd/en/publications/reports/2025/12/country-health-profile-2025-country-
notes_7e72146d/romania_ca47b392/1269b371-en.pdf 388 Collected through public consultations and workshop. 389 Organisation for Economic Co-operation and Development. (2022). Data shaping firms and markets (OECD Digital
Economy Papers, No. 344). OECD Publishing. https://doi.org/10.1787/7b1a2d70-en 390 TEHDAS Joint Action. (2022). Report on secondary use of health data through European case studies.
https://tehdas.eu/app/uploads/2022/08/tehdas-report-on-secondary-use-of-health-data-through-european-case-studies-
239
- Data quality accelerators have the potential to address the data usability deficit that
currently renders 87% of publicly hosted biomedical datasets inaccessible for machine
learning391, with the EU losing an estimated EUR 10.2 billion annually from the
absence of FAIR data392 and targeted curation demonstrating savings of 5,000
researcher-hours and USD 1.4 million per year in a single use case393.
The principal downside risk across all three instruments is that benefits are eroded by
infrastructure capture (49–65% of funding concentrated in top partners394), technological
obsolescence (15–20% annual CAPEX renewal requirement395,396), or administrative
delay. If the EHDS delivers even a fraction of its projected EUR 11 billion in economic
value over ten years at the scale of a 450-million population, the innovation return from
data accelerator projects would be significant. The overall R&I impact depends less on the
initial creation of infrastructure and guidance than on the sustained quality of governance,
access design and technology refresh funding over the operational lifecycle.
The guidance on AI use is expected to generate positive effects on innovation by reducing
the "wait-and-see" behaviour currently observed in AI-enabled drug development. While
68% of biopharma organisations plan to increase AI investment in R&D between 2025 and
2026397, investment remains conditional on regulatory signals regarding the acceptability
of AI-generated evidence. In analogous contexts, the provision of an operational
framework has triggered measurable shifts in methodological uptake: under the EMA's
Real-World Evidence framework, regulator-led RWD studies increased to 59 between
February 2024 and February 2025, a 47.5% increase year-on-year, while study feasibility
rose from 60% to 78% as the DARWIN EU network expanded to 30 data partners covering
around 180 million patients across 16 countries 398,399.
Public authorities
The costs on EMA regarding the development of the guidance are difficult to quantify.
However, it is known that implementation of coordinated systems (as it is with EHDS),
391 Fries, J. A., et al. (2022). Dataset debt in biomedical language modeling. https://edoc.mdc-
berlin.de/id/eprint/22134/1/22134oa.pdf 392 European Commission, Directorate-General for Research and Innovation, & PwC EU Services. (2018). Cost-benefit
analysis for FAIR research data: Cost of not having FAIR research data. Publications Office of the European Union.
https://doi.org/10.2777/02999 393 Elucidata (2025), Data Mine to Data Minefield: The Hidden Costs of Poor Data Quality in Biopharma R&D.
https://www.elucidata.io/blog/data-mine-to-data-minefield-the-hidden-costs-of-poor-data-quality-in-biopharma-r-d 394 European Court of Auditors (2016), Special Report No 04/2016: The European Institute of Innovation and Technology
must modify its delivery mechanisms and elements of its design to achieve the expected impact.
https://www.eca.europa.eu/lists/ecadocuments/sr16_04/sr_eit_en.pdf 395 Santos, F. M., & Mendonça, S. (2025), Innovation Intermediaries in the Digital Transformation Process,
Technovation. https://doi.org/10.1016/j.technovation.2025.102902 396 European Court of Auditors (2026), Opinion No 10/2026 on the proposal for a regulation establishing a budget
expenditure tracking and performance framework. https://www.eca.europa.eu/en/publications/OP-2026-10 397 Capgemini Research Institute. (2026). Smart bet, only option, or both?: Biopharma R&D turns to AI. Capgemini.
https://www.capgemini.com/wp-content/uploads/2026/01/120126CRI_Gen-AI-in-Lifesciences-_Final-interactive.pdf 398 European Medicines Agency. (2025, June 30). Real-world evidence framework to support EU regulatory decision-
making: 3rd report on the experience gained with regulator-led studies from February 2024 to February 2025. European
Medicines Agency. https://www.ema.europa.eu/en/documents/report/real-world-evidence-framework-support-eu-
regulatory-decision-making-3rd-report-experience-gained-regulator-led-studies-february-2024-february-2025_en.pdf 399 EMA Infosheet: https://www.ema.europa.eu/en/documents/other/infosheet-ema-review-real-world-data-studies-
september-2021-february-2025_en.pdf
240
requires significant investment in capacity-building, training, and public engagement. The
economic costs are borne at both Union and national levels, and additional resources are
needed for healthcare systems, especially public ones.
Testing environments and data quality accelerators share the same recognition-and-support
architecture as high impact health biotechnology strategic projects. The following
incremental costs apply to both.
EU-level supervisory costs. EU-level supervisory tasks under Articles 32 and 33 cover
recognition, monitoring, compliance verification and cross-border coordination for a
limited portfolio of high impact projects. These are non-fiscal administrative functions and
do not involve managing a direct funding portfolio. A bottom-up estimate of the staffing
requirement suggests approximately 0.3–0.5 FTE per single-country project per year for
ongoing supervision, rising to 0.5–1 FTE for multi-country projects given the additional
coordination layer, plus a one-off recognition effort of approximately 1–1.5 person-months
per project at initial designation400. On this basis, EU-level supervisory requirement is
estimated at 1–3 FTE under low uptake (2–3 projects), 2.5–8 FTE under medium uptake
(5–8 projects), and 5–15 FTE under high uptake (10–15 projects). The additional
complexity of health biotechnology strategic projects, which span multiple regulatory
frameworks (AI Act, Clinical Trials Regulation, EHDS, GMO legislation) and require
coordination across a broader range of Union agencies (EMA, EFSA, national competent
authorities) and sectoral stakeholders, supports placing estimates at the higher end of these
ranges for multi-country projects. The Chips Joint Undertaking, where 18 FTE supervise
a portfolio of approximately EUR 4.175 billion in EU funding involving direct programme
management401, provides a structural upper bound; the Act's recognition-and-coordination
function is materially less resource-intensive than direct programme management.
Technological obsolescence and refresh costs. Both articles establish infrastructure that
relies on AI-enabled digital components evolving significantly faster than traditional
research equipment. Computational power required for frontier AI experiments doubles
approximately every 3.5 months402 and 30–40% of software stacks require replacement or
major updates every 18–24 months403. Maintaining state-of-the-art status requires
continuous reinvestment equivalent to 15–20% of initial CAPEX annually404,405.The
400 There is no database for these figures available, an assumption was made given the expected amount of work per
project (see Rapid Assessment Study – forthcoming). 401 In the current Chips JU, 18 FTE supervise a budget of around EUR 4.175 billion in EU funding. The Chips Act
strategic project oversight model provides the closest available proxy for the administrative supervision function
envisaged under Articles 32 and 33 of the proposed Biotech Act. 402 Organisation for Economic Co‑operation and Development. (2018). OECD science, technology and innovation
outlook 2018: Adapting to technological and societal disruption.
https://www.oecd.org/content/dam/oecd/en/publications/reports/2018/11/oecd-science-technology-and-innovation-
outlook-2018_g1g98de3/sti_in_outlook-2018-en.pdf 403 Santos, F. M., & Mendonça, S. (2025), Innovation Intermediaries in the Digital Transformation Process,
Technovation. https://doi.org/10.1016/j.technovation.2025.102902 404 European Court of Auditors. (2026, February 24). Opinion No 10/2026 (pursuant to Article 322(1) TFEU) on the
proposal for a regulation establishing a budget expenditure tracking and performance framework.
https://www.eca.europa.eu/en/publications/OP-2026-10 405 Santos, F. M., & Mendonça, S. (2025). Innovation intermediaries in the digital transformation process. Technovation.
https://doi.org/10.1016/j.technovation.2025.102902
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Hartree Centre evaluation illustrates the financial implication: EUR 35.3 million in active
assets alongside EUR 31.9 million already retired or repurposed406.
Human capital costs. Both types of projects require interdisciplinary profiles bridging
medicine, data science and law, which are in critical shortage. AI talent concentration in
hospitals remains below 2% of the workforce in most Member States407. Operating testing
environments (Article 32) and data quality accelerators (Article 33) require permanent
specialist roles (data stewards, cloud engineers, validation scientists) that represent new
fixed costs for the public authorities hosting or co-managing these projects408,409.
Beyond the shared strategic project costs, data quality accelerators potentially create
incremental demands on public authorities that hold or govern health data. These
costs arise not from the EHDS baseline (which mandates data access) but from the
accelerator-grade quality uplift including curating, annotating, verifying provenance and
standardising datasets to a level suitable for AI training, validation and testing.
This quality uplift is labour-intensive and costly. Making experimental results "AI-ready"
by systematically recording metadata adds roughly 15% to experimentation costs 410. For
biobanks participating in accelerator-grade data provision, agreements range from EUR
100,000 to EUR 500,000 per project, reflecting the cost of providing "highly structured,
harmonized data" capable of supporting computational cloud services 411. This level of
curation goes substantially beyond standard EHDS access obligations. Effective
anonymisation at accelerator grade cannot be fully automated: "use case–specific
anonymisation" requires deep domain expertise to preserve statistical utility while ensuring
GDPR compliance412.
Grant dependency risk. The public authorities are most likely to host or co-manage
Article 33 accelerators (biobanks, registries) have funding structures incompatible with
permanent service obligations. Core budgets cover only 16–17% of IT and development
services, with 83–84% dependent on volatile project-based grants 413. Article 33 imposes
continuous curation, maintenance and data-holder support functions that require stable
operational funding. Without structural budget allocation, accelerator projects risk the
406 Technopolis Group (2018), Hartree Centre Phase 1 & 2 Baseline Evaluation. https://www.technopolis-group.com/wp-
content/uploads/2020/02/Hartree-Centre-Phase-12-Baseline-Evaluation.pdf 407 Organisation for Economic Co-operation and Development. (2026). Progress in implementing the European Union
coordinated plan on artificial intelligence (Volume 2): Uptake in high-impact sectors. OECD Publishing.
https://doi.org/10.1787/3ac96d41-en 408 BBMRI-ERIC. (2025). BBMRI-ERIC work programme 2025–2027. https://www.bbmri-eric.eu/wp-
content/uploads/Work_programme_2025-2027_WEB.pdf 409 European Commission, Directorate-General for Research and Innovation, & PwC EU Services. (2018). Cost-benefit
analysis for FAIR research data: Cost of not having FAIR research data. Publications Office of the European Union.
https://doi.org/10.2777/02999 410 Organisation for Economic Co-operation and Development. (2023). Artificial intelligence in science: Challenges,
opportunities and the future of research. OECD Publishing. https://doi.org/10.1787/a8d820bd-en 411 EIT Health. (n.d.). Costs and agreements. https://biobankshealthdata.eithealth.eu/guide/costs-and-agreements/ 412 Pilgram, L.,et. al.., & GCKD Investigators. (2024). The costs of anonymization: Case study using clinical data. Journal
of Medical Internet Research, 26, e49445. https://doi.org/10.2196/49445 413 BBMRI-ERIC. (2025). BBMRI-ERIC work programme 2025–2027. https://www.bbmri-eric.eu/wp-
content/uploads/Work_programme_2025-2027_WEB.pdf
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same "project trap" cycle observed in existing biobank infrastructure: facilities built up for
specific grant periods and subsequently degraded once funding expires 414.
Coordination needs with Health Data Access Bodies (an EHDS obligation) add an
institutional coordination layer: accelerators must align their data quality standards, access
procedures and governance with the HDAB framework operating in each participating
Member State. For accelerators operating across borders, this involves navigating the
heterogeneous implementation timelines and technical standards of multiple national
systems, adding administrative complexity that scales with the number of Member States
involved.
Overall, the incremental costs to public authorities for testing environments and data
quality accelerators are driven primarily by three factors: EU-level supervision of the
strategic project portfolio (25–30 FTE), continuous technology refresh to avoid
obsolescence (15–20% of CAPEX annually), and, for data quality accelerators specifically,
the accelerator-grade data curation burden that goes beyond baseline EHDS access
obligations.
The critical sustainability risk is concentrated in data quality accelerators. The public
authorities best positioned to operate data quality accelerators (biobanks, registries) are
also the most financially precarious: 83–84% grant-dependent, with fee recovery models
covering only a fraction of operational costs in comparable settings. In the context of data
quality accelerators these entities would have to provide continuous, high-quality data
stewardship as a permanent service, but their funding structures are designed for time-
limited projects. Unless stable operational funding is provided, there is a material risk that
accelerator projects are launched but cannot be sustained at the quality level required to
deliver their intended innovation and competitiveness effects.
Public health and safety
Biotechnology testing environments are the main driver of impacts in this category, as they
are expected to improve public health outcomes by enabling standardised, independent
validation of AI-enabled biomedical tools before large-scale deployment. The expected
effects operate through three channels.
Reducing the real-world performance gap. AI models validated through ad hoc firm-
level processes suffer performance declines of 15–30% when deployed against
heterogeneous patient populations and clinical workflows 415. Shared testing environments
providing access to diverse, representative datasets and standardised protocols are
expected to narrow this gap before deployment, reducing the risk of clinical failures such
as the Epic Sepsis Model case, where real-world AUC fell from 0.76–0.83 to 0.63, missing
67% of sepsis cases416.
414 Towards the European Health Data Space (TEHDAS). (2022, April 1). TEHDAS identifies funding options for
secondary use of health data. https://tehdas.eu/tehdas1/results/tehdas-identifies-funding-options-for-secondary-use-of-
health-data/ 415 Li, Y., et. al. (2025). Reducing misdiagnosis in AI-driven medical diagnostics: A multidimensional framework for
technical, ethical, and policy solutions. Frontiers in Medicine. https://doi.org/10.3389/fmed.2025.1594450 416 Li, Y., et. al. (2025). Reducing misdiagnosis in AI-driven medical diagnostics: A multidimensional framework for
technical, ethical, and policy solutions. Frontiers in Medicine. https://doi.org/10.3389/fmed.2025.1594450
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Improving reliability through structured multi-system validation. Evidence from
controlled testing architectures shows that where multiple AI systems cross-check outputs,
the probability of achieving top-quartile safety performance increases 5.9-fold compared
with single-model deployments 417. Article 32 environments are designed to replicate such
rigorous testing conditions at scale. This is particularly relevant given that frontier large
language models in clinical settings produce severely harmful recommendations in up to
22.2% of cases, with a Number Needed to Harm of approximately 11.5 418, and that by
November 2024 the FDA had recorded 182 recall events involving 60 AI-enabled devices,
with 43% occurring within one year of authorisation.
Reducing population-level bias. Testing against diverse datasets in shared facilities is
expected to reduce bias arising from non-representative validation data, a documented
patient safety risk where dermatology AI systems have shown false-negative melanoma
rates 28% higher for darker-skinned patients and critical care misdiagnosis rates 31%
higher for minority patients 419,420.
417 Goh, E. (2025). New Stanford–Harvard study: Widely used AI models can cause severe clinical harm in up to 22%
of cases [LinkedIn post]. LinkedIn. https://www.linkedin.com/posts/ethan-goh_new-stanfordharvard-study-widely-
used-activity-7402030275485962240-ywkw 418 Goh, E. (2025). New Stanford–Harvard study: Widely used AI models can cause severe clinical harm in up to 22%
of cases [LinkedIn post]. LinkedIn. https://www.linkedin.com/posts/ethan-goh_new-stanfordharvard-study-widely-
used-activity-7402030275485962240-ywkw 419 Abu-Mahfouz, N. (2026). Bias in medical AI: Algorithmic fairness and ethics challenges. Journal of Young
Investigators, 29(1), 1–3. https://www.jyi.org/2026-january-1/2026/1/8/bias-in-medical-ai-algorithmic-fairness-and-
ethics-challenges 420 Abu-Mahfouz, N. (2026). Bias in medical AI: Algorithmic fairness and ethics challenges. Journal of Young
Investigators, 29(1). https://www.jyi.org/s/202601-RA-Abu-Mahfouz-Bias-Medical-AI.pdf
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ANNEX 8: COMPETITIVENESS CHECK
1 OVERVIEW OF IMPACTS ON COMPETITIVENESS
Dimensions of
Competitiveness
Impact of the initiative
(++ / + / 0 / - / -- / n.a.)
References to sub-sections of
the main report or annexes
Cost and price
competitiveness + Section 6 and Annex 7
International
competitiveness ++ Section 6 and Annex 7
Capacity to innovate ++ Section 6 and Annex 7
SME competitiveness ++ Section 6 and Annex 7
2 SYNTHETIC ASSESSMENT
Cost and price competitiveness improves moderately across the biotech ecosystem,
driven primarily by the reduction of regulatory compliance costs for innovators and the
acceleration of competitive price dynamics in the biologicals market. The amendments to
the EU rules on clinical trials, ATMPs, GMMs, and to the General Food Law collectively
reduce duplicative procedural requirements, shorten authorisation timelines, and lower
administrative expenditure per product. Quantified savings range from tens of thousands
of euros per ATMP clinical trial application to EUR 112 to 225 million over 15 years from
clinical trial digitalisation alone. The biosimilar measure reinforces competitive pricing by
lowering development cost barriers for new market entrants. This builds on a baseline of
EUR 6 billion in annual European healthcare savings achieved in 2024. By enabling faster
entry and greater competition, the measure ensures this savings trajectory continues to
deepen. These gains are partially offset by the SPC extension and biosecurity screening
obligations. The SPC extension maintains higher originator prices for an additional year
for eligible biotechnological medicines at an estimated EUR 210 million annual cost to
public payers. Biosecurity screening obligations introduce compliance costs for synthetic
nucleic acid providers and their customers. Some cost disadvantages, including the still-
fragmented EU clinical trial landscape and persistently high manufacturing costs for
advanced biologicals, limit the overall scale of improvement.
International competitiveness strengthens substantially across several key dimensions of
the EU biotech sector. The proposed revision of the EU rules on clinical trials reverses the
EU's declining attractiveness as a location for globally mobile trial investment, addressing
the fall in the EU's share of global commercial clinical trials from 22% in 2013 to 12% in
2023, while China's share rose from 8% to 29% over the same period. The biosimilars
measure prevents the EU from becoming the last major jurisdiction without CES
flexibility, at a time when the US, Canada, and South Korea are already moving toward
waiver or elimination of this requirement, thereby defending the EU's position as the
world's largest biosimilar market at approximately 43% of a EUR 25.9 billion global
market. The GMMs intervention enables the EU to compete in high-growth global markets
245
such as biofertilisation, biocontrol and bioremediation, from which it has been effectively
absent under the existing framework. Remaining barriers to venture capital availability,
late-stage financing depth, and manufacturing cost levels relative to Asian competitors are
not addressed by the European Biotech Act proposal, limiting the ceiling of achievable
improvement.
Capacity to innovate is significantly enhanced through measures that collectively address
the EU's persistent structural failure to translate its strong scientific base into commercial
biotech innovation. The novel health products instruments (regulatory status repository,
regulatory sandbox, foresight panel) directly reduce the regulatory uncertainty that
currently suppresses high-risk, frontier research in the EU, with sandbox evidence from
comparable frameworks indicating 20 to 40% faster time-to-market, a 15 to 50% increase
in funding probability, and 20 to 30% gains in firm survival and patenting, with the
potential to accelerate 10 to 20 novel products per cohort. The revision of the EU rules on
GMMs unlocks an entirely blocked innovation pathway, enabling the EU to begin
developing commercial products in bioremediation markets projected to grow at a CAGR
of approximately 10 to 13% and bioleaching markets at approximately 9%, with
biofertilisation and biocontrol representing further high-growth opportunities, sectors
where the EU currently holds zero authorised products despite significant global market
momentum. The ATMPs and clinical trial revisions remove procedural barriers to
innovative trial designs, including adaptive, decentralised, and combined studies, enabling
the EU to support cutting-edge development modalities that its current framework
structurally hinders. The strategic projects and high-impact projects measures strengthen
the EU's translation infrastructure by supporting pilot, testing and demonstration facilities
and biomanufacturing innovation assets that convert research outputs into industrial
deployment, complemented by the access to funding pilots, which target the EU's EUR 40
billion annual investment gap by improving late-stage capital continuity and reducing
financing-round attrition. The Data and AI related policy measures further broaden
innovation capacity by establishing trusted AI testing environments and data quality
accelerators as high-impact strategic projects, and tasking EMA with guidance on AI
integration across the medicinal product lifecycle.
SME competitiveness is expected to improve strongly across the biotech ecosystem, as
SMEs and start-ups are the primary beneficiaries of the package's regulatory
simplification, infrastructure access, and support provisions. SMEs are disproportionately
burdened under the current system, lacking in-house regulatory affairs capacity, relying
heavily on costly external consultants, and facing compliance costs that consume a
structurally larger share of their resources than for large firms. Multiple interventions
directly address these conditions. The clinical trial revision reduces per-trial administrative
costs by EUR 2,714 to EUR 4,496 and introduces more predictable timelines that benefit
resource-constrained sponsors. The GMMs low-risk pathway lowers market entry barriers
for start-ups that would otherwise be unable to absorb the costs and timelines of the current
process. The ATMP ERA simplification removes a compliance burden that industry
identifies as particularly severe for smaller developers, who constitute the majority of the
ATMP pipeline. The General Food Law amendments provide expanded scientific pre-
submission advice that is of greatest value precisely for SMEs and first-time applicants
most likely to submit incomplete dossiers. The strategic projects and high-impact projects
measures create new market opportunities by opening shared pilot, testing, and small-batch
GMP infrastructure with systematic cross-border accessibility, with 82% of SMEs
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currently unable to self-finance comparable validation infrastructure. The biotech
ecosystem support network and access to funding pilots target the structural financing gap
that constrains SME scaling, with the Investment Pilot explicitly designed to support the
full company lifecycle including start-ups and scale-ups, addressing a broader annual
investment gap estimated at EUR 40 billion.
3 COMPETITIVE POSITION OF THE MOST AFFECTED SECTORS
Health biopharmaceutical, biologics and ATMP developers benefit most directly.
Regulatory simplification across clinical trials, ATMPs and GMMs reduces time-to-
market, lowers development costs, and improves the EU's attractiveness as a location for
late-stage clinical research and advanced therapy development. Strategic project
recognition and access to funding measures strengthen the translation infrastructure
connecting research to commercial deployment, partially closing the financing and scale-
up gap with the US and China.
Biosimilar developers gain from both regulatory modernisation and supply-side support.
Alignment of the EU's evidentiary requirements with the emerging international standard
preserves the EU's position as the world's leading biosimilar market and removes the risk
of regulatory disadvantage relative to the US, South Korea and Canada. Strategic project
support for EU-based biosimilar manufacturing reinforces the domestic developer base
against growing competition from South Korean and Indian producers.
Industrial biotechnology firms, particularly those active in biofertilisation, biocontrol,
bioremediation and bioleaching, gain access to a viable EU market authorisation pathway
for GMMs where none currently exists. This represents a qualitative shift in competitive
position rather than an incremental improvement, enabling EU-based firms to begin
competing in fast-growing global markets from which the current regulatory framework
has effectively excluded them.
Veterinary medicine companies benefit from a single regulatory pathway for GMO-
containing VMPs, reduced administrative burden on lifecycle management, and a new
sandbox instrument for next-generation animal health technologies. These measures
improve the EU's competitiveness in a sector where it holds the second-largest global
market share and where the pipeline is increasingly reliant on GMO-based vaccine
platforms.
Food and feed chain operators, including SMEs and first-time applicants, benefit from a
more supportive and timely EFSA authorisation process. Reduced stop-the-clock incidents
and earlier access to scientific guidance strengthen the EU's ability to bring innovative
food and feed products to market without sacrificing the quality standards that underpin its
international reputational advantage.
Synthetic nucleic acid synthesis providers operating responsibly gain from the levelling of
competitive conditions across the sector. Mandatory screening removes the cost advantage
currently enjoyed by non-compliant providers and positions EU suppliers more credibly in
international markets where biosecurity standards are increasingly expected by customers
and regulators alike
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ANNEX 9: SME CHECK
OVERVIEW OF IMPACTS ON SMES
Relevance for SMEs
Yes
(1) IDENTIFICATION OF AFFECTED BUSINESSES AND ASSESSMENT OF RELEVANCE421
Are SMEs directly affected? (Yes) In which sectors?
The health biotechnology and pharmaceutical sector is the most heavily affected sector, given
that over 60% of ATMP developers in Europe are SMEs, and that EU biotech firms are
structurally smaller on average and less likely to scale than their US counterparts. This sector
includes developers of advanced therapy medicinal products (ATMPs: gene therapies, cell
therapies, tissue-engineered products), biological medicinal products, and biosimilars.
Biomanufacturing and scale-up services, including firms providing GMP-compliant pilot and
testing infrastructure, for whom reduced permitting timelines and access to shared late-stage
infrastructure are directly relevant to their conduct of business and commercial viability.
Clinical research, including small sponsors (both commercial SMEs and academic innovators
and non-commercial trial sponsors) conducting clinical trials for novel biotechnology products,
who face disproportionate administrative and regulatory burdens relative to larger firms with
dedicated regulatory affairs capacity.
Industrial and environmental biotechnology, including start-ups and SMEs developing
genetically modified micro-organism (GMM)-based products in areas such as biofertilizers,
biocontrol agents, bioremediation, and bioleaching, for whom the absence of a workable and
proportionate regulatory pathway has effectively blocked market entry under the current
framework.
Veterinary biotechnology and animal health, including SMEs and emerging developers of next-
generation veterinary vaccines and biotechnology-derived animal health products, who are
directly affected by the GMO exemption and regulatory sandbox provisions under the amended
Veterinary Medicinal Products Regulation.
Food and feed biotechnology, including first-time and one-time applicants to EFSA pre-market
authorisation processes, disproportionately SMEs, who bear the highest relative cost of
incomplete or non-compliant dossiers and who stand to benefit most from extended pre-
421 The structural characterisation of the SME population in the EU biotechnology sector, including firm size distribution,
sector composition, startup ecosystem data, and employment figures, is drawn from the Market Analysis (Technopolis
Group, Orbis IP dataset, 2025) and the Final Report of the Landscape analysis study (forthcoming).
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submission advice covering both regulatory and scientific aspects, as well as from regulatory
sandboxes for food, feed and GMO-related products.
AI-enabled health biotechnology and digital health, including SMEs developing AI-based tools
for drug discovery, genomic analysis, and clinical development, who currently cannot self-
finance validation infrastructure (with 82% of SMEs unable to do so) and who face delays of
up to 18 to 24 months in accessing pilot-GMP capacity under current conditions.
Regenerative medicine and cell processing, including smaller SoHO entities and biotech firms
operating at the interface of SoHO, ATMP and medical device frameworks, for whom
regulatory sandboxes reduce the multi-framework compliance burden that currently falls
disproportionately on entities without large in-house regulatory affairs capacity.
Estimated number of directly affected SMEs
The estimated number of directly affected SMEs falls in a range of approximately 3,000 to
4,500, based on the available firm-level data for the EU biotechnology sector across the health
biotechnology, industrial biotechnology, food and feed biotechnology, veterinary
biotechnology, and AI-enabled health technology sectors. This figure is likely a conservative
estimate, as it does not fully capture SMEs in food, feed and veterinary biotechnology that are
subject to the relevant legislative amendments but are not classified as biotechnology
companies in standard firm-level databases.
Estimated number of employees in directly affected SMEs
Direct employment in the EU biotechnology sector stands at approximately 137,000
(Technopolis Group, Prodcom-based, 2024) to 238,000 (WifOR Institute, 2025). Since
manufacturing activities, which are the most labour-intensive, are structurally concentrated in
large firms while SMEs predominantly specialise in R&D and early-stage development, their
share of direct employment is estimated at approximately 40 to 50% of the sector total, pointing
to an indicative figure of approximately 55,000 to 120,000 employees422 in directly affected
SMEs.
Are SMEs indirectly affected? (Yes) In which sectors? What is the estimated number of
indirectly affected SMEs and employees?
SMEs are indirectly affected across a broad range of upstream and downstream sectors that are
economically linked to biotechnology activity.
Upstream: this includes providers of laboratory equipment, analytical instruments and
reagents; specialised contract research organisations (CROs); regulatory, legal and IP advisory
service firms; bioinformatics and digital health technology providers; and raw materials and
biological input suppliers.
Downstream: it encompasses medical devices and diagnostics firms supplying complementary
products, logistics and cold chain operators handling biological products, food processing and
manufacturing businesses affected by the food law amendments, agricultural input suppliers
422 Figures estimated by PPMI (see Rapid Assessment Study – forthcoming) based total number of companies according
to the Technopolis and Wifor reports,applying an assumed 40 to 50% SME employment share to the two total
employment figures from those sources.
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linked to the GMM and VMP value chains, and healthcare service providers benefiting from
improved availability of advanced therapies and biosimilars.
The total employment effects linked to the EU biotechnology industry, including upstream and
downstream value chain linkages, amount to approximately 913,000 jobs (WifOR Institute,
2025), implying a spillover multiplier of 2.8 on approximately 238,000 direct biotech jobs. A
disaggregated figure for employees in indirectly affected SMEs specifically is not available
(2) CONSULTATION OF SME STAKEHOLDERS
How has the input from the SME community been taken into consideration?
SME input was gathered through multiple consultation channels. The call for evidence (May to
June 2025, 222 contributions) gathered additional input from companies and business
associations representing SME interests. The public consultation (August to November 2025,
464 contributions) received submissions from 63 SMEs (comprising 28 micro-enterprises, 19
small enterprises and 16 medium-sized enterprises). Targeted stakeholder interviews were
conducted (see annex 2 for more details) including with representatives of SMEs, start-ups and
scale-ups across health, industrial, food and veterinary biotechnology. The assessment of
impacts incorporated SME-specific views directly into the analytical frameworks: SME
disproportionate burden is established as a core baseline assumption in the Biotech Ecosystem,
Novel Health Products, ATMPs, Clinical Trials, GMMs and SPC Extension IAs. The European
Biotech Act proposal itself explicitly lists support to SMEs, start-ups and scale-ups among its
objectives in Article 2(2)(c).
Are SMEs’ views different from those of large businesses? (Yes)
The consultation evidence documents several substantive differences between SMEs and large
enterprises. On regulatory burden, both groups cited fragmentation as a problem, but small
companies specifically highlighted high regulatory costs while large companies focused on the
unpredictability of authorisation procedures. On access to funding, large companies pointed to
public R&D under-investment as their primary concern, while also acknowledging the lack of
financial and administrative capacity of SMEs to access EU-level funding or protect their
intellectual property. On AI and data, large companies cited fragmented data ecosystems and
lack of data access, whereas SMEs raised a more foundational concern: a lack of information
and knowledge within companies about AI implementation and compliance. On biosecurity,
SMEs and NGOs specifically raised dual-use risks, a concern not prominently voiced by large
companies.
At intervention level, the assessment of impacts further document that SMEs face higher per-
unit compliance costs across clinical trials, IP management and biosecurity screening relative
to their size, reflecting their limited in-house regulatory and legal capacity compared to large
firms.
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(3) ASSESSMENT OF IMPACTS ON SMES423
What are the estimated direct costs for SMEs of the interventions?424
Qualitative assessment
The European Biotech Act proposal does not impose new mandatory costs on the general
biotechnology SME population. The one exception which is biosecurity screening is targeted
at a specific, narrow sub-sector of SME operators (nucleic acid synthesis providers) where the
obligation is proportionate to the public security objective, and where many providers already
screen voluntarily. For all other SMEs, the Act generates either net cost reductions through
regulatory simplification or access to new voluntary support instruments.
Quantitative assessment
The only new mandatory direct cost falling on SMEs is biosecurity screening for nucleic acid
synthesis providers: EUR 7.3 to 22.2 million per year across the approximately 77 EU custom
synthesis providers not currently screening (approximately EUR 95,400 per provider per year).
Customer-side compliance costs for SME research organisations ordering synthesis services
add a further EUR 16.4 million per year across the user base. All other cost items under the
interventions are either voluntary or generate net reductions relative to the baseline.
What are the estimated direct benefits/cost savings for SMEs of the interventions425?
Qualitative assessment
The European Biotech Act proposal delivers benefits to SMEs across four channels. First,
regulatory simplification reduces per-unit compliance costs that fall disproportionately on
smaller firms lacking in-house regulatory affairs capacity: ATMP framework reforms,
biosimilar CES removal, VMP GMO pathway consolidation, and clinical trial harmonisation
all reduce the absolute cost and time burden of regulatory engagement for SME sponsors and
developers. Second, shared infrastructure under Articles 32 and 33 converts prohibitive firm-
level capital expenditure (currently unaffordable for 82% of SMEs) into pooled access to
GMP-compliant pilot and testing environments, addressing delays of up to 18 to 24 months in
accessing pilot-scale capacity. Third, Article 31 AI guidance has the potential to reduce costly
bilateral EMA qualification interactions by providing freely accessible public guidance, a
measure whose value is asymmetrically concentrated in smaller actors that cannot absorb
bilateral engagement costs. Fourth, the EU Health Biotechnology Support Network reduces
search and navigation costs for SMEs across regulatory pathways, funding instruments and
investor connections, with comparable network support associated with a 14-percentage point
advantage in knowledge sharing and collaboration capability over unsupported firms.
Quantitative assessment
423 The costs and benefits data in this annex are consistent with the data in annex 3. The measure include the mitigating
measures listed in section 4 of this annex. 424 Direct costs as well as direct benefits and cost savings for SMEs resulting from the different interventions are
quantified in Annex 3 (Who is affected and how) and in the sections assessing the impact of respective interventions (see
also the sections analysing impact per policy measure in the Rapid Assessment Study – forthcoming). 425 The direct benefits for SMEs can also be cost savings.
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Clinical trial administrative savings: EUR 2,700 to 4,500 per multinational trial (15 to 25%
through alone a reduction in the staff time for regulatory interactions. On an aggregated level,
cost savings of EUR 1.5 to 3.1 billion per year across EU sponsor expenditure are expected,
with administrative costs currently representing 11 to 29% of total trial costs, a burden falling
proportionally harder on SMEs.
ATMP framework reforms: elimination of the additional 50-day assessment period and
reduction of substantial modification timelines from 96 to 47 days; ERA exemptions remove
0.15 to 0.3 FTE-years per clinical trial application across a developer base of which over 60%
are SMEs.
Biosimilar CES removal: EUR 19 to 26 million in direct trial cost savings per product,
shortening development timelines by 12 to 24 months; aggregate annual savings of EUR 222
to 467 million across 12 to 18 marketing authorisation applications per year.
VMP VNRA batching: staff time saving of 14,930 to 29,859 hours per year sector-wide,
equivalent to EUR 0.97 to 1.94 million per year; VMP GMO exemption saves approximately
EUR 7,000 per marketing authorisation dossier.
Article 31 AI guidance: where individual EMA qualification interactions are replaced by
relying on the free public guidance, 160 to 250 days could be saved per interaction, with benefit
asymmetrically concentrated in SMEs.
Shared testing environments and data accelerators (Articles 32 and 33): 1,100 to 3,400 data
users and 100 to 200 companies could be served per year in a medium uptake scenario (5–8
recognised testing environments and 5–8 data quality accelerators); of the 100 to 200
companies served through shared testing environments, approximately 60% are SMEs; delays
of up to 18 to 24 months in accessing pilot-GMP capacity eliminated for qualifying firms.
Removed administrative burdens: EUR 1.50 to 3.32 million per year across the SME
population from ATMP, VMP and biosimilar simplification measures combined.
What are the indirect impacts of this initiative on SMEs?426
Positive: ecosystem investment and market expansion. The strategic project recognition
framework and associated investment instruments are expected to mobilise EUR 15 to 28
billion in total investment at medium uptake, generating a broader market expansion from
which SMEs benefit as ecosystem participants, through increased demand for specialist
services, testing, regulatory consulting, logistics and supply chain inputs.
Positive: improved competitive conditions and time to market. The cumulative effect of
clinical trial harmonisation, ATMP simplification, biosimilar CES removal and VMP reforms
is to compress development timelines and reduce the cost of translation from research to
market across the sector. For SMEs not directly subject to these regulatory obligations but
426 Indirect impacts on SMEs are based on the sections assessing the impact of respective interventions (including
Strategic Projects, High Impact Projects, Biosimilars, SPC Extension, and Data and AI, as well as in the Access to
Funding IA). See also the sections analysing impact per policy measure in the Rapid Assessment Study – forthcoming.
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participating in the value chain as contract service providers, testing laboratories,
bioinformatics firms, or suppliers of inputs to larger development programmes, faster and
cheaper development activity among their clients translates into increased demand and more
stable revenue flows.
Positive: biosimilar market expansion. The EU biosimilar market is projected to grow at a
CAGR of 17.3% from 2025 to 2034, reaching approximately EUR 55.4 billion by 2034, driven
by ongoing patent expires on major biological medicines and increasing uptake of biosimilar
prescribing across Member States. The biosimilar CES removal accelerates EU competitive
positioning within this expanding market by reducing barriers to entry and shortening
timelines. SME biosimilar developers, which form part of the EU-headquartered developer
base currently holding 49% of EU biosimilar authorisations, stand to benefit from improved
commercial conditions within a growing market.
Adverse: SPC extension delay for biosimilar developer SMEs. The 12-month SPC
extension creates a directly adverse indirect impact for SME biosimilar developers. For
marginal development programmes targeting smaller markets or carrying higher development
costs, this reduction in expected return on investment may affect commercial viability at the
margin. The measure benefits originator SMEs while imposing a revenue delay on biosimilar
developer SMEs. Development programmes that have already advanced substantially are
unlikely to be discontinued solely due to a one-year delay, but the effect on investment
decisions at the margin is nonetheless to be taken into account.
(4) MINIMISING NEGATIVE IMPACTS ON SMES
Are SMEs disproportionately affected compared to large companies? (Yes)
If yes, are there any specific subgroups of SMEs more exposed than others?
Smaller firms may feel the impacts (in particularly linked to biosecurity screening requirement)
more acutely due to fixed costs representing a higher share of turnover. This reflects structural
characteristics of smaller firms rather than a differential obligation created by the Act, as the
obligations introduced by the interventions are size-neutral by design. The biosecurity
screening requirement applies uniformly to all custom nucleic acid synthesis providers, and
the adverse indirect effect of the SPC extension on biosimilar developers applies equally
regardless of firm size. For the broader SME population, the Act reduces rather than increases
existing compliance burdens, and no provision of the preferred option imposes obligations
specifically or more heavily on SMEs than on large companies. SMEs benefit proportionately
more from the policy measures overall.
Have mitigating measures been included in the proposal?
EU Health Biotechnology Support Network, single points of contact with dedicated SME
channels, shared infrastructure access provisions, voluntary participation design, and the
proportionate scope of the biosecurity obligation.
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CONTRIBUTION TO THE 35% BURDEN REDUCTION TARGET FOR SMES
Are there any administrative cost savings relevant for the 35% burden reduction target
for SMEs?
The preferred option introduces several simplification measures that generate administrative
cost savings for SMEs and contribute to the EU's 35% burden reduction target. Clinical trial
harmonisation reduces sponsor administrative costs by EUR 2,700 to 4,500 per multinational
trial (a 15 to 25% reduction in staff time under the Standard Cost Model), aggregating to EUR
1.5 to 3.1 billion per year across EU sponsor expenditure, with SMEs benefiting
disproportionately given that administrative expenses represent 11 to 29% of their total trial
costs. The elimination of the ERA requirement for qualifying GMO-ATMPs removes 0.15 to
0.3 FTE-years of administrative workload per clinical trial application across a developer base
of which over 60% are SMEs. The VMP VNRA batching reform saves 14,930 to 29,859 staff
hours per year sector-wide (EUR 0.97 to 1.94 million per year), and the biosimilar MAA
dossier simplification reduces per-application preparation costs by EUR 30,000 to 45,000 for
each product transitioning to a tailored clinical package. Electronic submission and
digitalisation measures contribute a further EUR 112 to 225 million cumulatively over 15
years. The establishment of single points of contact with dedicated SME channels and the EU
Health Biotechnology Support Network further reduce navigational and compliance costs for
smaller firms that lack in-house regulatory capacity, supporting compliance efficiency across
the sector.