Biotehnoloogia pakett

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EUROPEAN COMMISSION

Strasbourg, 16.12.2025

COM(2025) 1022 final/2

2025/0406 (COD)

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)

{SWD(2025) 1055 final}

(Text with EEA relevance)

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EXPLANATORY MEMORANDUM

1. CONTEXT OF THE PROPOSAL

• Reasons for and objectives of the proposal

Biotechnology and biomanufacturing are essential to the EU’s competitiveness, strategic

autonomy and economic security. They are a pillar of the Union’s societal wellbeing in key

areas such as health and food.

This strategic importance is underscored by the sector’s rapid expansion. Over the last decade,

the EU biotechnology industry has grown more than twice as fast as the overall EU

economy and is one of the most economically productive industries. The spillover effect is

also significant, each job in industrial biotechnology generates 3.4 additional jobs in the

broader economy. In 2022, it accounted for EUR 38.1 billion of Union GDP and contributed

to 913 160 jobs, with more than 75% of those jobs (685 000) coming from the health

biotechnology sector 1.

However, the EU lags behind other global regions when it comes to translating its world-

class science and innovation into commercially viable products, and even more so in

manufacturing such products at scale. Despite world-leading biotechnology science, reflected

by a publication record comparable to that of the US and China (Figure 1), the EU faces

structural barriers in clinical development, regulation and manufacturing. As a result, too

often Union start-ups end up investing, growing, employing, creating value and placing their

products on the market abroad rather than in the EU. This is especially true for health

biotechnology, where it is at times challenging for the legislative frameworks to keep pace

with the speed of scientific developments.

Figure 1: Top tier life science publications of the EU compared to the USA and China

1 https://www.europabio.org/wp-content/uploads/2025/03/WifOR_EuropaBio2025.pdf

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To remain a biotechnology powerhouse, the EU must make the most of its scale. Fragmented

governance and suboptimal coordination across Member States weaken the EU’s ability to

deploy industrial facilities at scale, resulting in underused biomanufacturing potential -

including in strategic areas such as biosimilars, where the EU has strong expertise but

insufficiently exploited capacity. It should also ensure a strong alignment between the

available labour supply and the specialised skills that the biotechnology and biomanufacturing

sectors will require in the future. Current skill shortages across key areas including R&D,

regulatory affairs, AI, and data analytics further hinder Europe’s competitiveness. At the same

time, the widening gender gap and the untapped potential of a diverse workforce represent

missed opportunities for innovation and resilience.

Access to finance for scale-up funding in the EU remains limited compared to other regions.

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 (Figure 2). EU public equity markets for biotechnology also remain comparatively

underdeveloped, with stock exchanges still largely fragmented across EU Member States 2.

As a result, many EU scale-ups choose to list abroad: over the last six years, 66 out of 67 EU

biotechnology companies that went public chose to list on non-EU stock exchanges,

illustrating the persistent structural disadvantages faced by EU-based innovators 3.

Figure 2: Health Biotechnology investment in the EU compared to the US and China

Aligned with the objectives of the AI Continent Action Plan and the Apply AI Strategy, the

EU must also tap into the massive potential of AI for biotechnologies, addressing obstacles

like limited testing environments, fragmented data, and exploiting the full potential of AI

across the lifecycle of biotechnology products, in particular for medicines. Further,

2 Joint Research Centre (2024), Exploring the global landscape of biotechnology Innovation: preliminary

insights from patent analysis, https://publications.jrc.ec.europa.eu/repository/handle/JRC137266. 3 From discovery to economic impact: Biotechnology Competitiveness for Europe, Vlaams Instituut voor

Biotechnologie, 2024

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Regulation (EU) 2024/1689 (AI Act)4, which entered into force in August 2024, lays down a

uniform legal framework in particular for the development, the placing on the market, the

putting into service and the use of AI systems and models in the Union, in accordance with

Union values, to promote the uptake of human centric and trustworthy AI. At the same time,

biotechnology introduces new biosecurity risks as the wider accessibility of these

technologies increases their potential for misuse, posing significant health threats. However,

divergent or absent national rules on screening biotechnology products with significant

potential for misuse, such as the synthetic DNA of dangerous pathogens, raise compliance

costs, fail to offer a level playing field to competitors, and weaken prevention.

Fragmentation and the complexity of the EU regulatory framework are factors that make

the EU less attractive for translating cutting-edge research and innovation into marketable

products. For instance, the global share of commercially sponsored clinical trials in the

European Economic Area has declined from 22% in 2013 to 12% in 2023, while China’s

share of commercial clinical trials rose from 5% to 18% in the same period, with the US share

remaining considerably more stable 5. Importantly, the overall reported decline in small

molecule trials suggests a strategic shift toward the development of biological medicines at

the expense of small molecule programs. The drop in the number of small molecule trials was

the most significant in Phase II trials from 62% in 2015 to 47% in 2024 and in Phase III trials

from 65% to 53% during the same period 6. In particular, the EU is losing ground to other

regions with increasingly agile regulatory and financial systems. Most of these regions issue

decisions on validated clinical trial applications within 60 days, whereas in the EU it takes on

average 113 days for multinational trials.

Highlight: the need to simplify and streamline the Clinical Trials Regulation (CTR)

Clinical trials in the EU are crucial to provide patients with early and equal access to

innovative treatments, uphold scientific excellence, and support the EU’s long-term

competitiveness and prosperity. By attracting investment in research and development

(R&D), creating jobs, and reducing healthcare costs, these trials deliver substantial economic

and societal benefits. They also significantly benefit patients by providing earlier access to

new therapies, including personalised therapies (e.g. for rare diseases and cancers), improving

quality of life, and strengthening the evidence base for clinical guidelines, marketing

authorisation and health technology assessments. The share of clinical trials with biological

medicines seems to be increasing at the expense of low molecule trials. Biological medicines

sales are key drivers of growth. In 2024, the European Union spent €228 Bn on medicines at

list prices, including €95 Bn on biological medicines, which now comprise 41% of total

pharmaceutical spending. Increased clinical trials in the Union for biological medicines could

potentially contribute to more manufacturing in the Union, higher number and earlier

regulatory submission of biological medicines for marketing authorisation applications and a

higher percentage of EU clinical data in marketing authorisation applications. A conducive

environment for clinical trials is essential to speed-up market access for novel medicines,

4 Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying

down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No

167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives

2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act) (Text with EEA

relevance), OJ L, 2024/1689, 12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj 5 European Federation of Pharmaceutical Industries and Association, Assessing the clinical trial

ecosystem in Europe (2024) assessing-the-clinical-trial-ecosystem-in-europe.pdf 6 Global Trends in R&D 2025 - IQVIA

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especially against global competition. There are still significant regulatory fragmentations

across Member States that limit the system’s efficiency. Against this background, further

regulatory streamlining and simplification of the authorisation and conduct of clinical trials

are imperative. This is a key point of the Draghi report on the future of European

Competitiveness 7, which highlights the need to address these inefficiencies, stressing the

importance of reducing regulatory delays and administrative burdens. It calls for harmonised

templates, stronger coordination between national ethics committees, and a greater emphasis

on using artificial intelligence (AI) and digital tools to streamline the process. At a time when

global competitors – particularly the US, China, and Japan – are rapidly improving their R&D

incentives and regulatory agility, Europe risks losing its competitive edge in clinical research.

The EU’s position in the global clinical trial landscape has already weakened, and immediate

action is needed to close this gap.

This is why a European Biotech Act was announced by the President of the European

Commission in the 2024 - 2029 Political Guidelines of the Commission 8, with the aim of

creating an enabling environment to make it easier to bring biotechnology products from the

laboratory to the factory and then onto the market, while maintaining the highest safety

standards for the protection of the population and the environment. As previously

acknowledged in the Communication on Biotechnology and Biomanufacturing (March 2024)

and the reports by Enrico Letta 9 (April 2024) and Mario Draghi 10 (September 2024), it is

necessary to address the challenges faced by EU companies, users and consumers to boost the

EU’s technological advancement, competitiveness and economic growth. In its resolution

‘Future of the EU biotechnology and biomanufacturing sector’ 11, the European Parliament

recommended ‘facilitating a fast and efficient uptake of biotechnology and biomanufacturing

through clear regulatory frameworks’. The European Parliament is now preparing an own-

initiative report on ‘Public health aspects of biotechnology and life sciences’ 12. More

recently, EU Member States urged the Commission to unlock the potential of biotechnologies,

by reducing fragmentation and simplifying the EU regulatory framework across policy

areas13.

Given the importance of health biotechnology amongst the other applications of

biotechnology as, it is appropriate that the European Biotech Act focusses on, and sets out

specific measures for, the health dimension of biotechnology. To ensure the effectiveness of

this proposal, its scope of application extends to health biotechnology in a comprehensive

manner and cover health within the wide meaning of Article 168 of the Treaty of the

Functioning of the European Union (TFEU) on the protection of public health. In this regard,

Article 168(1) TFEU emphasises that a high level of human health protection is to be ensured

7 Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,

European Commission, 9 September 2024. 8 European Commission (2024), Political Guidelines for the Next European Commission 2024-2029,

e6cd4328-673c-4e7a-8683-f63ffb2cf648_en 9 Enrico Letta (2024), Much more than a Market. Enrico Letta - Much more than a market (April 2024) 10 Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,

European Commission, 9 September 2024. 11 European Parliament (2025). Future of the EU biotechnology and biomanufacturing sector: leveraging

research, boosting innovation and enhancing competitiveness. Texts adopted - Future of the EU

biotechnology and biomanufacturing sector: leveraging research, boosting innovation and enhancing

competitiveness - Thursday, 10 July 2025 12 European Parliament: 2025/2087(INI) 13 Council of the European Union, A call for action on life sciences for the Union's competitiveness -

Council conclusions (approved on 30 September 2025) (13323/25).

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when defining and implementing all Union policies and activities. Article 168(4) TFEU

clarifies that this objective is, amongst others, to be pursued through measures setting high

standards of quality and safety for medicinal products and devices for medical use and of

organs and substances of human origin, blood and blood derivatives, measures in the

veterinary and phytosanitary fields which have as their direct objective the protection of

public health. Accordingly, and in line with the One Health approach, this Regulation should

apply to health biotechnology, understood as the application of biotechnology in the human

medical, veterinary, pharmaceutical and phytosanitary areas for the development of

biotechnology products and services. The Regulation should apply to their entire lifecycle,

including the related research, access to funding, development, innovation, testing, validation,

manufacturing, placing on the market and use activities.

The proposal for a European Biotech Act acknowledges the EU’s potential to be a global

leader. The region combines a highly skilled workforce, world-class scientific institutes,

innovative startups and scaleups, advanced infrastructure and large private capital pools that

could be used to support the domestic scale-up of promising companies. The proposal

therefore seeks to address the barriers hindering the development of the EU’s health

biotechnology sector, starting from early-stage research through to later-stage deployment and

scale-up. It introduces facilitation measures in the health biotechnology areas, including a

framework for the recognition of, and support for, health biotechnology strategic projects and

high impact health biotechnology strategic projects, aimed at reducing time-to-market, with

particular attention paid to the needs of small and medium-sized enterprises (SMEs), and

includes future-proofing provisions to anticipate the needs of health biotechnologies. Acting

decisively now will allow the EU to fully harness its fast-moving biotechnology sector,

reinforce strategic autonomy and economic security, and lay the foundations for a competitive

and forward-looking EU biotechnology sector.

With a view to ensure the effectiveness of the substantive provisions put forward in this

proposal, amendments to Union legislation in the areas of health and food and feed safety are

also established for regulatory simplification, that have an impact on innovation and the time

to market for biotechnology products and services, including where such legislation also

applies to products other than biotechnology products. In this regard, without an efficient,

accelerated and streamlined legislative framework for clinical trials in the Union, the other

measures in this Regulation, and in particular the framework for the recognition and support

of health biotechnology strategic projects and high impact biotechnology strategic projects

would be deprived of their effectiveness, as all health biotechnology medicinal products

require state of the art clinical research and a globally competitive regulatory framework for

clinical trials authorisation. Similarly, a timelier risk assessment process for products subject

to pre-market authorisation in accordance with Union food and feed legislation, including for

biotechnology innovations where pre-submission advice of the European Food Safety

Authority for aspects such as study design is paramount, as well as accelerated procedures are

needed for the effectiveness of the substantive facilitation measures put forward in this

proposal.

In a second stage, following this health-focused initiative, the Commission will address in

2026 the wider biotech ecosystem beyond health to ensure a competitive internal market for

all areas of biotechnology.

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Figure 3: Biotechnology and biomanufacturing sector in Europe, problem tree

• Consistency with existing provisions in the policy area

The European Biotech Act will seek to streamline the relevant EU legislative frameworks to

create an enabling environment for innovation and development in order to accelerate time to

market. With its primary focus on health, the present proposal will amend the Regulation on

clinical trials (CTR)14, the Regulation on advanced therapy medicinal products

(ATMPs)15, the Regulation on standards of quality and safety for substances of human

origin intended for human application (SoHO)16 and the Regulation on veterinary

medicinal products (VMPs) 17. In the field of food safety, the proposed measures are built on

the General Food Law18. The proposal will also amend the legislation on the deliberate

release of genetically modified organisms (GMO)19.

14 Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on

clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC Text with EEA

relevance, OJ L 158, 27.5.2014, pp. 1–76. ELI: http://data.europa.eu/eli/reg/2014/536/oj. 15 Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007

on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No

726/2004 (Text with EEA relevance), OJ L 324, 10.12.2007, pp. 121–137.

ELI: http://data.europa.eu/eli/reg/2007/1394/oj. 16 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 (Text with EEA relevance), OJ L, 2024/1938,

17.7.2024. ELI: http://data.europa.eu/eli/reg/2024/1938/oj. 17 Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on

veterinary medicinal products and repealing Directive 2001/82/EC (Text with EEA relevance), OJ L 4,

7.1.2019, pp. 43–167. ELI: http://data.europa.eu/eli/reg/2019/6/oj. 18 Regulation (EC) No 178/2002, of the European Parliament and of the Council of 28 January 2002

laying down the general principles and requirements of food law, establishing the European Food

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The proposal also considers other existing legislation that is being revised to ensure the

coherence of the overall EU regulatory system, in particular the Regulation on medical

devices (MDR) and the Regulation on in vitro diagnostic medical devices (IVDR) 20, as

well as the proposed simplification measures in food and feed safety legislation (food and

feed simplification package).

The Biotech Act will also exploit synergies with other EU legislation. It will complement the

Critical Medicines Act (CMA) 21 to strengthen EU-based biotechnology research and

manufacturing. The Act is also in line with the pharmaceutical strategy for Europe22 and

complements the ongoing revision of the EU pharmaceutical legislation23 to create the

appropriate conditions for biotechnology from the innovation stage. Moreover, the proposed

measures are complementary to the proposed regulation on plants obtained by certain new

genomic techniques and their use in food and feed.

• Consistency with other Union policies

As one of the flagship initiatives of the Competitiveness Compass24, the proposed Biotech

Act aligns with the EU’s broader innovation and competitiveness agenda, translating the

priorities of the Compass into concrete actions within the strategic sector of biotechnology.

In particular, the Biotech Act is part of the Commission’s life sciences strategy25. It was

presented as a central instrument to strengthen the Union’s biotechnology ecosystem,

streamline regulatory procedural pathways and boost Europe’s competitiveness in life

sciences, recognising biotechnology as a strategically critical and cross-sectoral technology.

Furthermore, the proposed Act is complementary to the other policy initiatives announced in

the Compass. First, it aims to improve access to later-stage capital for biotechnology firms,

Safety Authority and laying down procedures in matters of food safety, OJ L 31, 1.2.2002, pp. 1–24.

ELI: http://data.europa.eu/eli/reg/2002/178/oj. 19 Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the

deliberate release into the environment of genetically modified organisms and repealing Council

Directive 90/220/EEC - Commission Declaration, OJ L 106, 17.4.2001, pp. 1–39.

ELI: http://data.europa.eu/eli/dir/2001/18/oj. 20 Regulations (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical

devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No

1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance),

OJ L 117, 5.5.2017, pp. 1–175. ELI: http://data.europa.eu/eli/reg/2017/745/oj and (EU) 2017/746 of the

European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and

repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance), OJ L

117, 5.5.2017, pp. 176–332. ELI: http://data.europa.eu/eli/reg/2017/746/oj. 21 Critical medicines Act - Public Health - European Commission 22 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, Pharmaceutical Strategy for

Europe, COM/2020/761 final. 23 European Commission website, Reform of the EU pharmaceutical legislation 24 European Commission, European Competitiveness Outlook (Competitiveness Compass):

Competitiveness compass - European Commission 25 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, Choose Europe for life sciences A

strategy to position the EU as the world’s most attractive place for life sciences by 2030,

COM/2025/525 final.

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aligning with the start-up and scale-up strategy 26 and complementing the Scaleup Europe

Fund established under that strategy, as well as the Savings and Investments Union 27,

which seeks to mobilise larger pools of private capital, support investment within the EU, and

reduce financing costs for Union businesses.

Second, the provisions on biosecurity also reflect the Compass’s emphasis on talent as a

cornerstone of innovation and on the interdependence between economic strength and

security. In this context, the Act is consistent with the objectives put forward in the Union of

Skills 28 and contributes to EU security by reinforcing safeguards for dual-use

biotechnologies. It also complements the EU Regulation (EU) 2022/2371 on serious cross-

border threats to health 29, helping to ensure a coordinated Union-level response to health

risks that may arise from the misuse of emerging biotechnologies and to the strategic

technologies for Europe platform (STEP) 30 that also target biotechnologies.

Third, the emphasis on the use of AI in the proposed Act also aligns with the Competitiveness

Compass, and echoes the recent Apply AI strategy 31, the AI continent action plan 32, the

European AI Act 33 and the Data Union strategy 34, which stress the need to strengthen

Europe’s innovation capacity, technological competitiveness and secure, data-driven

ecosystems while supporting the biotechnology landscape.

Overall, the Biotech Act is also consistent with the vision for agriculture and food 35., as it

amends the General Food Law to broaden the scope of pre-submission advice provided by the

European Food Safety Authority (EFSA) to study design, and reforms the EFSA Panel system

to speed up risk assessment procedures.

26 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, The EU Startup and Scaleup

Strategy Choose Europe to start and scale, COM/2025/270 final. 27 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, Savings and Investments Union A

Strategy to Foster Citizens’ Wealth and Economic Competitiveness in the EU, COM/2025/124 final. 28 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, The Union of Skills, COM/2025/90

final. 29 Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on

serious cross-border threats to health and repealing Decision No 1082/2013/EU (Text with EEA

relevance), OJ L 314, 6.12.2022, pp. 26–63. ELI: http://data.europa.eu/eli/reg/2022/2371/oj. 30 Strategic Technologies for Europe Platform 31 Communication from the Commission to the European Parliament and the Council, Apply AI Strategy,

COM/2025/723 final. 32 https://ec.europa.eu/newsroom/dae/redirection/document/114523 33 Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying

down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No

167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives

2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act), OJ L, 2024/1689,

12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj. 34 Communication from the Commission to the European Parliament and the Council, Data Union

Strategy Unlocking Data for AI, COM(2025) 835 final. 35 Communication from the European Parliament, the Council, the European Economic and Social

Committee and the Committee of the Regions, A Vision for Agriculture and Food Shaping together an

attractive farming and agri-food sector for future generations, COM/2025/75 final

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Lastly, the proposed Act was informed by the preparation of upcoming and recent initiatives,

such as the future European Innovation Act 36 and the recently adopted bioeconomy

strategy 37, in order to ensure synergies.

Furthermore, climate change has shown the need to also prioritise the resilience of the Union,

including, for instance to focus on sustainable food systems, stronger health prevention and

innovative health solutions. In this context, biotechnology has been identified in the Farm to

Fork Strategy 38, which is a key component of the European Green Deal 39, as a technique

that is safe for consumers and the environment. The proposed Act is also consistent with the

European Commission’s objectives to achieve climate neutrality set out in the EU Climate

Law 40 and the Union’s Strategy on Adaptation to Climate Change 41.

In this context, the proposed European Biotech Act, including through its measures

supporting innovation, will accelerate the placing on the market of biotechnology products

that are adaptable to climate change, that contribute to health and food security through

sustainable biomanufacturing and to the protection of biodiversity. Such biotechnology

products have also the potential to replace products potentially more harmful for the

environment while providing great benefits for consumers and users. Biotechnology and

biomanufacturing will also need to comply with Union legislation in these areas, such as, the

Regulation concerning the Registration, Evaluation, Authorisation and Restriction of

Chemicals (REACH)42 or applying without prejudice to the provisions of Regulation (EU)

2024/1735 regarding sustainable biogas and biomethane technologies and biotechnology

climate and energy solutions43.

This also shows that the proposed Act is in line with the ‘do no significant harm’ principle.

The positive environmental impact of biotechnology and biomanufacturing was also

recognized by stakeholders in their responses to the Public Consultation.

36 European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-

your-say/initiatives/14593-European-Innovation-Act_en 37 European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-

your-say/initiatives/14555-Towards-a-circular-regenerative-and-competitive-bioeconomy_en 38 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, A Farm to Fork Strategy for a fair,

healthy and environmentally-friendly food system, COM/2020/381 final 39 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, The European Green Deal,

COM/2019/640 final. 40 Regulation (EU) 2021/1119 of the European Parliament and of the Council of 30 June 2021 establishing

the framework for achieving climate neutrality and amending Regulations (EC) No 401/2009 and (EU)

2018/1999 (‘European Climate Law’), OJ L 243, 9.7.2021, pp. 1–17. ELI:

http://data.europa.eu/eli/reg/2021/1119/oj. 41 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, Forging a climate-resilient Europe

- the new EU Strategy on Adaptation to Climate Change, COM/2021/82 final 42 Consolidated text: Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18

December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals

(REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing

Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council

Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and

2000/21/EC (Text with EEA relevance). ELI: http://data.europa.eu/eli/reg/2006/1907/2025-09-01 43 Consolidated text: Regulation (EU) 2024/1735 of the European Parliament and of the Council of 13

June 2024 on establishing a framework of measures for strengthening Europe’s net-zero technology

manufacturing ecosystem and amending Regulation (EU) 2018/1724 (Text with EEA relevance). ELI:

http://data.europa.eu/eli/reg/2024/1735/2025-08-17

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Finally, the proposed Biotech Act will support digital transformation in line with the

‘digital by default’ principle. One of its specific objectives is to “facilitate the application of

AI into the Union’s biotechnology and health technology manufacturing ecosystems and

frameworks, in line with Regulation (EU) 2024/1689”. The Act is expected, among others, to

support the use of data, digital platforms and analytical methodologies (e.g. reducing the need

for clinical data), in the development of biotechnology and in biomanufacturing.

Digitalisation will also be reinforced in networking cooperation of biotechnology clusters

(e.g. through the promotion of the development of infrastructure and digital platforms, and

AI-enabled technologies). Overall, accelerated digitalisation, in particular through greater data

use and AI integration, aims at contributing to the Union’s technological sovereignty.

Moreover, the proposed European Biotech Act will ensure coherence with relevant digital

policies, such as the Artificial Intelligence Act44, on development and testing of AI enabled

biotechnology solutions, as well as the EU Cybersecurity framework45, on access principles

and security safeguards.

2. LEGAL BASIS, SUBSIDIARITY AND PROPORTIONALITY

• Legal basis

The general objective of this Regulation 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 EU market, of biotechnology innovations, products

and services, (iii) while safeguarding high standards for the protection of human health,

animal health, patients and consumers, the environment, ethics, quality, food and feed safety,

and biosecurity.

This general objective translates into the establishment of measures to:

(i) strengthen the biotechnology sector and reinforce the EU’s research, development

and production capabilities, by establishing a framework for the recognition of, and

support measures for, strategic health biotechnology projects and high impact

strategic health biotechnology projects (pillar 1);

(ii) support funding of, investments in, and access to capital for, biotechnology

companies and projects, including through the setting up of an EU health

biotechnology investment pilot to fill the gap in spending on biotechnology

innovation (pillar 2);

(iii) improve the EU manufacturing capacity of, and expertise in biosimilars, including

through international cooperation (pillar 3);

44 Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying

down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No

167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives

2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act) (Text with EEA

relevance), OJ L, 2024/1689, 12.7.2024. ELI: http://data.europa.eu/eli/reg/2024/1689/oj 45 Regulation (EU) 2019/881 of the European Parliament and of the Council of 17 April 2019 on ENISA

(the European Union Agency for Cybersecurity) and on information and communications technology

cybersecurity certification and repealing Regulation (EU) No 526/2013 (Cybersecurity Act) (Text with

EEA relevance), OJ L 151, 7.6.2019, pp. 15–69. ELI: http://data.europa.eu/eli/reg/2019/881/oj

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(iv) facilitate the application of AI into the Union’s biotechnology and health technology

manufacturing ecosystems and frameworks, in line with the Regulation (EU)

2024/1689 (pillar 4);

(v) ensure a legislative framework that encourages innovation and takes account of

technological and scientific developments and progress, by establishing provisions

for health biotechnology products (pillar 5);

(vi) prevent the misuse of biotechnologies and strengthen biodefence capabilities (pillar

6).

(vii) enable the effectiveness of the measures under the pillars 1 to 6 through a legislative

framework conducive to the use of biotechnology innovations, by amending Union

legislation in particular on clinical trials, veterinary medicinal products, food and

feed safety and related legislation (pillar 7).

The appropriate legal basis is therefore as follows:

– Article 114 of the Treaty on the Functioning of the European Union (‘TFEU’) which

allows the EU to take measures that increase harmonisation and remove

fragmentation to create a level playing field within, and fully exploit the scale of, the

EU single market, so that the health biotechnology and biomanufacturing sectors can

thrive. In accordance with Article 114(3) TFEU, the proposal seeks to achieve the

objective of a high level of health and safety protection.

– Article 168(4) TFEU, which mandates the Union to contribute to the achievement of

a high level of human health protection through the adoption - in order to meet

common safety concerns - of (i) measures setting high standards of quality and safety

of organs and substances of human origin, blood and blood derivatives; (ii) measures

in the veterinary and phytosanitary fields which have as their direct objective the

protection of public health; and (iii) measures setting high standards of quality and

safety for medicinal products and devices for medical use.

– Article 173(3) TFEU, which allows the Union to decide on specific measures in

support of action taken in the Member States to ensure the conditions necessary for

the competitiveness of the Union’s industry, excluding any harmonisation of the laws

and regulations of the Member States. This article provides a legal basis for the

provisions in this Regulation regarding the EU health biotechnology investment

pilot, establishing the basis for future Union financial support together with

implementing partners, to support the financing of, and investments in, companies

and projects falling within the scope of the European Biotech Act.

• Subsidiarity (for non-exclusive competence)

The objectives of the proposal cannot be achieved by Member States acting alone, as the

issues tackled are of a cross-border nature and are not limited to single Member States or to

several Member States. 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.

Furthermore, the market drivers identified are shared across the Member States, affecting the

functioning of the single market and the global competitiveness of EU companies. Access to

finance is scattered across the EU and EU companies lack the capacity to access private

finance at a competitive scale, including at later stages of development. Similarly, European

biotechnology clusters are scattered across the EU, without sufficient continental scale to

compete globally. The development and deployment of AI solutions for biotechnology

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remains limited, also due to the low level of storage, access and sharing of data relevant for

biotechnology in the EU, including across borders. There is also a clear need across the EU to

attract, reskill and upskill the workforce.

Moreover, while several Member States have taken action to boost innovation in

biotechnology, the above-mentioned bottlenecks persist; improvements are expected to take

considerably more time and without achieving the levels needed to compete at global level.

For example, access to finance would remain scattered at EU level. The growth of clusters in

the EU would also remain limited, without sufficient benefits from cross-border connections.

Lastly, important regulatory barriers faced by European biotechnology companies stem from

EU legislation. Therefore, with a view to enable the effectiveness of the substantive measures

put forward in this proposal, it is proposed to simplify EU legislation in the area of health and

of food and feed safety to make it easier to innovate and place biotechnology products and

services on the Union market and to enhance legal clarity.

• Proportionality

The selected measures under the industrial policy and substantive part of the proposal are

targeted at the specific areas of interventions listed below.

– The provisions on strategic health biotechnology projects and high-impact strategic

health biotechnology projects are proportionate to the aims pursued, including by

recognising the first category of projects at Member State level, and the second

category at EU level on the basis of an assessment at Member State level. Moreover,

the recognition of such projects is based on clear criteria tailored to ensure that

projects that contribute substantially to the Union’s competitiveness, resilience, and

security fall within the enhanced support regime. Moreover, the recognition of such

projects does not restrict Member States’ ability to support additional projects

through other instruments. Member States benefit from flexibility as regards the

authorities that they intend to designate to recognise strategic health biotechnology

projects and assess applications for high-impact strategic health biotechnology

projects. This flexibility also applies to the single points of contact and the provision

of administrative, technical, and financial support, in line with Union law and the

national systems. Accelerated permitting timelines apply only to recognised projects

and are designed to streamline procedures without lowering any environmental,

health or safety standards.

Similarly, measures aimed at supporting networking among health biotechnology clusters are

limited to what is necessary to foster synergies in the internal market, while the EU Health

Biotechnology Support Network is aiming to build on and complement existing national and

EU structures, avoiding any duplication.

– On access to funding, the interventions focus on measures mobilising public funding

and private capital; public funding needs to be in line with State aid rules.

– The proposed interaction modalities with Member States in the context of a

European Health Biotechnology Steering Group allows for priorities to be adjusted,

including by ensuring that the support measures for strategic health biotechnology

project and high-impact strategic health biotechnology projects remain closely

aligned with the Regulation’s general objective.

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The proposed amending provision aimed at reducing the time-to-market of biotechnology

products and services focus on certain sectoral Union legislation where room for

simplification of regulatory and administrative complexities has been identified.

Simplification relates to changes that are necessary with a view to secure the effectiveness of

the substantive provisions put forward in this proposal and will improve the legal clarity,

certainty, and overall efficiency of the concerned EU legislative frameworks.

• Choice of the instrument

The proposal takes the form of a regulation of the European Parliament and of the Council.

A regulation is the most suitable legal instrument for Pillars 1 to 4, given the need for a

uniform application of the new rules, in particular the conditions and procedure for

recognising heath biotechnology strategic projects and high impact health biotechnology

strategic projects, and for their administrative, technical and financial support, and also more

broadly for companies and non-profit organisations active in the relevant biotechnology

sectors across the internal market. This is also the case for Pillar 5, regarding the provisions

on biotechnology health products, given that they aim to ensure a dialogue and more

flexibility across the Union legislative frameworks in the area of health. The choice of a

regulation as a legal instrument is also appropriate for Pillar 6 because only a regulation, with

its directly applicable legal provisions, can provide the necessary degree of uniformity needed

to boost EU biodefence and biosecurity and prevent biotechnology misuse.

In all cases, the choice of the instrument is justified considering that the Pillar 7 establishes

provisions amending several existing Union regulations in the area of health and food and

feed safety.

Lastly, a regulation is appropriate for the provisions regarding on evaluating this Regulation

which do not need to be transposed through national measures and are directly applicable.

3. RESULTS OF EX-POST EVALUATIONS, STAKEHOLDER

CONSULTATIONS AND IMPACT ASSESSMENTS

• Ex-post evaluations/fitness checks of existing legislation

The proposed measures amend several pieces of EU legislation in a targeted manner, without

modifying their objectives, the overall regulatory framework put in place or their functioning.

When relevant, these measures were informed by several studies or ongoing evaluations, such

as the ongoing evaluation of the EFSA. Regarding the Clinical Trials Regulation, an ongoing

study will contribute to the Commission’s report, which will be presented five years after the

application date of the legislation (1 January 2022).

The extensive consultation process and a comprehensive supporting study identifying over

200 regulatory challenges stemming from EU legislation have gathered evidence on the

challenges and problems, the relevant provisions of the legislation, and issues for which there

is no legislation.

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• Stakeholder consultations

Extensive stakeholder consultations were carried out to prepare for the proposal. A call for

evidence 46, opened for feedback from 14 May to 11 June 2025, gathered 222 valid individual

contributions47 from a wide range of stakeholders: business associations 48 (63), companies

(50), non-governmental organisations (NGOs) (44), academic and research institutions (20),

public authorities in the EU (14), EU citizens (14) and other categories (17) 49.

Figure 4: submissions to the call for evidence

The respondents were largely based in the EU (197 responses from 15 Member States).

Among these, most of the contributions came from Belgium (74), followed by Germany, (29),

France (20), the Netherlands (16), Denmark (12) and Spain (11). 25 contributions were

received from 7 non-EU countries (the United States, Switzerland, the United Kingdom,

Norway, Canada, Australia and Argentina).

With regard to current biotechnology related regulation, various stakeholder groups such as

academic/research institutions, NGOs, representatives of companies (including SMEs), and

public authorities underlined slow and complex regulatory frameworks that lead to long

authorisation/approval processes, thereby hindering innovation and delaying market access.

Representatives from businesses (both associations and large companies) referred to the

unpredictability of some authorisation procedures. Representatives from

academic/research institutions and business associations also expressed concerns regarding

outdated regulatory frameworks, while business associations mentioned in particular the

limited flexibility of the EU regulatory frameworks. In addition, NGOs/others, large

companies and SMEs, business associations and trade unions agreed that divergent national

rules and interpretation/implementation of EU rules create fragmented market entry

46 European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-

your-say/initiatives/14627-Biotech-Act_en 47 Three submissions were received from a single respondent and have been counted as one response. Two

submissions were received from another respondent and have been counted as one response. 48 Three respondents that selected trade unions are analysed together with business associations as

representing the industry. 49 In the analysis, they are grouped together with feedback from NGOs.

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conditions. Feedback from small companies indicated high regulatory costs as a result of the

regulatory fragmentation, while public authorities also acknowledged high compliance costs.

Lastly, some feedback pointed to inconsistencies between EU legislative frameworks, in

particular the CTR, ATMPs Regulation, MDR/IVDR, REACH Regulation and the General

Data Protection Regulation (GDPR).

Most stakeholders also indicated a shortage of risk-tolerant capital. Stakeholders highlight

fragmented funding schemes, limited early-stage financing, and low EU venture capital

share compared to the US and China. For instance, representatives from academic/research

institutes indicated that the EU’s venture capital accounted for only about 5% of global

venture capital. Representatives of large companies particularly underlined public R&D

under-investment, indicating poor alignment across policies and programmes. Some

contributions from NGOs/others also indicated the risk of dependence on foreign capital,

particularly in health and defense-related biotechnologies.

Stakeholders stressed the fundamental role of education and skills for the biotechnology and

biomanufacturing workforce. Stakeholders expressed concerns about talent drain and global

competition. This is exacerbated by existing regulatory and mobility barriers that hamper

cross-border and cross-sector mobility, as indicated in feedback from academic/research

institutions. In addition, stakeholders underlined the limited entrepreneurial pathways from

academia to company building. Moreover, many stakeholders experienced shortages in the

specialised and interdisciplinary competences needed for the biotechnology and

biomanufacturing workforce. Other limitations mentioned were an insufficient number of

STEM graduates, the lack of funding or low investment in life-long learning (e.g. digital, AI

competencies), and unequal access to upskilling programmes.

Stakeholders across all groups (including academic/research institutions, business

associations/trade unions, large companies, citizens, as well as NGOs/others and public

authorities) stressed the limited manufacturing capabilities in the Union. Some of the

underlying factors mentioned were, among others, the high costs, infrastructure and

investment gaps, limited digitalisation, supply chain vulnerabilities, and the fragmented

regulatory frameworks. SMEs underscored this statement, also pointing to the challenges

related to lack of recognition for quality control technologies.

Furthermore, incubation and acceleration limitations in the EU were mentioned. Many

stakeholder groups, such as academic/research institutions, large companies, NGOs/others

and public authorities, highlighted the need to bridge the gap between research and industry in

Europe’s biotechnology ecosystem. They expressed concerns on the barriers faced in

incubation and acceleration, such as funding gaps in early stages, a fragmented support

landscape, regulatory burdens, hindrances in public-private collaboration and cultural/skill

barriers. Business associations’ and public authorities’ feedback was in line with this

statement, underlining that the EU lacks cohesive pathways to commercialisation. Large

companies specifically pointed out the lack of financial and administrative capacity of SMEs

and start-ups to access EU-level funding or to protect their intellectual property.

Stakeholders overall recognised the pivotal role of AI and data to advance biotechnology. As

part of the challenges faced however, academic/research institutions and large companies

indicated a lack of access to data and secure data sharing, fragmented data ecosystems

including limited data interoperability, unclarity on data governance and insufficient

coordination. Business associations and public authorities also mentioned fragmented

computing power and uneven access to testing infrastructures. Furthermore, SMEs

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referred to a lack of information and knowledge among companies about AI implementation

and compliance. Feedback from NGOs/others overall echoed these statements, while also

advocating to take into consideration the environmental impact of AI infrastructures. Most

stakeholders additionally pointed out regulatory fragmentation, technical and legal barriers,

innovation barriers, and governance gaps. AI skills shortages were also mentioned by several

stakeholder groups, as well as ethical uncertainties.

Finally, on biosecurity, stakeholders mentioned that while biotechnology and

biomanufacturing offer transformative opportunities across multiple application areas, these

must be governed by policies that balance innovation with safety, equity, and environmental

protection. Various challenges were pointed out by different stakeholder groups in relation to

biosecurity. For instance, academic/research institutions, NGOs and public authorities

mentioned a fragmented biosecurity governance and regulatory complexity as major

issues. Specifically, disjointed EU and national regulations that hinder coherent biosecurity

frameworks were highlighted. Public authorities furthermore indicated limited collaboration

as a key challenge – for instance gaps in cooperation between national authorities and limited

cross-border collaboration. Regarding nucleic acid screening, academic/research institutions,

and NGOs mentioned inconsistent compliance in screening due to current voluntary systems

as a threat to biosecurity. Finally, dual-use risks were mentioned by SMEs and NGOs.

A public consultation 50 was carried out from 4 August to 10 November 2025. A total of 359

contributions were received. No duplicates or campaigns were identified. The contributions

considered for the analysis 51 were submitted by 91 companies/businesses and 61 business

associations, 47 NGOs, 44 academic/research institutions, 54 EU citizens and 9 non-EU

citizens, and 21 public authorities. A further 2 contributions were submitted by 2 trade unions,

2 consumer associations, and 1 by an environmental organisation 52, while 27 additional

respondents identified themselves as ‘Other’.

50 European Commission ‘Have your say’ website: https://ec.europa.eu/info/law/better-regulation/have-

your-say/initiatives/14627-Biotech-Act/public-consultation_en 51 Four trade unions were analysed under business associations. 52 In the statistics, the 2 trade unions, 2 consumer organisations and the environmental organisation are

reflected with the respondents who identified themselves as ‘other’.

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Figures 5 and 6: submissions to the public consultations and industry submissions per

company size

Concerning the industry sector, most of the contributions came from SMEs (53 in total out

of which 12 medium-, 17 small-, and 24 micro-sized SMEs) and 38 contributions came from

large enterprises. Of the contributing public authorities, 8 had a national remit and 8 had a

regional scope, 2 of them were local authorities and 3 were international organisations.

As part of all contributions received, 16 respondents identified as private investors,

including 13 from the EU and 3 from outside of the EU (Switzerland and the UK). Most of

them identified as company/business. When asked about the type of investment they

provided, 8 stated that they provided ‘Venture capital’, 5 chose ‘Business Angel’, 4 ‘Private

equity’, 3‘Corporate Venture Capital (CVC)’, and 1 ‘Other’.

Lastly, 43 respondents of all contributions received indicated being part of a cluster or of a

cluster organisation. These represented 26 companies/businesses, 15 business associations, 1

NGO and 1 ‘Other’.

There is a strong overall interest from stakeholders to the biotechnology sector and

acknowledgment of its great potential, in line with the EU’s economic, social and

environmental policy goals. More precisely, a strong majority of respondents agreed that

biotechnology and biomanufacturing products could positively impact the EU’s economy and

the society, also recognizing its contribution to the environment 53. Respondents considered

biotechnology and biomanufacturing products that reached the EU market to be safe and

secure 54. However, they did not consider that information to users and consumers 55 on

biotechnology and biomanufacturing products in the EU was sufficiently accessible and

broadly communicated. Moreover, only a minority of respondents were willing to pay a price

premium for such products56.

Answers to the public consultation on the EU regulatory framework were in line with the

focus of the proposed Act. The main regulatory barriers 57 identified by stakeholders

concerned the assessment and obtaining authorisation to market products, followed by

the pre-commercial testing or clinical trials stage, in commercialising products as well as

in the scaling-up production or manufacturing and product development.

Another finding of the public consultation relates to the perception of the EU regulatory

environment compared to that of some countries outside the EU. The EU regulatory

environment is perceived by some stakeholders to have a lower level of predictability58 and

it is also seen as more complex and unclear 59, leading to more compliance costs 60 and

53 Positive economic impact: 90.3% strongly agreed/agreed (324/359); Positive social impact: 89.7%

strongly agreed/agreed (322/359); Positive environmental impact: 80.2% strongly agreed/agreed (288/359)

54 76.3%: 175 strongly agreed, 99 agreed (out of 359). 55 28.1%: 30 strongly agreed, 71 agreed (out of 359). 56 15.6%: 13 strongly agreed, 43 agreed (out of 359). 57 Agreement/strong agreement on these barriers ranged from 63% to 76%. 58 More predictable: 40.8%: 45 strongly disagreed/92 disagreed (out of 336). 59 Less complex and clearer: 64.6%: 99 strongly disagreed/116 disagreed (out of 333).

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slower access to the market 61. Views on whether the EU regulatory environment ensures a

higher level of safety and security were rather mixed 62. Public authorities (57,9%, 11/19),

NGOs (46,5%, 20/43), other stakeholders (48,5%, 15/31) and academic/research institutions

(42,9%, 18/42) had a positive stance.

These findings underscore the urgent need to take action to simplify and streamline the

regulatory environment, making it flexible and innovation-friendly so that biotechnology

products and services can reach the EU market more quickly.

Furthermore, respondents reported low level of access to private investments in the EU, in

particular in accessing to publicly listing, private equity, debt financing, venture capital (VC)

across series B (expansion stage) and C (growth stage) and capital markets/shareholders 63. It

should be noted that stakeholders also expressed low level of accessibility to some public

funding, especially for support for capacity expansion, debt/equity instruments, and

commercialisation support64. Stakeholders indicated less difficulties in accessing strategic

research or sales partnerships/collaborations, angels, venture capital at start-up/early-stage

(series A) and corporate funding 65 and public grants and subsidies 66.

When asked about the factors driving forward investments in a biotechnology company,

there were no major differences in the answers. Some factors scored highly, which are (i)

groundbreaking technology; (ii) regulatory certainty; (iii innovative science; (iv) scientific

evidence; (v) experienced management team; and (vi) sufficient protection of intellectual

property rights 67.

On clusters, the five main barriers faced by EU biotechnology clusters and/or cluster

organisations preventing them from reaching their full potential were identified as: (i)

insufficient financial support; (ii) insufficient public support; (iii) incapacity to reach a critical

mass of stakeholders; (iv) insufficient start-up incubators or business support infrastructure;

and (v) insufficient collaboration among existing clusters68.

Stakeholders identified the main challenges impacting the EU biomanufacturing sector as: (i)

global competition; (ii) length and/or complexity of permitting processes for new facilities;

(iii) difficulty of scaling up from pilot to industrial production; (iv) high energy costs; and

(v) the high cost of raw material and/or of the operations69. A majority of respondents also

agreed that major challenges are also posed by the inconsistent environmental and

sustainability policies, vulnerabilities in the supply chains and other operational costs70.

60 Leads to lower costs for complying with the regulation: 62%: 98 strongly disagreed/109 disagreed (out

of 334). 61 Enables biotechnology and biomanufacturing products to reach the market faster: 65.7%: 126 strongly

disagreed/92 disagreed (out of 332) 62 Ensures a higher level of safety and security: 21.4% disagreed/strongly disagreed. (72/337) 36.8%

agreed/strongly agreed (124/337). 41.8% were neutral or Not applicable/I don’t know (141/337). 63 Agreement/strong agreement that there is easy access to these options ranged from 3.9% to 6.7%. 64 Agreement/strong agreement that there is easy access to these options ranged from 4.2% to 5.6%. 65 Agreement/strong agreement that there is easy access to these options ranged from 11.4% to 21.2%. 66 Agreement/strong agreement that there is easy access was 19.2% (69/359). 67 Agreement/strong agreement on these factors ranged from 72.4% to 79.9%. 68 Agreement/strong agreement on these barriers ranged from 46.2% to 58.5%. 69 Agreement/strong agreement on these challenges ranged from 58.2%% to 66.9%. 70 Agreement/strong agreement on these challenges ranged from 50.1% to 51.5%.

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The public consultation also confirmed the challenges faced by the EU workforce.

Stakeholders’ views were aligned on three main challenges: (i) the limited financial,

entrepreneurial skills and mindsets; (ii) the insufficient regulatory and quality assurance

expertise; and (iii) the shortage of vocational skills71.

Some stakeholders indicated having difficulties accessing or using data for the development

of biotechnology or biomanufacturing products72. Stakeholders also emphasised that

technological challenges and challenges in the implementation of regulatory frameworks were

the main barriers to both the use of AI in R&D73 and to the deployment of AI-based

biotechnology products74. When asked about the types of support needed for

biotechnology companies, in particular for SMEs, stakeholders stressed (i) skills

development and AI training; (ii) access to annotated datasets; (iii) partnerships with public

research institutions or AI hubs/factories; (iv), dedicated funding instruments; and (v)

regulatory sandboxes for testing biotech-related AI models75.

When it comes to the application of biotechnology in defence and security, the main

challenges identified by stakeholders were: (i) the risks to strategic autonomy in

biomanufacturing (and availability of medical and non-medical countermeasures); (ii)

cybersecurity risks to biotechnology infrastructure and AI tools used in biotechnology; (iii)

vulnerabilities in the resilience of biotechnology supply chains; and (iv) threats related to

biosecurity and biosafety including misuse of biotechnology76. The four main opportunities

that biotechnology for defence and security were creating were: (i) to develop new innovative

medical countermeasures; (ii) to facilitate detecting biological and chemical threats, (iii)

to increase food security; and (iv) to develop materials with new functions and / or

improved characteristics77.

In addition, targeted consultation activities were carried out, as detailed below, including in

the context of an external study announced in the Commission Communication ‘Building the

future with nature: Boosting Biotechnology and Biomanufacturing in the EU’ (Action 1)78.

First, the following consultation activities took place on the analysis of regulatory problems

and challenges faced by the biotechnology sector and on the mapping of applicable EU and

national legislations to biotechnologies:

• survey for public authorities;

• survey for other stakeholders, including industry representatives and patient

organisations;

71 Agreement/strong agreement on these challenges ranged from 51.8% to 58.5%. 72 21.4% replied partially (77/359) and 18.4% replied Yes (66/359) totalling 39.8%. However 44% replied

Not applicable/I don’t know (158/359 answers) and 16.2% replied No (58/359). 73 Technological challenges:61.3%%: 65 strongly agreed/155 agreed (out of 359); challenges in the

implementation of regulatory frameworks: 59.1%: 81 strongly agreed/ 131 agreed (out of 359). 74 Technological challenges:51.5%: 63 strongly agreed/122 agreed (out of 359); challenges in the

implementation of regulatory frameworks: 52.1%: 81 strongly agreed/106 agreed (out of 359). 75 Agreement/strong agreement on the needed types of support ranged from 59.1% to 65.5% 76 Agreement/strong agreement on the four main challenges ranged from 42.3% to 51.5% 77 Agreement/strong agreement on the three main opportunities ranged from 43.7% 48.2%. 78 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.

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• interviews with representatives of SMEs and large enterprises, and representatives of

the spin-off, alliance/platform, scale-up and EU association sectors;

• five thematic workshops covering (i) health/pharma; (ii) agriculture/environment;

(iii) food and feed; (iv) bio-based chemicals and plastics; and (v) bio-based materials.

Second, to analyse the impacts of identified policy provisions, evidence was collected on the

impacts of these provisions.

On clinical trials, evidence has been collected (by November 2025) through:

• three workshops organised by the European Commission in June, September, and

November 202579, with representatives of national competent authorities and ethics

committee members from across the EU to exchange views with experts to inform

how policy options would be defined;

• targeted interviews;

• targeted survey to various stakeholder groups:

• a survey targeted to sponsors and clinical research organisations received

48 responses 80.

• another targeted survey collected views from 44 public authorities

representing 25 EU/EEA countries81.

• a survey tailored to patient representatives received 1 response from a

disease-specific patient representing an organisation at national level.

Evidence on the impacts of options on genetically modified microorganisms was collected

through 25 interviews (by November 2025).

Finally, targeted consultation activities were also conducted as part of the supporting study

for the evaluation of EFSA.

• Collection and use of expertise

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’82 and in the

Draghi83 and Letta84 reports.

79 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. 80 32 from commercial sponsors, 6 from non-commercial sponsors, 3 from Clinical Rresearch

Organisations (CROs), and 7 from other stakeholders such as non-profits, hospital owners, advocacy

groups, research infrastructures, trade associations and life sciences providers 81 20 responses from ethics committees, 20 from national competent authorities, 3 from ministries or

government bodies, and 1 from a respondent identified as both a ministry and an ethics committee 82 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. 83 Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,

European Commission, 9 September 2024.

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In addition, the above-mentioned external study commissioned by the European Commission

(‘Analysis of the Regulatory Framework for Biotechnology and Biomanufacturing in the

EU’) provides an extensive 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 the challenges, their causes and the consequences

for stakeholders. The study also assesses the impacts of policy options related to the EU

regulatory framework.

• Impact assessments

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’s

adoption. Instead, an analytical staff working document (SWD) will be prepared. The

analytical SWD will explain the proposal and will present the underlying evidence and impact

analysis, including cost-benefit analysis. A large number of provisions of the proposal

concern simplification measures which typically do not offer viable alternatives and do not

modify the objectives of the amended legislation. Nevertheless, the proposed measures are

based on extensive stakeholder consultations, complemented with an analysis of the current

situation to ensure a transparent, proportionate, and evidence-based approach.

• Regulatory fitness and simplification

The proposal lays down measures to strength the EU biotechnology and biomanufacturing

ecosystem and reduce time-to-market for biotechnology products in the EU.

The proposed Act aims to simplify the existing regulatory framework and remove

regulatory burdens hampering the innovation and competitiveness of EU operators. In

particular, the measures seek to clarify and reduce procedural timelines across the full

development cycle (e.g. by alleviating complex and disproportionate requirements) and

provide a flexible regulatory environment for a fast-growing innovative sector (e.g. through

regulatory sandboxes and by enabling an increasing use of data and AI). As such, all actors, in

particular companies, will benefit from a more predictable EU regulatory framework, i.e.

increased legal certainty, reduced procedural timelines, and a flexible and collaborative

regulatory environment. Overall, these measures are expected to enable companies to bring

innovation to the market. SMEs in particular are expected to benefit from these measures

through reduced entry barriers in the field of biotechnology. The supporting measures also

target the needs of SMEs, start-ups and scale-ups.

National and regional authorities will benefit from streamlined, more coherent procedures

and improved coordination, reducing duplication of work, and supporting more consistent

regulatory decisions across the Union.

The proposed measures are targeted amendments that preserve the objectives of the existing

regulations to maintain and safeguard a high level of protection of health and the

environment. Similarly, measures to prevent the misuse of biotechnologies and strengthen

EU biodefence capabilities, including monitoring AI-enabled biological risks, will ensure that

innovation is accompanied by robust safeguards for public health and security.

84 Enrico Letta (2024), Much more than a Market. Enrico Letta - Much more than a market (April

2024)https://www.consilium.europa.eu/media/ny3j24sm/much-more-than-a-market-report-by-enrico-

letta.pdf

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Furthermore, EU biotechnology businesses, and in particular those with the potential to be

transformative for the biotechnology ecosystem are expected to have improved access to

capital throughout the different stages of their development and better access to the

infrastructure needed to assess the industrial potential of their innovation, thus contributing to

a thriving biotechnology and biomanufacturing ecosystem in the EU. Strategic biotechnology

projects, which the proposal aims to foster, may also include activities addressing the growing

skills gap in biotechnology and biomanufacturing and are expected to contribute to a

workforce capable of supporting innovation, industrial scale-up and long-term

competitiveness. Investors and financial intermediaries will benefit from a more predictable

pipeline of projects and clearer regulatory certainty, supporting greater availability of risk-

tolerant capital in the EU.

The initiative will foster, in line with the Union policy and legislation on AI, the use of AI

across the biotechnology ecosystem, giving companies – and more particularly SMEs –

more guidance and opportunities to integrate trustworthy, high-quality AI solutions into

research, testing and production processes.

End-users, including patients and citizens will benefit from biotechnology products that

meet their needs. Faster time-to-market and, improved clinical-trial performance are expected

to result in earlier access to safe, effective, high-quality and affordable biotechnology

products, including advanced therapies, diagnostics, biosimilars and innovative

biomanufactured products which will also benefit healthcare systems.

Overall, these targeted measures combined are expected to (i) facilitate the growth of the EU

biotechnology and biomanufacturing industry in the EU; (ii) improve the global

competitiveness and innovation capacity of the EU’s biotechnology companies; and (iii)

increase the EU’s strategic autonomy in critical technological areas.

• Fundamental rights

The Act respects the fundamental rights and principles laid down in the Charter of

Fundamental Rights of the European Union85.

The proposed measures simplifying EU legislation and the new initiatives on EU industrial

policy are expected to contribute to the smooth functioning of the internal market and, in

particular, support the freedom to conduct a business (Article 16 of the Charter). The

measures under this proposal seek to enable innovation, expand the EU’s manufacturing

capacity and clarify procedures for biotechnologies to reach the market. The proposed

measures will also ensure a high level of human health protection and will enhance the right

of access to preventive healthcare and the right to benefit from medical treatment under the

conditions laid down by national laws and practices, as provided in Article 35 of the Charter.

Similarly, the proposal will help ensure a high level of environmental protection and improve

the quality of the environment, in line with Article 37 of the Charter.

4. BUDGETARY IMPLICATIONS

Without prejudice to the outcome of the negotiations on the next Multiannual financial

framework (MFF) proposal, strategic health biotechnology projects and high-impact strategic

85 Charter of Fundamental Rights of the European Union,

ELI: http://data.europa.eu/eli/treaty/char_2012/oj

EN 23 EN

biotechnology projects may be supported by Union programmes, funds and instruments, in

accordance with the objectives set out in the regulations establishing those funds and

programmes. A contribution is expected to come from the “health, biotechnology, agriculture

and bioeconomy” window under the European Competitiveness Fund which, according to the

proposal of the Commission, would receive a total allocation of EUR 20.4 billion over the

MFF 2028-2034. Two agencies, EMA and EFSA are proposed to be reinforced in staff and

financially to conduct tasks related to these projects. The necessary financial resources will be

compensated from applicable programmes under the agencies' headings in the 2028-2034

MFF and where possible by additional income to be generated from third parties. The

Legislative Financial and Digital Statement (LFDS) also presents estimated budgetary impact

under Heading 4 including related human and administrative resources.

5. OTHER ELEMENTS

• Implementation plans and monitoring, evaluation and reporting arrangements

In the short term, implementation will focus on completing the strategic mapping of the

Union’s biotechnology ecosystem within six months of the Regulation’s entry into force, and

on setting up the new governance and support structures, including the EU Health

Biotechnology Support Network, the Foresight Panel for Emerging Health Innovation and the

European Health Biotechnology Steering Group. To support Member States in implementing

the Regulation, to promote a uniform application of the Regulation and to clarify technical or

operational elements where needed, the Commission may issue guidance on specific matters,

including the criteria and procedures for recognising strategic health biotechnology projects

and high-impact health biotechnology strategic projects, and the coordination between the EU

Health Biotechnology Support Network and other relevant networks. Member States will be

required to designate national single points of contact and begin applying the streamlined

regulatory procedures.

Monitoring will rely on the strategic mapping as a continuous evidence base, complemented

by regularly updated information on the list of strategic health biotechnology projects and

high-impact health biotechnology projects.

In the medium term, the strategic mapping of the biotechnology ecosystem will be updated

periodically and used to inform project selection and guide the deployment of Union support.

Five years after the Regulation’s entry into application, and every five years thereafter, the

Commission will evaluate the Regulation’s effectiveness and impact, and report its findings to

the European Parliament, the Council, the European Economic and Social Committee and the

Committee of the Regions.

• Detailed explanation of the specific provisions of the proposal

Chapter I – Subject Matter, Scope and Definitions

This Chapter sets out the subject matter of this proposal, which consists of measures that

articulate its overall objective (i) to improve the functioning of the internal market by

establishing a framework to strengthen the competitiveness of the biotechnology sector, from

research to production, (ii) to create the conditions for the development and timely placing on

the Union market, of biotechnology innovations, products and services, (iii) while

safeguarding high standards for the protection of human health, animal health, patients and

consumers, the environment, ethics, quality, food and feed safety, and biosecurity. This

Chapter also specifies the scope of the proposal, which applies to health biotechnology

EN 24 EN

products and services during their entire lifecycle, including related activities on research,

funding, development, innovation, testing, validation, manufacturing, placing on the market

and use. Lastly, this Chapter establishes definitions for key terms used throughout the

proposal, including ‘biotechnology’, ‘health biotechnology’, ‘biotechnology product’,

‘biotechnology service’ and ‘biomanufacturing’.

Chapter II – Union health biotechnology and biomanufacturing

This Chapter introduces the concepts of health biotechnology strategic projects and high

impact health biotechnology strategic projects and establishes a framework for the recognition

and the support of such projects aimed at strengthening the EU’s industrial biomanufacturing

capacity and value chains. Strategic projects should mobilise and focus action at Union and

Member State level, including on public and private investments and accelerated permitting

and other support measures, to boost Europe's competitiveness and resilience in

biotechnology. To build a strong EU biotechnology ecosystem, provisions are included to

encourage pro-competitive collaboration between projects, networks and clusters. These

measures are to be underpinned by a strategic mapping of the Union’s biotechnology

ecosystem to identify capacities, gaps, dependencies and investment needs, thereby guiding

the prioritisation of strategic and high-impact projects and informing Union policy and

funding decisions. This Chapter also sets up an EU health biotechnology support network of

national and regional antennas to support biotechnology projects and innovators in navigating

regulatory procedural pathways relevant to health biotechnologies and identifying

opportunities for funding, scaling up and networking, leveraging and complementing the

activities of existing national and European networks that support SMEs, start-ups and scale-

ups, and innovators.

Finally, this Chapter establishes the European Health Biotechnology Steering Group,

composed of representatives of Member States and the Commission and its tasks, which

include facilitating communication among Member States, the Commission, and various

stakeholders to ensure biotechnology projects are recognised and implemented effectively.

Chapter III – Access to funding

This Chapter establishes an EU health biotechnology investment pilot in partnership with the

European Investment Bank Group and other implementing partners, which brings together

equity instruments and venture-style debt tailored to biotechnology-specific risk profiles, in

order to mobilise private investment into the sector. Projects contributing to an EU late-stage

Capital Booster Pilot will be recognised by the Commission as high-impact strategic health

biotechnology projects. Companies, projects and initiatives falling within the scope of this

Regulation may be considered for Union and Member State financial support, in line with

applicable State aid rules.

Chapter IV – Extension of the supplementary protection certificate

This chapter introduces an extension of 12 months of the Supplementary Protection

Certificate (SPC) for medicinal products developed by means of biotechnology processes and

for Advanced Therapy Medicinal Products. This provision aims at incentivising the

development of products developed with innovative biotechnology technologies which will

bring a therapeutic advantage to patients. This incentive will also support the clinical

EN 25 EN

development and the manufacturing of these products in the Union, subject to compliance

with applicable competition rules.

Chapter V - Enhancing competitiveness in biosimilars

This Chapter supports EU competitiveness in the field of biosimilars by encouraging the

development of EMA guidelines on facilitating the authorisation of biosimilar medicinal

products. This Chapter also includes measures supporting strategic health biotechnology

projects focused on biosimilar research, development, manufacturing and marketing

authorisation and promotes international cooperation between economic operators and

biotechnology clusters in this area, subject to compliance with applicable competition rules.

Any funding from Member States should be in line with applicable State aid rules.

Chapter VI – Artificial intelligence and data as biotechnology enablers

This Chapter aligns with the AI-first policy introduced in the Apply AI Strategy and

encourages the adoption and integration of AI in actions supporting biotechnology, in order to

foster innovation, efficiency and technological sovereignty in biotechnology and

biomanufacturing. It also provides for guidance to be issued by the EMA on the use of AI

across the medicinal-product lifecycle and creates trusted AI testing environments and data-

quality accelerators as high-impact strategic health biotechnology projects to advance safe AI-

enabled biotechnology.

Chapter VII – Regulatory tools for novel health biotechnology products

This Chapter sets out a flexible, collaborative and anticipatory approach to regulate novel

health biotechnology products by reinforcing and complementing existing mechanisms in

Union law, notably (i) those introduced in the revised Directive 2001/83/EC on the interaction

and combinations between medicinal products and medical devices, and on regulatory

sandboxes; and (ii) the mechanisms provided under the [revised] MDR, IVDR, the revised

Pharmaceutical Regulation and the SoHO Regulation, which allow for the provision of

opinions, recommendations or binding decisions on the regulatory status of products. This

Chapter lays down a Union-wide, cross-framework regulatory status repository, which will

compile relevant opinions, recommendations, decisions and guidance, thus fostering

transparency, consistency and mutual learning across Union and national authorities.

Recognising the need for anticipatory governance, this Chapter also sets up a foresight panel

for emerging health innovation to advice the Commission and conduct structured horizon-

scanning and cross-framework dialogue on forthcoming scientific and technological

developments. Lastly, this Chapter provides for the establishment of a Union level regulatory

sandbox for health biotechnology products at an early stage of development that fall outside

existing health legal frameworks.

Chapter VIII – Biodefence and preventing biotechnology misuse

This Chapter establishes a framework for preventing the misuse of biotechnology products of

concern. It includes provisions for screening, reporting, and tracking suspicious transactions

of biotechnology products of concern, and enforcement mechanisms to ensure compliance.

This Chapter sets out specific conditions for the Commission to recognise high-impact

strategic health biotechnology projects in the form of EU biodefence capability projects, that

may be given particular consideration for funding under Union basic acts, subject to

compliance with applicable State aid rules. Ultimately, the Regulation seeks to promote a high

EN 26 EN

level of protection against biotechnological threats, while fostering innovation and

competitiveness in the biotechnology sector.

Chapter IX – Amendments to Regulations (EC) No 178/2002, (EC) No 1394/2007, (EU)

No 536/2014, (EU) 2019/6, (EU) 2024/795 and (EU) 2024/1938

This Chapter introduces amendments to EU legislative frameworks in the areas of health and

food and feed safety with the aim of simplifying procedures and accelerating time to market

that are necessary to ensure the effectiveness of the substantive provisions established in this

proposal by creating legislative frameworks conducive to innovation. Further, it establishes

amendments to Regulation (EU) 2024/795 (STEP Regulation)86 regarding the status of health

biotechnology strategic projects and of high impact health biotechnology strategic projects

under that Regulation.

Amendments to Regulation (EC) No 178/2002 (General Food Law)

This Regulation proposes amendments to Regulation (EC) No 178/200287 laying down the

general principles and requirements of food law, in order to streamline risk assessment

processes. Key changes include (i) broadening pre-submission advice to include scientific

matters, such as study design and testing strategies, while merging it with the renewal-related

advice into a single, unified procedure to simplify application procedures; (ii) shortening the

procedural delay for non-compliance with the study notification requirements at pre-

submission phase from six to three months to reduce time-to-market; (iii) requiring EFSA

staff to chair panels and serve as vice-chairs of the Scientific Committee (without voting

rights) to improve efficiency and coherence across Panels; and (iv) introducing provisions for

regulatory sandboxes, allowing Member States to test innovative technologies under

harmonised conditions that foster innovation while safeguarding consumer health and safety.

Such amendments should contribute, amongst others, to accelerating the risk assessment

process carried out by EFSA for products that are subject to pre-market authorisation in

accordance with Union food and feed law and foster innovation in the sector. As such, those

are necessary amendments with a view to ensure the effectiveness of the substantive measures

put forward in this proposal towards the strengthening of an innovative biotechnology sector

in food and feed safety.

Amendments to Regulation (EC) No 1394/2007 (Advanced Therapy Medicinal Products

Regulation)

To speed up access to advanced investigational therapy medicinal products that consist or

contain GMOs that are complex innovative products, this Regulation proposes special

provisions for facilitating related clinical trials. In this regard, it is proposedto amend

Regulation (EC) No 1394/2007 to provide that when controlling under Regulation (EU) No

536/2014 for risks from the deliberate release into the environment of GMOs, sponsors are to

86 Regulation (EU) 2024/795 of the European Parliament and of the Council of 29 February 2024

establishing the Strategic Technologies for Europe Platform (STEP), and amending Directive

2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013,

(EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU)

2021/241, ELI: http://data.europa.eu/eli/reg/2024/795/oj 87 Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying

down the general principles and requirements of food law, establishing the European Food Safety

Authority and laying down procedures in matters of food safety, OJ L 31, 1.2.2002, pp. 1–24. ELI:

http://data.europa.eu/eli/reg/2002/178/oj

EN 27 EN

be exempted from the requirement to submit an environmental risk assessment in respect of

certain clearly delineated categories of advanced investigational therapy medicinal products

that consist or contain GMOs which present no or negligible risks to human health and the

environment. Sponsors of clinical trials are, however, to submit a declaration as part of the

clinical trial application that explains why the advanced investigational therapy medicinal

products concerned fall into one or more of the specific categories of products presenting no

or negligible risks to human health and the environment. The Committee for Medicinal

Products for Human Use (CHMP) referred to in Article [148] of Regulation […] [revised

Regulation No (EC) 726/2004] is to verify this declaration. For the same considerations of a

risk-proportionate approach, this Regulation also proposes that the above-mentioned

categories of advanced investigational therapy medicinal products be exempted from the

GMO related requirements of Regulation (EU) No 536/2014 regarding manufacturing and

import.

Scientific and technological advances are driving forward the development of ATMPs. To

future-proof the ATMP regulatory framework and ensure that it can encompass certain

innovative products that could benefit from the ATMP framework, without them falling under

other EU legal frameworks, the [revised Directive 2001/83/EC] empowers the Commission to

adopt delegated acts to amend the definitions laid down in the ATMP Regulation of a gene

therapy medicinal product and a somatic cell therapy medicinal product, without extending

the scope of these definitions. It should be also possible to amend the definition of a tissue

engineered product in the light of technical and scientific advancements.

Amendments to Regulation (EU) No 536/2014 (Clinical Trials Regulation)

This Chapter, critical to improving Europe’s clinical-trial framework, aims to cut approval

timelines, foster greater collaboration across borders, and improve regulatory efficiency,

without compromising safety, quality, or ethical standards. Simplification and acceleration of

procedures are necessary for ensuring the effectiveness of the enabling substantive measures

put forward in this proposal. Authorisation timelines will be shortened for multinational

clinical trials from 106 days to 75 days, including validation and ethical review. When there is

no request for information to the sponsor, timelines for initial clinical trial authorisations will

be reduced from 75 days to 47 days from submission to decision. Given the growing scientific

and regulatory expertise in ATMPs, the additional 50 days for assessing these products will be

eliminated. The assessment period for substantial modifications will be reduced from 96 days

to 47 days, with options for parallel substantial modifications. If there is no request for

information to sponsor, the timelines for the assessment of substantial modifications will be

reduced from 64 days to 33 days from submission till decision. The reporting Member State’s

role will be strengthened so that it can lead the scientific, ethical, and regulatory assessment

harnessing mutual trust between Member States and reliance on the assessment of the

reporting Member State. Communication between sponsors and Member States will be

improved during assessments. A single, core dossier for investigational products will simplify

clinical trials using the same investigational medicine and help the conduct of registration

trials and the preparation of marketing authorisation applications in Europe. Simplifications

for low-intervention clinical trials will be further supported by introducing a new category of

‘minimal-intervention’ clinical trials. Mandatory EU harmonised templates will enable

harmonisation. A single assessment process will be defined for combined studies involving

the investigation of a medicine together with a medical device or an in-vitro diagnostic. The

legal basis for processing personal data in clinical trials in accordance with Regulation (EU)

2016/679 requirements will be harmonised. Accelerated and simplified procedures will

enable multinational clinical trials to be carried out on in relation to public health

EN 28 EN

emergencies. The uptake of the use of AI systems and digitalisation in clinical trials will be

fostered. Clinical trial sandboxes will be created to test innovative approaches. Annex I to

Regulation (EU) No 536/2014 is also amended to ensure consistency with the amendments to

Regulation (EC) No 1394/2007 proposed in this Regulation, regarding certain categories of

advanced investigational therapy medicinal products containing or consisting of GMOs.

Amendments to Regulation (EU) 2019/6 (Veterinary Medicine Products Regulation)

Biological veterinary medicinal products, derived from living sources, have more complex

lifecycle and variation handling than chemically synthesised medicines. Regulation (EU)

2019/688 introduced variations not requiring assessment to reduce administrative burden,

which will be further optimised in this section without affecting quality, safety, or efficacy.

To cut administrative burden for innovations, this section foresees that the assessment of

human health and environmental impacts of veterinary medicinal products containing

genetically modified organisms should be made solely under the Environmental Risk

Assessment (ERA) pursuant to Regulation (EU) 2019/6, removing the need for assessment

under the Union GMO legislation, while reinforcing obligations under Regulation 2019/6.

The section also clarifies that administering veterinary medicinal products does not place

treated animals or their products under the Union GMO legislation. Also, the Commission is

empowered to adapt technical requirements in Annex II to Regulation 2019/6 to scientific and

technical progress. Veterinary medicinal products developed by means of biotechnology

processes to diagnose, treat or prevent zoonotic diseases are entitled to an extra year of SPC.

Finally, the introduction of regulatory sandboxes for animal health innovation will allow new

technologies, methods, or products to be tested, marketed, or used under proportionate

oversight where no specific EU legislation exists, fostering responsible innovation in

veterinary medicine

Amendments to Regulation (EU) 2024/795 (STEP Regulation)

This provision introduce amendments to Regulation (EU) 2024/795 to establish that health

biotechnology strategic projects, including high-impact health biotechnology strategic

projects recognised in accordance with this Regulation are to be deemed to contribute to the

STEP objectives referred to in Article 2 paragraph 1, point (a)(iii) or point (b) of the STEP

Regulation, as appropriate.

Amendment to Regulation (EU) 2024/1938 (SoHO)

Substances of human origin (SoHO) are a key pillar of biotechnology as they can become

starting materials for innovative medicinal products. This section introduces a regulatory

sandbox in the SoHO framework. It enables access to very innovative but regulatory

challenging therapies and products while generating insights that can inform updates to

regulatory frameworks, ensuring that they remain flexible, adaptive and fit for purpose in the

face of evolving scientific and technological advancements.

Chapter X – Final provisions

88 Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on

veterinary medicinal products and repealing Directive 2001/82/EC (Text with EEA relevance), OJ L 4,

7.1.2019, pp. 43–167. ELI: http://data.europa.eu/eli/reg/2019/6/oj

EN 29 EN

This Chapter contains provisions on (i) monitoring; (ii) delegation of power; (iii) committee

procedure, (iv) an obligation for the Commission to prepare regular reports to the European

Parliament and to the Council for the evaluation of this Regulation; (v) handling of

confidential information, and entry into force and application.

EN 30 EN

2025/0406 (COD)

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)

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty on the Functioning of the European Union, and in particular

Articles 114, 168(4) and 173(3) thereof,

Having regard to the proposal from the European Commission,

After transmission of the draft legislative act to the national parliaments,

Having regard to the opinion of the European Economic and Social Committee,

Having regard to the opinion of the Committee of the Regions,

Acting in accordance with the ordinary legislative procedure,

Whereas:

(1) Biotechnology is a strategic technology central for the Union’s competitiveness,

strategic autonomy and innovation leadership. It has applications across several

sectors, with prominence in the health area. In 2021, the Union was the second largest

contributor to the global value of biotechnologies. Between 2008 and 2018, the

biotechnology industry in the Union grew more than twice as fast as the overall

economy, making it one of the fastest growing innovative industries in the Union.

Health biotechnology specifically contributes over 80% to the value of the overall

biotechnology market and it is a key driver of today’s innovative medical industry.

Biological medicines, including biosimilars count for 40% of overall pharmaceutical

sales in the Union.

(2) While recognised globally for its scientific excellence, the Union continues to face

structural challenges in translating cutting-edge research and innovation into large-

scale development, testing, manufacturing and deployment of biotechnology. As a

result, the significant potential of biotechnology applications across several sectors to

contribute to major societal challenges, modernise the Union economy and strengthen

Union strategic autonomy and security remains largely underexploited.

(3) This is due in particular to limited access to risk capital and other sources of funding,

skills shortages within the internal market, slow permitting processes that hinder the

timely deployment of projects and initiatives aiming to bring biotechnology

innovations to the market, as well as fragmented and at times complex regulatory

frameworks.

EN 31 EN

(4) To address this competitiveness gap, this Regulation should aim to improve the

functioning of the internal market by establishing a framework to strengthen the

competitiveness of the health biotechnology sector from research and innovation to

production, to create the conditions for research, development, timely placing on the

Union market and production of health biotechnology innovations, products and

services, including by simplifying and streamlining the Union legislative frameworks,

while safeguarding high standards for the protection of human and animal health,

patients, the environment, ethics, quality, food and feed safety and biosecurity.

(5) Given the importance of health biotechnology amongst the other applications of

biotechnology as referred to in recital (1), it is appropriate that this Regulation

focusses on, and sets out specific measures for, the health dimension of biotechnology.

To ensure the effectiveness of this Regulation, its scope of application should extend

to health biotechnology in a comprehensive manner and cover health within the wide

meaning of Article 168 TFEU on the protection of public health.

(6) Article 168(1) TFEU emphasises that a high level of human health protection is to be

ensured when defining and implementing all Union policies and activities. Article

168(4) TFEU clarifies that this objective is, amongst others, to be pursued through

measures setting high standards of quality and safety for medicinal products and

devices for medical use and of organs and substances of human origin, blood and

blood derivatives, measures in the veterinary and phytosanitary fields which have as

their direct objective the protection of public health.

(7) Accordingly, and in line with the One Health approach, that aims to comprehensively

and sustainably balance and optimise the health of people, animals, and ecosystems1,

this Regulation should apply to health biotechnology, understood as the application of

biotechnology in the human medical, veterinary, pharmaceutical and phytosanitary

areas for the development of biotechnology products and services. This Regulation

should apply to their entire lifecycle, including the related research, access to funding,

development, innovation, testing, validation, manufacturing, placing on the market and

use activities.

(8) With a view to ensuring the effectiveness, consistence and unity of some of the legal

acts that this Regulation should amend to foster the Union’s competitiveness in

biotechnology, this Regulation should in certain cases also apply to products and

activities other than biotechnology products and activities, so as to avoid the creation

of different sets of rules for biotechnology and non-biotechnology products and

activities. This is in particular the case in the area of health for Union legislation

regarding clinical trials, and in the food and feed safety area, for Regulation (EC) No

178/2002 of the European Parliament and of the Council2.

(9) This Regulation should apply without prejudice to the harmonised legal framework for

the development, the placing on the market, the putting into service and the use of

1 European Commission: Group of Chief Scientific Advisors and Directorate-General for Research and

Innovation, One Health governance in the European Union, Publications Office of the European Union,

2024, https://data.europa.eu/doi/10.2777/8697309 . 2 Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying

down the general principles and requirements of food law, establishing the European Food Safety

Authority and laying down procedures in matters of food safety, OJ L 31, 1.2.2002, p. 1.

ELI: http://data.europa.eu/eli/reg/2002/178/oj.

EN 32 EN

artificial intelligence (AI), laid down by Regulation (EU) 2024/16891689 of the

European Parliament and of the Council3.

(10) This Regulation should not affect to the application of the Directive 2010/63/EU of the

European Parliament and of the Council4 on the protection of animals used for

scientific purposes and of Regulation (EC) 2006/1907 of the European Parliament and

of the Council5.

(11) The Union has adopted other initiatives to strengthen the competitiveness of particular

sectors of the Union economy. In this regard, Regulation (EU) 2024/1735 of the

European Parliament and of the Council6 focuses on clean and resource-efficient

technologies which include, in particular, net-zero technologies. That Regulation

establishes a framework to ensure the Union’s access to a secure and sustainable

supply of net-zero technologies listed in Article 4 thereof. Such technologies include

sustainable biogas and biomethane technologies and biotechnology climate and energy

solutions. However, as acknowledged by Regulation (EU) 2024/795 of the European

Parliament and of the Council7, biotechnologies have applications beyond the clean

and resource-efficient technologies. It is therefore appropriate that this Regulation

applies without prejudice to the provisions of Regulation (EU) 2024/1735 regarding

sustainable biogas and biomethane technologies and biotechnology climate and energy

solutions.

(12) Health biotechnology strategic projects should serve as targeted instruments to

mobilise public and private investments through coordinated action among the Union,

the Member States, the industry, the research community and other relevant actors.

They should contribute to the Union’s biotechnology objectives, by strengthening

industrial capacity and value chains, scaling up critical research and technology

infrastructures, accelerating innovation and technology deployment such as New

Approach Methodologies (NAMs), or advanced data and digital platforms.

Accordingly, this Regulation should lay down provisions for the recognition and

support of such projects by the Member States and should establish criteria for such

3 Regulation (EU) 2024/1689 of the European Parliament and of the Council of 13 June 2024 laying

down harmonised rules on artificial intelligence and amending Regulations (EC) No 300/2008, (EU) No

167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU) 2019/2144 and Directives

2014/90/EU, (EU) 2016/797 and (EU) 2020/1828 (Artificial Intelligence Act) (OJ L, 2024/1689,

12.7.2024, ELI: http://data.europa.eu/eli/reg/2024/1689/oj). 4 Consolidated text: Directive 2010/63/EU of the European Parliament and of the Council of 22

September 2010 on the protection of animals used for scientific purposes (Text with EEA relevance).

ELI: http://data.europa.eu/eli/dir/2010/63/2019-06-26 5 Consolidated text: Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18

December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals

(REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing

Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council

Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and

2000/21/EC (Text with EEA relevance). ELI: http://data.europa.eu/eli/reg/2006/1907/2025-09-01. 6 Regulation (EU) 2024/1735 of the European Parliament and of the Council of 13 June 2024 on

establishing a framework of measures for strengthening Europe’s net-zero technology manufacturing

ecosystem and amending Regulation (EU) 2018/1724 (Text with EEA relevance), OJ L 1735 28.6.2024,

p. 1. ELI: http://data.europa.eu/eli/reg/2024/1735/oj. 7 Regulation (EU) 2024/795 of the European Parliament and of the Council of 29 February 2024

establishing the Strategic Technologies for Europe Platform (STEP), and amending Directive

2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013,

(EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU)

2021/241 (OJ L, 2024/795, 29.2.2024. ELI: http://data.europa.eu/eli/reg/2024/795/oj).

EN 33 EN

recognition. With a view to facilitate the implementation and ensure a consistent

approach across the Union, the Commission could issue guidance on the application of

those criteria. Recognition of health biotechnology strategic projects would deliver

clear benefits for the most innovative businesses by accelerating permitting, reducing

administrative burden, improving legal certainty and facilitating access to financial

support. It would thus strengthen their capacity to scale biotechnology innovations

faster. For authorities, the framework streamlines coordination, avoids duplication of

assessments, and supports consistent, efficient decision-making.

(13) NAMs applied in biological research, early discovery, preclinical development, and

the regulatory and quality testing of medicinal products and medical technologies,

have the potential to generate scientific and technological data that are comparable to,

or in some cases more informative and generated more rapidly than, those obtained

through current standard methods. The resulting advantage will contribute to

strengthen the innovation ecosystem and enhanced European competitiveness in

biotechnology.

(14) Certain health biotechnology strategic projects have the potential to contribute to the

Union’s objectives in biotechnology in a manner that is systemic and can produce a

multiplier effect. Such projects act as catalysts for cooperation between academia,

industry and public authorities, and can serve as anchors for regional biotechnology

clusters and innovation ecosystems across Member States. Experience in several

Member States has shown that such projects can quickly raise industrial capability,

attract investment and strengthen the Union’s position in global value chains.

Accordingly, such projects should be recognised as high impact health biotechnology

strategic projects by the Commission and could be given particular consideration for

Union funding, priority access to administrative support and fast-tracked procedures at

Member State level. As regards national funding of such projects, Regulation (EU)

2024/7958 provides measures for the support of critical and emerging strategic

technologies and their respective value chains within programmes implemented under

shared management. That Regulation amends the basic acts of several shared-

management funds, namely Regulations (EU) 2021/10569, (EU) 2021/105710 and

(EU) 2021/1058 of the European Parliament and of the Council11 , in order to enable

Member States to steer their national and regional programmes towards investments in

critical technologies, including biotechnologies. Without prejudice to the applicable

rules governing each such funding instrument, and in line with applicable State aid

rules, this approach may therefore be applied to high-impact health biotechnology

strategic projects, which are deemed in accordance with this Regulation as to

contribute to the STEP objectives.

8 Regulation (EU) 2024/795 of the European Parliament and of the Council of 29 February 2024

establishing the Strategic Technologies for Europe Platform (STEP), and amending Directive

2003/87/EC and Regulations (EU) 2021/1058, (EU) 2021/1056, (EU) 2021/1057, (EU) No 1303/2013,

(EU) No 223/2014, (EU) 2021/1060, (EU) 2021/523, (EU) 2021/695, (EU) 2021/697 and (EU)

2021/241, ELI: . 9 Regulation (EU) 2021/1056 of the European Parliament and of the Council of 24 June 2021 establishing

the Just Transition Fund (OJ L 231, 30.6.2021, p. 1, ELI: http://data.europa.eu/eli/reg/2021/1056/oj). 10 Regulation (EU) 2021/1057 of the European Parliament and of the Council of 24 June 2021 establishing

the European Social Fund Plus (ESF+) and repealing Regulation (EU) No 1296/2013 (OJ L 231,

30.6.2021, p. 21, ELI: http://data.europa.eu/eli/reg/2021/1057/oj). 11 Regulation (EU) 2021/1058 of the European Parliament and of the Council of 24 June 2021 on the

European Regional Development Fund and on the Cohesion Fund (OJ L 231, 30.6.2021, p. 60, ELI:

http://data.europa.eu/eli/reg/2021/1058/oj).

EN 34 EN

(15) The strategic importance of biotechnology for European competitiveness has already

been established, including through the proposed a European Competitiveness Fund

(ECF) for the Multiannual Financial Framework (MFF) period 2028-2034, which

includes a dedicated ‘Health, Biotech, Agriculture and Bioeconomy’ window. The

Draghi Report on the Future of European Competitiveness12 recommends that the

Union should focus resources on a limited number of world-class centres of excellence

in life sciences and biotechnology. High impact biotechnology health strategic projects

have the potential to contribute to this focus of efforts and be a tool for an impactful

use of resources in the MFF period 2028-2034, to help position the Union among the

leading regions for biotechnology. Examples of categories of such high impact

projects and specific criteria should be established for their recognition by the

Commission. Amongst those categories, high impact health biotechnology strategic

projects in the form of biotechnology development accelerators providing, amongst

others, trusted testing or demonstration facilities replicating real-world

biomanufacturing processes, should play a key role in translating Europe’s scientific

excellence into productive industrial capacity. By pooling advanced equipment and

expertise and offering criteria-based access, including for small and medium-sized

enterprises, start-ups and scale-ups, such projects should reduce duplication of efforts,

lower entry barriers, and foster the specialised skills required for advanced

biomanufacturing. Similarly, high impact health biotechnology strategic projects in the

form of centres of excellence for advanced therapies, including for advanced therapy

medicinal products, should combine research, regulatory science and manufacturing

capabilities, enabling faster, safer and more efficient development of innovative

therapies. When connected to digital and data infrastructures, they should have the

potential to accelerate clinical translation, improve quality control and facilitate patient

access across the Union.

(16) To maximise the Union-wide benefits of investments made in projects or entities

operating infrastructures, facilities and services supported and established or

recognised in accordance with this Regulation, such projects or entities should provide

open, non-discriminatory, transparent and criteria-based access to users from all

Member States, including academic institutions, industrial undertakings, with

particular attention to SMEs, start-ups and scale-ups, and public research bodies.

Access conditions should be proportionate and ensure fair treatment among users,

taking into account the objectives and capacity of each infrastructure, the need to

guarantee equitable opportunities for SMEs, start-ups and scale-ups, and research

actors, and appropriate safeguards to protect security, confidentiality, intellectual

property and economic-security interests.

(17) Effective implementation of objectives pursued in this Regulation relies on good

governance and partnership between all actors at the relevant territorial levels and

socio-economic actors. In particular, biotechnology strategic projects aimed at

targeting talent and skills shortages vital to supporting biotechnology and

biomanufacturing industries and to ensuring a workforce capable to supporting

innovation, industrial scale-up and long-term competitiveness should be designed and

developed with the full involvement of the relevant social partners. Such active

engagement is essential to ensure that social implications are addressed from the outset

and to foster responsible innovation.

12 Draghi, Mario. The future of European competitiveness: A competitiveness strategy for Europe,

European Commission, 9 September 2024.

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(18) Directive (EU) 2022/2555 of the European Parliament and of the Council13 lays down

obligations for essential and important entities to ensure a high common level of

cybersecurity throughout the Union, including requirements on risk management,

incident reporting and the protection of network and information systems. Therefore,

entities established or supported under this Regulation and falling within the scope of

the Directive (EU) 2022/2555 should comply with the requirements set out in that

Directive.

(19) In order to safeguard the Union’s security, public order and strategic interests, access

to biotechnology infrastructures and datasets of health biotechnology strategic projects

and of high impact health biotechnology strategic projects recognised in accordance

with this Regulation and that receive funding in accordance with Union programmes,

in relation to such infrastructures or datasets, should be governed by the rules

established in those programmes. This addresses risks linked to unlawful technology

transfer, hostile interference or strategic dependency.

(20) To provide an evidence base for future Union action to further strengthen the

biotechnology and biomanufacturing sectors, the Commission should carry out a

strategic mapping of the Union’s biotechnology ecosystem. That mapping should

analyse industrial capacities, infrastructures and facilities relevant to biotechnology

research, development, testing and manufacturing, and assess factors affecting the

Union’s ability to attract and retain investment in biomanufacturing, including access

to public and private risk-tolerant capital across all stages of the innovation cycle, the

development and coordination of biotechnology clusters and biomanufacturing

ecosystems across the Union, and assess challenges and needs in terms of the

workforce.

(21) Recognising the transformative role of data and AI in the area of biotechnology and

biomanufacturing, that mapping should also assess access to data, computing capacity

and digital infrastructure for the health biotechnology sector and identify measures to

foster responsible AI-enabled biotechnology innovation and possible measures to

mitigate related risks, building on analyses done in the context of existing Union

initiatives such as the European Health Data Space14 , the Apply AI Strategy15, the

Data Union Strategy16, the AI Continent Action Plan17 and the European Strategy for

AI in Science18. With a view to ensuring appropriate cooperation with the Member

States and optimising the use of relevant knowledge and expertise available at Union

13 Directive (EU) 2022/2555 of the European Parliament and of the Council of 14 December 2022 on

measures for a high common level of cybersecurity across the Union, amending Regulation (EU) No

910/2014 and Directive (EU) 2018/1972, and repealing Directive (EU) 2016/1148 (NIS 2 Directive), OJ

L 333, 27.12.2022, pp. 80. ELI: http://data.europa.eu/eli/dir/2022/2555/oj. 14 Regulation (EU) 2025/327 of the European Parliament and of the Council of 11 February 2025 on the

European Health Data Space and amending Directive 2011/24/EU and Regulation (EU) 2024/2847 (OJ

L, 2025/327, 5.3.2025, ELI: http://data.europa.eu/eli/reg/2025/327/oj). 15 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions: Apply AI Strategy, COM(2025)723

final of 8 October 2025. 16 Communication from the Commission to the European Parliament and the Council, Data Union

Strategy, Unlocking Data For AI, COM(2025) 835 final, 19 November 2025. 17 https://ec.europa.eu/newsroom/dae/redirection/document/114523 18 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions: European Strategy for Artificial

Intelligence in Science – Harnessing AI for research, innovation and excellence in the Union,

COM(2025)724 final of, 8 October 2025.

EN 36 EN

level, such mapping should be conducted by the Commission in cooperation with

relevant Union agencies and bodies, including, where relevant, the AI Board

established under the Regulation (EU) 2024/1689, and with the European Health

Biotechnology Steering Group (‘the Steering Group’) established in accordance with

this Regulation, to facilitate its implementation, provide advice to the Commission and

to the Member States, and ensure coordinated action in particular with regard to health

biotechnology strategic projects and high impact health biotechnology strategic

projects.

(22) In order to ensure a transparent, coherent and efficient process for the identification of

health biotechnology strategic projects, each Member State should designate a

competent authority responsible for assessing and verifying whether a project fulfils

the conditions set out in this Regulation for its recognition as a health biotechnology

strategic project. The designated authority should carry out the assessment through a

fair, transparent and time-bound process. Where a project is found to fulfil the

conditions for recognition as a biotechnology strategic project, the designated

authority should issue a formal recognition decision.

(23) Considering their systemic and cross-border relevance and the benefits associated with

their status as high impact health biotechnology strategic project, the recognition of

such projects should take place through a two-tier process, involving authorities

designated by the Member States for that purpose and the Commission. Such

authorities should assess and transmit the applications and their assessment to the

Commission in view of the adoption of a Commission decision. This two-tier process

should ensure that such projects are subject to an additional Union-level verification

and benefit from consistent recognition standards across the Union. With a view to

ensure peer review, cooperation with the Member States and coherent implementation

across the Union, in adopting its decision the Commission should take into account the

views of the European Health Biotechnology Steering Group established by this

Regulation.

(24) With a view to enabling the efficient alignment between the Union funding procedures

and the objectives of this Regulation regarding the support to high impact strategic

health biotechnology projects, and to ensure that projects with the highest Union

added value can rapidly benefit from priority support, in addition to the recognition of

such projects through a Commission decision, the Commission could have the

possibility to recognise such projects also in the context of calls for proposals

launched under the relevant Union funding programmes.

(25) To achieve critical mass and ensure that strategic investments deliver wider benefits,

creating positive spill-over effects that reinforce the Union’s competitiveness,

networking and cooperation among health biotechnology strategic projects, high

impact health biotechnology strategic projects, research organisations, industrial

clusters and other relevant actors across borders, should be promoted and facilitated by

the Commission and the Member States, with a view to help pooling national and

Union resources and facilities, promote the development of interoperable

infrastructures and digital platforms and facilitate knowledge transfer. This

cooperation should be in compliance with Union competition law.

(26) Such networking and cooperation should integrate, collaborate with, or build upon,

existing networks emerging from other Union initiatives relevant for biotechnology,

including those operating under the European Cluster Collaboration Platform, the

European Cluster Alliance, networks supported under Horizon Europe, the Smart

EN 37 EN

Specialisation Partnerships, and the European Network of Centres of Excellence for

Advanced Therapy Medicinal Products (ATMPs) announced by the Commission in

the European Strategy for Life Sciences19, the European Reference Networks as

defined in Directive 2011/24/EU of the European Parliament and of the Council20 and

the EU Network of Comprehensive Cancer Centres announced by Europe’s Beating

Cancer Plan21. Such cooperation should aim to reinforce synergies, facilitate access to

regional and Union level funding, and enhance the coordination of biotechnology-

related innovation ecosystems across the Union.

(27) In order to reduce complexity and increase efficiency, transparency and consistency in

the permit-granting process for health biotechnology strategic projects and high impact

health biotechnology strategic projects, there should be a single point of contact at

national level that is responsible for facilitating and coordinating the entire permit-

granting process. The single point of contact should be the interface between the

promoters of health biotechnology strategic projects or of high impact health

biotechnology strategic projects and the relevant permitting authorities. To that end,

Member States should establish or designate one or more authorities as single points

of contact. With a view to ensure streamlined processes, that single point of contact

should be the same as the single point of contact referred to in Regulation (EU) ../..

[Regulation on speeding-up environmental impact assessmentsc - permitting

regulation], responsible for facilitating and coordinating all aspects of the

environmental assessments. It should be for Member States to decide whether a single

point of contact is also an authority that makes permitting decisions. To ensure the

effective implementation of their responsibilities, Member States should provide their

single points of contact, as well as any authority involved in the permit-granting

process with sufficient personnel and resources.

(28) The Union has progressively recognised health biotechnology as a strategic sector

contributing to Union’s overall resilience. Regulation (EU) 2024/795 identifies

biotechnology among the strategic technologies essential for reducing the Union’s

strategic dependencies and strengthening its economic and industrial resilience. The

Commission Communication Commission Communication ‘Building the future with

nature: Boosting Biotechnology and Biomanufacturing in the EU’ further identifies

biotechnology and biomanufacturing as strategic technologies for Europe’s

competitiveness, resilience and autonomy, and furthermore explicitly recognises that

health biotechnology is essential for health-system resilience. In view of this

consistent Union framework confirming biotechnology’s systemic contribution to

resilience, health biotechnology strategic projects and high impact health

biotechnology strategic projects should therefore be deemed to contribute to the

objectives referred to in Article 14 of Regulation […] [Regulation on speeding-up

environmental assessments – permitting regulation].

19 Communication from the Commission to the European Parliament, the Council, the European

Economic and Social Committee and the Committee of the Regions, A strategy for European life

sciences: Choose Europe for life sciences – A strategy to position the EU as the world’s most attractive

place for life sciences by 2030, COM(2025) 525 final of 2 July 2025. 20 Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the

application of patients’ rights in cross-border healthcare, OJ L 88, 4.4.2011, pp. 45–65.

ELI: http://data.europa.eu/eli/dir/2011/24/oj. 21 Communication from the Commission to the European Parliament and the Council, Europe's Beating

Cancer Plan, COM/2021/44 final of 3 February 2021.

EN 38 EN

(29) In light of their contribution to the Union’s competitiveness, resilience and

preparedness, health biotechnology strategic projects recognised by the Member States

in accordance with this Regulation should be considered to be in the public interest.

Similarly, Member States should grant such projects the highest national significance

available under their national law, meaning the strongest designation applicable to

major strategic projects, and should apply the corresponding procedural advantages,

including priority treatment and coordinated and accelerated permit-granting, and

adopt facilitation measures in compliance with Union law.

(30) In view of the potential for cross-border and systemic benefits of high impact health

biotechnology strategic projects, on the basis of its case-by-case assessment, a

permitting authority can conclude that the public interest served by the project

overrides the public interests related to nature and environmental protection and that

consequently the project can be authorised, provided that all relevant conditions set

out in Directives 2000/60/EC22, 2009/147/EC23 or 92/43/EEC24 of the European

Parliament and of the Council, or in Union legislative acts on nature restoration, are

met.

(31) To ensure predictability and administrative efficiency, the overall duration of the

permit-granting process should be limited to ten months from the acknowledgement of

a complete application, for biotechnology health strategic projects, and to eight

months, for high impact health biotechnology strategic projects, given the need to

prioritise the speed of their implementation over any other type of biotechnology

project. In exceptional and duly justified circumstances an extension of up to three

months should be permitted.

(32) Member States whose territories are concerned by health biotechnology strategic

projects or high impact health biotechnology strategic projects should take all

appropriate measures to facilitate their timely and effective development and

deployment. Such measures should include the provision of administrative support,

upon the request of project promoters, as well as, without prejudice to Union

competition law, of public financial and technical support, with a particular attention

paid to SMEs, start-ups and scale-ups.

(33) The Commission should complement the action of the Member States in support of

health biotechnology strategic projects, closely cooperating with them, including

through the European Health Biotechnology Steering Group established by this

Regulation, to ensure synergy and optimal outcomes. In particular, the Commission

should assist project promoters in identifying relevant funding opportunities available

under existing Union funding programmes, including through actions of the EU Health

Biotechnology Support Network established in this Regulation with the purpose of

assisting biotechnology actors in navigating regulatory health biotechnology

procedural pathways and identifying funding, scaling up and networking opportunities

across the Union. Further, to strengthen the Union’s biotechnology innovation

ecosystem, the Commission should also promote measures that enhance access of

22 Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a

framework for Community action in the field of water policy, OJ L 327, 22.12.2000, p. 1. ELI:

http://data.europa.eu/eli/dir/2000/60/oj. 23 Directive 2009/147/EC of the European Parliament and of the Council of 30 November 2009 on the

conservation of wild birds, OJ L 20, 26.1.2010, pp. 7-25. ELI: http://data.europa.eu/eli/dir/2009/147/oj. 24 Council Directive 92/43/EEC of 21 May 1992 on the conservation of natural habitats and of wild fauna

and flora, OJ L 206, 22.7.1992, p. 7. ELI: http://data.europa.eu/eli/dir/1992/43/oj

EN 39 EN

small and medium-sized enterprises, start-ups and scale-ups to research and

technological infrastructures, including those funded through Union programmes.

(34) High impact health biotechnology strategic projects should benefit from financial,

technical and administrative support measures. In addition, in order to ensure that

Union resources for biotechnology are channelled towards the actions that have the

potential to deliver the most benefits at Union level, high impact health biotechnology

strategic projects could be given particular consideration for financial support, in the

context of the preparation, adoption and implementation by the Commission of work

programmes for the relevant Union programmes, funds and instruments.

(35) The scale and nature of the Union support for high impact health biotechnology

strategic projects might require long-term coordination and large-scale public and

private investment. In this context, public-private partnerships play a key role in

pooling expertise, sharing risks and accelerating the uptake of innovation.

Consequently, the Commission could envisage to propose in the future the

establishment of appropriate legal entities to mobilise investments, coordinate research

and innovation activities and support for the industrial deployment of biotechnology

and biomanufacturing capacities across Member States, while ensuring close

alignment with Union policy objectives. Those legal arrangements could take the form

of European Partnerships where the Union together with private and/or public

partners, acting in full compliance with competition rules, commit to jointly

supporting the development and implementation of a programme of activities,

including those related to market, regulatory or policy uptake.

(36) With a view to ensuring that the most favourable provisions apply cross-frameworks,

the provisions of this Regulation regarding the permit granting process, the priority

status of health biotechnology strategic projects and of high impact health

biotechnology strategic projects and the administrative, technical or financial support

for such projects should apply without prejudice to more favourable provisions laid

down in other Union legislation.

(37) Biotechnology undertakings, especially SMEs, start-ups and scale-ups, and non-profits

face challenges in navigating the regulatory processes, financing, scaling up and

networking opportunities in the Union. To address those challenges, the Commission

should manage, coordinate and support an EU Health Biotechnology Support

Network, composed of national and regional antennas, leveraging and complementing

existing structures such as the European Enterprise Network. The Network should

assist developers and project promoters, in particular SMEs, start-ups, and scale-ups,

in navigating more efficiently the legislative framework, health biotechnologies

regulatory pathways and funding opportunities at Union and national level. Moreover,

the EU Health Biotechnology Support Network should provide support for health

biotechnology strategic projects and enhanced assistance for high impact health

biotechnology strategic projects. The Commission should make available to the

Network an AI powered interactive tool to assist developers and project promoters, in

particular SMEs, start-ups, and scale-ups, in navigating more efficiently the regulatory

framework and pathways and funding opportunities at EU and national level.

(38) The European Health Biotechnology Steering Group (‘the Steering Group’) should be

established to provide advice to the Commission and to the Member States with a view

to facilitate the implementation of this Regulation, foster cooperation with the

Commission and among the Member States, and the exchange of best practice. The

EN 40 EN

Steering Group should be composed of representatives from all Member States and the

Commission.

(39) Member States should provide to the Steering Group, on an annual basis, an overview

of the health biotechnology strategic projects and of the high impact health

biotechnology strategic projects that they recognise, as well as of the existing and

emerging cooperation initiatives and networks among such projects. Such overview is

aimed at informing monitoring of progress in the implementation of this Regulation,

supporting coordination and proposals of measures to enhance the Union’s

biotechnology and biomanufacturing ecosystem and facilitate exchange of best

practices. In such overview, Member States should identify progress, obstacles and

best practices.

(40) To ensure effective governance and learning across the Union, the Steering Group

should periodically review systemic challenges in the financing and deployment in

particular for high impact health biotechnology strategic projects and recommend

corrective measures to the Commission and to Member States.

(41) Given the capital-intensive nature of biotechnology and the high probability of non-

commercialisation of individual projects, access to finance is a structural bottleneck

for the sector. To boost the potential of biotechnology to contribute to the Union’s

competitiveness, resilience and the creation and maintenance of quality jobs, sufficient

funding tailored to the sector’s risk profile needs to be mobilised across the financing

life cycle.

(42) To address key challenges in the functioning of Union capital markets, the

Commission is implementing the Savings and Investment Union (SIU) Strategy. The

SIU will reduce market fragmentation, create better investment opportunities for

citizens and help to expand funding options for businesses. In particular, it will seek to

improve access to equity and debt financing for all companies, including startups and

scaleups, strengthen the role of venture capital and institutional investors and better

align Union public funding instruments with SIU objectives. Recent Commission

guidance on legislative programmes25 also clarifies that the biotechnology sector can

be the target of Union, national and regional legislative programmes via reference to

the Competitiveness Compass, supporting favourable prudential treatment of

investments made under such programmes.

(43) The Union’s biotechnology sector faces a persistent financing gap compared with

other leading regions, particularly for the scale-up and industrial deployment stages.

The Union has been acting to address this, including through the flagship InvestEU

programme established by Regulation (EU) 2021/523 of the European Parliament and

of the Council26. InvestEU supports biotechnology investments in a transversal

manner, enabling investment in biotechnology projects and enterprises targeting all

stages of development, including start-up to scale-up stages as well as deployment.

The recent agreement between the Council and the European Parliament on enhancing

the InvestEU programme increases the Union guarantee by EUR 2.9 billion unlocking

nearly EUR 55 billion in additional public and private investments, including

investment into biotechnology. Overall, InvestEU has already mobilized EUR 7.5

25 C(2025) 7231 final 26 Regulation (EU) 2021/523 of the European Parliament and of the Council of 24 March 2021

establishing the InvestEU Programme and amending Regulation (EU) 2015/1017, OJ L 107, 26.3.2021,

pp. 30–89. ELI: http://data.europa.eu/eli/reg/2021/523/oj.

EN 41 EN

billion of biotechnology investments. During the 2026-2027 period, mobilization of at

least EUR 4 billion of additional biotechnology investments is expected. InvestEU

implementing partners play a key role in helping to stimulate investment in

biotechnology projects and enterprises. Both the EIB as well as EIF support

biotechnology – including health biotechnology – via several InvestEU financial

products. HERA Invest further boosts investments in health biotechnology. The

project pipeline is strengthened through InvestEU advisory, supporting initiatives such

as the European Tech Championship Initiative of the European Investment Bank.

(44) Complementing the European Innovation Council support for deep tech and

disruptive innovators in the area of biotechnology, an EU Health Biotechnology

Investment Pilot to mobilise public and private investment and strengthen the Union’s

competitiveness and resilience should be created in partnership with the European

Investment Bank Group (EIBG) or other implementing partners, for implementation in

indirect management, linking equity and guarantee instruments with venture debt

tailored to biotech-specific risk profiles.

(45) The Health Biotechnology Investment Pilot would aim to mobilise a substantial

amount of capital, from the EIBG, Union budget, public national schemes and private

sector investors (including institutional investors), to narrow the sector investment

gap, currently estimated at EUR 40 billion annually, amounting to EUR 400 billion for

the next 10 years, and ensure the sector's long term competitiveness and strategic

autonomy.

(46) The Health Biotechnology Investment Pilot should be tailored to biotechnology risk

profiles and lifecycle needs on the Union market. It should be possible to include

newly created and established instruments, encompassing advisory services, direct and

indirect individual investments, direct and indirect intermediated financing or portfolio

financing. The detailed instruments, eligibility and risk parameters, and indicative

allocations should be specified in the operational design of the Pilot.

(47) The Pilot may receive Union financial support through Union programmes. Pending

the establishment of the Pilot, a scheme, also covering ongoing investment activities,

launched with the support of the EIBG under the current Multiannual Financial

Framework 2021-2027 and supported under the InvestEU programme, will mobilise

up to 10 billion in investments in the biotechnology sector in 2026 and 2027 .

(48) Union public equity markets for biotechnology remain shallow relative to global peers,

which constrains late-stage financing and exit options for European start-ups and

scale-ups. Stock exchanges are still largely fragmented across Member States, with

limited specialised research coverage and dedicated market-making, prompting

European scale-ups to list abroad. To address this bottleneck for a competitive Union

biotechnology sector and complement the SIU strategy, which seeks to promote

integration and increase the depth of Union capital markets, projects contributing to a

Union late-stage capital booster pilot should be recognised by the Commission as

high-impact health biotechnology strategic projects in accordance with the conditions

laid down in this Regulation.

(49) Biotechnology is central for the Union’s sovereignty, strategic autonomy and

innovation leadership. In this regard, the Union is taking action to pursue its policy

objectives in biotechnology, including through the Framework Programme for

Research and Innovation established by Regulation (EU) 2021/695 of the European

EN 42 EN

Parliament and of the Council27 which is supporting the implementation of the Life

Sciences Strategy, and other relevant ‘Choose Europe’ initiatives.

(50) The Commission has proposed a European Competitiveness Fund (ECF)28 for the

MFF period 2028-2034, aiming to increase European competitiveness, notably in

strategic sectors and technologies along the investment journey. It is proposed to be

structured along four policy windows reflecting strategic priorities crucial to Union

competitiveness and resilience. It proposes funding to support the biotechnology

sector through a ‘Health, Biotech, Agriculture and Bioeconomy’ window.

(51) Companies, projects and initiatives falling within the scope of this Regulation could be

given particular consideration for financial support from Union led initiatives,

including those that aim to leverage private capital, and from Union funding

programmes and instruments, as projects in a strategic technology and, where

appropriate, in a strategic deep tech area. Such initiatives, programmes and

instruments include the cohesion policy programmes, the InvestEU programme, the

EIBG’s TechEU programme and the European Tech Champions Initiative, supported

by InvestEU, and launched by the EIBG with several Member States, and the

European Innovation Council established under the Horizon Europe Programme, as

well instruments for the duration of the MFF 2028-2034.

(52) Further, high-impact health biotechnology strategic projects are projects with a high

European added value, including cross-border projects, expected to bring structural

economic transformation, productivity, long-term growth and quality jobs in the

biotechnology sector, and benefiting the Single Market. Considering the necessity to

align Union, public and private spending with Union competitiveness priorities29, such

projects could be given particular consideration for Union financial support including

in the form of blended financing, under Union programmes, funds and financial

instruments.

(53) Regulation (EU) 2024/795 establishes that the development and manufacturing in the

Union of biotechnologies, together with digital technologies and deep tech innovation,

clean and resource-efficient technologies are essential for the purpose of reducing the

Union’s strategic dependencies, and for the green and digital transitions, thus ensuring

the sovereignty and strategic autonomy of the Union and promoting the

competitiveness and sustainability of the Union’s industry. Accordingly, that

Regulation establishes a Strategic Technologies for Europe Platform (STEP) to better

channel and mobilise resources within the existing Union programmes towards critical

investment, including in Union-wide and cross-border projects, that have the aim of

supporting the development or manufacturing of critical and emerging technologies

and their respective value chains, in strategic sectors, including in biotechnology.

27 Regulation (EU) 2021/695 of the European Parliament and of the Council of 28 April 2021 establishing

Horizon Europe – the Framework Programme for Research and Innovation, laying down its rules for

participation and dissemination, and repealing Regulations (EU) No 1290/2013 and (EU) No

1291/2013, OJ L 170, 12.5.2021, pp. 1. ELI: http://data.europa.eu/eli/reg/2021/695/oj. 28 As per Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE

COUNCIL on establishing the European Competitiveness Fund ('ECF’), including the specific

programme for defence research and innovation activities, repealing Regulations (EU) 2021/522, (EU)

2021/694, (EU) 2021/697, (EU) 2021/783, repealing provisions of Regulations (EU) 2021/696, (EU)

2023/588, and amending Regulation (EU) [EDIP]. 29 Commission Staff Working Document, Impact Assessment Report on the European Competitiveness

Fund, SWD(2025) 555 final.

EN 43 EN

(54) Union-level funding may be leveraged to facilitate investments in health

biotechnology strategic projects and high impact health biotechnology strategic

projects recognised in accordance with this Regulation. Such projects may benefit

from access to existing Union funding instruments, where they fulfil the criteria

established in those instruments. Authorities in charge of the Union programmes

covered by Regulation (EU) 2024/795 should consider supporting biotechnology

health strategic projects and high impact health biotechnology strategic projects

recognised in accordance with this Regulation. Therefore, Regulation (EU) 2024/795

should be amended to provide that health biotechnology strategic projects and high-

impact health biotechnology strategic projects recognised in accordance with this

Regulation should be deemed to contribute to the STEP objectives of supporting the

development or manufacturing of critical technologies in biotechnologies throughout

the Union, or safeguarding and strengthening their respective value chains and also in

addressing shortages of labour and skills critical to all kinds of quality jobs in support

of that objective, as appropriate.

(55) Member States may provide financial support to biotechnology as a strategic

technology for the Union’s innovation capacity, sovereignty, resilience and leadership,

including in the implementation of the relevant Union programmes. In this regard,

Member States should act in compliance with Union competition law and make use as

appropriate of the relevant frameworks. This includes the criteria for the analysis of

the compatibility with the internal market of State aid to promote the execution of

important projects of common European interest30 (IPCEIs), the guidance on the basis

of a compatibility assessment conducted by the Commission regarding aid to promote

research, development and innovation31, the Commission Regulation (EU) No

651/201432 and the Clean Industrial Deal State Aid Framework33.

(56) Strategic projects in health biotechnology may require blended financing from private,

national and Union sources. National funding should be in full compliance with State

Aid rules. The Commission, including through the European Biotechnology Support

Network, should support project promoters in liaising with potential investors.

Similarly, the European Health Biotechnology Steering Group established by this

Regulation should coordinate financing for biotechnology health strategic projects and

high-impact health biotechnology strategic projects.

(57) Medicinal products developed with innovative biotechnology technologies which will

bring a therapeutic advantage to patients should be incentivised with an extension of

the Supplementary Protection Certificate.

(58) The significant advances in analytical methodologies and biocompatibility assessment

tools enable more precise demonstration of comparability between biosimilar

medicines (‘biosimilars’) and their reference biological medicinal products. Building

30 Communication from the Commission Criteria for the analysis of the compatibility with the internal

market of State aid to promote the execution of important projects of common European interest 2021/C

528/02, C/2021/8481, OJ C 528, 30.12.2021, pp. 10. 31 Communication from the Commission Framework for State aid for research and development and

innovation 2022/C 414/01, C/2022/7388, OJ C 414, 28.10.2022, pp. 1. 32 Commission Regulation (EU) No 651/2014 of 17 June 2014 declaring certain categories of aid

compatible with the internal market in application of Articles 107 and 108 of the Treaty Text with EEA

relevance, OJ L 187, 26.6.2014, pp. 1. ELI: http://data.europa.eu/eli/reg/2014/651/2023-07-01. 33 COMMUNICATION FROM THE COMMISSION – Framework for State Aid measures to support the

Clean Industrial Deal (Clean Industrial Deal State Aid Framework), C/2025/7600, OJ C, C/2025/3602,

4.7.2025.

EN 44 EN

on its ongoing work on a Reflection paper on a tailored clinical approach in biosimilar

development34, the European Medicines Agency35 (‘the Agency’) should develop non-

binding guidance giving consideration to a potential reduction of the clinical data

required for the development and marketing authorisation procedures for biosimilars,

based on robust analytical and other non-clinical evidence.

(59) The manufacturing capacity and expertise for biosimilars in the Union can greatly

contribute to ensure Union competitiveness, strategic autonomy and resilience, both

from a health and sustainability perspective. Therefore, Member States should

recognise, and support projects that fulfil the conditions laid down in this Regulation

for strategic projects for biosimilars manufacturing.

(60) Biosimilars can play an important role in diversifying and strengthening supply chains,

promoting competition and fostering economic growth in the Union and for its global

partners. Accordingly, the promoters of strategic projects for biosimilars and the

companies active in this area should be encouraged to establish or strengthen

cooperation with international biotechnology clusters.

(61) AI can enhance the development, safety, efficiency and scale-up of biotechnology and

biomanufacturing, provided that its use is responsible and aligned with Union

legislation. To pursue this, the Commission and the Member States should promote an

AI-first policy approach as introduced in the Apply AI Strategy when implementing

this Regulation and the exchange of knowledge, standards and best practices relevant

to the responsible application of the AI-First Policy Approach36. The responsible and

effective integration of AI can enhance research, development and regulatory

processes and thereby support the competitiveness of Union innovators in

biotechnology. The Commission and the Member States should therefore encourage

the uptake of such approaches and facilitate the exchange of knowledge, standards and

best practices relevant to their application. That cooperation should remain fully

compliant with Union competition rules.

(62) The rapid expansion and increasing complexity of AI applications throughout the

medicinal-product lifecycle requires structured and coherent guidance to ensure their

safe, effective and trustworthy use. The Agency is developing expertise in this area

through initiatives such as the Good Manufacturing Practice (GMP) Annex 22 –

Artificial Intelligence, Q&A in AI in Pharmacovigilance, the GCP Annex to the

Guideline on computerised systems and electronic data in clinical trials and AI in

Clinical Development. It is therefore appropriate for the Agency to develop non-

binding guidance on the deployment and use of systems based on advanced

technologies, including of AI systems and of general-purpose AI models across

development, manufacturing, clinical trials, and post-authorisation activities for

compliance with applicable Union legislation in the health area. To ensure consistency

34 EMA Reflection paper on a tailored clinical approach in biosimilar development, 17 March 2025, draft

accessible at: https://www.ema.europa.eu/en/documents/other/reflection-paper-tailored-clinical-

approach-biosimilar-development_en.pdf 35 [Revised REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL laying

down Union procedures for the authorisation and supervision of medicinal products for human use and

establishing rules governing the European Medicines Agency, amending Regulation (EC) No

1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC) No 726/2004, Regulation

(EC) No 141/2000 and Regulation (EC) No 1901/2006] 36 Communication from the Commission to the European Parliament and the Council, Apply AI Strategy,

COM/2025/723 final.

EN 45 EN

across the health and digital domains, when developing or updating such guidance, the

Agency should cooperate with the Commission, including the AI office and should

consult relevant national competent authorities and stakeholders, and relevant expert

coordination groups established under Union legislation in the health and digital areas,

as appropriate.

(63) Moreover, the Agency should develop non-binding guidance on the deployment and

use of AI systems and of general-purpose AI models also in the procedures for the

authorisation of medicinal products, with a view to optimising processes and

increasing efficiency of regulatory activities. Such guidance should be developed and

published in agreement with the Commission, the AI Board and the competent

authorities.

(64) In order to accelerate the development and scale-up of biotechnology innovations that

are enabled, enhanced or significantly supported by AI and advanced computational

methods, the Union requires dedicated testing environments that combine

experimental, computational and data-driven capabilities. Given their essential role for

supporting AI-enabled biotechnology innovations, it is appropriate to establish

requirements in this Regulation for the recognition by the Commission and the support

for high-impact health biotechnology strategic projects in the form of biotechnology

testing environments, under certain conditions.

(65) Such environments could provide the wet-lab, bioprocess, pilot-line and translational

validation capacities necessary for AI-enabled biotechnology development, and should

complement, without duplicating, the functions of regulatory sandboxes established

under Union or national law as well as the testing and experimentation facilities

established in accordance with Regulation (EU) 2024/1689. Where relevant, they

should also leverage health data and the European Health Data Space in accordance

with Union legislation. These infrastructures should support the development of

biotechnology applications where the use of AI has the potential to accelerate

progress, in particular in health-related areas such as advanced therapies, where AI can

improve efficacy and safety — for example through optimised CRISPR site

prediction, tumour antigen identification, sequence engineering, delivery-vehicle

design, or the matching of diverse patient cancer-cell variants with CAR-T cell types.

(66) Having high-quality, interoperable, provenance-verified and well-annotated datasets is

essential for the development, testing and validation of trustworthy and competitive AI

systems and models used in biotechnology applications. For example, datasets

generated in the course of provision of healthcare are usually recorded in a way that

supports their initial purpose, such as diagnosis or treatment. Often, they are

technically not easily usable and fit for training, testing and validation of AI systems,

for example due to the use of different data standards or lacking annotations. Given the

potential of AI systems and models to support research and innovation in

biotechnology applications, it is important to ensure that high-quality data are

available for training, testing and validating AI systems and models used in health

biotechnology applications. To make such data more easily usable for those purposes,

it is appropriate to facilitate the enhancement of the quality of that data. Therefore, this

Regulation should lay down provisions for the recognition by the Commission of high

impact health biotechnology strategic projects in the form of biotechnology data

quality accelerators, to provide assistance to entities that lawfully hold relevant data to

improve data quality, standardize such data and make further improvements.

EN 46 EN

(67) Such biotechnology data quality accelerator projects should complement Union

initiatives such as data labs37 and by addressing the specific data-quality requirements

of biotechnology, ensuring that biological and health datasets are reliable,

interoperable and usable for the development of advanced AI models.

(68) The processing of personal data by the entities that lawfully hold the relevant data and

by the biotechnology data quality accelerators, in the context of biotechnology data

quality accelerators projects, takes place in the public interest. The Commission

should specify in the decision recognising the project as a high impact health

biotechnology strategic project, the specific provisions concerning the processing of

personal data necessary in order to achieve the objectives of the project. Such

provision may in particular include the categories of data, the specific roles of the

parties engaged in the processing, and the entities to which the personal data may be

disclosed. Where biotechnology data quality accelerators are recognised by the

Commission through calls for proposals, the Commission should be empowered to

adopt, by means of an implementing act, specific provisions concerning the processing

of personal data, through a decision prior to the launch of the call and the beneficiaries

of the call should be subject to the obligations laid down in that decision.

(69) Electronic health data referred to in Article 51 of Regulation (EU) 2025/327 of the

European Parliament and of the Council38, enhanced by biotechnology data quality

accelerators should be made available in accordance with that Regulation. The

biotechnology data quality accelerators support the objectives of the European Health

Data Space by contributing to improving the quality of data that is to be made

available under that space.

(70) To enable innovation and competitiveness in biotechnology, it is necessary to ensure

that SMEs, start-ups and scale-ups, and research organisations can access the high

computing capacity and AI resources required for advanced research, development and

biomanufacturing. Those actions may be supported through Union funding

programmes, funds and financial instruments, in accordance with the regulations

governing them. The Commission should ensure effective coordination with other

Union initiatives offering computing capacities to maximise efficiency and avoid

duplication. The Commission, including through the European Biotechnology Support

Network, should provide information and support, in particular to SMEs, start-ups and

scale-ups, for accessing high computing capacity and AI resources relevant to

biotechnology and biomanufacturing activities.

(71) Very innovative health biotechnology products or services vary significantly in the

degree to which they align or can align with existing Union legislative frameworks

and procedures. These products, despite their complexity, should however be

efficiently and adequately assessed within a single regulatory pathway, possibly

through a combination pathway. This is notwithstanding the fact that such health

biotechnology products or services, in the form of preparations, devices, diagnostics,

or other, for human use, exhibit characteristics that challenge the Union legislative

37 Proposed in the Communication from the Commission to the European Parliament, the Council, the

European Economic and Social Committee and the Committee of the Regions, A European Strategy for

Artificial Intelligence in Science – Paving the way for the Resource for AI Science in Europe (RAISE),

COM(2025) 724 final of 8 October 2025. 38 Regulation (EU) 2025/327 of the European Parliament and of the Council of 11 February 2025 on the

European Health Data Space and amending Directive 2011/24/EU and Regulation (EU) 2024/2847, OJ

L, 2025/327, 5.3.2025, ELI: http://data.europa.eu/eli/reg/2025/327/oj .

EN 47 EN

frameworks in the area of health (‘health biotechnology products’), for example

because they are under development and could potentially fall under the scope of an

Union legislative framework but there are questions related to the relevance of other

Union legislative frameworks; and/or because they combine different products,

technologies, processes, or components regulated under different Union legislative

frameworks; and/or because they require targeted adaptations of certain requirements

of the applicable Union legislative frameworks, ideally at an early stage of

development. These characteristics are not mutually exclusive and may overlap.

(72) Developers of such health biotechnology products can consequently face regulatory

uncertainty, potentially delaying or preventing patient access to beneficial

technologies and creating barriers to innovation and access to finance, hampering

competitiveness. To offer developers efficient and predictable regulatory procedural

pathways, the Union legislative frameworks in the health area should be equipped with

the right tools and should integrate consultative and collaborative approaches, to be

able to assess these health biotechnology products efficiently and timely. In addition,

developers of health biotechnology products should be supported in navigating

regulatory procedural pathways for their products in the best possible way. This

Regulation should therefore provide for measures and facilitators to ensure efficient

pathways to developers with reduced time-to-market, while safeguarding all existing

provisions to protect public health.

(73) At the same time, the Union has the strong experience and expertise to handle

regulatory complexity, and important measures to deal with health biotechnology

products have already been proposed. Directive 2001/83/EC of the European

Parliament and of the Council39 clarifies which legislative frameworks apply to

combinations of medicinal products and other products and establishes a single

authorisation pathway for them. In addition, existing Union legislative frameworks in

the area of health such as [revised Regulation (EU) 2017/745 of the European

Parliament and of the Council, [revised Regulation (EU) 2017/746], [revised

Regulation No (EC) 726/2004], Regulation (EU) 2024/1938 of the European

Parliament and of the Council40 contain specific mechanisms to manage the

determination of the regulatory status of products that do not fall clearly within a

Union legislative framework in the area of health. These mechanisms include the

possibility of requesting a recommendation or opinion from the respective advisory

bodies or the Agency, as applicable, at Union level, and eventually the possibility for

binding decisions of the Commission on the regulatory status. These mechanisms

should ensure predictability and conclusive opinions for products of which the status is

being debated, avoiding cases where it remains unclear which framework applies, and

the assessment of the product is consequently halted or delayed.

(74) Developers of health biotechnology products, in particular SMEs, start-ups and scale-

ups, often lack the regulatory expertise and capacity needed to identify, anticipate and

plan their entry into the appropriate regulatory procedural pathways. In order to

39 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the

Community code relating to medicinal products for human use, OJ L 311, 28.11.2001, p. 67, ELI:

http://data.europa.eu/eli/dir/2001/83/oj. 40 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 (OJ L, 2024/1938, 17.07.2024, ELI:

http://data.europa.eu/eli/reg/2024/1938/oj).

EN 48 EN

address this challenge, the EU Health Biotechnology Support Network, acting as a

service provider, should provide preliminary support to such developers by facilitating

information on, and access to, applicable legislative frameworks, and should point to

relevant opinions, recommendations, guidance and decisions.

(75) To allow developers to anticipate and navigate procedures to determine the regulatory

status, a Union-wide and cross-framework Regulatory Status Repository should be

established. That Repository should compile relevant opinions, recommendations,

decisions and guidance developed under the mechanisms established in the Union

legislative frameworks in the area of health with a view to determine the regulatory

status of a product. That Repository should also include the recommendations on the

classifications of products as advanced therapy medicinal products (ATMPs) issued by

the Committee for Advanced Therapies, established in accordance with Regulation

(EC) No 1394/2007 of the European Parliament and of the Council41 prior to the date

of application of Regulation (EC) No 726/2004. Such repository should be accessible

for developers and authorities to enable them to understand how similar health

biotechnology products are evaluated in terms of status, and what considerations are

put forward. This will guide developers and authorities, to improve efficiency, foster

transparency, and ensure consistency and mutual learning across Union and national

authorities. This Regulatory Status Repository should not include opinions,

recommendations, decisions and guidance on the regulatory status of AI systems and

models within the scope of the Regulation (EU) 2024/1689.

(76) Existing mechanisms for addressing health biotechnology products, including those

for determining their regulatory status as described above, provide for consultation

among various advisory bodies and the Agency. However, such procedures are

typically focused on individual products on a case-by-case basis. There is, therefore, a

need for more systematic coordination across Union legislative frameworks to better

identify and prepare for emerging innovations driving the development of health

biotechnology products that may challenge existing Union legislative frameworks in

the area of health. With an expected increase in health biotechnology products entering

the regulatory system, there is a growing need for horizontal foresight anticipating

technological developments through structured horizon-scanning activities which will

enable the regulators to adopt regulatory approaches proactively, rather than reactively

addressing each new difficult case.

(77) To that end, this Regulation should establish a Foresight Panel for Emerging Health

Innovation to complement existing mechanisms by providing a platform for horizontal

coordination and forward-looking analysis. The Panel should conduct horizon

scanning to identify emerging technologies at an early stage and discuss cross-cutting

regulatory issues, thereby informing and anticipating discussions on health

biotechnology products that may subsequently arise within individual frameworks. It

should provide expertise on emerging science and technology in the field of health

underpinning the development of health biotechnology products to the Commission,

the Agency and to relevant Union-level advisory bodies and competent authorities and

other entities in the Member States in the area of health.

41 Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007

on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No

726/2004, OJ L 324, 10.12.2007, p. 121. ELI: http://data.europa.eu/eli/reg/2007/1394/oj.

EN 49 EN

(78) This Panel should complement, without replacing, existing classification

mechanisms established under the respective Union legislative frameworks, which

remain exclusively competent to provide opinions, recommendations or binding

determinations on the regulatory status of specific products. Member States, as

authorities primarily responsible for decisions on regulatory status, should be closely

involved in the Panel’s work, sharing practical expertise and experience to inform

cross-framework dialogue, support harmonisation efforts, and designate experts that

bring the Member State perspective.

(79) Health biotechnology products increasingly challenge Union legislation in the area of

health and necessitate further flexibility of that legislation, in

particular regarding health biotechnology products that could be candidates for

regulatory sandboxes under such frameworks. The development and implementation

of those sandboxes can clearly benefit from effective consultation across the

authorities responsible for regulatory sandboxes falling within the scope of Union

legislative acts other than this Regulation. By facilitating the exchange of information

and experiences between sandboxes, including on regulatory approaches,

technological challenges, and emerging scientific understanding, the Union can

develop more coherent and responsive regulatory responses to health biotechnology

products. The activities of sandboxes should be carried out in full compliance of

antitrust information exchanges provisions under Union competition law. The

Foresight Panel for Emerging Health Innovation could play a role in promoting such

coherence and knowledge sharing.

(80) The Commission should be able to establish regulatory sandboxes for health

biotechnology products which are at a very early stage of development and do not fall

within the scope of existing Union legislative acts in the area of health, thus not being

in a position to benefit from the regulatory sandboxes established in accordance with

those other acts. Those sandboxes should provide a controlled environment in which

to explore and assess innovative technologies. The sandboxes should operate

according to a specific sandbox plan that specifies the duration of the sandbox, risk

mitigation measures and supervision arrangements. For the development and

implementation of the sandbox plan for such products, the Commission may consult

advisory bodies and Agencies established under the Union legislative acts in the area

of health for example to determine which requirements or rules laid down in those acts

could, or could not, be applied to the products concerned. The outcome of the sandbox

would be a recommendation by the Commission on an existing appropriate regulatory

procedural pathway for authorising the product in question. The lessons learned from

those sandboxes should lead to reflections on possible regulatory actions to be taken at

Union level for the products or categories of products concerned. Accordingly, this

approach would provide a flexible Union response to emerging innovations while

building an evidence base for potential future legislative developments.

(81) Biotechnologies are critical for the Union’s defence and security. Closer coordination

between civil and defence research, development and manufacturing can accelerate

safe innovation and reduce fragmentation. Therefore, this Regulation should make

provisions for the recognition by the Commission and support of projects contributing

to an EU Biothreat Radar as high impact health biotechnology strategic projects,

subject to conditions established in this Regulation.

(82) Furthermore, this Regulation should make provisions for the recognition by the

Commission and support of high impact biodefence capability projects, as part of the

category of high impact health biotechnology strategic projects, subject to conditions

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laid down in this Regulation. Such projects should make a significant contribution to

objectives such as the prevention or mitigation of the misuse of biotechnologies. As

such, those projects should benefit from priority status in administrative procedures in

accordance with this Regulation and could be given particular consideration for

support under national and Union funding programmes and instruments, including

from those budgets allocated to defence.

(83) Without prejudice to Member States’ competences and in accordance with the Union

funding programmes and instruments, biotechnology activities relevant to defence,

security, safety, preparedness, and resilience, including dual-use technologies could

be given particular consideration, where appropriate, for support under the European

Defence Fund, the Union Research Framework Programmes and other Union funding

instruments.

(84) Moreover, where national authorities so decide, expenditure on such dual-use

infrastructures and related biodefence activities may be counted toward relevant

defence spending targets.

(85) The biotechnology landscape is evolving at an unprecedented speed, driven by

advances in synthetic biology and genome editing, which, coupled with AI, make

biotechnology stand at the forefront of innovation, offering unprecedented

opportunities for advancing health and protecting against biological threats. These

advances also make biotechnological misuse faster, cheaper, and more accessible.

Biotechnologies can pose serious and distinctive risks that call for continuous

assessment and anticipatory safeguards. Therefore, a limited set of biotechnology

products with significant potential for misuse (‘biotechnology products of concern’)

require a specific framework to prevent and protect against their misuse.

(86) Union and international rules address certain aspects related to biological threats,

biological incidents or biological risks, in particular in relation to serious cross-border

threats to health42, the control of exports, brokering, technical assistance, transit and

transfer of dual-use items43, resilience in biosafety and biosecurity through the

Biological and Toxin Weapons Convention (BTWC)44, the Chemical Weapons

Convention (CWC), the contained use of genetically modified micro-organisms45,

workers’ protection from risks related to exposure to biological agents at work46, in

relation to AI systems and models through Regulation (EU) 2024/1689. However, the

42 Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on

serious cross-border threats to health and repealing Decision No 1082/2013/, p. 26.

ELI: http://data.europa.eu/eli/reg/2022/2371/oj. 43 Regulation (EU) 2021/821 of the European Parliament and of the Council of 20 May 2021 setting up a

Union regime for the control of exports, brokering, technical assistance, transit and transfer of dual-use

items , OJ L 206, 11.6.2021, pp. 1. ELI: http://data.europa.eu/eli/reg/2021/821/oj. 44 Council Decision (CFSP) 2023/2636 of 20 November 2023 amending Decision (CFSP) 2021/2072 in

support of building resilience in biosafety and biosecurity through the Biological and Toxin Weapons

Convention, no longer in force. OJ L, 2023/2636, 22.11.2023, ELI:

http://data.europa.eu/eli/dec/2023/2636/oj 45 Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained

use of genetically modified micro-organisms (Recast) (Text with EEA relevance), OJ L 125, 21.5.2009,

p. 75. ELI: http://data.europa.eu/eli/dir/2009/41/oj. 46 Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the

protection of workers from risks related to exposure to biological agents at work (seventh individual

directive within the meaning of Article 16(1) of Directive 89/391/EEC), OJ L 262, 17.10.2000, p. 21.

ELI: http://data.europa.eu/eli/dir/2000/54/oj.

EN 51 EN

approach remains fragmented and does not sufficiently address all aspects related to

the misuse related to biotechnologies. A consistent and high level of protection

throughout the Union should therefore be ensured in order to guarantee biotechnology

remains trustworthy and provides legal certainty for economic operators in the

biotechnology sector.

(87) There are divergent requirements in Member States for screening, verification,

reporting and tracking of suspicious transactions for biotechnology products of

concern, which includes benchtop equipment and sequences of concern. This lack of

harmonisation creates additional costs for economic operators, especially for those

with strong security systems in place, and might distort competition within the internal

market as well as potentially create barriers to trade and innovation.

(88) A Union framework for strengthening monitoring of the potential misuse of

biotechnology products of concern is therefore needed and requested by industry

actors, including SMEs, to safeguard the free movement of goods and ensure a level

playing field in the internal market. This framework needs to take into account recent

international developments and good practices in other jurisdictions and relevant

industry consortia and standard-setting fora, including to promote interoperability for

Union operators active globally and providing for a level playing field in the internal

market.

(89) To ensure that oversight remains proportionate and appropriately calibrated to the

risks, and in line with existing Union harmonisation legislation, the complementary

harmonisation measures established in this Regulation to prevent misuse should only

apply to a limited subset of biotechnology products of concern which pose the highest

risk of misuse, and whose misuse has the highest consequences, such as certain

sequences of concern or benchtop nucleic synthesis equipment able to create such

sequences of concern. For the purposes of legal clarity and certainty, such products

should be listed in Annex I to this Regulation. As biotechnology will continue to

rapidly evolve, the Union framework should remain flexible and capable of

responding to emerging biotechnology products, materials, and scientific evidence

regarding potential risks. Therefore, the Commission should be empowered to adopt

delegated acts to amend Annex I to respond swiftly to scientific and security

developments and in consultation with relevant experts including the Advisory Group

on Biosecurity established under this Regulation, while following the existing

international and other relevant regulatory frameworks

(90) The Union framework should be comprehensive to apply to the making available to,

introduction, or use of, biotechnology products of concern, by any natural or legal

person in the Union as well as to the making available to any natural or legal person

outside the Union.

(91) To reduce risks at the point of sale within the Union, economic operators should verify

the legitimate need and peaceful purposes of prospective customers before making

available the biotechnology products of concern included in Annex I to this

Regulation.

(92) Apart from economic operators, other natural and legal persons that are not economic

operators, including researchers, laboratories, universities, or research institutes, may

also make available and use biotechnology products of concern. Such persons should

be subject to the same screening obligations as economic operators, while preserving

freedom of research and academic freedom in accordance with Article 13 of the

Charter of Fundamental Rights of the European Union and Article 179 of the Treaty

EN 52 EN

on the Functioning of the European Union, except where knowledge and material are

shared with persons employed within the same legal entity. Biotechnology products of

concern should not be made available to members of the general public.

(93) Benchtop nucleic acid synthesis equipment poses a particular challenge to the

verification of legitimate need and the tracking and monitoring of sequences of

concern. Such equipment should therefore contain an automatic mechanism to screen

for sequences of concern.

(94) This Regulation should lay down provisions requiring economic operators to report

suspicious transactions throughout the supply chain, regardless of whether the

prospective customer is a member of the general public or an economic operator,

private or public, and should apply in relation to biotechnology products that are

considered of concern provided the risk or threat they may pose, which includes

certain sequences of concern and biotechnology products. Reporting and recording for

three years the suspicious transactions would allow other operators to be aware of the

risks of the concerned product, while avoiding duplicate reporting, and allowing

authorities to monitor and assess the risks and verify compliance with the obligations

laid down in this Regulation.

(95) Suspicious transactions should be detected and reported rapidly through harmonised

procedures, with Member States designating national contact points that provide clear

reporting channels, as well as record data and ensure compliance, with a view to

contributing to safeguarding national and Union’s safety.

(96) Where a biotechnology product of concern falls also under categories regulated under

other Union legislation, to avoid duplication of reporting, where a suspicious

transaction of that biotechnology product of concern has already been reported under

one legal framework, it should not be reported again.

(97) Licensed biotechnology products containing nucleic acid sequences, including

authorised medicinal products for human and veterinary use, should not be subject to

verification of legitimate need, as they have undergone regulatory assessment and do

not constitute independent biological threats. However, the stand-alone nucleic acid

sequences in synthetic form should fall within the scope of legitimate-need screening,

as they may be misused and be relevant to biosecurity oversight.

(98) Certain tools with a potential to be misused without further modification and to cause

serious harm to public health and safety, agricultural crops and other plants, to

animals, the environment, material or government security (dual-use research of

concern - ‘DURC’) are increasingly affordable and accessible, also through progress

in AI capabilities, which elevates the risk of misuse by actors lacking appropriate

competence, oversight, legitimate or peaceful intent. A proportionate and risk-based

framework is therefore necessary to minimise opportunities for misuse of DURC,

including on AI models in biological applications, while preserving legitimate

research and innovation.

(99) Supervision by the public authorities is needed to ensure that research, innovation and

commercial operations are conducted responsibly and securely. This in turn can build

public trust in biotechnology. Effective supervision requires adequately resourced and

trained national inspection authorities with adequate investigative powers,

complemented by risk-based audits to verify the effectiveness of the screening

obligations laid down in this Regulation, as well as training and awareness-raising for

the staff of the designated inspection authorities and stakeholders, and regular

EN 53 EN

exchanges among inspection authorities and economic operators, including operators

involved in online marketplaces. Moreover, Member States should lay down rules on

penalties applicable to infringemens of the provisions laid down in this Regulation

regarding the prevention of biotechnology misuse. Such penalties should be effective,

proportionate and dissuasive.

(100) The Commission should monitor Member States in the enforcement of this legislation,

including by requesting information and records to check the screening and suspicious

transaction reporting frameworks of economic operators.

(101) Considering the evolving biosecurity landscape and the misuse risks of biotechnology

products of concern, this Regulation should establish an Advisory Group on

Biosecurity (‘the Advisory Group’) to monitor the landscape of biological risks and

alert the Commission when it identifies new biotechnology products of concern. The

Advisory Group should complement the work of existing expert groups in health

security. It should be composed of globally leading independent scientists. Its

members should be selected and operate in accordance with the Commission Decision

of 30 May 2016 establishing horizontal rules on the creation and operation of

Commission expert groups. The members of the Advisory Group should be appointed

by the Commission based on up-to-date scientific or technical expertise in the area of

biosecurity, biodefence and AI.

(102) AI offers significant potential to enhance the Union’s competitiveness and innovation

capacity, including in the area of biotechnology. This potential should be realised in a

safe and responsible manner. In this regard, Regulation (EU) 2024/1689 lays down

harmonised rules for placing on the market putting into service and use of AI systems

and models in the Union, prohibitions of certain AI practices, harmonised

transparency rules for certain AI systems, rules on market monitoring, market

surveillance, governance and enforcement as well as measures to support innovation.

AI systems and general-purpose AI models can lower the barrier for actors to misuse

biotechnology. The provisions of Regulation (EU) 2024/1689 governing AI systems

and general-purpose AI models aim to mitigate this. Further, AI models, as described

in Regulation (EU) 2024/1689, used in biological applications, that are not covered by

Regulation (EU) 2024/1689 (‘AI models in biological applications’) can also pose

risks, including different types of systemic biological risks.

(103) AI models in biological applications encompass both specialised tools and more

general models trained on large datasets of biological sequences that can be adapted

for a variety of downstream tasks. Such models in biological applications can aid in

the development of novel, more dangerous biological threats, increasing the ceiling of

harm of biotechnology misuse. Capabilities of such AI models in biological

applications therefore need to be monitored, investigating and assessing risks to

identify any models posing biological systemic risks and ensuring necessary risk

mitigation measures are taken. In addition, systemic resilience would need to improve

to prevent, detect and respond to any misuse incidents.

(104) The Advisory Group should therefore monitor the capabilities of AI models in

biological applications, working closely with scientists and companies developing

such models and should be tasked to issue a qualified alert to the Commission if it

identifies that an AI model in biological applications not covered by Regulation (EU)

2024/1689 poses biological systemic risk. The Advisory Group should inform the

Scientific Panel of independent experts established under Article 68 of Regulation

(EU) 2024/1689, if it has reasonable grounds to suspect that an AI model covered by

EN 54 EN

that Regulation poses biological systemic risks. That panel could in turn issue a

qualified alert to the AI Office in accordance with Regulation (EU) 2024/1689.

Considering that the AI Office established by Commission Decision C(2024) 39047

has as its mission to develop Union expertise and capabilities in the field of AI and to

contribute to the implementation of Union law on AI, that office should participate in

the establishment of the Advisory Group.

(105) The European Health Biotechnology Steering Group established by this Regulation

should also ensure proper coordination and information exchanges among Member

States on the enforcement of the biosecurity provisions in this Regulation, consulting

the Advisory Group, other relevant existing bodies and external experts where

appropriate.

(106) This Regulation should establish a framework of measures, in particular for health

biotechnology strategic projects and high impact health biotechnology strategic

projects, to ensure the growth of the health biotechnology sector. This Regulation and,

in particular, the measures in Chapters II to VIII, should serve the aim of creating and

reinforcing favourable conditions for health biotechnology, from research and

development to the timely placing on the Union market and production of

biotechnology innovations and products. The pathway to placing on the the market of

health biotechnology innovations and products are governed by important and

comprehensive sets of regulatory rules and procedures. Reviewing and streamlining

these rules and procedures is an inherent part to achieve the aim of facilitating and

accelerating the development, placing on the market and production of health

biotechnology innovations and products. The practical effectiveness of the measures of

this Regulation, in particular those in Chapters II to VIII, depends to a large extent on

a review and streamlining of certain rules and procedures applicable to health

biotechnology innovations and products so as to facilitate timely access to the market.

As set out in recitals [5 to 7], health biotechnology must be understood broadly and

encompasses also the veterinary and phytosanitary fields which have as their direct

objective the protection of public health.

(107) For instance, a timelier and facilitated risk assessment process for products subject to

pre-market authorisation in accordance with Union food law, accelerated procedures

and measures facilitating innovation, such as measures on regulatory sandboxes are

needed for the efficiency of the facilitation measures laid down in this Regulation.

(108) Regulation (EC) No 178/2002 lays down the general principles and requirements of

food law, so as to form a common basis for measures governing food law at both

Union and national level. For the purposes of risk assessment at Union level, it

establishes the European Food Safety Authority (‘the Authority’), as the responsible

Union risk assessment body in matters primarily relating to food and feed safety.

(109) Considering the increasing prevalence of diet-related health issues, it is essential to

expand the Authority’s mandate to encompass all aspects of nutrition and to enable it

to provide advice concerning the nutritional properties of food products and practices,

including those derived from advanced biotechnological processes.

(110) It has been observed that a significant number of application and notification dossiers

submitted to the Authority are either incomplete or do not meet the applicable

47 Commission Decision of 24.1.2024 establishing the European Artificial Intelligence Office C(2024)

390.

EN 55 EN

regulatory and scientific specifications requirements to enable the best quality

scientific assessment by the Authority, resulting in the need for requests for additional

information during the risk assessment process and, consequently, leading to

sometimes significant delays. This is also the case where biotechnology innovations

and products are concerned, as such products would benefit strongly from pre-

submission scientific advice on study design and testing strategies. Applicants or

notifiers of such products, in particular small and medium-sized enterprises do not

always have a clear understanding of the applicable regulatory and scientific

requirements when compiling application dossiers, in particular as regards the types

and details of studies to conduct. It is thus appropriate to enlarge the scope of the

general pre-submission advice provided by the Authority at the request of a potential

applicant or notifier to encompass non-committal advice on regulatory aspects

including applicable rules and guidance documents, as well as scientific advice on

study design and testing strategies. This advice should be provided by the staff and

experts of the Authority to ensure the most updated scientific advice. Given the

broadening of the scope of the general pre-submission advice which is already

available for both new and renewals of approvals/authorisations, it is no longer

necessary to provide for a specific pre-submission advice for renewals.

(111) Practice has shown that the existing procedural consequences in the event of non-

compliance with the notification requirement of commissioned studies at pre-

submission phase appear to be too severe, particularly for small and medium-sized

enterprises, and could impede competitiveness and innovation in the food chain. It is

therefore necessary to shorten the existing procedural consequence in the event of non-

compliance from six months to three months following the re-submission of the

relevant application or notification.

(112) In order to strengthen the coherence of risk assessments carried out by different

Scientific Panels within the Authority, foster stronger synergies and promote greater

harmonisation across guidance documents and scientific opinions, for the benefit of

applicants while enhancing the effectiveness and efficiency of the Authority’s risk

assessment processes, it is appropriate that the staff of the Authority chairs the

Scientific Committee and the Scientific Panels, without voting rights. The Scientific

Committee should continue to be composed by experts.

(113) The food and feed sector is experiencing rapid technological advancements, including

biotechnology, AI, smart farming techniques, development of new approach

methodologies, that could contribute to reduction of animal testing and circular

economy practices promoting resource efficiency and waste reduction. It is therefore

appropriate to provide Member States with the possibility of setting up regulatory

sandboxes that can provide an environment for the testing of those innovations in a

controlled manner, incentivising research and development, whilst allowing for

adaptive regulatory practices that can be modified based on feedback and results from

live trials. Regulation (EC) No 178/2002 should therefore be amended accordingly.

(114) Given the diversity of sectors covered by Union food law, and the fact that Member

States have diverse food systems, cultural preferences, local market conditions, and

research and risk assessment bodies, regulatory sandboxes should be established a

national level in order to ensure the necessary flexibility to allow for experimentation

specifically tailored to address local needs, preferences, and consumer behaviours. For

the same reasons, and in order to support innovation along the whole food chain,

regulatory sandboxes should be allowed also at retail level and, thus, making available

products under the regulatory sandboxes to food business operators or consumers

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should not be considered as placing on the market. However, in order to ensure that

the establishment of regulatory sandboxes does not jeopardise food safety or

consumers’ information and that they are established and function in such a way as to

enable the collection of sound and useful information to inform future regulatory

changes, rules should be laid down concerning the objectives pursued within

regulatory sandboxes, the modalities for their adoption, amendment and revocation,

the control of the activities carried out under the regulatory sandbox, monitoring and

reporting as well as rules ensuring the protection of human and animal health and of

the environment.

(115) Regulatory sandboxes should not be allowed for some products. Experience has shown

that certain types of novel foods trigger ethical or cultural concerns among various

consumer segments regarding their acceptability. Since those aspects are best

addressed within the applicable rigorous regulatory framework established by

Regulation (EU) 2015/2283 of the European Parliament and of the Council48, it is

appropriate to exclude novel foods from the scope of regulatory sandboxes. For GMOs

legal pathways 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 there should not be a duplication of

paths in order to maintain 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. As regards innovations concerning novel

plastic recycling technologies for plastics intended to come into contact with food,

chapter IV of Commission Regulation (EU) 2022/161649 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.

(116) To ensure uniform conditions and principles for the setting up, operation and

supervision of Regulatory sandboxes, implementing powers should be conferred on

the Commission in the context of Regulation (EC) No 178/2002. Those implementing

powers should be exercised in accordance with Regulation (EU) 182/2011 of the

European Parliament and of the Council50. In case of emergencies, the Commission

may provisionally adopt an measures in accordance with an urgency procedure

requesting the suspension of the regulatory sandbox concerned.

48 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). 49 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). 50 Regulation (EU) No 182/2011 of the European Parliament and of the Council of 16 February 2011

laying down the rules and general principles concerning mechanisms for control by Member States of

the Commission’s exercise of implementing powers (OJ L 55, 28.2.2011, p. 13, ELI:

http://data.europa.eu/eli/reg/2011/182/oj).

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(117) Considering the additional financial burden established on the Authority with the

expansion of its mandate following the amendments set out in this Regulation, the

possibility of establishing fees in order to fully or partially fund EFSA’s new tasks

could be considered.

(118) Clinical trials with advanced investigational therapy medicinal products (ATMPs),

including those consisting or containing genetically modified organisms (GMOs)

within the meaning of Article 2 of Directive 2001/18/EC of the European Parliament

and of the Council51, can provide early access to transformative treatments for patients

with rare or otherwise untreatable conditions and are important to prepare for the

marketing authorisation of the medicinal products for such treatments. The nature and

design of certain advanced investigational therapy medicinal products is such that the

risks to human health and the environment resulting from a deliberate release of a

GMO into the environment are, in practice, either excluded or negligible. For example,

in viral vectors, which are genetically modified viruses used to deliver genetic material

into cells, the wild-type virus genome is largely removed resulting in replication-

defective recombined particles. As these particles cannot reproduce themselves, they

present at most a negligible risk to human health and the environment.

(119) Consequently, when controlling under Regulation (EU) No 536/2014 for risks from

the deliberate release into the environment of GMOs, a risk-proportionate approach

should be applied and Regulation (EC) No 1394/2007 should be amended with respect

to certain, clearly delineated categories of advanced investigational therapy medicinal

products that consist or contain GMOs, which present no or negligible risks to human

health and the environment. Whilst it is appropriate to exempt such clearly delineated

categories of advanced investigational therapy medicinal products from the

requirement to submit an environmental risk assessment, sponsors of clinical trials

should, however, submit a declaration as part of the clinical trial application that

explains why the advanced investigational therapy medicinal products concerned falls

into one or more of the specific categories of products presenting no or negligible risks

to human health and the environment. The Committee for Medicinal Products for

Human Use (CHMP) referred to in Article [148] of Regulation […] [revised

Regulation No (EC) 726/2004] should verify this declaration. For the same

considerations of a risk-proportionate approach, the above-mentioned categories of

advanced investigational therapy medicinal products should also be exempted from the

requirements of Regulation (EU) No 536/2014 regarding manufacturing and import.

Annex I to the Regulation (EU) No 536/2014 should also be amended to ensure

consistency with the aforementioned amendments to the Regulation (EC) No

1394/2007.

(120) Scientific and technological advances are driving the development of advance therapy

medicinal products (ATMPs). To future proof the ATMPs legislative framework, the

power to adopt delegated acts should be delegated to the Commission to amend

Regulation (EC) No 1394/2007, by clarifying the definition, without extending its

scope, of what constitutes a tissue engineered product, in light of technical and

scientific advancements in the field of ATMPs. To that effect, the Commission should

carry out appropriate consultations of the Agency and of the Substances of Human

Origin Coordination Board (‘the SCB’).

51 Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the

deliberate release into the environment of genetically modified organisms and repealing Council

Directive 90/220/EEC, OJ L 106, 17.4.2001, p. 1, ELI: http://data.europa.eu/eli/dir/2001/18/oj .

EN 58 EN

(121) The measures established in this Regulation, including regarding health biotechnology

strategic projects and high impact health biotechnology strategic projects, access to

funding, biosimilars and the application of artificial intelligence in the health

biotechnology sector aim to strengthen the health biotechnology sector. Those

measures aim to foster research, development, testing, and preparing for market entry

of health biotechnology products and services. This is the case for the centres of

excellence for advanced therapies, the overall aim of which is to accelerate the placing

on the market of advanced therapies, accelerate clinical translation, improve quality

control and facilitate patient access across the Union. Similarly, the biotechnology

development accelerators aim to provide trusted testing or demonstration facilities for

process testing, validation, and small batch manufacturing, including for the initial

phases of clinical trials. Similarly, time to market for biotechnology products is one

key factor that impacts investments in the sector and accordingly access to funding for

developers and start-ups in the biotechnology sector. Many of the products subject to

those measures are expected to be biological medicinal products (‘biologicals’), for

which clinical research and trials are an essential step on their way to the market.

Therefore, the measures established in this Regulation, in particular on biotechnology

health strategic projects and high impact health biotechnology strategic projects, are

intrinsically intertwined with, and depend on, the strengthening of clinical research in

Europe. This is because all biotechnology products expected to be developed or

supported through the health biotechnology strategic projects and high impact health

biotechnology strategic projects are depending to a very large extent on an efficient

and vibrant ecosystem of clinical research in the Union.

(122) Amending Regulation (EU) No 536/2014 of the European Parliament and of the

Council52 to bring simplification and shorten the time for biotechnology innovations to

reach the Union market is crucial to streamline and accelerate clinical trials processes

in the Union and to make the legislative framework competitive globally so as to

attract more clinical research to the Union. Without an efficient, accelerated and

streamlined legislative framework for clinical trials authorisation in the Union, the

other measures in this Regulation, and in particular the framework for the recognition

and support of health biotechnology strategic projects and high impact health

biotechnology strategic projects would be deprived of their effectiveness, as all health

biotechnology medicinal products require state of the art clinical research and a

globally competitive regulatory framework for clinical trials authorisation.

(123) The clinical trials offer early access to the most innovative therapies, contribute to a

sustainable healthcare system, maintain scientific excellence and specialised skills and

they also support prosperity in the Union. Enabling the development of innovative

biological medicines through clinical trials is particularly important, since those

medicines often provide life-saving therapeutic options, including in cancer care or

against rare genetic conditions, and, due to their complexity, they are often more

difficult and expensive to develop. Increased clinical trials in the Union for biological

medicines could potentially contribute to more manufacturing in the Union, higher

number and earlier regulatory submission of biological medicines for marketing

authorisation applications and higher percentage of EU clinical data in marketing

authorisation applications. In relation to this, biological medicines sales are key

52 Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on

clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158,

27.5.2014, p. 1, ELI: http://data.europa.eu/eli/reg/2014/536/oj).

EN 59 EN

drivers of growth. In 2024, the European Union spent €228 billion on medicines at list

prices, including €95 billion on biological medicines, which now comprise 41% of

total pharmaceutical spending. Spending on biological medicines continues to outpace

that of small molecules (~5%) by 3x and the total prescription market, at a rate of

14.7% in the most recent period53. In this context, simplifying Regulation (EU) No

536/2014 and accelerating multinational clinical trials appears necessary with a view

to accelerate time to market of heath biotechnology innovations and thus secure the

effectiveness of the substantive provisions laid down in this Regulation.

(124) At the same time, Regulation (EU) No 536/2014 applies to all clinical trials

irrespective of the type of investigational medicinal product, whether it be biological

or chemical molecules. However, the amendments to Regulation (EU) No 536/2014

through this Regulation, for streamlining and simplifying that Regulation, are

particularly relevant for biologicals. This is because the development of biologicals

relies heavily on multinational clinical trials to be able to recruit the necessary number

of patients.

(125) Moreover, the limitation of the scope of the envisaged amendments to biologicals

would be against the core principle of Regulation (EU) No 536/2014 to create a

harmonised EU-level system for clinical trials authorisations. It would create two

authorisation pathways for chemical medicines and biologicals and it would not be

appropriate to distinguish these procedurally, considering the coordinated assessment

procedure established in Regulation (EU) No 536/2014 and the single EU Portal and

database as IT system provided for in that Regulation for the electronic submissions

and assessment of all applications. In addition, providing for different timelines for

biological and chemical medicines could create uncertainty for developers and could

be perceived as creating double standards for clinical research on medicines, where the

biotechnology products, often more complex, would benefit from shorter and more

streamlined timelines. Such fragmented approach could potentially also increase the

burden on regulators and could lead to different national interpretations regarding the

implementation of the respective authorisation procedures. This in turn would risk

putting multinational clinical trials at disadvantage with more associated negative

effects for biological development. Further, such an approach could have a particularly

negative impact on combination trials testing combination medicinal products, where

biological and chemical active substances are combined within a single

pharmaceutical form, to treat debilitating medical conditions for example but not

limited to breast, lung, colorectal cancers or autoimmune diseases, as well as on trials

comparing a biological and a chemical medicinal products or on trials using a

chemical medicine as a standard of care treatment in the control arm . Consequently,

the amendments to Regulation (EU) No 536/2014 should apply to both biologicals and

chemicals.

(126) The Union has unique advantages as a place for multinational clinical trials due to its

large population, rich genetic diversity, scientific excellence and robust research

infrastructures, and high ethical, quality and safety standards. To fully leverage these

strengths and considering the key and increasing role of research and clinical trials for

a thriving health biotechnology sector, it is necessary to amend the Regulation (EU)

No 536/2014 to further streamline and speed up the authorisation processes especially

for multinational clinical trials.

53 See figure 2, EU spending growth at list price levels by segment and leading therapy area, in Annex to

this document.

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(127) To accelerate and streamline the approval processes in multinational clinical trials it is

necessary to give a stronger leading role to the reporting Member State and further

strengthen the principles of mutual trust and reliance. The assessment by the reporting

Member State, including of the ethical aspects of the trial, should serve as a reference

for the other Member States concerned. Member States concerned should complement

the assessment by the reporting Member State only when necessary, and be entitled to

raise considerations from ethical, relevant national law or national standard of care

perspectives. Strengthening reliance on the reporting Member State’s assessment

would reduce duplication of work and allow Member States and sponsors to allocate

resources more effectively, while ensuring high level of protection of subjects and the

robustness of data.

(128) Defined timelines in the context of clinical trials approval are necessary to guarantee

speed and enhance predictability of the authorisation process, especially for

multinational clinical trials. Defined maximum timelines should allow the Member

State authorities with efficient planning to reduce periods of inactivity and thus

regulatory delays between the assessment phases and enable short procedure for

clinical trial approval overall. Stronger reliance on the reporting Member State would

also result in efficiency gains, improve resource allocation and would enable the

shortening of the consecutive assessment steps without compromising the quality of

the assessments. It would benefit the sponsors as well, as it will result in a quicker start

of a clinical trial, as well as in increased transparency and predictability for more

effective planning. To reduce regulatory bottlenecks by allowing coordinated

interaction between Part I and Part II assessments in multinational clinical trials, their

respective assessment timelines should be aligned.

(129) Recognising the importance of advanced therapeutic medicinal products (ATMPs) as

drivers of innovation in biotechnology and regenerative medicine, it is appropriate to

introduce a series of regulatory provisions to simplify and shorten the timelines for

authorisation of clinical trials in the Union. In particular, to accelerate the conduct of

clinical trials investigating the ATMPs, the authorisation procedure should be

shortened by removing the additional 50 days of assessment period which is currently

applicable

(130) Furthermore, to leverage the mutual trust and foster the high ethical standards, the

ethics committees should be involved in the assessment of ethical aspects of Part I of

the application dossier. This ethical perspective should be integrated in the assessment

report by the reporting Member State. Member States concerned should be able to

raise, where relevant, consolidated considerations integrating inputs from their

responsible ethics committees. The mandatory integration of ethical review in Part I

assessment by the reporting Member State would ensure that the ethical review is

conducted in a more harmonised and transparent manner. Such integration should also

result in fewer and more consistent considerations and therefore support overall

robustness of the evaluation with decreased burden for sponsors and national

regulatory bodies.

(131) It is appropriate that an enhanced EU portal provides technical means for a clear and

timely communication between the involved Member States and the sponsor during

the assessment, when requests for information are issued.

(132) To increase further the efficiency and speed of Part I assessments in multinational

clinical trials, when translations of Part I documents are required by national law,

these should be assessed with the Part II. Considerations regarding the accuracy of

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these translations will be raised by the Member States concerned with the sponsor in

the Part II assessment process. Moving the assessment of translation quality into Part

II of the application will allow the reporting Member State to focus on the technical

and scientific assessment of the trial, while Member States concerned would retain

their ability to verify the linguistic accuracy and suitability for their territories.

(133) To ensure that the sponsor of clinical trials can adapt them dynamically through their

life cycle to changed circumstances or to consider the scientific developments and

ensure smooth conduct of the clinical trial, a submission of parallel substantial

modification should be allowed. Such submissions should be allowed when the

substantial modification, despite an ongoing approval of another one, concerns distinct

and independent aspects of the dossier. Allowing parallel substantial modifications

would support increased flexibility and responsiveness of the regulatory system. It

would facilitate updates related to subjects' safety and enable timely response to

emerging scientific knowledge or allow operational adaptations to improve patients

access and trial efficiency.

(134) To further support the efficiency and consistency of clinical trial submissions across

the Member States, it is appropriate to develop and oblige the use of harmonised

templates for the submission of Part II documents of clinical trial applications. The use

of harmonised templates is expected to simplify the application and assessment

processes reducing administrative burden both for sponsors and Member States.

Harmonised templates may be updated in the light of technical and scientific

evolution. Member States concerned may choose to rely also on the assessment of the

reporting Member State of common aspects and elements in Part II application further

streamlining initial authorisation and for additional efficiency gains.

(135) Innovative and personalised therapies often combine the use of medicinal products

with medical devices, including in vitro diagnostic medical devices. During the

development of such therapies, clinical trials of one or more medicinal products may

need to be combined with clinical investigation of one or more medical devices or

performance studies of one or more in-vitro diagnostic medical devices. The

authorisation and conduct of such combined studies are complex due to the application

of requirements of two or three Union legislative frameworks in the area of health and

the fact that these are typically conducted across several Member States. In order to

support innovation and make efficient use of sponsors’ and Member States’ resources,

it is necessary to put in place a dedicated pathway for the authorisation and conduct of

such combined studies, involving coordinated assessment across Member States.

(136) The experience gained during the Covid-19 pandemic has shown the need for the

Union to swiftly take up measures to strengthen the development and access to crisis-

relevant medicines, including to accelerate, simplify, and streamline the authorisation

of multinational clinical trials relevant to prevent, treat or diagnose the disease caused

by an emerging serious cross-border threat to health. Regulatory flexibility, including

an accelerated authorisation procedure for clinical trials, is necessary to address and

possibly contain an emerging health threat in a timely, efficient and coordinated

manner. Therefore, it is appropriate to allow for an accelerated procedure for the

authorisation of multinational clinical trials in situations where a public health

emergency at Union level has been recognised in accordance with Article 23(1) of

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Regulation (EU) 2022/2371 of the European Parliament and of the Council54, or in

situations of an emerging serious cross-border threat to health that is likely to lead to

the recognition of a public health emergency at Union level. This should also

complement measures from the Regulation (EU) 2022/2372 of the Council55 on a

framework of measures for ensuring the supply of crisis-relevant medical

countermeasures in the event of a public health emergency at Union level.

(137) Based on the experiences gained from the application of Regulation (EU) No

536/2014, it is appropriate to further tailor the requirements for the authorisation and

oversight of clinical trials according to the risks they pose to the subjects. In this

context, the risk categorisation scheme should be further refined by differentiating

between minimal-intervention clinical trials that present post-marketing authorisation

trials and low-intervention clinical trials that use authorised medicinal products with

proven scientific evidence on the efficacy and safety but are used outside their initial

marketing authorisation.

(138) Clinical trials that meet the criteria for minimal-intervention clinical trials should only

require an ethical review before the clinical trial can begin. An enhanced application

of a risk-proportionate approach will contribute to fostering a regulatory framework

that is conducive to research and innovation. Sponsors, particularly non-commercial

ones who conduct the majority of minimal-intervention and low-intervention clinical

trials in the Union, will greatly benefit from simplified and risk-proportionate

regulatory requirements through a reduced administrative burden, while not

compromising subjects’ safety, well-being, and rights. A reinforced application of a

risk-proportionate regulatory framework further allows Member States to concentrate

on their assessment on clinicals trials associated with greater risk to the subjects.

(139) To ensure that clinical trials accurately represent the target population in all its

diversity, and to enhance the treatments available for vulnerable populations,

medicinal products which are likely to offer significant clinical benefit should be fully

and appropriately studied for their effects in these specific groups, including as regards

requirements related to their specific characteristics and the protection of the health

and well-being of subjects belonging to these groups. The protection of vulnerable

populations, in this context, such as incapacitated subjects, minors and pregnant or

breastfeeding women, requires a proper consideration of the risks of exclusion against

risks of inclusion in clinical trials. This is in accordance with the 2024 version of the

World Medical Association's Declaration of Helsinki.

(140) Electronic health data accessed under Chapter IV of Regulation (EU) 2025/327 can

offer valuable insights for clinical trials, particularly regarding the protocol or the

investigational medicinal products dossier design. Therefore, sponsors should be able

to utilize this data when applying for clinical trial authorisation or modifications.

Additionally, competent authorities should consider this data during the assessment of

such applications.

54 Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on

serious cross-border threats to health and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022,

ELI: http://data.europa.eu/eli/reg/2022/2371/oj) 55 Council Regulation (EU) 2022/2372 of 24 October 2022 on a framework of measures for ensuring the

supply of crisis-relevant medical countermeasures in the event of a public health emergency at Union

level.

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(141) The development of a medicinal product may require various clinical trials until robust

data regarding its safety and efficacy are available to support the submission of a

marketing authorisation application. The knowledge of the products is built gradually

during this development. Using the same dossier for an investigational medicinal

product in different clinical trials helps to ensure the collection of consistent and

complete information, streamlines product development, supports efficient assessment,

management and oversight, and can speed up the time to the market. For this reason, a

sponsor should be able to request the establishment of an investigational medicinal

product core dossier and rely on this dossier by referencing it in all clinical trials

related to the investigational product concerned. In order to keep the core dossier

updated, sponsors should be able to request its modification. One of the Member

States concerned by the trials with investigational medicinal product should assume

the role of core dossier depositary Member State and take responsibility for verifying

completeness and suitability of the core dossier and managing the requests for its

updates. Member States concerned in the core dossier should rely on the assessment

by the depositary Member State. The depositary Member State may consult the

Member States concerned as appropriate.

(142) In the development of biosimilar medicinal products, the rapid evolution of analytical

and functional characterisation methods for complex biological and biotechnological

active substances calls for tailored clinical approach in biosimilar development with

reduced need for confirmatory comparative clinical efficacy trials. Submission of a

simplified investigational medicinal product dossier (IMPD) for biosimilar medicines

to replace, as appropriate quality and quality control data, with a reference to the

relevant additional quality substance master file or corresponding certificates would

complement the shift in more risk proportionate clinical data requirements. This dual

simplification and streamlining should focus on the regulatory scrutiny of key

comparability data rather than require duplicative submission and assessment of the

full IMPD quality dossier. Combining streamlined and robust quality data assessment

with targeted clinical data generation should support an integrated and efficient

development pathway for biosimilars with reduced administrative burden and

development costs for biosimilar manufacturers, in particular in the Union.

Accelerated access to biosimilar medicines to the market should support patients'

access to more affordable biological therapies.

(143) To further optimise the use of resources for both the sponsors and Member States, the

possibility to refer, in a clinical trial application, to an active substance master file or a

corresponding certificate, or a certificate confirming that the quality of the substance is

suitably controlled by the relevant monograph of the European Pharmacopeia, or a

certified platform technology master file should be available as appropriate for any

investigational medicinal product, including for ATMPs. In these cases, the simplified

IMPD must contain all relevant data to the active substance or its manufacturing,

which is not covered in the referenced master file or certificate.

(144) To address the increased significance of delivery of investigational medicinal products

and auxiliary medicinal products to subjects, Regulation (EU) No 536/2014 should be

amended to provide a framework for the controlled transport within a Member State,

where the clinical trials have been authorised, of such products directly to subjects'

residences or through a dispensing pharmacy or by an authorised person, under the

investigator's oversight. This ensures responsible and transparent delivery practices

and adapts to the real word necessities, as demonstrated during the COVID 19

EN 64 EN

pandemic. Distribution through a dispensing pharmacy or by an authorised person

could be considered in particular in cluster trials.

(145) To enhance regulatory efficiency, to ensure consistency in the implementation of

Regulation (EU) No 536/2014 across the Union, and to facilitate predictability of

requirements for the developers of medicinal products, it is necessary to provide a

framework for the harmonisation of national requirements regarding the distribution of

investigational and auxiliary medicinal products, notably for decentralised and

multinational clinical trials. To achieve such harmonisation, the inspection working

groups, which provide input and recommendations on all matters relating, directly or

indirectly, to good clinical practice, good manufacturing practice, and good

distribution practice should draw up guidelines, in collaboration with the Commission,

and revise them as necessary to reflect technical and scientific progress in the field of

clinical trials. In consideration of the specialised knowledge and experience of its

members, who represent the Member States, the inspection working groups are

particularly well-suited to facilitate the coordination of national requirements,

eliminate unnecessary administrative obstacles, and promote a more efficient and

harmonised approach to the conduct of clinical trials within the Union.

(146) To facilitate the implementation of Regulation (EU) No 536/2014, while at the same

time preserving the protection of quality of investigational medicinal products and

ensuring greater predictability for sponsors, it is also appropriate to provide the

general principles on how to ensure quality in the processes not subject to a

manufacturing and import authorisation, such as re-packaging and re-labelling.

(147) Verification of compliance with the legal requirements of manufacturing of

investigational medicinal products by relevant entities through a system of

supervision, is of fundamental importance to ensure that the objectives of this

Regulation are effectively achieved. The provisions of Directive (EU) …/… [reference

to be added after adoption cf. COM(2023) 192 final] regarding the supervision system

and the cooperation on inspections, and provisions of [Regulation (EU) …/… of the

European Parliament and the Council [reference to be added after adoption cf.

COM(2023) 193 final] regarding the cooperation between national competent

authorities and the Agency for inspections in third countries should apply to the

supervisions of manufacturing of investigational medicinal products.

(148) Verification of compliance with the provisions of Regulation (EU) No 536/2014,

including for verification of compliance with good clinical practices, through a system

of supervision, is of fundamental importance to ensure that the objectives of this

Regulation are effectively achieved. Therefore, the competent authorities of the

Member States should have the power to perform on site or remote inspections,

including unannounced inspections, where necessary. Where needed, the competent

authority of a Member State should also be able to request support from another

Member State or the Agency to carry out a joint inspection, or to request a Member

State or the Agency to carry out the inspection on their behalf.

(149) The disruptive and innovative approaches to clinical trials may require adaptations to

the rules governing clinical trial approvals and conduct. To harness the benefits of this

innovation while providing necessary safeguards, it is essential to create a safe space

for testing new regulatory approaches and technologies. This includes, where

appropriate, the use of AI in trial design, data collection, analysis, and participant

interaction. For that reason, it is necessary to provide for a possibility of setting up a

controlled experimental environment in the form of a regulatory sandbox, allowing

EN 65 EN

regulators to test new methods for authorising and conducting clinical trials, for

example, when some requirements of the dossier cannot be fully complied with, while

ensuring strong safeguards for participant protection and data robustness. Insights

gained from sandbox activities should inform future guidance and, where appropriate,

legislative amendments.

(150) The processing of personal data under Regulation (EU) No 536/2014 should comply

with the requirements for the protection of personal data, including genetic data and

data concerning health, laid down in Regulations (EU) 2016/67956 and (EU)

2018/172557 of the European Parliament and of the Council. It is appropriate to clarify

that the basis for the processing of personal data in the context of clinical trials is laid

down in Regulation (EU)No 536/2014, pursuant to Article 6(1), point (c), of

Regulation (EU) 2016/679. The Agency should have access to personal data necessary

to perform its tasks in the public interest or complying with legal obligations in

accordance with Articles 40, 80 and 81 of Regulation (EU) No 536/2014. The

Commission should have access to personal data necessary for it to perform its task in

accordance with Articles 78, 79, 80, 81, of Regulation (EU) No 536/2014.

(151) In particular, Regulation (EU) No 536/2014 should be amended torequire the

processing of personal data by the sponsors and investigators where this is necessary

to comply with the legal obligations imposed on them to ensure the safety and efficacy

of medicinal products, when they request authorisation for and conduct clinical trials.

This includes obligations to perform research activities in accordance with an

authorised protocol, to perform safety reporting, and to perform archiving in

accordance with Regulation (EU) No 536/2014. The relevant information to be

collected according to the authorised protocol will contain personal data of the

subjects, including genetic data or data concerning health. The processing of such

special categories of personal data in the context of clinical trials takes place for

reasons of public interest in the area of public health, in particular for ensuring high

standards of medicinal products in compliance with Article 9(2), point (i), of

Regulation (EU) 2016/679. Additionally, personal data may encompass identification

details, such as sex and age, social insurance numbers and contact information.

Moreover, sponsors may collect and process other data necessary for implementing the

authorised protocol, such as the personal data of investigators. The categories of

personal data to be collected and processed in the context of a specific clinical trial

should be specified in the authorised protocol. Regulation (EU) No 536/2014 should

be amended to establish specific safeguards for the processing of personal data,

including genetic data or data concerning health, in compliance with Article 9(2),

points (i) and (j), of Regulation (EU) 2016/679. For instance, it should require

informed consent to participate in the clinical trial, as well as to maintain

confidentiality of records and personal data of participants. The protocol should

specify further appropriate safeguards such as specific technical and organisational

56 Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the

protection of natural persons with regard to the processing of personal data and on the free movement of

such data, and repealing Directive 95/46/EC (General Data Protection Regulation) (OJ L 119, 4.5.2016,

p. 1, ELI: http://data.europa.eu/eli/reg/2016/679/oj). 57 Regulation (EU) 2018/1725 of the European Parliament and of the Council of 23 October 2018 on the

protection of natural persons with regard to the processing of personal data by the Union institutions,

bodies, offices and agencies and on the free movement of such data, and repealing Regulation (EC) No

45/2001 and Decision No 1247/2002/EC (OJ L 295, 21.11.2018, p. 39, ELI:

http://data.europa.eu/eli/reg/2018/1725/oj).

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measures that should be employed, including pseudonymisation, integrity and

confidentiality controls, encryption and access restrictions. In addition, any clinical

trial should be subject to ethical review.

(152) Since this Regulation amends Regulation (EU) No 536/2014 to establish a harmonised

framework for the processing of personal data in the context of clinical trials, Member

States should not be able to maintain or introduce under Article 9(4) of Regulation

(EU) 2016/679 further conditions, including limitations and specific provisions such

as requesting the consent of natural persons in the sense of that Regulation, with

regard to the processing of personal data, including genetic data or data concerning

health under Regulation (EU) No 536/2014 as amended by this Regulation.

(153) Personal data which is collected and processed under each authorised protocol in

accordance with Regulation (EU) No 536/2014 as amended by this Regulation may be

further processed by the same controller for the purposes of other clinical trials,

conducted in accordance with Regulation (EU) No 536/2014. Such data may include

names, contact details, health and genetic data of subjects. It should also be possible to

further process such personal data by the same controller for scientific research

purposes.

(154) To further address the issue of fragmentation within and across Member States on the

application of the measures applicable to the conduct of clinical trials and, as regards

certain aspect that remain national, and drive further harmonisation, it is necessary to

enable closer cooperation between and across Member States’ competent authorities

and ethics committees. For that purpose, the role and tasks of the Clinical Trials

Coordination and Advisory Group (CTAG) should be extended. The CTAG should in

particular be empowered to issue or endorse guidance documents related to clinical

trials conduct and supervision, to ensure uniform interpretation and harmonised

implementation of Regulation (EU) No 536/2014 across the Member States.

(155) Ethics committees involved in the assessment of clinical trials application should

collaborate in a dedicated forum with the objective to strengthen cooperation in the

area of ethical aspects of clinical trials which are of national competence.

(156) Regulation (EU) No 536/2014 outlines the responsibilities of Member States in

designating competent authorities and ethics committees for regulatory activities,

including oversight. To perform their roles as required by the provisions of this

Regulation amending Regulation (EU) No 536/2014, these competent authorities and

responsible ethics committees should be vested in the necessary powers, have at their

disposal qualified personnel and sufficient resources to perform their duties

effectively. Regulation (EU) 536/2014 emphasizes the importance of communication

and coordination to ensure consistent and efficient regulatory actions within Member

States. It is also essential to define how the Commission will verify the correct

implementation of the law by the competent authorities. Regulation (EU) No 536/2014

should be amended accordingly.

(157) The integration of AI in clinical trials presents opportunities to enhance the clinical

trials’ design, execution, and oversight. This technological advancement offers

substantial benefits to clinical trial sponsors, regulators, and ultimately patients.

Among the possible enhancements are improved endpoint determination, advanced

statistical analysis, optimized patient selection, enhanced data handling and analysis.

While AI tools aim to accelerate the development of medicinal products, it is

imperative that their use in clinical trials adheres to applicable legislation. This

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includes, when applicable, compliance with Regulation (EU) 2024/1689, Regulation

(EU) 2017/746, Regulation (EU) 2017/745 and Regulation (EU) 2016/679.

(158) Sponsors hold the responsibility to evaluate the potential impact and risk of AI tools

on patient safety based on guidelines. Untested systems may introduce gender and

other biases and errors, risking unreliable outcomes or failures in interpreting medical

data accurately. Such risks could lead to misdiagnosis, incorrect treatment, or

inaccurate patient selection, especially hazardous in extensive clinical trials with

numerous participants. The guidelines on the developments and deployment of AI

tools developed by the Agency, in cooperation with the Clinical Trials Coordination

and Advisory Group, and as appropriate, with other expert groups established under

Union law, should assist the sponsors, national competent authorities and ethics

committees in assessment of AI tools benefits and risks in the context of the lifecycle

of clinical trials.

(159) To further strengthen the competitiveness of the European Union in clinical research

and ensure timely access of patients to innovative medicines, it is necessary to monitor

the effectiveness of the provisions in thisRegulation amending Regulation (EU) No

536/2014 to streamline and simplify the authorisation and conduct of multinational

clinical trials. Such monitoring should be based on key performance indicators such as

the increase in the number of clinical trials in the Union over the period of five years,

as this indicator reflects both the attractiveness of the Union and the capacity of the

European regulatory system to support clinical research with maintained high data

quality and patients’ safety standards. Regulation (EU) No 536/2014 should be

amended accordingly.

(160) The management of changes through the lifecycle of veterinary medicinal products is

subject to regulatory approvals. The handling of variations for biological products is

particularly critical because of the impact that changes in the source materials or the

manufacturing process can have on the safety and efficacy attributes of the finished

product. It is necessary to continue ensuring that changes introduced during the

lifecycle of a veterinary medicinal do not alter the positive benefit-risk balance while

avoiding unnecessary administrative burden. To this end, the process for

implementation of variations not requiring assessment laid down in Article 61 of

Regulation (EU) 2019/6 of the European Parliament and of the Council58 should be

further optimised.

(161) Advances in biotechnology bring new opportunities for the development of veterinary

medicinal products, including the possibility to develop vaccines with improved safety

and efficacy profiles in a much shorter timeframe. The possibility to deploy and use

vaccines quickly is essential to react to outbreaks of certain animal diseases thereby

reducing the risks for human health, contributing to animal welfare and reducing

economic losses for farmers.

(162) Safety for veterinary medicinal products is assessed during marketing authorisation

procedures in accordance with Regulation (EU) 2019/6. The competent authorities

responsible for the granting of marketing authorisations are required to verify the

safety for the target species, for the user, for consumers and for the environment.

Likewise, the conduct of clinical trials is subject to the approval and supervision by

58 Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on

veterinary medicinal products and repealing Directive 2001/82/EC (OJ L 4, 7.1.2019, p. 2, ELI:

http://data.europa.eu/eli/reg/2019/6/oj).

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competent authorities responsible for veterinary medicinal products. Regulation (EU)

2019/6 further requires that such trials are conducted in accordance with Good Clinical

Practice, which includes the obligation for sponsors to ensure that there are no

environmental grounds precluding the conduct of the trial.

(163) Regulation (EU) 2019/6 and the Union GMO legislation (Directives 2001/18/EC59 and

2009/41/EC60, Regulations (EC) 1829/200361, 1830/200362 and 1946/200363 of the

European Parliament and of the Council share the same protection goals as regards the

protection of human and animal health and the environment from genetically modified

organisms. Since parallel assessments and documentation and increased administrative

burden is not conducive to increased protection of human health or the environment

and has negative effects on the use of biotechnology in veterinary medicine, the risks

for human and animal health and to the environment from veterinary medicinal

products containing or consisting of genetically modified organisms should be solely

assessed in accordance with Regulation (EU) 2019/6. This simplification should be

coupled with a reinforcement of existing obligations as regards the conduct of clinical

trials with veterinary medicinal products that contain or consists of GMOs.

(164) To remove any legal uncertainty for developers, marketing authorisation holders and

users, it should also be clarified that given the purpose of veterinary medicinal

products to treat animals, their administration does not bring the treated animals or

their products under the scope of the Union GMO legislation.

(165) The Commission should be empowered to adopt delegated acts to amend Annex II to

Regulation (EU) 2019/6 in order to adapt it to scientific and technical progress.

(166) Veterinary medicinal products developed by means of biotechnology processes to

diagnose, treat or prevent zoonotic diseases should be entitled to an extra year of

supplementary protection certificate (‘SPC’) in order to support their development.

(167) Scientific and technical progress in biotechnology enables the development of new

technologies, methods or products that may not fit into existing Union legislation. The

lack of harmonised requirements is an impediment to the development, marketing and

use of new concepts that may, however, bring benefit to animal healthcare. Regulatory

sandboxes may be established to facilitate the development, placing on the market or

use of innovative technologies, methods or products related to animal health which are

directly or indirectly related to the development, manufacturing or use of veterinary

medicinal products under conditions that ensure protection of animal and public health

as well as the environment. A regulatory sandbox should only be established if there is

no Union legislation governing the marketing and use of the relevant technology,

method or product.

59 Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the

deliberate release into the environment of genetically modified organisms and repealing Council

Directive 90/220/EEC (OJ L 106, 17.4.2001, p. 1). 60 Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained

use of genetically modified micro-organisms (OJ L 125, 21.5.2009, p. 75,). 61 Regulation (EC) No 1829/2003 of the European Parliament and of the Council of 22 September 2003

on genetically modified food and feed (OJ L 268, 18.10.2003, p. 1). 62 [Regulation (EC) No 1829/2003 of the European Parliament and of the Council of 22 September

2003on genetically modified food and feed (OJ L 268, 18.10.2003, p. 1). 63 Regulation (EC) No 1946/2003 of the European Parliament and of the Council of 15 July 2003 on

transboundary movements of genetically modified organisms (OJ L 287, 5.11.2003, p.1).

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(168) A regulatory sandbox may be established by the Commission, by way of an

implementing act following a recommendation of the Agency which should analyse

expected potential benefits and risks as well as existing regulatory challenges.

Technical and scientific requirements for the technologies, methods or products under

the regulatory sandbox and procedures should be developed and published by the

Agency. The Agency should ensure that the requirements and procedures it develops

are proportionate and are adapted to the specific risks. A regulatory sandbox may be

terminated at any time where, following the identification of negative impacts on

animal or public health or the environment, the benefit-risk balance becomes negative

and there are no satisfactory risk mitigation measures that could be implemented.

(169) Technologies, methods or products developed under a regulatory sandbox should only

be placed on the market or used on the basis of an authorisation granted by the

Commission. Depending on the specific characteristics of the products concerned, a

class authorisation to market or use technologies, methods or products may be

possible. Member States should be empowered to take interim measures where serious

risks to animal or public health or the environment are identified. In such cases,

Member States should swiftly inform the Agency.

(170) To ensure legal certainty, the termination of a regulatory sandbox should not affect the

validity of the authorisations to place on the market or use technologies, methods or

products already granted, unless the regulatory sandbox has been terminated on

grounds related to the protection of public or animal health or the environment.

(171) To provide legal certainty to developers and competent authorities alike, time limits

should be established also in the Regulation (EU) 2024/1938 and for all actors

involved in the consultation process, at national and Union level, including the SoHO

competent authorities, the Substances of Human Origin Coordination Board (‘the

SCB’), established in that Regulation and advisory bodies established under other

relevant Union legislation. Consequently, Regulation (EU) 2024/1938 should be

amended to provide the power for the Commission to adopt implementing acts to

establish such time limits, that should be ambitious and determined based on

experience gathered with the consultation process as of the entry into application of

that Regulation.

(172) The field of substances of human origin is characterised by rapid scientific and

technological innovation, giving rise to health biotechnology approaches that may

present scientific or regulatory challenges under existing legal requirements. To

support the development of such innovations at early stages while maintaining public

health protection, Member States should be able to establish regulatory sandboxes for

substances of human origin that cannot yet be developed in full compliance with the

requirements of Regulation (EU) 2024/1938, provided that the innovative

characteristics or methods are expected to contribute distinctively to quality, safety,

effectiveness, or patient access to treatment. The sandbox activities should enable a

discussion on the development of common approaches and the potential adaptation of

legislative frameworks based on accumulated experience. Any substances of human

origin developed through regulatory sandboxes should only be distributed for human

application when properly authorised, with initial authorisations limited to the

regulatory sandbox duration. This framework should enable controlled

experimentation with innovative regulatory approaches while preserving the essential

safeguards for public health and safety. Regulation (EU)2024/1938 should be

amended accordingly.

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(173) The regulatory sandboxes in the field of substances of human origin should be

conducted under the supervision of the concerned SoHO competent authorities, and,

where relevant, competent authorities under other Union and Member State legislation

concerned. The latter authorities should be in particular involved where the

preparation of the SoHO requires steps using products regulated under another Union

legislative framework, or where SoHO is presented as a therapy together with products

regulated under another such Union framework.

(174) In order to ensure uniform conditions for the implementation of this Regulation

regarding the recognition by the Commission of high impact biotechnology strategic

projects, the modalities for the processing of personal data necessary to achieve the

purpose of such projects in the form of biotechnology data quality accelerators and the

rules for the selection, composition, number of members, and functioning of the

Foresight Panel for Emerging Health Innovation, implementing powers should be

conferred on the Commission.

(175) In order to ensure uniform conditions for the implementation of this Regulation,

implementing power should be conferred on the Commission to detail the criteria to

clarify in what cases a project is to be deemed to have a strong systemic and catalytic

potential within the Union’s biotechnology ecosystem and accelerate innovation, detail

the criteria for the recognition of centres of excellence for advanced therapies,

including advanced therapy medicinal product, establish procedural rules for the

recognition of high impact health biotechnology strategic projects and the format of

the assessment report to be submitted by the designated authorities in relation to

applications for recognition of high impact health biotechnology strategic projects,

establish regulatory sandboxes for health biotechnology products and common

principles, criteria and practical arrangements for the assessment of applications

received from developers and for the establishment and supervision of the regulatory

sandboxes and related sandbox plans. Those powers should be exercised in accordance

with Regulation (EU) No 182/2011.

(176) The power to adopt acts in accordance with Article 290 of the Treaty on the

Functioning of the European Union should be delegated to the Commission in respect

of modifying Annex I to this Regulation listing the biotechnology products of concern.

It is of particular importance that the Commission carries out appropriate consultations

during its preparatory work, including at expert level, and that those consultations be

conducted in accordance with the principles laid down in the Interinstitutional

Agreement on Better Law-Making of 13 April 2016. In particular, to ensure equal

participation in the preparation of delegated acts, the European Parliament and the

Council receive all documents at the same time as Member States' experts, and their

experts systematically have access to meetings of Commission expert groups dealing

with the preparation of delegated acts.

(177) The European Data Protection Supervisor and the European Data Protection Board

were consulted in accordance with Article 42 of Regulation (EU) 2018/172564 and

delivered an opinion [date].

64 Regulation (EU) 2018/1725 of the European Parliament and of the Council of 23 October 2018 on the

protection of natural persons with regard to the processing of personal data by the Union institutions,

bodies, offices and agencies and on the free movement of such data, and repealing Regulation (EC) No

45/2001 and Decision No 1247/2002/EC, OJ L 295, 21.11.2018, pp. 39–

98, ELI: http://data.europa.eu/eli/reg/2018/1725/oj)

EN 71 EN

(178) Since the objectives of this Regulation cannot be sufficiently achieved by the Member

States but can rather, by reason of the scale or effects of the action, be better achieved

at Union level, the Union may adopt measures in accordance with the principle of

subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance

with the principle of proportionality as set out in that Article, this Regulation does not

go beyond what is necessary in order to achieve those objectives.

HAVE ADOPTED THIS REGULATION:

CHAPTER I

SUBJECT MATTER, SCOPE AND DEFINITIONS

Article 1

Subject matter and scope

1. This Regulation establishes a framework to strengthen the competitiveness of the

health biotechnology sector in the Union. It creates and reinforces favourable

conditions for health biotechnology as defined in Article 2(1), point (2), from

research and development to the timely placing on the Union market and production

of biotechnology innovations and products, while safeguarding high standards of

protection of human health, patient safety and animal health, the environment, ethics,

quality of products, food and feed safety and biosecurity.

2. This Regulation lays down measures regarding:

(a) the establishment of a framework for the recognition of, and support measures

for, health biotechnology strategic projects and high impact health

biotechnology strategic projects;

(b) novel health biotechnology products and regulatory sandboxes to support

innovation and take into account technological and scientific developments and

progress;

(c) the support to promoters of biotechnology projects, SMEs, start-ups and scale-

ups and non-profit developers of biotechnology products, by establishing an

EU Health Biotechnology Support Network;

(d) the support for funding of, investments in, and access to capital for

biotechnology companies and projects;

(e) the enhancement of the manufacturing capacity of, and expertise for

biosimilars in the Union, including through international cooperation;

(f) the application in a facilitated manner of advanced technologies, including AI

in biological applications, into the Union’s health biotechnology ecosystems,

while monitoring and mitigating, in line with the Union harmonisation

legislation on AI, biological risks arising from the use of such technologies;

(g) the placing on the market in particular of health biotechnology products and

biotechnology services in accelerated and streamlined procedures;

(h) the prevention of the misuse of biotechnologies and the strengthening of

biodefence capabilities, without prejudice to, and in complementarity with,

activities financed under any defence related Union funding programmes and

instruments.

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3. This Regulation applies to health biotechnology innovations and products and their

ecosystem during their entire lifecycle, including related research, funding,

development, innovation, testing, validation, manufacturing, placing on the market,

and use activities.

4. The amendments to the Union legislation laid down in Articles 56 to 61 are not

limited to health biotechnology products and activities, but also relate to the other

products, services and activities that fall in the scope of that legislation.

5. This Regulation does not affect the application of Directive 2010/63/EU on the

protection of animals used for scientific purposes and of Regulation (EU) 1907/2006

concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals

(REACH).

6. This Regulation shall apply without prejudice to Regulation (EU) 2024/1689 laying

down harmonised rules on artificial intelligence.

7. This Regulation shall apply without prejudice to Regulation […][[Regulation on

speeding-up environmental impact assessments -permitting regulation].

Article 2

Definitions

1. For the purposes of this Regulation, the following definitions apply:

(1) ‘biotechnology’ 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;

(2) ‘health biotechnology’ means the application of biotechnology for the

promotion, protection, or restoration of human health and biotechnological

applications relevant to animal health, plant health, veterinary public health,

and food safety, insofar as these areas contribute directly or indirectly to the

protection of human health and align with the Union’s public health objectives,

as set out under Article 168 of the Treaty on the Functioning of the European

Union;

(3) ‘biotechnology product’ means any good, technology or activity resulting from

the application of biotechnology, including any process, action, technique, tool

or knowledge involving biotechnology;

(4) ‘advanced biotechnology innovation’ means a biotechnology product, process,

service or enabling technology that demonstrates, on the basis of preliminary

scientific or technical evidence, the potential to achieve a substantial

improvement over existing solutions in terms of efficacy, safety, sustainability,

accessibility, and/or cost-effectiveness, and that, by reason of its novelty,

technical complexity and/or market-creating potential, entails a high level of

technological or commercial risk and it is likely to create new markets or

significantly disrupt existing ones;

(5) ‘biomanufacturing’ means the production of biotechnology products at a

commercial scale;

(6) ‘biotechnology cluster’ means a geographic concentration of interconnected

companies, research institutions and organisations focused on biotechnology

and life sciences, fostering collaboration and innovation;

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(7) ‘project promoter’ means any undertaking or consortium of undertakings

developing a health biotechnology strategic project referred to in Article 3 or a

high impact health biotechnology strategic project referred to in Article 4;

(8) ‘permit-granting process’ means a process that covers all relevant permits to

build, expand, convert and operate health biotechnology strategic projects and

high impact health biotechnology strategic projects, including building permits

and environmental assessments and authorisations where required, and

encompassing all applications and procedures from the acknowledgement that

the application for such permits is complete to the notification of the decision

on the outcome of the procedure by the single point of contact concerned;

(9) ‘deep tech’ means an innovation with the potential to deliver transformative

solutions and that is based on cutting-edge advances in science, technology and

engineering;

(10) ‘SME’ means a micro, small or medium-sized enterprise within the meaning of

the Annex to Commission Recommendation 2003/361/EC65;

(11) ‘European Investment Bank Group (EIBG)’ means the European Investment

Bank, the European Investment Fund or any subsidiary of the European

Investment Bank;

(12) ‘national promotion bank or institution’ means a legal entity as defined in

Article 2, point (21), of Regulation (EU) 2021/523 of the European Parliament

and of the Council66;

(13) ‘implementing partner’ means an entity implementing, in indirect management,

support under the EU health biotechnology investment pilot;

(14) ‘AI system’ means an AI system system as defined in Article 3(1) of

Regulation (EU) 2024/1689;

(15) ‘general-purpose AI model’ means an AI model as defined in Article 3point

(63) of Regulation (EU) 2024/1689;

(16) ‘general-purpose AI system’ means a general-purpose AI system as defined in

Article 3point (66) of Regulation (EU) 2024/1689;

(17) ‘clinical trial’ means a clinical trial as defined in Article 2(2), point (2) of

Regulation (EU) No 536/2014;

(18) ‘advanced therapy medicinal product’ means an advanced therapy medicinal

product as defined in Article 2(1) of Regulation (EC) No 1394/2007;

(19) ‘New Approach Methodologies (NAMs)’ means innovative methods that do

not involve live animals, such as in vitro (cell or tissue-based), in chemico

(chemical-based), or in silico (computer-based) approaches, as well as

combinations of these;

(20) ‘biological threats’ means risks posed by harmful biological agents such as

pathogens or toxins that can cause disease or significant societal consequences,

whether arising naturally, through accidental release, or via deliberate misuse;

65 Commission Recommendation of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises (Text with EEA relevance) (notified

under document number C(2003) 1422), OJ L 124, 20.5.2003, pp. 36–41. ELI: http://data.europa.eu/eli/reco/2003/361/oj. 66 Regulation (EU) 2021/523 of the European Parliament and of the Council of 24 March 2021 establishing the InvestEU Programme and amending Regulation

(EU) 2015/1017, OJ L 107, 26.3.2021, pp. 30–89. ELI: http://data.europa.eu/eli/reg/2021/523/oj.

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(21) ‘biodefence’ means actions, policies, and measures that are designed, in

particular by state actors, for preventive, protective or peaceful purposes, to

counter biological threats, reduce risks, and prepare for, detect, assess, respond

to, and recover from biological threats;

(22) ‘biosecurity’ means the protection, control and accountability of high-

consequence biological agents, technologies, materials and toxins of concern,

as well as of critical relevant information against unauthorised access, loss,

theft, misuse, diversion or intentional release by those who intend to misuse

them;

(23) ‘biotechnology product of concern’ means any good, service or technology,

including software resulting from the application of science and technology to

living organisms, their parts, products or models with significant potential for

biological misuse that are listed in Annex I, including any thresholds or

exclusions;

(24) ‘benchtop nucleic acid synthesis equipment’ means any equipment that allows

a user to synthesise nucleic acids individually or in a core research facility.

2. For the purpose of the provisions regarding biosecurity and the prevention of

biotechnology misuse laid down in Chapter VIII, Section 2, the following definitions

apply:

(a) ‘making available’ means any supply, whether in return for payment or free of

charge;

(b) “legitimate” means in good faith, in the ordinary course of recognised

professional, research or commercial activities, and in accordance with

applicable Union and national law;

(c) ‘legitimate need’ in a biotechnology product of concern means the need for

such biotechnology for legitimate and peaceful purposes, including handling,

production, cultivation, experimentation, preservation, destruction, internal

transport, by a legitimate member of the scientific community or a legitimate

enterprise, consistent with applicable international treaties, laws, standards and

oversight;

(d) ‘suspicious transaction’ means any transaction concerning biotechnology

products of concern for which there are reasonable grounds, taking into

account all relevant factors, to doubt the legitimacy of the prospective

customer’s intentions.

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CHAPTER II

UNION HEALTH BIOTECHNOLOGY AND BIOMANUFACTURING

SECTION 1

RECOGNITION OF HEALTH BIOTECHNOLOGY STRATEGIC PROJECTS IN THE UNION

Article 3

Health biotechnology strategic projects

1. To enable access to the support measures laid down in Section 2 of Chapter II,

Member States shall recognise projects located in the Union, by means of a reasoned

decision, as health biotechnology strategic projects if they make a substantial

contribution to at least one of the following specific objectives:

(a) strengthening the industrial capacity and value chains in the health

biotechnology sector, through one or more of the following activities:

(i) pooling resources and expertise among research organisations,

biotechnology industry actors and/or public authorities within the Union;

(ii) creating new, or significantly expanding, production facilities for

biotechnology products, in particular in biotechnology sectors where

such facilities do not exist or where they are limited, including for

biosimilars;

(iii) creating or upgrading industrial scale biomanufacturing sites with

innovative, sustainable, safe and digitally enabled processes and

technologies;

(iv) reducing dependencies on third-country suppliers for key biotechnology

inputs and intermediates;

(v) integrating advanced digital and AI-driven manufacturing and supply-

chain management systems to enhance productivity, traceability and

sustainability across biotechnology value chains;

(b) scaling-up or upgrading critical research and technology infrastructures

underpinning the development, testing and validation of health biotechnology

products, including but not limited to pilot or testing infrastructures for

biomanufacturing, data and digital platforms, through one or more of the

following activities:

(i) establishing, expanding or upgrading pilot, testing and demonstration

infrastructures linking research, development, validation and industrial

deployment capacities for biotechnology products and processes; or

(ii) integrating advanced digital, data and AI capabilities to enhance

modelling, simulation and process optimisation; or

(iii) establishing interoperable infrastructures connecting research

organisations, industry and public authorities across the Union; or

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(iv) promoting and integrating the use of NAMs in areas such as biological

research, discovery and preclinical development, regulatory and quality

testing and production of medicinal products and medical technologies.

(c) accelerating innovation and technology deployment in health biotechnology

through one or more of the following activities:

(i) introducing or scaling up breakthrough innovations in biotechnology that

have the potential to strengthen the Union’s industrial competitiveness,

including AI-enabled technologies and tools;

(ii) supporting SMEs, start-ups and scale-ups, universities and research

centres in accessing advanced biomanufacturing and laboratory

capacities;

(iii) promoting technology transfer and collaboration with corresponding

facilities in third countries, where Union-led partnerships are established

under Union law.

(d) addressing talent and skills needs or preventing shortages of talent and skills

critical to all kinds of jobs in support of the strengthening of the health

biotechnology and biomanufacturing sectors, and supporting the creation and

maintenance of quality jobs in the EU through one or more of the following

activities:

(i) attracting and retaining talent in the Union and aiming to provide

adequate upskilling or reskilling opportunities covering the broad range

of skills required for biotechnology and biomanufacturing, including

technical skills, data science, AI, intellectual property and project

management, and entrepreneurial skills, through activities including

apprenticeships, traineeships, continuing education and training, in close

cooperation with regional and local authorities, education and training

institutions, businesses and social partners;

(ii) establishing public-private partnerships between universities, vocational

education and training providers, businesses, in particular SMEs, start-

ups and scale-ups, social partners and applied research institutes;

(iii) establishing university alliances, also in cooperation with employers, to

improve their delivery on innovation and the development of skills and

talent.

(e) contributing to strengthening the EU’s preparedness and response capacity to

priority health threats by supporting the development, manufacturing and

supply of medical countermeasures.

2. The projects referred to in paragraph 1 may be located on the territory of two or more

Member States.

Article 4

High impact health biotechnology strategic projects

1. To enable access to the support measures laid down in Section 2 of Chapter II,

projects located in the Union fulfilling the criteria to be recognised as health

biotechnology strategic projects, which demonstrate by virtue of their scale, scope or

cross-border relevance, a strong systemic and catalytic potential within the Union’s

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biotechnology ecosystem to accelerate innovation and enhance the translation of

research into market applications shall be recognised by the Commission as high

impact health biotechnology strategic projects, including in the following cases:

(a) the project is a biotechnology development accelerator that fulfils the

conditions laid down in Article 5;

(b) the project is a centre of excellence for advanced therapies, including for

advanced therapy medicinal products that fulfils the conditions laid down in

Article 6;

(c) the project contributes to an EU biotechnology late-stage capital booster pilot,

fulfilling the conditions laid down in Article 23;

(d) the project contributes to the development of trusted testing environments for

advanced biotechnology innovations, fulfilling the conditions laid down in

Article 32(1) or is a health biotechnology data quality accelerator, fulfilling the

conditions laid down in Article 33.

(e) the project contributes to the EU Biothreat Radar fulfilling the conditions laid

down in Article 41(1) or it is a biodefence capability high impact strategic

project fulfilling the conditions laid down in Article 42(1).

2. The Commission may adopt implementing acts to detail the conditions set out in

paragraph 1, to clarify in which cases a project is to be deemed to have a strong

systemic and catalytic potential within the Union’s biotechnology ecosystem to

accelerate innovation and enhance the translation of research into market

applications. These implementing acts shall be adopted in accordance with the

examination procedure referred to in Article 65(2).

Article 5

Biotechnology development accelerators

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union as high impact health

biotechnology strategic projects in the form of biotechnology development

accelerators, only where they comply with the conditions laid down in Article 4(1),

and they fulfil at least three of the following conditions:

(a) provide trusted testing or demonstration facilities replicating real-world

biomanufacturing processes, including good manufacturing practices (GMPs)

compliant processes, or their enabling technologies, for process testing,

validation, and small batch manufacturing, including for the investigational

medicinal products for early stages of clinical trials; such enabling technologies

may include digital technologies, with specific applicability in biotechnology

and biomanufacturing;

(b) aim to operate state-of-the-art equipment, laboratories and technical expertise

to support biotechnology and biomanufacturing processes and provide access

thereof;

(c) aim to support hands-on and work-based training programmes aligned with the

Union’s skills and workforce development objectives in the biotechnology and

biomanufacturing sectors or in relation to enabling technologies, such as digital

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technologies, with specific applicability in biotechnology and

biomanufacturing;

(d) conduct applied research in biotechnology or biomanufacturing, or in relation

to enabling technologies, with specific applicability in biotechnology and

biomanufacturing;

(e) seek to engage in partnerships among industry, academia, and public

authorities to ensure the integration of research, innovation, and training in

biotechnology and biomanufacturing or their enabling technologies.

Article 6

Centres of excellence for advanced therapies

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union as high impact health

biotechnology strategic projects in the form of centres of excellence for advanced

therapies, including for advanced therapy medicinal products (ATMPs), only where

they comply with the conditions laid down in Article 4[(1) and reinforce the Union’s

capability in the area of advanced therapies, by fulfilling all of the conditions set out

in paragraph 2 of this Article.

2. The centres referred to in paragraph 1 shall fulfil all of the following conditions:

(a) specialise in at least one advanced therapy, such as cell and gene therapies;

(b) provide or coordinate advanced infrastructures including downstream

processing, delivery models and the manufacturing of therapies referred to in

point (a);

(c) integrate quality, regulatory science, and safety testing functions supporting

Union-wide development of advanced therapies;

(d) establish structured cooperation among clinical centres, research organisations,

industrial developers of biotechnology products, investors and regulators;

(e) provide multiple services enabling the transition of advanced therapies from

laboratory research to commercial manufacturing, including:

(i) provide acceleration programmes to transform innovative ideas into

viable business propositions;

(ii) provide incubation programmes assisting early-stage companies

requiring GMP infrastructure, technical and regulatory expertise;

(iii) carry out networking and partnership facilitation to foster alliances;

(iv) ensure access to clinical and hospital settings, including for paediatric

patients, for testing, clinical validation, and feedback;

(v) provide education and training for researchers, clinicians, and

developers; and

(vi) ensure the possibility of cross-border access to users from any Member

State.

3. The Commission may adopt implementing acts to detail the conditions listed in

paragraph 2 of this Article, with a view to ensure a consistent approach in their

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implementation across the Member States. These implementing acts shall be adopted

in accordance with the examination procedure referred to in Article 65(2).

Article 7

Designation of the competent authority responsible for assessing applications for

recognition of health biotechnology strategic projects and high-impact health

biotechnology strategic projects

1. Member States shall designate an authority (‘the designated authority’) responsible

for assessing applications for recognition of health biotechnology strategic projects

and high impact health biotechnology strategic projects.

2. Member States shall inform the Commission within six months from the entry into

force of this Regulation of the authority designated pursuant to paragraph 1.

Article 8

Application for recognition of a health biotechnology strategic projects or a high impact

health biotechnology strategic project

1. An application for the recognition of a project as a health biotechnology strategic

project or as a high impact health biotechnology strategic project shall be submitted

by the project promoter to the designated authority referred to in Article 7 of a

Member State on whose territory the project is located.

2. The application referred to in paragraph 1 of this Article shall contain the

relevant evidence related to the fulfilment of the conditions laid down in Article 3 as

regards health biotechnology strategic projects or in Article 4, as regards high impact

health biotechnology strategic projects.

Article 9

Recognition by Member States of health biotechnology strategic projects

1. The designated authority shall assess the application for the recognition of a project

as a health biotechnology strategic project within one month of the receipt of the

complete application and communicate a reasoned decision to the project promoter.

The assessment process shall be fair and transparent.

2. Where the designated authority concludes that the project fulfils the conditions of

Article 3, it shall recognise the project as a health biotechnology strategic project.

3. Member States shall ensure that applicants have easy access to information on

procedures for the settlement of disputes concerning the recognition process,

including, where applicable, alternative dispute resolution mechanisms provided for

by national law.

4. Where a project is located on the territory of two or more Member States, the

decision recognising the project as a biotechnology strategic project issued by the

designated authority of a Member State shall be recognised by the designated

authorities of other Member States.

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Article 10

Recognition by the Commission of high impact health biotechnology strategic projects

1. The designated authority shall assess the application for the recognition of a project

as a high impact health biotechnology strategic project within one month of the

receipt of the complete application and shall communicate its assessment report to

the Commission. The assessment process shall be fair and transparent.

2. Where the designated authority concludes that the project fulfils the conditions of

Article 4, the Commission shall, by means of implementing acts, adopt a decision

approving or rejecting the application for recognition referred to in paragraph 1 of

this Article, based on the assessment referred to in that paragraph and taking into

account the views of the Steering Group referred to in Article 20.

3. By way of derogation from Article 8 and to paragraphs 1 and 2 of this Article, a

project may also be recognised as a high impact health biotechnology strategic

project in the framework of calls for proposals launched under Union programmes

for the purpose of identifying, selecting and funding such projects, in line with the

basic acts setting up those programmes.

The Commission shall recognise a project as a high impact health biotechnology

strategic project in the context of a call for proposals where it fulfils the conditions

set out in Article 4(1) and the specific criteria set out in those calls, based on the

evidence submitted by the applicant.

4. The Commission shall adopt implementing acts laying down the format of the

assessment report referred to in paragraph 1 of this Article and the procedural rules

for the recognition of high impact health biotechnology strategic projects. These

implementing acts shall be adopted in accordance with the examination procedure

referred to in Article 65(2).

SECTION [2]

SUPPORT OF HEALTH BIOTECHNOLOGY STRATEGIC PROJECTS AND HIGH IMPACT HEALTH

BIOTECHNOLOGY STRATEGIC PROJECTS

Article 11

Single points of contact

1. Each Member State shall designate one or more authorities as single points of contact

at the relevant administrative level to facilitate and coordinate the permit-granting

process for health biotechnology strategic projects and high impact health

biotechnology strategic projects and shall provide information on the general

administrative support and the technical and financial support set out in this [Section]

through a dedicated webpage.

2. This single point of contact shall be the same as the single point of contact referred to

in Article 3(2) of the Regulation (EU) ../.. [Regulation on speeding-up environmental

impact assessments -permitting regulation], responsible for facilitating and

coordinating all aspects of the environmental assessments, pursuant to applicable

Union and Member States rules.

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3. The single point of contact shall be the sole point of contact for the project promoter

during the permit-granting process and shall assist the project promoter in handling

any administrative matter relevant to the permit-granting process.

4. It shall coordinate the exchange of documents and information between the project

promoters and the competent authorities and shall notify the promoter of the outcome

of the decision-making process related to permit-granting, in accordance with

national administrative arrangements. The authorities involved in the permit-granting

process and other authorities concerned shall specify and make available to the single

point of contact concerned the requirements and the scope of information requested

of a project promoter.

5. The single point of contact shall direct project promoters to the relevant national and

regional antennas of the EU Health Biotechnology Support Network referred to in

Article 19.

6. Project promoters shall be allowed to submit to the single points of contact any

documents relevant to the permit-granting process in electronic form.

7. Member States shall promote the reuse of existing data, studies and authorisations in

order to avoid duplication of procedures, reduce administrative burden and ensure

consistency of decision-making. For that purpose, they shall ensure that, when

assessing an application, competent authorities duly take into account all relevant

studies, assessments and valid permits or authorisations already carried out or issued

for the same project or its components, provided that they remain applicable and up

to date.

8. Member States shall ensure that the single points of contact and all authorities

involved in the permit-granting process have a sufficient number of qualified staff

and adequate resources.

9. Member States shall ensure that applicants have easy access to information on

procedures for the settlement of disputes concerning the permit-granting process,

including, where applicable, alternative dispute resolution mechanisms provided for

by national law.

Article 12

Priority status of health biotechnology strategic projects

1. Health biotechnology strategic projects shall be considered as contributing to the

strengthening of the biomanufacturing capacity and to the supply resilience of

biotechnology products in the Union and, therefore, shall be considered to be of

public interest.

Health biotechnology strategic projects shall be deemed to contribute to the resilience

objectives referred to in Article 14 of Regulation [Regulation on speeding-up

environmental impact assessments – permitting regulation].

2. For the purposes of this Article, health biotechnology strategic projects shall be

understood to cover also high impact health biotechnology strategic projects.

3. High impact health biotechnology strategic projects shall be considered to be of

public interest and may be considered to have an overriding public interest with

specific consideration given to the high impact strategic nature of such projects in

accordance with Article 14 of Regulation [Regulation on speeding-up environmental

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impact assessments – permitting regulation ] and point I of the Annex to that

Regulation.

4. Where a project is recognised as a health biotechnology strategic project, Member

States shall grant that project the status of project with the highest national

significance possible, where such a status exists in national law and shall ensure that

the relevant process for permit-granting and the licensing procedures, including

environmental assessments and spatial planning, are treated in the most rapid way

possible in accordance with Union and national law and shall benefit from any

accelerated procedures provided for in applicable Union and national law.

5. Health biotechnology strategic projects shall also benefit, where applicable, from the

tacit-approval in accordance with Article 14 and point II of the Annex to [COM

Proposal 2025(984) for a Regulation on speeding-up environmental impact

assessments – permitting regulation].

6. The permit-granting process shall not exceed ten months for health biotechnology

strategic projects, and eight months for high impact health biotechnology strategic

projects, from the date of acknowledgement of the completeness of the permit

application. In duly justified cases requiring complex procedures under Union or

national legislation, such as in the case of multi-site or multi-purpose projects, the

competent authority may extend the period by up to three additional months,

provided that the reasons for such extension are communicated in writing to the

project promoter.

7. Where an environmental impact assessment is required pursuant to Directive

2011/92/EU, the step of the preparation of the environmental impact assessment

report referred to in Article 1(2), point (g)(i), of that Directive shall not be included

in the maximum duration of the permit-granting process referred to in paragraph [5]

of this Article.

8. No later than 45 days from the receipt of the permit-granting application, the single

point of contact shall acknowledge that the application is complete or, if the project

promoter has not sent all the information required to process the application, request

the project promoter to submit a complete application without undue delay,

specifying which information is missing. In the event that the submitted application

is deemed to be incomplete for a second time, the single point of contact may, within

30 days of the second submission, make a second request for information. The single

point of contact shall not request information in areas not covered in the first request

for additional information and shall be entitled only to request further evidence to

complete the identified missing information. The date of the acknowledgement of the

completeness of the application from the single point of contact shall serve as the

start of the permit-granting process for that particular application.

9. All dispute resolution procedures, litigation, appeals and judicial remedies relating to

health biotechnology strategic projects before any national court, tribunal or panel —

including mediation or arbitration — shall be treated as urgent, to the extent that

national law allows such urgency, and without prejudice to the normal rights of

defence of individuals or local communities. Project promoters of health

biotechnology strategic projects shall be able to avail themselves of such urgency

procedures, where applicable. This shall include the dispute-settlement provision in

accordance with Article 14 and point III of the Annex to the Regulation

[…][Regulation on speeding-up environmental impact assessments].

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Article [13]

Administrative support

1. Upon request of a project promoter, Member States shall provide administrative

support to biotechnology projects located on their territory, including health

biotechnology strategic projects and high impact health biotechnology strategic

projects and shall take all appropriate measures to facilitate their timely and effective

implementation, including:

(a) assistance to project promoters to ensure compliance with applicable

administrative, regulatory, and reporting obligations;

(b) support and facilitation of permitting and authorisation procedures; and

(c) assistance to inform the public and those in the vicinity of the project with the

aim of increasing public acceptance of the project;

2. High impact health biotechnology strategic projects shall benefit from priority access

to the administrative support measures referred to in paragraph 1,

3. The administrative support referred to in paragraphs 1 and 2 shall be provided

including through the single points of contact and the national and regional antennas

of the EU Health Biotechnology Support Network referred to in Article 19.

4. Member States shall provide online and in a centralised and easily accessible

manner, information relevant to promoters of biotechnology projects, including

health biotechnology strategic projects and high impact health biotechnology

strategic projects covering at least the following elements:

(a) the designated authority referred to in Article 7(1);

(b) the single points of contact referred to in Article 11;

(c) the national and regional antennas of the EU Health Biotechnology Support

Network referred to in Article 19;

(d) the permit-granting process, including information on dispute settlement;

(e) advice on financing and investment services;

(f) business support services, including corporate tax declaration, local tax rules

and labour law.

5. When providing the administrative support referred to in paragraph 1 of this Article,

Member States shall pay particular attention to SMEs, start-ups and scale-ups. Where

appropriate, Member States shall ensure that a dedicated channel for communication

with SMEs, start-ups and scale-ups is available within the single points of contact to

provide guidance and respond to queries related to the implementation of this

Regulation.

Article 14

Financial and technical support

1. Without prejudice to Articles 107 and 108 TFEU, Member States may make use,

where applicable, of the relevant frameworks for providing public support to health

biotechnology strategic projects and high impact health biotechnology strategic

projects, including national promotional banks and other relevant public support

instruments, as provided for in Article 24, paragraphs (4), (5) and (6). Where public

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support is granted, Member States shall ensure that such support is coordinated with

other support measures at Union or national level and is in line with applicable State

aid rules.

2. Projects recognised as high impact health biotechnology strategic projects:

(a) may be given particular consideration for Union financial support including in

the form of blended financing, under Union programmes, funds and financial

instruments and for national support as provided for in Article 25, if the basic

regulations setting up such Union programmes allow it;

(b) shall benefit from priority status in administrative procedures, including in the

permit-granting process, as provided for in Article 12]and of priority access to

administrative support referred to in Article 13.

3. The Commission, in cooperation with the Member States and, where appropriate,

with the Steering Group referred to in Article 20, shall take the following measures

to support the implementation of health biotechnology strategic projects and of high

impact health biotechnology strategic projects, including through the EU Health

Biotechnology Support Network referred to in Article 19:

(a) support project promoters in identifying funding opportunities at Union level,

and facilitate the liaison between project promoters and investors;

(b) promote actions that strengthen the biotechnology innovation ecosystem;

(c) facilitating access, in particular for SMEs, to relevant research and

technological infrastructures, including where such infrastructures are funded

through Union funding programmes, funds and financial instruments.

Article 15

Networks of health biotechnology clusters

1. The Commission and the Member States shall promote and facilitate the cooperation

and the establishment of networks among promoters of health biotechnology

strategic projects, of high impact health biotechnology strategic projects and other

relevant actors. A particular focus shall be placed on fostering cross-border synergies

between regional and national health biotechnology clusters, and on supporting the

networks constituted under the EU Competitiveness Coordination Tool pilot, in full

compliance with EU competition law.

2. Such networks shall fulfil one or more of the following activities:

(a) facilitate synergies between innovation ecosystems at local, regional and Union

levels;

(b) support the establishing of EU-wide interregional biotechnology value chains;

(c) pool national and Union resources and facilities across several Member States,

bridging and upscaling research, pilot and industrial-scale biomanufacturing,

including through cooperation between regional biotechnology clusters;

(d) provide transparent, open, and non-discriminatory cross-border access at

market prices to research organisations, SMEs, start-ups and scale-ups,

healthcare providers, and industrial actors from across the Union;

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(e) facilitate knowledge transfer, standardisation and inter-cluster collaboration, in

line with competition rules, and the dissemination of best practices;

(f) promote the development of infrastructure and digital platforms, and AI-

enabled technologies supporting biotechnology and biomanufacturing.

3. The networks referred to in this Article may establish governance arrangements

appropriate to their objectives and may, where necessary, constitute themselves as

legal entities under Union law, as appropriate for the implementation of specific

actions and investments.

4. The Steering Group referred to in Article 20 shall provide advice for the support of

the federation and networking of biotechnology clusters.

SECTION 3

ACCESS PRINCIPLES AND STRATEGIC MAPPING

Article 16

Access principles and security safeguards

1. Health biotechnology strategic projects and high impact health biotechnology

strategic projects recognised in accordance with this Regulation that receive financial

support in accordance with Union programmes shall offer open, non-discriminatory,

transparent, and criteria-based access at market prices to their facilities, equipment,

services and training programmes for users, including SMEs, start-ups and scale-ups

and other industrial actors, research organisations or training institutions.

The projects referred to in the first subparagraph shall ensure that access to, and the

operation of their infrastructures, facilities and services comply, where applicable,

with the requirements of Directive (EU) 2022/2555 of the European Parliament and

of the Council67, including with the relevant cybersecurity risk-management and

reporting obligations.

2. The access criteria referred to in paragraph 1 of this Article shall ensure

proportionality and fair treatment among users, while taking into account all of the

following:

(a) the objectives and capacity of the infrastructure concerned;

(b) the need to ensure equitable opportunities in particular for SMEs, start-ups and

scale-ups and research actors;

(c) any safeguards necessary for the protection of security, confidentiality or

economic-security interests, in particular those referred to in paragraph [3].

3. In order to safeguard the Union’s security, public order and strategic interests, access

to biotechnology infrastructures and biotechnology datasets of projects referred to in

67 Directive (EU) 2022/2555 of the European Parliament and of the Council of 14 December 2022 on

measures for a high common level of cybersecurity across the Union, amending Regulation (EU) No

910/2014 and Directive (EU) 2018/1972, and repealing Directive (EU) 2016/1148 (NIS 2 Directive)

(Text with EEA relevance), OJ L 333, 27.12.2022, pp. 80–152. ELI:

http://data.europa.eu/eli/dir/2022/2555/oj

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paragraph 1 of this Article shall be governed by the rules laid down in the relevant

Union funding programmes under which those projects are funded.

Article 17

Strategic mapping of the Union’s biotechnology ecosystem

1. The Commission, in close cooperation with the Steering Group referred to in Article

20 and where appropriate the AI Board established under the Regulation (EU)

2024/1689, shall conduct, no later than six months after the entry into force of this

Regulation, and maintain thereafter a strategic mapping of the biotechnology

ecosystem in the Union.

2. The strategic mapping shall provide a comprehensive overview of the Union’s

biotechnology and biomanufacturing landscape, to assess existing capacities and

infrastructures, detect gaps, unused capacities, dependencies, and systemic

challenges across the value chains. It shall cover in particular the following areas:

(a) industrial capacity and infrastructures, including on critical intermediates and

key input, relevant to biotechnology research, development, testing, and

manufacturing, and assessment of their distribution, interconnections and

potential gaps;

(b) access to risk-tolerant capital, by analysing public and private funding sources

supporting biotechnology across all stages of development and identifying gaps

in risk-tolerant financing and market incentives;

(c) biotechnology clusters and biomanufacturing ecosystems, by mapping existing

and planned clusters across the Union and assessing opportunities for

coordination, investment, and both cross-border and interregional

collaboration;

(d) skills, upskilling and reskilling, by analysing current and projected workforce

needs, identifying gaps in education and training, and assessing measures to

attract, retain, and upskill talent;

(e) use of data and AI, by assessing access to data, computing and digital

infrastructures for biotechnology and identifying opportunities to foster

responsible AI-enabled innovation and mitigate related risks.

3. The strategic mapping shall be based on information from relevant Union bodies and

agencies, and, where appropriate, industry stakeholders and research organisations.

The Commission may request Member States to submit data necessary for this

purpose, while ensuring the protection of confidential and commercially sensitive

information. The Member States shall submit such data within 30 days from the

request of the Commission.

4. The Commission shall present the findings of the strategic mapping to the Steering

Group.

5. The results of the strategic mapping shall be used for the following purposes:

(a) supporting the identification and prioritisation by the Member States and the

Commission, as appropriate, of potential health biotechnology strategic

projects and high impact health biotechnology strategic projects;

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(b) informing Union policy and funding priorities in biotechnology and

biomanufacturing, including actions in accordance with this Regulation, as

well as initiatives under Union programmes supporting research, innovation,

skills development and industrial competitiveness;

(c) informing the advice of the Steering Group on health biotechnology strategic

projects and high-impact health biotechnology strategic projects and on

initiatives supporting research, innovation, skills and industrial competitiveness

in the biotechnology sector.

Article 18

More favourable treatment

The provisions of this Regulation regarding the permit granting process, the priority status of

health biotechnology strategic projects and of high impact health biotechnology strategic

projects and support for such projects shall apply without prejudice to more favourable

provisions laid down in other Union rules.

SECTION 4

EU HEALTH BIOTECHNOLOGY SUPPORT NETWORK

Article 19

EU Health Biotechnology Support Network

1. The Commission shall set up, coordinate and support an EU Health Biotechnology

Support Network (‘the Network’), consisting of national and regional antennas in the

Member States (‘the antennas’).

2. The Network shall assist and support the developers of health biotechnology

products, in particular SMEs, start-ups and scale-ups, the promoters of biotechnology

projects, including health biotechnology strategic projects and high impact health

biotechnology strategic projects (‘project promoters’) in identifying the relevant

applicable rules and funding, scaling-up and networking opportunities.

3. The Network shall fulfil in particular the following missions:

(a) provide information on the national and Union rules applicable to the

development and placing on the market of health biotechnology products,

including on the applicable authorisation procedures for health biotechnology

products;

(b) information for the identification and use of the applicable regulatory

frameworks and regulatory support mechanisms with regard to innovative

health biotechnology products, as provided for in Article 34;

(c) facilitate the interactions of project promoters with potential public and private

investors including venture-capital funds, corporate partners and national

promotional banks and relevant funding structures and existing networks of

investors, including with the European Innovation Council Trusted Investors

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Network68 through matchmaking initiatives, including host pitch sessions,

demo days and investor forums, in cooperation with the Steering Group

referred to in Article 20, the European Innovation Council and other relevant

Union initiatives;

(d) provide information and support to project promoters for intellectual property

procedures and technology transfer and promote investors’ awareness of Union

regulatory frameworks and responsible-innovation principles;

(e) support project promoters in the identification of scaling up resources,

including business support networks providing advice on commercial readiness

of health biotechnology projects and testing and training facilities, state-of-the-

art pilot plant facilities that simulate a real production environment, and

relevant research and technology infrastructures across the Union, including

technology centres, cutting-edge facilities, and data-sharing platforms to

support the development and testing of health biotechnologies;

(f) support biotechnology actors in the responsible and effective integration of AI,

by providing sector-specific guidance and promoting best practices and

standards for trustworthy AI, in coordination with the bodies established under

Regulation (EU) 2024/1689, and by providing information and support, in

particular to SMEs, start-ups and scale-ups;

(g) facilitate liaison and exchanges among project promoters with a view to

fostering networking and cooperation, including to support networks of health

biotechnology clusters referred to in Article 15;

(h) provide incubation, acceleration and mentorship programmes for

biotechnology start-ups and scale-ups and connect project promoters with

projects and initiatives that address skills and expertise needs in health

biotechnology and biomanufacturing, including with testing, training and

technical support facilities, and regional skills partnerships;

(i) support Member States and the single points of contact in facilitating projects

promoters’ access to administrative support provided in accordance with

Article 13.

4. The Network shall complement and, to the extent possible, rely on existing relevant

organisations and networks at Union and Member State and regional level, including

the European Enterprise Network.

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 of this Article, including to the ability to leverage,

complement and strenghten existing national and European networks that support

SMEs, start-ups and scale-ups, and innovators.

The Commission shall organise the management, coordination and support of the

Network.

68 The European Innovation Council (EIC) Trusted Investor Network brings together investors from

across Europe, including venture capital funds, public investment banks, foundations, and corporate

venture arms with experience and commitment to co-invest in promising deep tech start-ups in Europe,

alongside the European Innovation Council Fund. List of members accessible at:

https://eic.ec.europa.eu/eic-fund/trusted-investor-network_en

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6. The Commission may support the Network through Union funds, programmes, and

instruments, in accordance with the objectives established in their respective basic

acts.

7. Member States shall take all necessary measures to facilitate the fulfilment of the

tasks of the Network.

SECTION 5

EUROPEAN HEALTH BIOTECHNOLOGY STEERING GROUP

Article 20

European Health Biotechnology Steering Group

1. The European Health Biotechnology Steering Group (the “Steering Group”) is

hereby established.

2. The Steering Group shall provide advice to the Commission and to the Member

States to facilitate the implementation of this Regulation and shall carry out the tasks

provided for in this Regulation.

Article 21

Composition and functioning of the Steering Group

1. The Steering Group shall be composed of representatives from all Member States

and the Commission. It shall be chaired by a representative of the Commission (the

‘Chair’).

2. Each Member State shall nominate a member and an alternate member as its

representatives to the Steering Group. Where relevant as regards function and

expertise, a Member State may nominate different representatives in relation to the

different subgroups of the Steering Group, while not exceeding a representative per

subgroup. Nominated permanent representatives shall ensure the necessary

coordination within their respective Member State. The Commission and the

Member States shall have voting rights.

3. The Steering Group shall, upon a proposal by the Commission, adopt its rules of

procedure by a simple majority of its members. Where appropriate, the Chair may

invite external experts to attend meetings of the Steering Group.

4. The Steering Group shall meet as needed in order to allow the effective performance

of its tasks provided for in this Regulation. Where necessary, the Steering Group

shall meet on the basis of a reasoned request by the Commission or by a Member

State. The Commission shall coordinate the work of the Steering Group by means of

a secretariat that provides technical and logistical support.

5. The Steering Group shall carry out the following tasks:

(a) facilitate the exchange of information and best practices among Member

States, the Commission, and relevant stakeholders in relation to the recognition

and the implementation of health biotechnology strategic projects and high

impact health biotechnology strategic projects;

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(b) discuss, at least once a year, the progress in the recognition of health

biotechnology strategic projects and high impact health biotechnology strategic

projects and provide advice including to overcome systemic challenges faced

by such projects;

(c) provide advice for supporting the federation and networking of biotechnology

clusters, as provided for in Article [15[(4)];

(d) discuss and coordinate funding for health biotechnology strategic projects,

including high-impact health biotechnology strategic projects, without

prejudice to the basic acts of the relevant Union programmes; this may include

facilitating the liaison between project promoters and potential private and

public investors, such as the European Investment Bank Group, national

promotional banks and institutions and export credit agencies, to mobilise

additional financing, including from private or venture capital sources;

(e) provide its views regarding the recognition of a project as a high impact health

biotechnology strategic project, in accordance with Article [10][(2)];

(f) facilitate the coordination and information exchange among the Member States

on enforcement of the biosecurity provisions in this Regulation and other

emerging biosecurity topics.

6. The Steering Group may establish subgroups for the purpose of this Regulation.

7. The Steering Group shall take the necessary measures to ensure the safe handling and

processing of confidential and commercially sensitive information.

8. The Steering Group shall use its best endeavours to reach consensus, where possible.

Members with diverging positions may request that their positions and the grounds

on which they are based be recorded in the Steering Group’s position.

CHAPTER III

ACCESS TO FUNDING

Article 22

EU health biotechnology investment pilot

1. To support the financing of, and investments in, companies and projects falling

within the scope of this Regulation, the Commission, together with the European

Investment Bank Group (EIBG) or other implementing partners, shall develop an EU

Health Biotechnology investment pilot (‘the pilot). The pilot is established for an

initial period of two years, after which it shall be reviewed.

2. The pilot shall support the full lifecycle of companies and projects in the area of

health biotechnology, including SMEs, start-ups and scale-ups through direct and

indirect financing, other than direct equity operations, without prejudice to the basic

acts to be agreed under the next Multiannual Financial Frameworks. It shall

complement and be developed in a coordinated manner with other EU financing

instruments.

3. The pilot shall be designed as a mechanism that may use and leverage different

funding streams and instruments to accelerate and catalyse investments into the

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health biotechnology sector. It may be used to provide Union support through Union

programmes.

4. The pilot shall pursue the following objectives:

(a) support early-stage applied research and innovation, technology transfer and

spin-offs, with appropriate financing mechanisms, including equity;

(b) provide support to projects, SMEs, including start-ups and scale-ups, and mid-

caps across the Union, which are providing solutions and developments that

contribute to the objectives of this Regulation;

(c) finance late-stage development initiatives, industrial scale-up and production

capacity build-up for companies that contribute to the objectives of this

Regulation, through venture loans and other suitable debt or quasi-equity

instruments;

(d) anchor growth and manufacturing activities in the Union in order to gain or

maintain strategic autonomy and resilience, as well as boost competitiveness of

the sector;

(e) mobilise private investments, including from institutional investors such as

pension funds, and strengthen the availability of long-term risk finance for

biotechnology companies established in the Union. Financial actors, including

private institutional investors, shall be targeted by leveraging expertise in

catalysing private capital and use appropriate risk-sharing mechanisms to

achieve this objective;

(f) assist early and growth-stage companies through blended and concessional

finance, encompassing equity or debt operations, complementing the direct

equity support provided by the European Innovation Council Fund and the

Scale-Up Europe Fund under the Horizon Europe, including via the

development of new products;

(g) provide advisory support throughout the investment cycle, encompassing

concrete capacity-building measures. These interventions shall be aimed at

reinforcing the competencies and institutional preparedness of developers and

promoters of projects and financial intermediaries to successfully develop and

implement their initiatives.

Article 23

EU biotechnology late-stage capital booster pilot

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union contributing to an EU

biotechnology late-stage capital booster as high-impact health biotechnology

strategic projects, only where in addition to the conditions laid down in Article

[4][(1)], the projects facilitate access to capital markets in accordance with applicable

law, and are led by private-sector operators or consortia, with the potential

participation of market-infrastructure providers and investors.

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2. The projects referred in paragraph 1 of this Article shall pursue at least one of the

following objectives or activities:

(a) facilitating cross-border investment in accordance with Union law;

(b) mobilising long-term capital and attracting private investment, including

institutional investors, and through private markets, with credible commitments

or structures that support liquidity and follow-on financing;

(c) improving cross-border investors’ access and issuers’ visibility through

practical steps and deliverables and demonstrating a credible issuance and

investor pipeline with target numbers and timelines;

(d) enhancing biotechnology sector-specific investment expertise through

exchange of best practices on these topics ;

(e) mobilising private capital through biotechnology accelerators and venture

builders, including potential use of risk-sharing mechanisms.

3. The projects referred in paragraph 1 shall:

(a) ensure non-discriminatory, transparent and criteria-based access for eligible

issuers;

(b) ensure the possibility of cross-border participation from any Member State;

(c) include proportionate risk-management, governance and reporting

arrangements and operate without prejudice to applicable Union financial

services legislation and the mandates of competent authorities.

4. The provisions of this Regulation regarding the application for, and the recognition

of, high-impact health biotechnology strategic projects laid down in Articles 8 and

[10], respectively, apply to projects referred to in this Article.

Article 24

Biotechnology as a strategic technology eligible for Union and national financial support

1. Union programmes may support biotechnology as a strategic technology for the

Union’s innovation capacity, sovereignty, resilience and leadership in line with the

objectives set out in the Regulations establishing those Union programmes.

2. The Commission may adopt calls, windows or compartments for biotechnology and

may establish instruments in the implementation of those programmes, funds and

instruments, that support biotechnology companies, projects and initiatives falling

within the scope of this Regulation, in line with the objectives and rules set out in the

regulations establishing those programmes, funds and instruments.

3. Companies, projects and initiatives falling within the scope of this Regulation may

be targeted for financial support from Union-led funding initiatives and from Union

funding programmes and instruments, as projects in a strategic technology and, as

appropriate, in a strategic deep tech area.

4. Member States may, in line with applicable State aid rules, provide financial support

to biotechnology as a strategic technology for the Union’s innovation capacity,

sovereignty, resilience and leadership.

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5. Member States shall pursue the support as referred to in paragraph 4, including for

health biotechnology strategic projects and high impact health biotechnology

strategic projects, in the implementation at national level of the relevant Union

programmes that are shared-management basic acts.

6. Where State aid instruments, designed in compliance with Union competition law

and making use of related EU guidance, are used by Member States for the purpose

of supporting the health biotechnology sector or parts thereof, Member States shall

give particular consideration to high-impact health biotechnology strategic projects

for support under such instruments.

Article 25

Funding for high impact health biotechnology strategic projects

1. High impact health biotechnology strategic projects may be given particular

consideration for financial support under Union funds, programmes and instruments

in accordance with the objectives set out in the regulations establishing those funds,

programmes and instruments.

2. Where high impact health biotechnology strategic projects benefit from financial

support under Union funds, programmes and instruments, in accordance with the

respective legal bases and eligibility criteria of those funds, programmes and

instruments, such support may be used in combination with financing from the

European Investment Bank Group, from national promotional banks and institutions

or from other development or public financial institutions, as well as in combination

with financing from private-sector finance institutions and from public-sector or

private-sector investors, including through public–public or public–private

partnerships.

3. When preparing and implementing the annual and multiannual work programmes of

the relevant Union funds, programmes and instruments referred to in paragraph 1, the

Commission may give particular consideration to actions supporting high-impact

health biotechnology strategic projects.

4. The Commission shall ensure the coordination and the complementarity among the

relevant Union funds, programmes and instruments that support actions under this

Regulation, and shall provide strategic guidance for the implementation of such

funds, programmes and instruments with regard in particular to the high impact

health biotechnology strategic projects, including in cooperation with the Steering

Group, referred to in Article 20, where appropriate.

Article 26

Coordination of financing for health biotechnology strategic projects

The Steering Group referred to in Article 20 may coordinate investments into health

biotechnology strategic projects, including high impact health biotechnology strategic

projects, with the project promoters and other relevant interested parties, in compliance with

Union competition law.

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CHAPTER IV

EXTENSION OF THE SUPPLEMENTARY PROTECTION CERTIFICATE

Article 27

Extension of the supplementary protection certificate concerning best-in-class

biotechnology medicines developed in the Union

1. Where a marketing authorisation is granted by the Union to a medicinal product for

human use developed by means of biotechnological processes referred to in

paragraph 1 of Annex I to Regulation (EU) …/… [reference to be added after

adoption cf. COM(2023) 193 final] or to an advanced therapy medicinal product

referred to in paragraph 2 of that Annex, and that is protected either by a

supplementary protection certificate in accordance with Regulation (EC) No

469/2009 of the European Parliament and of the Council69, or by a patent which

qualifies for the granting of such supplementary protection certificate, the holder of a

patent or of such certificate shall be entitled to a 12-month extension of the periods

referred to in Article 13, paragraphs (1) and (2), of Regulation (EC) No 469/2009,

provided that the marketing authorisation applicant demonstrates that all of the

following conditions are met:

(a) the medicinal product contains a new active substance distinctly different from

that of any authorised medicinal product in the Union;

(b) the medicinal product has a mechanism of action distinctly different and shows

a level of safety and efficacy which is at least equivalent to that of any

authorised medicinal product in the Union for the same disease;

(c) the clinical trials evaluating the efficacy of the medicinal product and

supporting its marketing authorisation were conducted in more than two

Member States;

(d) at least a manufacturing step, excluding packaging, quality testing and

certification is performed in the Union.

2. The European Medicines Agency (‘the Agency’) shall assess compliance with the

conditions referred to in paragraph 1 as part of the marketing authorisation procedure

concerned.

3. Where compliance is confirmed, the Agency shall issue a statement to that effect.

4. A copy of the statement referred to in paragraph 3 of this Article shall be included in

the application for a certificate lodged under article 7 of Regulation (EC) No

469/2009.

69 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, pp. 1.

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CHAPTER V

ENHANCING COMPETITIVENESS IN BIOSIMILARS

Article 28

Guidance by the Agency on biosimilars

The Agency, in consultation with the Commission, shall develop and update non-binding

guidance on a tailored regulatory approach for the development of biosimilars, reflecting

advances in manufacturing and analytical testing. The guidance shall consider a potential

reduction of the clinical data required for the development and approval of biosimilars,

without affecting their quality, safety and efficacy.

Article 29

Biotechnology health strategic projects for biosimilars

To enable access to the support measures laid down in Section II of Chapter II, Member

States shall recognise projects located in the Union as biotechnology health strategic projects

in the form of biotechnology health strategic projects for biosimilars only where they make a

substantial contribution to at least one the specific objectives referred to in Article [3][(1)] and

fulfil either of the following conditions:

(a) they contribute to the setting up and extension of innovative biomanufacturing

capacity, and infrastructures for analytical testing procedures;

(b) they contribute to the research, development and marketing authorisation of

biosimilars, and where appropriate to strengthening the use of platform technologies;

this includes analytical methodologies that would reduce the need for clinical data

for biosimilars, without affecting their quality, safety and efficacy.

Article 30

International partnerships

Where appropriate, promoters of projects related to biosimilars and other companies working

in this area, shall explore opportunities to establish or strengthen cooperation with

international biotechnology clusters, including with a view to fulfilling the conditions referred

to in Article [29] for the recognition of biotechnology health strategic projects for biosimilars.

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CHAPTER VI

ARTIFICIAL INTELLIGENCE AND DATA AS BIOTECHNOLOGY ENABLERS

Article 31

Guidance on the deployment and use of systems based on advanced technologies,

including AI, in the lifecycle of medicinal products

1. The Agency shall publish and regularly update, as appropriate, non-binding guidance

on the deployment and use of systems based on advanced technologies, including

AI, in the lifecycle of medicinal products development, including during pre-clinical

research, clinical development and trials, manufacturing and post-authorisation

monitoring.

Such guidance shall be developed, updated and published in agreement with the

Commission, including with the AI Office.

Such guidance shall ensure full coherence with the requirements laid down in

Regulation (EU) 2024/1689 and with any guidance issued under that Regulation

regarding general-purpose AI models or AI systems.

2. In developing and updating the guidance referred to in paragraph 1, the Agency shall

consult the relevant authorities, at national and European level, and stakeholders as

appropriate.

To the extent that the guidance concerns the deployment and use of systems based on

advanced technologies, including AI, across the clinical trials lifecycle, the Agency

shall further cooperate with the Clinical Trials Coordination [and Advisory] Group

(‘CTAG’) referred to in Article [85] of Regulation (EU) No 536/2014, with the

Medical Device Coordination Group (‘MDCG’) referred to in Article 103 of

Regulation (EU) 2017/745 and with the Artificial Intelligence Board referred to in

Article 65 of Regulation (EU) 2024/1689, as appropriate and shall publish that

guidance in agreement with the consulted entities referred to in this subparagraph.

3. The Agency shall develop and publish in agreement with the Commission, including

the AI Office where appropriate, and in cooperation with the national competent

authorities, non-binding guidance on the deployment and use of advanced

technologies, including AI, in the procedures for the authorisation of medicinal

products.

Article 32

Biotechnology testing environments for advanced biotechnology innovations

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union as high impact health

biotechnology strategic projects in the form of trusted testing environments for

advanced health biotechnology innovations, where such innovations are enabled,

enhanced or significantly supported by AI or advanced computational methods, only

where they comply with the criteria laid down in Article 4(1) and substantially

strengthens the Union’s capacity for responsible experimentation, development,

testing and validation of such innovations and they fulfils all of the following

conditions:

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(a) operate under trusted conditions ensuring compliance and alignment with

relevant Union and national legislation and complements where appropriate

testing and experimentation facilities and AI regulatory sandboxes established

in accordance with Regulation (EU) 2024/1689, while ensuring consistency

and synergies in their implementation;

(b) seek, where appropriate, to leverage AI systems or other advanced

computational tools, alongside advanced technologies and analytics, to

optimise workflows and increase efficiency;

(c) aim to enable innovation in biotechnology areas where the use of AI-enabled or

computationally enhanced methods can be particularly impactful, such as

enhancing efficacy and safety of immunology treatments and of ATMP gene

therapies, or developing NAMs that combine advanced experimental and

computational approaches;

(d) make available, under fair and transparent conditions, evidence, results and

lessons learned generated within such testing environments, to inform Union

guidance, standardisation and best-practice frameworks, and, where

appropriate, the design or implementation of regulatory sandboxes in

accordance with Union or national law.

2. The Commission, in cooperation with the Member States, shall promote and

facilitate, including through existing networks such the European Digital Innovation

Hubs and testing and experimentation facilities and relevant expert groups

established under Union legislations, networking, knowledge-sharing and capacity-

building among projects and initiatives providing such testing environments.

3. The provisions of this Regulation regarding the application for, and the recognition

of, high-impact health biotechnology strategic projects laid down in Articles 8 and

10, respectively, apply to projects referred to in this Article.

Article 33

Biotechnology data quality accelerator

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union as high impact health

biotechnology strategic projects in the form of biotechnology data quality

accelerators, only where they comply with the criteria laid down in Article 4(1) and

fulfil the conditions laid down in paragraph 2 of this Article and they make a

significant contribution to the curation, maintenance and responsible use of high-

quality, appropriately annotated and provenance-verified datasets that are essential

for the training, validation and testing of AI systems and models used in health

biotechnology applications.

2. The projects referred to in paragraph 1 shall:

(a) aim to foster the development and deployment of trustworthy and competitive

AI systems in health biotechnologies, including large-scale and general-

purpose models relevant for biological, biomedical or biomanufacturing use

cases;

(b) assist entities that lawfully hold relevant data and, as regards health data,

holders as defined in Article 2(2), point (t), of Regulation (EU) 2025/327

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(‘health data holders’) to improve data quality, standardize and make other

improvements to such data as referred to in paragraph 1 of this Article;

(c) contribute to the development of Union standards and quality frameworks for

data representativeness, provenance, interoperability and annotation in

biotechnology;

(c) give due consideration to the interoperability with platforms deployed pursuant

to the European Health Data Space (EHDS) and other relevant data spaces;

(d) be aligned with and complement Union initiatives such as the Data Union

Strategy, including data labs and AI factories, while addressing the specific

requirements of biotechnology datasets, including biological metadata,

scientific taxonomies, experimental traceability and regulatory-grade data

quality.

3. The provisions of this Regulation regarding the application for, and the recognition

of, high-impact health biotechnology strategic projects laid down in Articles 8 and

10, respectively, apply to projects referred to in this Article.

4. The processing of personal data by the entities that lawfully hold the relevant

datasets enhanced as provided for in paragraph 2, point (b) of this Article, and by the

biotechnology data quality accelerator projects takes place in the public interest.

5. Entities that lawfully hold relevant datasets enhanced as provided for in paragraph 2,

point (b) of this Article, shall make available such datasets under fair, reasonable and

non-discriminatory conditions, ensuring equitable access for users including research

organisations, SMEs and public institutions, under the conditions referred to in

Article 16 of this Regulation.

Electronic health data referred to in Article 51 of Regulation (EU) 2025/327 shall be

made available in accordance with that Regulation.

6. Entities that lawfully hold relevant datasets enhanced as provided for in paragraph 2,

point (b) of the Article, shall support, where appropriate, the integration of such

datasets into Union infrastructures, including the European Research Area data

spaces, data labs, AI factories and the infrastructures operated by high impact health

biotechnology strategic projects.

7. The decision of the Commission regarding the recognition of a high impact health

biotechnology strategic project in the form of a biotechnology data quality

accelerators, referred to in Article 10(2), shall specify the modalities of processing of

personal data necessary to achieve the purpose of the project. In particular the

Commission shall specify the categories of data to be processed, the roles of the

entities participating in the project, the categories of the entities which may use the

curated data and the safeguards.

8. With regard to biotechnology data quality accelerators recognised in the context of a

call for proposals as provided for in Article 10(3), the Commission shall, by means

of implementing acts, adopt, before the launch of the related call, a decision

establishing the modalities of processing of personal data necessary to achieve the

purpose of the project. That decision shall specify the categories of data to be

processed, the roles of the entities participating in the project, the categories of the

entities which may use the curated data and the safeguards. The selected

beneficiaries shall comply with the conditions laid down in that decision.

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CHAPTER VII

REGULATORY TOOLS FOR NOVEL HEALTH BIOTECHNOLOGY PRODUCTS

SECTION 1

SUPPORT IN DETERMINING THE REGULATORY STATUS OF NOVEL HEALTH BIOTECHNOLOGY

PRODUCTS

Article 34

Assistance on regulatory procedural pathways

1. The EU Health Biotechnology Support Network referred to in Article 19 shall, upon

request, assist developers, in particular SMEs, start-ups and scale-ups, with

identifying and using the appropriate regulatory procedural pathway and regulatory

support mechanisms with regard to innovative health biotechnology products or

biotechnology services for human use that exhibit characteristics that raise questions

on the application or applicability of the Regulation (EU) 2017/745, Regulation (EU)

2017/746, Regulation (EU) 2024/1938, Regulation (EU) …/… [reference to be

added after adoption cf. COM(2023) 193 final] and Regulation (EU) …/…

[reference to be added after adoption cf. COM(2023) 192 final] Regulation (EC)

1394/2007 and Directive 2010/45/EU.

2. The support provided pursuant to this Article shall not duplicate procedures

pertaining to recommendations or opinions on regulatory status set out in with

Regulation (EU) 2017/745, Regulation (EU) 2017/746, Regulation (EU) 2024/1938,

Regulation (EU) …/… [reference to be added after adoption cf. COM(2023) 193

final] and Regulation (EU) …/… [reference to be added after adoption cf.

COM(2023) 192 final] .

3. The support referred to in paragraph 1 shall be provided in particular on the

following:

(a) procedures for seeking guidance on the regulatory status and on the nature and

scope of such guidance;

(b) applicable rules for the authorisation of health biotechnology products that

combine different products, technologies, processes, or components regulated

under different regulatory frameworks;

(c) regulatory sandboxes established in Article 40 and under [revised Regulation

(EU) 2017/745], [revised Regulation (EU) 2017/746], Regulation (EU)

2024/1938 and in Regulation (EU) …/… [reference to be added after adoption

cf. COM(2023) 193 final].

4. In providing the support referred to in this Article, the EU Health Biotechnology

Support Network referred to in Article 19 may request the assistance of the Foresight

Panel for Emerging Health Innovation.

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Article 35

Union regulatory status repository

1. The Commission shall compile, maintain, develop and make publicly available a

regulatory status repository (‘regulatory status repository’).

2. The regulatory status repository shall contain:

(a) decisions, opinions, scientific recommendations regarding the regulatory status

of a health innovations, issued pursuant to the mechanisms laid down in Article

4 of Regulation (EU) 2017/745, Articles 61 and 62 of Regulation (EU) …/…

[reference to be added after adoption cf. COM(2023) 193 final], Article 13 of

Regulation (EU) 2024/1938, and, where relevant, pursuant to similar

mechanisms laid down in other legislative acts;

(b) the summaries of the scientific recommendations delivered by the Agency,

prior to the application of Regulation (EU) …/… [reference to be added after

adoption cf. COM(2023) 193 final], in accordance with Article 17 of

Regulation (EC) No 1394/2007 on whether a product falls within the definition

of an advanced therapy medicinal product or not;

(c) the discussion papers delivered by the Foresight Panel for Emerging Health

Innovation.

3. Member States shall make publicly available, through the relevant national platforms

or registries, decisions, opinions, scientific recommendations, and other outputs

issued at national level concerning the regulatory status of health biotechnology

products. Member States shall inform the Commission where such information is

made available.

Article 36

Time limits in the regulatory status process

With a view to ensuring the timely assessment of the regulatory status of health biotechnology

products, the advisory bodies and other relevant entities mandated under [revised Regulation

(EU) 2017/745, [revised Regulation (EU) 2017/746], Regulation (EU) 2024/1938

Regulation], Regulation (EU) …/… [reference to be added after adoption cf. COM(2023) 193

final] and Regulation (EU) …/… [reference to be added after adoption cf. COM(2023) 192

final] to provide a recommendation or opinion, including preparatory consultations, on the

regulatory status of a product, shall act swiftly, without prejudice to the time limits for the

forming of such recommendations or opinions established in the above legal acts.

SECTION 2

FORESIGHT ON EMERGING HEALTH INNOVATION

Article 37

Foresight Panel for Emerging Health Innovation

1. A Foresight Panel for Emerging Health Innovation is hereby established ('the

Foresight Panel').

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2. The Foresight Panel shall provide regulatory, scientific and technical expertise on

emerging science and technology in the field of health underpinning the development

of health biotechnology products to the Commission, the Agency and to relevant

Union-level advisory bodies and competent authorities and other entities in the

Member States in the area of health. The Foresight Panel shall operate in accordance

with the Commission’s framework for expert groups.

3. The Foresight Panel shall carry out the following tasks:

(a) conduct horizon scanning by analysing, identifying and discussing emerging

science and technology with the potential to drive the development of health

biotechnology products, including upon request from the Commission, the

Agency, Union-level advisory bodies or competent authorities in the Member

States in the area of health, and develop and publish related considerations in

the form of discussion papers

(b) engage with the Agency and relevant Union-level advisory bodies and

competent authorities and other entities in the Member States in the area of

health, to facilitate cross-framework dialogue and consistency;

(c) engage with existing relevant networks to contribute to enhancing regulatory

expertise regarding health biotechnology products.

(d) accommodate exchanges among the authorities responsible for the setting up

and the operation of regulatory sandboxes in accordance with article 39(5).

4. For the purpose of performing the tasks referred to in paragraph 2, point (a), of this

Article, the Foresight Panel may engage in preliminary discussions with the Agency

or relevant Union level advisory bodies in the area of health, networks and informal

task forces, national competent authorities, developers, and other relevant actors and

shall implement a collaborative approach with a view to ensuring an effective uptake

of its discussion papers.

5. The Foresight Panel shall consist of scientific and regulatory experts from the SoHO

Coordination Board (‘the SCB’), the Medical Devices Coordination Group (‘the

MDCG’), the Coordination group on Health Technology Assessment (‘the

HTACG’), the Agency and the competent authorities of the Member States,

appointed by the Commission in view of their regulatory, scientific or technical

expertise in the relevant identified fields and frameworks. The panel may invite

external experts selected to assist with specific tasks when such relevant external

expertise is needed.

6. The Commission shall adopt an implementing act laying down detailed rules on the

selection, composition, number of members, and functioning of the Foresight panel.

The implementing act shall be adopted in accordance with the examination procedure

referred to in Article 65(2).

Article 38

Support to the Foresight Panel for Emerging Health Innovation

1. The Commission shall chair and provide the secretariat for the Foresight Panel and

shall provide the support necessary to ensure it can efficiently perform its tasks.

2. The Commission shall in particular have the following tasks:

(a) to provide administrative and technical support to the Foresight Panel;

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(b) to facilitate and manage remote and physical meetings of the Foresight Panel;

(c) to ensure that the work of the Foresight Panel is carried out in an independent

manner;

(d) to facilitate the dissemination of the discussion papers produced by the

Foresight Panel with relevant competent authorities and advisory bodies;

(e) to ensure that remuneration and expenses are provided to the experts

composing the Foresight Panel;

(f) to monitor compliance with the rules of procedure of the Foresight Panel;

(g) to issue annual reports on the work of the Foresight Panel, including on the

number of discussion papers delivered by the Panel.

3. The Foresight panel shall establish its own rules of procedure.

SECTION 3

REGULATORY SANDBOXES AS TOOLS FOR NOVEL HEALTH BIOTECHNOLOGY PRODUCTS

Article 39

Regulatory sandboxes provided for in the applicable frameworks and cross-framework

communication

1. Where a regulatory sandbox is established at Member State level for a health

biotechnology product in accordance with [revised Regulation (EU) 2017/745],

[revised Regulation (EU) 2017/746], Regulation (EU) 2024/1938, the authorities

responsible for the operation of that sandbox shall, where appropriate and in

accordance with the relevant legislative act referred to in this paragraph, conduct

consultations with the competent authorities and the Commission, responsible for the

operation of sandboxes under the other relevant Union legislative acts referred to in

this paragraph and in paragraph 2 of this Article, and with the Foresight Panel

referred to in Article 37, regarding the design and the implementation of the

regulatory sandbox.

2. Where a regulatory sandbox is established at Union level for a health biotechnology

product in accordance with Regulation (EU) …/… [reference to be added after

adoption cf. COM(2023) 193 final] or with Article [40] of this Regulation, the

Commission or the Agency shall consult, where appropriate and in accordance with

the legislative acts referred to in this paragraph, the Agency, the SCB, the MDCG,

and the Foresight Panel referred to in Article 37, regarding the design and the

implementation of the regulatory sandbox.

3. The authorities responsible, pursuant to the applicable legislative act, for setting up a

regulatory sandbox referred to in paragraphs 1 and 2 of this Article, shall ensure that

due consideration is given to the regulatory challenges posed by combination

products, and to consultations with the relevant authorities with expertise regarding

the associated parts of such products.

4. For the purposes of the consultations referred to in paragraphs 1 and 2 of this Article,

all authorities shall endeavour to provide their contribution swiftly, without prejudice

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to time limits set out in the provisions of the Union legislative acts in the area of

health governing the regulatory sandbox referred to in those paragraphs.

5. The Commission, the Agency, the MDCG and the SCB shall, through the Foresight

Panel, facilitate the exchange of views and experiences among the authorities

responsible for the setting up and the operation of regulatory sandboxes for health

biotechnology products. Those exchanges shall include the following:

(a) promoting knowledge sharing, by facilitating the exchange of information,

experiences and best practices, including on regulatory approaches,

technological challenges, and emerging scientific insights and the appropriate

regulatory responses (cross-framework knowledge sharing);

(b) identifying potential implications for the evolution or adaptation of the relevant

Union legislative acts in the area of health (cross-framework regulatory

learning).

Article 40

Regulatory sandboxes for novel health biotechnology products not falling under other

regulatory sandboxes in Union legislation in the area of health

1. Upon a substantiated request from developers, the Commission may set up a

regulatory sandbox that provides a controlled regulatory environment for the testing

and development of a health biotechnology product, that:

(a) cannot be appropriately accommodated in any of the regulatory sandboxes

available under the Union legislation in the area of health referred to in Article

39, paragraphs (1) and (2); and

(b) whose development is hindered by the challenge to identify a suitable

regulatory procedure in the area of health.

A regulatory sandbox shall not be set up for health biotechnology products which are

likely to fall under the scope of the Union legislation in the area of health referred to

in Article 39, paragraphs (1) and (2).

The sandbox shall be set up in accordance with this Article.

2. Such regulatory sandbox shall set out a time limited framework to allow for the

generation of evidence and data, in a real-world environment and under supervision

of one or more competent authorities.

3. Developers wishing to participate in a regulatory sandbox referred to in paragraph 1

shall submit a substantiated application to the Commission. That application shall

include the following:

(a) a justification for the establishment of a regulatory sandbox, including a

description of the product in question, its level of development, and a

justification with regard to the impossibility of appropriately accommodating

the proposed sandbox in any of the regulatory sandboxes available under the

Union legislation in the area of health referred to in Article 39, paragraphs (1)

and (2).

(b) the identification of existing regulatory challenges;

(c) the assessment of potential benefits and potential risks of the health

biotechnology product to be tested or developed.

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4. Where the Commission concludes, on the basis of its assessment, that the application

shall be accepted, it shall take a decision regarding the establishment of a regulatory

sandbox, by means of an implementing act, in accordance with the examination

procedure referred to in Article 65(2). That implementing act shall set out the

duration of the regulatory sandbox and the principles for operating the regulatory

sandbox.

5. The testing and development activities within the regulatory sandbox shall take place

in accordance with a sandbox plan developed and updated as appropriate by the

Commission based on the principles referred in paragraph 4 of this Article. The

regulatory sandbox plan shall:

(a) set out the objectives, the specific innovations to be tested in the regulatory

sandbox, the relevant activities to be carried out within the regulatory sandbox,

the geographical and temporal scope of those activities, as well as the relevant

conditions and requirements thereof;

(b) be informed by data provided by, and consultations with, the developer of the

health biotechnology product concerned;

(c) identify the participants in the regulatory sandbox and their respective roles;

(d) include appropriate measures to mitigate potential risks, in particular to health

and to the environment;

(e) include conditions regarding the suspension or the termination of the regulatory

sandbox;

(f) set out the supervision measures and the related responsibilities.

6. When assessing the applications received in accordance with paragraph 3 of this

Article and when developing and implementing the sandbox plan, the Commission

may consult the Agency, the SCB, the MDCG, or the Foresight Panel, as appropriate.

7. Participants in the regulatory sandbox, in particular the developer, shall remain liable

under applicable national legislation for any harm inflicted on third parties as a result

of the testing taking place in the sandbox. They shall inform the Commission without

undue delay of any information which might entail the amendment of the regulatory

sandbox or concerns the quality, safety or efficacy of products developed as part of a

regulatory sandbox.

8. The regulatory sandboxes shall not affect the supervisory and corrective powers of

the competent authorities. In case of identification of risks to public health or safety

concerns associated with the use of products covered by a sandbox, competent

authorities shall take immediate and adequate temporary measures in order to

suspend or restrict their use and inform the Commission. Where such mitigation is

not possible or proves to be ineffective, the development and testing process shall be

suspended without delay until an effective mitigation takes place.

9. When concluding the regulatory sandbox, the Commission shall, at the request of a

developer and after having consulted the bodies referred to in paragraph [6] of this

Article, deliver a recommendation on an existing appropriate regulatory procedural

pathway for authorising the placing on the market and post-marketing surveillance

and vigilance of the products concerned.

10. When a product is submitted for authorisation following a recommendation delivered

in accordance with paragraph 9 of this Article, due consideration by the authorities

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responsible for the assessment of the application for authorisation shall be given to

data and evidence collected in the regulatory sandbox.

11. The Commission, after consulting competent authorities of the Member States, and

after seeking the opinion of the bodies consulted in accordance with paragraph [6] of

this Article, may publish a report on the lessons learned from the regulatory sandbox

and, where appropriate, conclusions regarding possible measures at Union level for

the regulation of the health biotechnology product or similar innovation categories

concerned by the regulatory sandbox.

12. The Commission may, by means of implementing acts, lay down common principles,

criteria and practical arrangements for the assessment of applications received from

developers and for the establishment and supervision of the regulatory sandboxes and

for sandbox plans referred to in this article. These implementing acts shall be

adopted in accordance with the examination procedure referred to in Article 65(2).

CHAPTER VIII

BIODEFENCE AND PREVENTING BIOTECHNOLOGY MISUSE

SECTION 1

UNION BIODEFENCE AND BIOSECURITY

Article 41

EU biothreat radar high impact health biotechnology strategic projects

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union as high-impact health

biotechnology strategic projects contributing to the EU Biothreat Radar for the

detection, characterisation, identification, analysis and assessment of biological

threats, including novel, unknown and engineered pathogens to ensure pathogen-

agnostic cross-border surveillance and early threat detection, as well as the generation

and sharing of data required for this, only where they comply with the conditions laid

down in Article 4[(1)] and make a substantial contribution to at least one of the

following:

(a) detection, characterisation, identification, analysis and assessment of biological

threats, including novel, unknown and engineered pathogens;

(b) interoperable and pathogen-agnostic cross-border surveillance, as well as the

generation and sharing of data required for such surveillance;

(c) building sampling and detection infrastructure for early detection of novel pathogens

and situational awareness across environmental and clinical sources, including basic

logistics for collection and transport, and support for the deployment of advanced

detection methods, such as metagenomic sequencing;

(d) ensuring the appropriate use of internationally recognised pathogen data standards;

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(e) ensuring that sequencing data generated through early detection activities is shared in

a timely manner through the European Nucleotide Archive (ENA)70, to enable access

and use by actors across the Union for the development, validation and deployment

of advanced pathogen detection and characterisation methods, by engaging in

partnerships among industry, academia, public authorities and defence actors to

ensure data sharing and integration of warning systems.

2. The provisions of this Regulation regarding the application for, and the recognition

of, high-impact health biotechnology strategic projects laid down in Articles 8 and

10, respectively, apply to projects referred to in this Article.

Article 42

Biodefence capability high impact strategic project

1. To enable access to the support measures laid down in Section 2 of Chapter II, the

Commission shall recognise projects located in the Union as high impact health

biotechnology strategic projects for biodefence capability only where they comply

with the conditions laid down in Article 4(1) and make a substantial contribution to at

least one of the following:

(a) preventing or mitigating misuse of biotechnologies;

(b) rapid surge capacity for safe sampling, testing sequencing and swift manufacturing

of rapid diagnostics;

(c) analysis and assessment capacity of testing and sequencing data that can be

mobilised across Member States;

(d) robust pathogen-agnostic pharmaceutical and non-pharmaceutical defences against

biological threats;

(e) development, validation and benchmarking of methods for the detection and

attribution of genetic engineering, including the creation of open genetic engineering

detection tools;

(f) civilian and defence research, testing or demonstration infrastructures for

biotechnology activities relevant to defence, security and resilience, provided that

governance ensures clear separation of mandates and access regimes, with

appropriate confidentiality and security safeguards, in line with relevant

requirements arising from the Convention on the Prohibition of the Development,

Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and

on their Destruction (‘BTWC’), Union and national law.

2. The provisions of this Regulation regarding the application for, and the recognition

of, high-impact health biotechnology strategic projects laid down in Articles 8 and

10, respectively, apply to projects referred to in this Article.

70 ENA, https://www.ebi.ac.uk/ena.

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SECTION 2

PREVENTION OF BIOTECHNOLOGY MISUSE

Article 43

Biotechnology products of concern

1. Biotechnology products of concern in Annex I shall only be made available to,

introduced, or used by any natural or legal person in the Union, as well as made

available to any natural or legal person outside the Union, that has a legitimate need

for those products, in accordance with this Section.

2. The Commission is empowered to adopt delegated acts in accordance with Article 64

(2) to amend Annex I by adding, removing or modifying categories of biotechnology

products of concern, setting or adjusting thresholds or exclusions, and specifying

technical parameters, in order to reflect developments in scientific evidence,

biosecurity and biosafety risks or patterns of misuse, also considering the latest

developments under relevant international fora and instruments.

Article 44

Verification of legitimate need

1. An economic operator that makes available on the Union market, including through

online marketplaces, biotechnology products of concern, shall, for each transaction,

verify proof of identity of the prospective customer, record the transaction, including

the quantities ordered, and assess whether the customer has a legitimate need.

2. For the purposes of conducting the verification referred to in paragraph 1, the

economic operator shall request the following information from the prospective

customer prior to facilitating the exchange:

(a) proof of identity of the person;

(b) institutional or corporate affiliation;

(c) documentation establishing the legitimacy of the institution or corporation,

such as address, any official registration number, evidence of legal personality

and of a purpose, and, where applicable, evidence of authorisations,

certifications or biosafety approvals appropriate to the intended use;

(d) information on the intended use of the product.

The first subparagraph, with the exception of transaction recording, shall not apply

where the economic operator has conducted an equivalent verification for the same

customer within the preceding five years and the new transaction does not

significantly deviate in nature or scale from previous transactions.

3. When assessing legitimate need, the economic operator shall take into account all

relevant circumstances, in particular, as applicable:

(a) the demonstrable need for the biotechnology product of concern and the

legitimacy of its intended use;

(b) the background of the applicant;

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(c) the applicant’s compliance history with the economic operator and, where

available, with other operators, including past incidents or refused orders;

(d) credentials that demonstrate evidence of the legitimate need, including relevant

academic publications, history or track record in a related domain;

(e) documentation establishing the existence of suitable facilities, competencies

and biosafety arrangements appropriate to the intended use.

4. The economic operator shall refuse to make the biotechnology products of concern

available in the case of a suspicious transaction.

5. The economic operator shall report to the national contact point referred to in Article

46(3) any suspicious transaction, or attempted suspicious transaction, in accordance

with Article 46(5).

6. Economic operators shall keep and retain records of the transactions referred to in

this Article for three years and shall make them available without undue delay to the

competent authorities upon request.

7. Paragraphs 1 to 7 shall also apply by analogy to persons that are not economic

operators, except in the case where the biotechnology product of concern is supplied

to a person that is employed by the same legal entity.

Article 45

Benchtop equipment

Benchtop nucleic acid synthesis devices made available in the Union shall contain a

mechanism to screen for sequences of concern as defined in Annex I, provided that databases

of sequences of concern are not stored on the equipment itself, in an unencrypted manner or a

manner that could allow users to extract the database.

Article 46

Prevention and reporting of biotechnology misuse

1. For the purpose of preventing and detecting biotechnology misuse, economic

operators and online marketplaces shall report suspicious transactions, having regard

to all circumstances and in particular where the prospective customer:

(a) is not clear about their identity or affiliations, or provides information that

cannot be confirmed or verified, including inconsistent addresses or

unverifiable company details;

(b) would not be expected, in the normal course of business, to place such an

order, including where there is no link to life science research or

biotechnology, or no plausible requirement for biotechnology products of

concern;

(c) proposes an intended use that does not match their reported job role or

institutional affiliation;

(d) requests unusual labelling or shipping procedures, including misidentification

of goods on packaging or changes to the recipient’s name after the order has

been placed but before shipment;

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(e) proposes unusual methods of payment, including cash for high-value items,

personal credit cards for institutional purchases, or payment through non-bank

third parties, or offers unusually favourable terms including above market

prices;

(f) requests unusual confidentiality conditions regarding the order, including with

respect to their identity, the final destination or the destruction of transaction

records;

(g) requests delivery to an address without a legitimate biotechnology business or

research justification, including a residential address.

2. Economic operators and online marketplaces shall have appropriate, reasonable and

proportionate procedures in place to detect suspicious transactions, adapted to the

specific environment in which biotechnology products of concern are made

available.

3. Each Member State shall set up at least one national contact point with clearly

identified contact details, web form or other effective tool for the reporting of

suspicious transactions of biotechnology products of concern. The contact point shall

be part of or have direct links to law enforcement and national inspection authorities.

4. Economic operators and online marketplaces shall refuse a suspicious transaction.

They shall report any suspicious transaction or attempted suspicious transaction

within 24 hours of determining that it is suspicious. Reports shall include, where

possible, the identity of the prospective customer and the facts that led to the

suspicion and shall be addressed to the national contact point of the Member State

where the transaction was concluded or attempted.

5. Where a biotechnology product of concern falls also under categories regulated

under other EU legislation, to avoid duplication of reporting, where the transaction

for that biotechnology product of concern has already been reported as a suspicious

transaction under one legal framework, it shall not be reported again. Where in

doubt, its intended use should be prioritised for reporting obligations, pursuant to

Regulation (EU) 2021/821[71] and Regulation (EU) 2019/1148[72].

Article 47

Training and awareness-raising

1. Member States shall ensure adequate resources for, and the provision of, training for

law enforcement authorities, first responders and customs authorities to recognise

biotechnology products of concern and to react in a timely and appropriate manner to

suspicious activity.

71 Regulation (EU) 2021/821 of the European Parliament and of the Council of 20 May 2021 setting up a

Union regime for the control of exports, brokering, technical assistance, transit and transfer of dual-use

items, OJ L 206, 11.6.2021, pp. 1–461. ELI: http://data.europa.eu/eli/reg/2021/821/oj. 72 Regulation (EU) 2019/1148 of the European Parliament and of the Council of 20 June 2019 on the

marketing and use of explosives precursors, amending Regulation (EC) No 1907/2006 and repealing

Regulation (EU) No 98/2013 (Text with EEA relevance), OJ L 186, 11.7.2019, pp. 1–20.

ELI: http://data.europa.eu/eli/reg/2019/1148/oj.

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2. Member States shall organise awareness-raising actions, including on the issue of

insider threats, adapted to the specificities of each sector that uses biotechnology

products of concern.

3. To facilitate cooperation and effective implementation, and avoid duplicate

reporting, Member States shall organise regular exchanges between law enforcement

authorities, national supervisory authorities, economic operators, online marketplaces

and representatives of sectors that use biotechnology products of concern.

4. Economic operators shall inform their personnel about the conditions under which

biotechnology products of concern may be made available and shall raise personnel’s

awareness accordingly.

Article 48

National inspection authorities

1. Each Member State shall designate a competent authority responsible for the

inspection and control of compliance with the obligations laid down in this Section.

2. Member States shall ensure that the national inspection authority has the resources

and investigative powers necessary to perform their tasks, including the power to

request information and records, to carry out on-site inspections and, where

appropriate, to conduct test purchases, including online.

3. Member States shall ensure that the national inspection authorities regularly run

simulation exercises to test the procedures in place and to ensure appropriate

response to incidents.

4. Member States shall ensure the participation of national inspection authorities, as

appropriate, in the relevant activities of the Steering Group, in particular for the

exchange of information on implementation practices, inspection findings and

emerging risks.Member States shall ensure risk-based audits of economic operators,

verifying, in particular, the existence and effectiveness of screening mechanisms for

legitimate need, record-keeping as provided for in Article [44][(6)] and detection of

suspicious transactions and incidents, and response procedures.

Article 49

Commission enforcement support and monitoring

The Commission may support and monitor national competent authorities in the enforcement

of this section, by taking actions such as requesting information and records and running

training exercises.

Article 50

Audits

Member States shall ensure risk-based audits of economic operators, verifying, in particular,

the existence and effectiveness of screening mechanisms for legitimate need, record-keeping

as provided for in Article 44[(6)] and detection of suspicious transactions and incidents, and

response procedures.

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Article 51

Penalties

1. Member States shall lay down the rules on penalties applicable to infringements of

this Section and shall take all measures necessary to ensure that they are

implemented. The penalties provided for shall be effective, proportionate and

dissuasive.

2. Member States may impose fines on economic operators not exceeding 5% of their

annual total worldwide turnover in the preceding financial year when Member States

finds that the provider intentionally or negligently infringed the relevant provisions

of this Section.

3. In fixing the amount of the fine or periodic penalty payment, regard shall be had to

the nature, gravity and duration of the infringement, taking due account of the

principles of proportionality and appropriateness.

Article 52

Advisory group on biosecurity

1. An Advisory Group on Biosecurity (‘the Advisory Group’) is hereby established.

2. The Advisory Group shall provide independent scientific advice to the Commission

on biosecurity risks arising from the rapid development of biotechnology, including

from AI models as described in Regulation (EU) 2024/1689 in biological

applications (‘AI models in biological applications’). It shall be selected and operate

in accordance with the Commission’s framework for expert groups73.

3. The tasks of the Advisory Group shall include:

(a) monitoring advances in biotechnology to advise the Commission on emerging

biosecurity challenges, including on any potentially necessary updates to the

list of biotechnology products of concern laid down in Annex I and on risk-

based audits of economic operators;

(b) monitoring the capabilities and risk profile of AI models in biological

applications throughout their life cycle;

(c) contributing to the preparation of Union guidance and best practices for

responsible innovation on AI models in biological applications;

(d) facilitate dialogue and coordination among scientific, industry, and security

stakeholders and support, where appropriate, international cooperation on

biosecurity.

4. Where the Advisory Group has reasonable grounds to suspect that an AI model in a

biological application not covered by Regulation (EU) 2024/1689, poses biological

systemic risk, it shall issue a qualified alert to the Commission and to the Member

States. A qualified alert may be issued following a decision of the Advisory Group or

at the initiative of at least 50% of its members. The alert shall be concise and duly

73 Commission Decision establishing horizontal rules on the creation and operation of Commission expert

groups, C(2016)3301.

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reasoned and shall indicate at least the point of contact of the developer of the model

concerned and the factual basis for the alert.

5. Where the Advisory Group has reasonable grounds to suspect that an AI model

covered by Regulation (EU) 2024/1689 poses biological systemic risk, it shall inform

the scientific panel of independent experts referred to in Article 68 Regulation (EU)

2024/1689. That panel may issue a qualified alert to the AI Office in accordance with

Regulation (EU) 2019/1689.

6. The Advisory Group shall be composed of up to 25 globally leading independent

experts appointed by the Commission based on their recognized expertise in the

areas of biotechnology, biosecurity, biodefence and AI.

7. The members of the Advisory Group shall perform their tasks with impartiality and

objectivity. The Advisory Group shall liaise, where appropriate, with other Union

and international expert structures addressing biotechnology, AI, or biosecurity to

ensure coherence and efficiency, including the scientific panel referred to in Article

68 of Regulation (EU) 2024/1689.

8. The Advisory Group may adopt opinions, recommendations, or principles on matters

within its mandate.

Article 53

Biological systemic risk

1. The Commission shall monitor biological systemic risk from AI models in biological

applications and propose mitigating actions, based on advice provided by the

Advisory Group and in line with the Union harmonisation legislation on AI,

including boosting biodefence capabilities or regulation, including on assessment and

mitigation of systemic risk from those AI models, as appropriate.

2. Where a qualified alert is issued by the Advisory Group as referred to in Article

52(3), point (d), the Commission and the Member States shall take appropriate

measures to ensure a proper control of risks.

Article 54

Monitoring and guidance

The Commission, based on advice by the Advisory Group on Biosecurity, and where

appropriate, in cooperation with the Steering Group, may issue and regularly update guidance,

to assist actors in the supply chain and the competent authorities. The guidance may provide:

(a) clarifications regarding the biotechnology products of concern listed in the Annex I;

(b) clarification on the criteria for determining the sequences of concern referred to in

Annex I;

(c) information and methodologies for the assessment of legitimate need for the

purposes of this Section;

(d) information on how to exchange relevant information between competent authorities,

national contact points and among Member States;

(e) information on how to recognise, refuse, and report suspicious transactions;

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(f) obligations for natural or legal persons that are not economic operators that make

available biotechnology products of concern;

(g) requirements regarding benchtop nucleic acid synthesis equipment referred to in

Article 45;

(h) information on risk-based audits of economic operators referred to in Article 50;

(i) any other information deemed useful for effective implementation, including on the

investigative powers of national inspection authorities, test purchases, information

requests from, and resources of, such authorities, or requested by relevant economic

operators.

Article 55

Coordination on biosecurity and biosafety

The Steering Group referred to in Article 20 shall facilitate the coordination of and

information exchange on the enforcement of the provisions in this section among Member

States.

CHAPTER IX

AMENDMENTS TO REGULATIONS (EC) No 178/2002, (EC) No 1394/2007, (EU) No

536/2014, (EU) 2019/6, (EU) 2024/795 and (EU) 2024/1938

Article 56

Amendments to Regulation (EC) No 178/2002

Regulation (EC) No 178/2002 is amended as follows:

(1) in Article 3, the following points 19, 20 and 21 are added:

‘19. ‘regulatory sandbox’ means a controlled environment where participants can

test innovative products or substances and related processes as well as data and

other regulatory requirements at a pre-market stage under a set of defined rules

and monitoring and for a limited period of time;

20. ‘regulatory sandbox plan’ means a plan setting out the scope, the requirements

and the conditions governing the operation of a specific regulatory sandbox;

21. ‘participants’ means any natural or legal person participating in a regulatory

sandbox to whom specific tasks are assigned in the regulatory sandbox plan,

such as business operators, Union and national agencies, final consumers,

academia and research institutions.’;

(2) in Article 22(5), point (a) is replaced by the following:

‘(a) scientific advice and scientific and technical support on human nutrition;’

(3) Article 28 is amended as follows:

(a) paragraph 3 is replaced by the following:

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‘3. The Scientific Committee shall be composed of the first Vice-Chairs of

the Scientific Panels and six independent scientific experts who do not

belong to any of the Scientific Panels.’

(b) paragraph 6 is replaced by the following:

‘6. The Scientific Committee and the Scientific Panels shall be chaired by

the staff of the Authority without the right to vote. The Scientific

Committee and the Scientific Panels shall each choose two Vice-Chairs

from among their members.’

(c) in paragraph 9, the following point (h) is added:

‘(h) the role of the Authority when chairing the Scientific Committee and the

Scientific Panels.’

(4) in Article 32a, paragraph 1 is replaced by the following:

‘1. Where Union law contains provisions for the Authority to provide a scientific

output, including a scientific opinion, the Authority shall, at the request of a

potential applicant or notifier, provide advice on the content of the application

or notification, prior to its submission, including the rules applicable to and the

required content thereof as well as on the design of the studies and testing

strategies to support such an application or notification. Such advice provided

by the Authority shall be without prejudice and non-committal as to any

subsequent assessment of applications or notifications by the Scientific Panels.’

(5) Article 32b is amended as follows:

(a) in paragraph 4, the third subparagraph is replaced by the following:

‘The assessment of the validity or the admissibility of such re-submitted

application or notification shall commence three months after the date of re-

submission of the application and provided that a notification of the studies

pursuant to the second subparagraph has taken place.’

(b) in paragraph 5, the third subparagraph is replaced by the following:

‘The assessment of the validity or admissibility of such re-submitted

application or notification shall commence three months after the date of re-

submission of the application and provided that all studies that had previously

been notified in accordance with paragraph 2 or 3 are included in the

resubmitted application or notification.’;

(c) paragraph 6 is replaced by the following:

‘6. Where the Authority detects, during its risk assessment, that studies

notified in accordance with paragraph 2 or 3 are not included in the

corresponding application or notification in full, and in the absence of a

valid justification of the applicant or notifier to that effect, the applicable

time limits within which the Authority is required to deliver its scientific

output shall be suspended. That suspension shall end three months after

the submission of all data of those studies.’

(6) in Article 32c, paragraph 1 is deleted.

(7) the following Chapter IIIA is inserted:

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‘CHAPTER IIIA

REGULATORY SANDBOXES

Article 49a

General provisions on regulatory sandboxes

1. A Member State or several Member States jointly may establish regulatory

sandboxes in accordance with this Article and the procedure set out in Article

49b.

2. Regulatory sandboxes may be established in relation to the following:

(a) all stages of the production, processing and distribution of food with the

exception of novel foods, and also of the feed produced for, or fed to

food-producing animals;

(b) food contact materials, with the exception of plastic recycled materials;

(c) products, other than food and feed, containing or consisting of

genetically modified organisms as defined in Article 2, point (2), of

Directive 2001/18/EC.

The making available of products within a regulatory sandbox shall not be

regarded as placing on the market.

3. Regulatory sandboxes shall pursue one or more of the following objectives:

(a) facilitating the development, testing and validation of technologies,

products and substances before they obtain authorisation or approval for

placing on the market, where so required by Union law;

(b) testing data requirements, including the type and design of studies

required for conducting a safety and/or efficacy assessment;

(c) testing alternative regulatory requirements and appraising their

performance as regards the attainment of the objectives of the applicable

Union sectoral law in comparison to the existing requirements; in the

areas where Union law provides for an approval or authorisation, as well

as in the area of food information to consumers.

4. Member States shall monitor and supervise the operation of regulatory

sandboxes that they establish and ensure compliance with the regulatory

sandbox plan.

5. A participant to an established regulatory sandbox shall immediately inform

the competent authorities of the Member State(s) concerned if it considers or

has reason to believe that the conditions of the regulatory sandbox plan have

not been complied with and/or there are potential risks to public health, animal

health or welfare, plant health or to the environment, which may require the

revocation of the regulatory sandbox or the amendment of the regulatory

sandbox plan to provide for mitigating measures. Participants shall also

immediately inform the competent authorities of any other information that

concerns the quality, safety or efficacy of the subject matter of the relevant

regulatory sandbox.

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6. Member States shall immediately notify to the Commission and, where

relevant, to the Authority any violation of the conditions set out in the

regulatory sandbox plan and/or the identification of any potential risks to

public health, animal health or welfare, plant health or to the environment.

7. Member States shall suspend or revoke a regulatory sandbox at any time on

their own motion, or at the request of the Commission in accordance with

paragraph 9, in either of the following cases:

(a) the requirements and conditions governing the regulatory sandbox plan

are not met;

(b) where necessary to protect public health, animal health or welfare, plant

health or the environment and there is no possibility for effective

mitigation measures.

Member States shall inform the Commission, the Authority and the other

Member States without delay of the suspension or revocation of a regulatory

sandbox and of the reasons.

8. Where after the setting up of a regulatory sandbox in their territory, a Member

State identifies risks to public health, animal health and welfare, plant health

and to the environment which can be fully mitigated by amendments to the

regulatory sandbox plan, it shall communicate to the Commission, the

Authority and the other Member States the draft amendments in accordance

with the procedure laid down in Article 49b.

9. Where the Commission considers that one of the cases referred to in paragraph

7 is fulfilled, it shall immediately adopt implementing acts in accordance with

the procedure referred to in Article 58(2) requesting the suspension or the

revocation of the regulatory sandbox concerned.

However, in emergencies, the Commission may provisionally adopt an

implementing act requesting the suspension of the regulatory sandbox

concerned after consulting the Member State(s) concerned and informing the

other Member States. As soon as possible, and at most within 10 working days,

the measure taken shall be confirmed, amended or revoked in accordance with

the procedure referred to in Article 58(2) and the reasons for the Commission’s

decision shall be made public without delay.

10. A Member State may prolong the duration once of a regulatory sandbox for a

limited time where this is justified by the need to attain the objective of the

specific regulatory sandbox at hand and shall inform the Commission, the

Authority and the other Member States thereof.

11. The Commission may, by means of implementing acts, specify common

principles or practical arrangements for the establishment and supervision of

regulatory sandboxes, including the establishment of sandboxes involving

several Member States pursuant to this Article, Article 49b and 49c. Those

implementing acts shall be adopted in accordance with the procedure referred

to in Article 58(2).

Article 49b

Establishment of regulatory sandboxes

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1. Where a Member State deems it appropriate to establish a regulatory sandbox,

it shall communicate to the Commission, the Authority and the other Member

States a draft regulatory sandbox plan, which shall contain the following

elements:

(a) the objectives of the regulatory sandbox;

(b) a description of the specific areas that the sandbox will cover, including

the products or substances, processes, technologies and practices;

(c) a clearly defined geographical scope;

(d) a clearly defined and limited temporal scope;

(e) the regulatory or scientific justifications for setting up the regulatory

sandbox;

(f) an identification of the relevant provisions of Union law that apply for

the purposes of the regulatory sandbox and those that do not apply or are

adapted;

(g) the procedure for the application and selection for participants, including

clearly defined eligibility criteria, the modalities governing the provision

of the explicit and prior consent from participating final consumers as

well as the modalities by which the participants may end their

participation;

(h) the possible involvement of the Authority, other Union agencies and

national agencies, where relevant, provided that they have expressed

interest to join the regulatory sandbox;

(i) the activities allowed to be carried out and the conditions and

requirements that apply;

(j) an assessment that identifies how potential risks to public health, animal

health or welfare, plant health or the environment are mitigated;

(k) details on how activities will be monitored, including responsibilities of

the competent authorities entrusted with the supervision of the

implementation of the sandbox plan.

2. Where several Member States deem it appropriate to jointly establish

regulatory sandboxes, they shall collectively communicate a draft regulatory

sandbox plan to the Commission, the Authority and the other Member States.

The regulatory sandbox plan shall specify the activities to take place in each of

the participating Member States in addition to the elements listed in paragraph

1.

3. Member States shall engage with relevant stakeholders during the preparation

of a draft regulatory sandbox plan to gather diverse perspectives and foster

collaboration.

4. The Member State(s) which deem it appropriate to set up a regulatory sandbox

alone or jointly, shall communicate the draft regulatory sandbox plan to the

Commission, the Authority and other Member States at least 60 days prior to

the intended commencement of the sandbox activities. Member State(s) shall

consider any feedback or recommendations from the Commission, the other

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Member States and the Authority before deciding whether to establish the

regulatory sandbox.

5. Member State(s) shall communicate to the Commission, the Authority and the

other Member States any subsequent draft amendment to regulatory sandbox

plans and the reasons thereof. Paragraphs 1 to 4 shall apply mutatis mutandis.

Article 49c

Other responsibilities, monitoring and reporting obligations regarding regulatory

sandboxes

1. Regulatory sandboxes shall not affect the enforcement and monitoring

responsibilities of the competent authorities set out in Article 17 and in other

sectoral legislation.

2. Participants, with the exception of final consumers, in particular the operator

that is the developer of the product or substance concerned, shall remain liable

under applicable national legislation for any harm inflicted on third parties as a

result from the testing taking place in the sandbox.

3. Member States shall submit annual reports to the Commission on the results

from the implementation of regulatory sandboxes, including good practices

developed, lessons learnt and recommendations on their setup and, where

relevant, on the application of the relevant sectorial Union legislation. Those

reports shall be made publicly available by the Commission.

4. The Authority shall also ensure the necessary revisions of its guidance where

relevant and appropriate on the basis of those annual reports.

Article 57

Amendments to Regulation (EC) No 1394/2007

Regulation (EC) No 1394/2007 is amended as follows:

(1) Article 2 is amended as follows:

(i) in paragraph 1, the following point (e) is added:

‘(e) ‘viral vector’ means a genetically modified virus that is used to deliver

genetic material into cells.’

(ii) the following paragraph 6 is added:

‘6. The Commission is empowered to adopt delegated acts in accordance

with Article 25a to amend this Regulation in order to amend the

definitions referred to in paragraph 1, regarding what constitutes a tissue

engineered product, in light of technical and scientific advancements in

the field of advance therapy medical products and taking into account

definitions agreed at Union and international level without extending the

scope of this definition. The delegated acts shall be adopted after

consultations with the European Medicines Agency and the SoHO

Coordination Board.’;

(2) The following Article 4a is inserted:

‘Article 4a

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Advanced therapy investigational medicinal products containing or consisting of

genetically modified organisms presenting no or negligible risks

1. By way of exemption from Article 5a of Regulation (EU) No 536/2014 [as

added by the revised Regulation No (EC) 726/2004], sponsors of clinical trials

that concern advanced therapy investigational medicinal products as defined in

Article 2(7) of that Regulation, consisting or containing GMOs, are not

required to submit an environmental risk assessment, if those products belong

to at least one of the following categories:

(a) non-viable or replication deficient viral vector that is used to deliver a

genetic sequence of human origin, and the vector does not carry an

antimicrobial resistance gene;

(b) genetically modified somatic cells, that cannot secrete or produce

infectious agents due to the genetic modification;

(c) genetically modified bacteria that do not carry an antimicrobial resistance

gene;

(d) genetic material altered using genome editing techniques (ex vivo or in

vivo), provided that it has generally negligible adverse effects on human

health and the environment.

2. The exemption provided for in paragraph 1 of this Article is subject to the

sponsor submitting, through the EU Portal and as part of the clinical trial

application dossier, a reasoned declaration confirming that the advanced

investigational therapy medicinal product concerned falls into one or more of

the categories referred to in points (a) to (d) of paragraph 1, of this Article. The

Committee for Medicinal Products for Human Use (CHMP) referred to in

Article [148] of Regulation […] [revised Regulation No (EC) 726/2004] shall

verify this declaration and the reasons provided, and the CHMP may, to this

end, access the information on the clinical trial application in the EU portal.

The CHMP shall communicate its opinion on the declaration to the sponsor and

to the reporting Member State within 21 days after the submission date referred

to in Article 5(1) of Regulation (EU) No 536/2014 [as revised by European

Biotech Act].

3. The reporting Member State, giving due consideration to the opinion of the

CHMP, shall assess if the conditions of paragraph 1 of this Article apply or if

the sponsor is to be requested to submit an environmental risk assessment

pursuant to Article 5a of Regulation (EU) No 536/2014 [as introduced by the

revised Regulation No (EC) 726/2004].

4. Sponsors of clinical trials concerning advanced investigational therapy

medicinal products that fall under paragraph 1 of this Article are also exempted

from complying with the GMO related requirements of Article 61(2), point (a),

of Regulation (EU) No 536/2014 [as introduced by the revised Regulation No

(EC) 726/2004] regarding the authorisation of manufacturing and import of

advanced investigational therapy medicinal products.

5. The exemptions provided for in this Article shall apply only for the duration of

the clinical trial, limited to the activities within the clinical trial.’;

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(3) Article 25a is replaced by the following:

‘Article 25a

Exercise of the delegation

1. The power to adopt delegated acts is conferred on the Commission subject to

the conditions laid down in this Article.

2. The power to adopt delegated referred to in Article 2, paragraph 6, and in

Article 24 shall be conferred on the Commission for a period of five years from

[insert date xx, from the entry into force of this Regulation].

The Commission shall draw up a report in respect of the delegation of power

not later than nine months before the end of the five-year period. The

delegation of power shall be tacitly extended for periods of an identical

duration, unless the European Parliament or the Council opposes such

extension not later than three months before the end of each period.

3. The delegation of power referred to in Article 2, paragraph 6, and in Article 24

may be revoked at any time by the European Parliament or by the Council. A

decision to revoke shall put an end to the delegation of the power specified in

that decision. It shall take effect the day following the publication of the

decision in the Official Journal of the European Union or at a later date

specified therein. It shall not affect the validity of any delegated acts already in

force.

4. Before adopting a delegated act, the Commission shall consult experts

designated by each Member State in accordance with the principles laid down

in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making.

5. As soon as it adopts a delegated act, the Commission shall notify it

simultaneously to the European Parliament and to the Council.

6. A delegated act adopted pursuant to Article 2, paragraph 6, and Article 24 shall

enter into force only if no objection has been expressed either by the European

Parliament or by the Council within a period of two months of notification of

that act to the European Parliament and the Council or if, before the expiry of

that period, the European Parliament and the Council have both informed the

Commission that they will not object. That period shall be extended by two

months at the initiative of the European Parliament or of the Council.

Article 58

Amendments to Regulation (EU) No 536/2014

Regulation (EU) 536/2014 is amended as follows:

(1) Article 2 is amended as follows:

(a) point (3) is replaced by the following:

‘(3) ‘Low-intervention clinical trial’ means a clinical trial which fulfils all of

the following conditions:

(a) the investigational medicinal products, excluding placebos, are

authorised;

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(b) according to the protocol of the clinical trial, the use of the

investigational medicinal product is evidence-based and supported

by published scientific evidence on the safety and efficacy of those

investigational medicinal products concerned; and

(c) the additional diagnostic or monitoring procedures do not pose

more than minimal additional risk or burden to the safety of the

subjects compared to normal clinical practice in any Member State

concerned;’

(b) the following point (3a) is inserted:

‘(3a) ‘Minimal-intervention clinical trial’ means a clinical trial which fulfils all

of the following conditions:

(a) the investigational medicinal products are authorised;

(b) according to the protocol of the clinical trial, the investigational

medicinal products are used in accordance with the terms of

marketing authorisation; and

(c) the additional diagnostic or monitoring procedures do not pose

more than minimal additional risk or burden to the safety of the

subjects compared to normal clinical practice in any Member State

concerned’;

(c) points 12 and 13 are replaced by the following:

‘(12) ‘Member State concerned’ means the Member State where an application

for authorisation of a clinical trial or a combined study of a substantial

modification has been submitted under Chapters II, IIa or III of this

Regulation respectively;”

'(13) ‘Substantial modification’ means 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;’

(d) the following point (13a) is inserted:

‘(13a) ‘Parallel substantial modification’ means a substantial modification for

which an application is submitted to a Member State concerned before a

decision on a previous application for a substantial modification to the

same clinical trial is notified by that Member State to the sponsor;’

(e) point (21) is replaced by the following:

‘(21) ‘Informed consent’ means a subject’s free and voluntary expression of

his or her willingness to participate in a particular clinical trial, after

having been informed of all aspects of the clinical trial that are relevant

to the subject’s decision to participate or, in case of minors and of

incapacitated subjects, an authorisation or agreement from their legally

designated representative to include them in a clinical trial, including

consent given through the use of electronic systems, methods and

processes, and signed electronically in accordance with Union law or

equivalent standards;’

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(f) the following points (36), to 47 are inserted:

(36) ‘Consideration’ means a justified concern or divergent view raised by a

Member State concerned in the process of an assessment of an

application for an authorisation of a clinical trial or for a substantial

modification on the aspects that, if unresolved, will result in a negative

decision on the clinical trial or substantial modification application;

(37) ‘Reporting Member State’ means the Member State concerned that:

(a) is responsible for the assessment and authorisation of the clinical

trial application in mono-national clinical trials, or

(b) is leading the assessment for the authorisation of a multinational

clinical trial or of a substantial modification regarding aspects

covered by Part I of the application dossier, or

(c) is leading the assessment for the authorisation of a multinational

combined study;

(38) ‘Investigational medicinal product core dossier’ means a dossier,

containing documents referred to in point (Ga), Part II of Annex I

concerning the investigational medicinal product, established at the

request of the sponsor in view of supporting the development of the

investigational medicinal product.

(39) ‘Core dossier depositary Member State’ means a Member State

responsible for assessing suitability and completeness of the

investigational medicinal product core dossier to be established and for

the regulatory oversight of an already established dossier;

(40) ‘Core dossier competent Member States’ means the Member States

concerned for all corresponding clinical trials and the Member States

indicated by a sponsor at the time of the initial request for the

establishment of the investigational medicinal product core dossier;

(41) ‘Corresponding clinical trial’ means a clinical trial tested to the

investigational medicinal product for which an establishment of an

investigational medicinal product core dossier has been requested and

any subsequent clinical trial tested to that investigational medicinal

product;

(42) ‘Distribution’ means all activities, consisting of procuring, holding,

supplying, shipping across Member States or exporting investigational

medicinal product or auxiliary medicinal products, , including delivery of

investigational and auxiliary medicinal products to the clinical trial

participants;

(43) ‘Direct delivery to the subject’ means controlled and documented direct

delivery of an investigational medicinal product or an auxiliary medicinal

product to the subject’s place of residence in a Member State, where the

clinical trial has been authorised;

(44) ‘Combined study’ means a clinical trial concerning one or more

medicinal products combined with a performance study of one or more in

vitro diagnostic medical devices, as defined in Article 2 point (42) of

Regulation (EU) 2017/746 of the European Parliament and of the

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Council *and/or clinical investigation of one or more medical devices as

defined in Article 2 point (45) of Regulation (EU) 2017/745 of the

European Parliament and of the Council **;

(45) 'Regulatory sandbox' means a regulatory framework that allows for the

development and testing of innovative or adapted regulatory approaches

in a controlled environment pursuant to a specific plan, for a limited time

and under regulatory supervision, that enables innovation driven

approaches to an authorisation and conduct of clinical trials that

otherwise would not be possible or appropriate given current legal

framework;’

(46) ‘AI system’ means AI system as defined in Article 3(1) of Regulation

(EU) 2024/1689 of the European Parliament and of the Council***;

(47) ‘serious cross-border threat to health’ means serious cross-border threat

to health as defined in Article 3(1) of Regulation (EU) 2022/2371 of the

European Parliament and of the Council****‘

* Regulation (EU) 2017/746 of the European Parliament and of the

Council of 5 April 2017 on in vitro diagnostic medical devices and

repealing Directive 98/79/EC and Commission Decision 2010/227/EU

(JO 5.5.2017, L117/176., ELI: http://data.europa.eu/eli/reg/2017/746/oj).

** Regulation (EU) 2017/745 of the European Parliament and of the

Council of 5 April 2017 on medical devices, amending Directive

2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No

1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC

(JO 5.5.2017, L 117/1., ELI: http://data.europa.eu/eli/reg/2017/745/oj).

*** Regulation (EU) 2024/1689 of the European Parliament and of the

Council of 13 June 2024 laying down harmonised rules on artificial

intelligence and amending Regulations (EC) No 300/2008, (EU) No

167/2013, (EU) No 168/2013, (EU) 2018/858, (EU) 2018/1139 and (EU)

2019/2144 and Directives 2014/90/EU, (EU) 2016/797 and (EU)

2020/1828 (OJ L, 2024/1689, 12.7.2024,

ELI: http://data.europa.eu/eli/reg/2024/1689/oj)

**** Regulation (EU) 2022/2371 of the European Parliament and of the

Council of 23 November 2022 on serious cross-border threats to health

and repealing Decision No 1082/2013/EU (OJ L 314, 6.12.2022, p. 26,

http://data.europa.eu/eli/reg/2022/2371/oj).

(2) Article 3 is replaced by the following:

‘Article 3

General principles

1. A clinical trial may be conducted only if:

(a) the rights, safety, dignity and well-being of subjects are protected and

prevail over all other interests; and

(b) it is designed to generate reliable and robust data.

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2. Member States concerned shall cooperate closely and efficiently to ensure the

effective and timely application of the provisions of this Regulation.

3. Member States shall take into account whether a clinical trial is a minimal-

intervention or low-intervention clinical trial and, where this is the case, adapt

the regulatory requirements throughout the lifecycle of such clinical trial, in

particular with regard to the application dossier, the authorisation procedures,

the safety reporting and oversight.’

(3) Articles 4 and 5 are replaced by the following:

’Article 4

Prior authorisation

A clinical trial shall be conducted only if it has been authorised by the Member State

concerned in accordance with this Regulation. Applications for an authorisation shall

be subject to scientific and ethical review.

In clinical trials concerning more than one Member States (multinational clinical

trials) all the Member States concerned including the reporting Member State shall

cooperate in good faith and in spirit of mutual trust and reliance. The reporting

Member State shall have a leading role in the assessments.

The ethical review shall be performed by an ethics committee in accordance with the

law of the Member State concerned. The reporting Member State shall involve its

ethics committee in the assessment of ethical aspects of Part I of the application

dossier referred to in Article 6.

Each Member State shall ensure that the organisation, timelines and procedures for

the review by an ethics committee are compatible with the timelines and procedures

set out in this Regulation for the assessment of the application for authorisation of a

clinical trial and substantial modifications thereof.

Article 5

Submission of an application

1. In order to obtain an authorisation, the sponsor shall submit an application

dossier to the intended Member States concerned throughout the Portal referred

to in Article 80 (‘the EU portal’) referred to in Article 25. The date on which

the sponsor submits the application for an authorisation of a clinical trial is

referred to within this Chapter as the submission date.

2. The authorisation procedure of a clinical trial consists of three steps:

(a) a validation of the application dossier, as set out in Article 5b;

(b) an assessment, that consists of:

– an assessment of Part I, as set out in Article 6, of the elements of

the application dossier listed in Part I of Annex I, that constitute

Part I of the assessment dossier, and

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– an assessment of Part II, as set out Article 7 of the application

dossier, of the elements listed in Part II of Annex I, that constitute

Part II of the application dossier.

(c) a decision resulting either an authorisation, conditional authorisation or

refusal of an authorisation, as set out in Article 8.’

(4) the following Articles 5a and Article 5b are inserted:

“Article 5a

Appointment of the reporting Member State

1. In clinical trials concerning only one Member State, this Member State is the

reporting Member State.

2. In clinical trials concerning more than one Member States, the sponsor shall

propose one of the Member States concerned as the reporting Member State.

All Member States concerned willing to become the reporting Member State

shall declare their willingness through the EU portal.

The sponsor shall, when applying for a low-intervention clinical trial propose

one of the Member States concerned where the use of the investigational

medicinal product is evidence-based as a reporting Member State.

3. If the proposed Member State accepts the proposal by expressing willingness

to become the reporting Member State, it shall be the reporting Member State.

4. If the proposed Member State does not accept the proposal, the following rules

shall apply, and their application shall be supported by the EU Portal:

(a) where there is only one other Member State concerned willing to become

the reporting Member State, that Member State shall become the

reporting Member State;

(b) where there is more than one Member State concerned willing to become

the reporting Member State or none of the Member States concerned is

willing to become the reporting Member State, the reporting Member

State shall be designated automatically by the EU Portal in application of

the recommendation referred to in article 85(2)(c).

5. Within three days from the submission date, all Member States concerned, the

sponsor and the reporting Member State shall be notified by the EU Portal of

the appointment of the reporting Member State.

Article 5b

Validation of Part I of the application dossier

1. Within seven days from the submission date, the reporting Member State shall

validate Part I of application dossier referred to in Article 6 and notify the

sponsor, through the EU portal, of the following:

(a) whether the clinical trial applied for falls within the scope of this

Regulation;

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(b) whether the application dossier is complete in accordance with Part I of

Annex I;

(c) whether it confirms that the clinical trial is a minimal-intervention or a

low- intervention clinical trial, respectively, if such a claim was made by

the sponsor.

2. Where the reporting Member State has not notified the sponsor within the

period referred to in paragraph 1, the clinical trial applied for shall be deemed

to fall within the scope of this Regulation and the application dossier shall be

considered complete and, if applicable, the clinical trial shall be considered a

minimal-intervention or low-intervention clinical trial.

3. Where the reporting Member State finds that the application dossier is not

complete, or that the clinical trial applied for does not fall within the scope of

this Regulation, or, if applicable, has doubts whether the clinical trial is a

minimal-intervention or low-intervention clinical trial, the reporting Member

State shall:

(a) inform the sponsor thereof through the EU portal and shall set a deadline

of maximum seven days for the sponsor to comment on the application or

to complete the application dossier through the EU portal;

(b) within seven days from the submission of the comments or the completed

application dossier referred to in point (a) notify the sponsor as to

whether or not the application complies with the requirements set out in

paragraph 1 points (a), (b) and (c).

In case the reporting Member State requests the sponsor to comment on the

application pursuant to this paragraph, the period referred to in paragraph 1

may be extended by a maximum of 14 days.

4. Where the reporting Member State has not notified the sponsor within the

period referred to in paragraph 3, point (b), the clinical trial applied for shall be

deemed to fall within the scope of this Regulation, the application dossier shall

be considered complete in accordance with Part I of Annex I and the clinical

trials is deemed to be a minimal-intervention or a low-intervention clinical

trial, if claimed by the sponsor.

5. Where the sponsor has not provided comments or completed the application

dossier within the period referred to in paragraph 3, point (a), the application

shall be deemed to have lapsed in all Member States concerned.

6. For the purpose of this Chapter, the date on which the sponsor is notified in

accordance with paragraph 1 or paragraph 3, point (b) shall be the validation

date of the application. Where the sponsor is not notified within these time

periods, the validation date shall be the last day of respective periods referred

to in paragraph 1 or paragraph 3, point (b).”

(5) Article 6 is replaced by the following:

’Article 6

Assessment report – Aspects covered by Part I of the assessment report

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1. The reporting Member State shall assess the application relying on the

information and the documents listed in Part I of Annex I, with regard to the

following aspects:

(a) compliance with Chapter V as with respect to the following:

(i) the anticipated therapeutic and public health benefits taking

account of all of the following:

– characteristic of and knowledge about the investigational

medicinal products;

– relevance of the clinical trial, including whether the groups of

subjects participating in the clinical trial represent the

population to be treated, or if not, the explanation and

justification provided in accordance with point 17(y) of Part I

of Annex I; the current state of scientific knowledge; whether

the clinical trial has been recommended or imposed by

regulatory authorities in charge of the assessment and

authorisation of the placing on the market of medicinal

products; where applicable, taking into account any opinion

formulated by the Paediatric Committee on paediatric

investigational plan in accordance with Chapter VII of

Regulation (EU) …/…[reference to be added after adoption

cf. COM(2023)196final];

– reliability and robustness of the data generated in clinical

trial, taking into account of statistical approaches, design of

the clinical trial and methodology, including sample size and

randomisation, comparator and endpoints;

(ii) risk and inconveniencies for the subjects, taking into account all of

the following:

– characteristic of and knowledge about the investigational

medicinal product and the auxiliary medicinal product;

– characteristic of the investigational medicinal product;

– safety measures, including provisions for risk minimisation

measures, monitoring, safety reporting, and the safety plan;

– risk to subjects’ health posed by the medical condition for

which the investigational medicinal product is being

investigated;

– aspects related to the protection of the subjects’ safety, well-

being and fundamental rights as a clinical trial participant.

(b) compliance with the requirements concerning the manufacturing and

import of investigational medicinal product set out in Chapter IX;

(c) compliance with the labelling requirements set out in Chapter X;

(d) completeness and adequacy of the investigator’s brochure.

The adequacy of the translations of the documents, when translations are

required pursuant to Article 26 and Article 69, submitted in Part I shall be

assessed in Part II.

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2. The reporting Member State shall draw up an assessment report. The

assessment of the aspects referred to in paragraph 1 shall constitute Part I of the

assessment report.

The ethics committee of the reporting Member State shall review, from the

ethical perspective, aspects covered by Part I of the assessment report. That

ethical review shall complement the scientific and regulatory assessment and

shall cover Part I of the application dossier in order to evaluate whether the

subjects’ rights, safety and well-being are being ensured in the clinical trial.”

2a. Notwithstanding paragraph 2, where the clinical trial is a minimal-intervention

clinical trial, the assessment of the reporting Member State shall be limited to

an ethical review by its ethics committee of the aspects referred to points (a)

and (d) of paragraph 1.

3. The assessment report shall contain one of the following conclusions

concerning the aspects addressed in Part I of the assessment report:

(a) the conduct of the clinical trial is acceptable in view of the requirements

set out in this Regulation:

(b) the conduct of the clinical trial is acceptable in view of the requirements

set out in this Regulation, but subject to compliance with specific

conditions which shall be specifically listed in that conclusion; or

(c) the conduct of the clinical trial is not acceptable in view of the

requirements set out in this Regulation.

4. The reporting Member state shall submit, through EU portal, the final Part I of

the assessment report, including its conclusions, to the sponsors and to the

other Member States concerned within 42 days from the submission date.

5. For clinical trials involving more than one Member State concerned, the

assessment process shall include three phases:

(a) an initial assessment phase within 28 days from the submission date;

(b) a review phase within seven days from the end of the initial assessment;

(c) a consolidation phase within seven days from the end date of the review

phase.

During the initial assessment phase, the reporting Member State shall assess

Part I of the application dossier and draw up a draft Part I of the assessment

report and circulate it to all other Member States concerned within 28 days

from the submission date.

During the review phase, within seven days from the circulation of the draft

assessment report all Member States concerned shall review the application

based on the draft Part I of the assessment report and shall share considerations

for their Member States relevant to the application. The consideration may be

raised only on one of the following grounds:

(a) one of the grounds referred to in Article 8(2);

(b) issues that would lead to a negative opinion of the ethics committee of

the Member State concerned.

During the consolidation phase, the reporting Member State shall take due

account of the considerations of the other Member States concerned and

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finalise Part I of the assessment report and shall record how all considerations

have been dealt with. The reporting Member State shall submit the final Part I

of the assessment report to the sponsor and all other Member States concerned

within seven days from the end of the review phase.”

5a. Where the clinical trial is a minimal-intervention clinical trial, other Member

States concerned may only raise during the review phase considerations

referred to in paragraph 5related to ethical aspects of the draft assessment

report.”

6. For the purpose of this Chapter, the date on which the final Part I of the

assessment report is submitted by the reporting Member State to the sponsor

and to the other Member States concerned through the EU portal shall be the

reporting date.”

7. Between the validation date and the reporting date, only the reporting Member

State may request additional information from the sponsor, taking into account

the considerations referred to in paragraph 5.

For the purpose of obtaining and reviewing this additional information from

the sponsor, the reporting Member State may extend the period referred to in

paragraph 4 by maximum of 28 days.

The sponsor shall submit the requested information within the period set by the

reporting Member State which shall not exceed 14 days from the receipt of the

request.

Upon receipt of the requested additional information, the Member State

concerned shall review additional information provided by the sponsor and

shall identify and share with the reporting Member State any unaddressed

considerations, relevant for the application. The coordinated review shall be

performed within maximum 7 days of the receipt of the additional information

and the further consolidation shall be performed within maximum seven days

of the end of the coordinated review. When finalising Part I of the assessment

report, the reporting Member State shall take due account of the considerations

of the other Member States concerned and shall record how the considerations

have been dealt with.

Where the sponsor does not provide additional information within the period

set by the reporting Member State in accordance with the third subparagraph,

the application shall be deemed to have lapsed in all Member States concerned.

The request for additional information and additional information shall be

submitted through the EU Portal.’

(6) Article 7 is replaced by the following:

‘Article 7

Assessment report – Aspects covered by Part II of the application dossier

1. Each Member State concerned shall assess, for its own territory, the application

with respect to the following aspects. Such assessment shall constitute Part II

of the assessment report:

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(a) compliance with the requirements for informed consent set out in

Chapter V;

(b) compliance of the arrangements for rewarding or compensating subjects

with the requirements set out in Chapter V;

(c) compliance of the arrangements for recruitment of subjects with the

requirements set out in Chapter V;

(d) compliance with Regulation (EU) 2016/679 of the European Parliament

and of the Council*;

(e) compliance with Article 49;

(f) compliance with Article 50;

(g) compliance with Article 76;

(h) compliance with applicable rules for the collection, storage and future

use of biological samples of the subject;

(i) accuracy of the translations of the documents and information submitted

in Part I of the application dossier, when such documents are required to

be submitted in the national language in accordance with Article 26 and

69.

2. Each Member State concerned shall complete the assessment within 42 days

from the submission date and submit, through the EU portal, Part II of the

assessment report, including its conclusions, to the sponsor.

Each Member State concerned may within the period referred to in this

paragraph, and through EU portal, request on duly justified grounds additional

information , from the sponsor regarding the aspects covered in paragraph 1 or

to request to complement the documentation, required pursuant to Part II of

Annex I, if such documentation is missing or documentation provided is not

adequate or is incomplete.

The Member State concerned may decide within 28 days of the submission

date to rely on the ethical review of the ethics committee of the reporting

Member State of the common elements of the application dossier of Part II and

inform the sponsor accordingly.

3. Each Member State concerned may extend the assessment period referred to in

paragraph 2 by a maximum of 28 days:

(a) to requests additional documentation or information, as referred in

paragraph 2, from the sponsor regarding Part II of the assessment for its

territory;

(b) to align with the timeline for the assessment referred to in Article 6,

when it has been extended to allow for a request for information by the

reporting Member State related to Part I assessment and its review.

The sponsor shall submit the requested additional information and

documentation within the period set by the Member State concerned which

shall not exceed 14 days from the receipt of the request.

Upon receipt of the additional information and documentation, the Member

State concerned shall complete its assessment within maximum of 14 days

from the submission of the requested information by the sponsor.

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Where the sponsor does not provide additional information and documentation

within the period set by the Member State concerned in accordance with this

paragraph, the application shall be deemed to have lapsed in that Member State

concerned.

* Regulation (EU) 2016/679 of the European Parliament and of the Council of

27 April 2016 on the protection of natural persons with regard to the

processing of personal data and on the free movement of such data, and

repealing Directive 95/46/EC (General Data Protection Regulation), OJ L 119,

4.5.2016., ELI: http://data.europa.eu/eli/reg/2016/679/oj.’

(7) in Article 8, paragraphs 1 and 2 are replaced by the following:

‘1. Each Member State concerned shall notify the sponsor through the EU portal

and by way of one single decision as to whether the clinical trial is authorised,

authorised subject to conditions, or whether authorisation is refused.

The notification shall be made within five days from the reporting date or from

the last day of the assessment referred to in Article 7, whichever is later.

2. Where the conclusion of the reporting Member State as regards Part I of the

assessment report is that the conduct of the clinical trial is acceptable or

acceptable subject to compliance with specific conditions, that conclusion shall

be deemed to be the conclusion of the Member States concerned.

A clinical trial subject to conditions may start, unless the Member State

concerned specified that the condition is suspensive. Unless otherwise

specified, a fulfilment of the condition shall not require a submission of a

request for a substantial modification.

Notwithstanding the first subparagraph of this paragraph, a Member State

concerned may disagree with the conclusion of the reporting Member State as

regards Part I of the assessment report only on the following grounds, provided

that the corresponding consideration was raised during the process pursuant to

Article 6(5) point (b) and the Member State concerned considers that it was not

sufficiently addressed:

(a) participation in the clinical trial would lead to a subject receiving an

inferior treatment than in normal clinical practice in the Member State

concerned; or

(b) infringement of its national law as referred to in Article 90.

Where a Member State concerned disagrees with the conclusion, it shall

communicate its disagreement, together with a detailed justification, through

the EU portal, to the Commission, to all Member States, and to the sponsor.’

(8) Article 9 is replaced by the following:

‘Article 9

Persons assessing the application

1. Member States shall ensure, including through the institutional safeguards, that

persons validating and assessing the application do not have conflicts of

interest, are independent of the sponsors, or the clinical trial site and the

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investigators involved and of persons financing the clinical trial, as well as free

of any other undue influence and ensure their sufficient independence in

performance of their tasks.

In order to guarantee independency and transparency, the Member States shall

ensure that persons validating and assessing the application as regards the

aspects covered in Parts I and II of the assessment report have no financial or

personal interests which could affect their impartiality. These persons shall

make an annual declaration of their financial interest.

2. Member States shall ensure that the assessment is done by persons who

collectively have the necessary qualifications and experience.

These persons shall be sufficiently equipped and empowered to perform their

tasks.

3. At least one layperson shall participate in the assessment.’

(9) in Article 10, the following paragraph 6 is added:

’6. Where potential subjects of a clinical trial belong to vulnerable populations,

Member States concerned and sponsors shall consider and weigh the harms and

benefits of their inclusion as opposed to their exclusion from a clinical trial.

The Member States concerned and sponsors shall assess in particular whether

the exclusion of those subjects from a clinical trial could inadvertently

perpetuate or exacerbate their vulnerabilities, particularly in relation to their

specific health needs.’

(10) Article 11 is replaced by the following:

‘ Article 11

Submission and assessment of applications limited to aspects covered by Part I of the

assessment report

1. Where the sponsor so requests, the application for authorisation of a clinical

trial, its assessment and the conclusion shall be limited to the aspects covered

by Part I of the assessment report.

After the notification of the conclusion on the aspects covered by Part I of the

assessment report, the sponsor may, within two years, apply for an

authorisation limited to aspects covered by Part II of the assessment report.

Where the sponsor submits only Part I of the application dossier to all of the

Member States concerned, the sponsor shall declare at the time of the first

submission of Part II of the application dossier to any of the Member States

concerned that the sponsor is not aware of any new substantial scientific

information that would change the validity of any item submitted in the

application on the aspects covered by Part I of the assessment report. If an

update of Part I of the application dossier is necessary, the sponsor shall submit

a substantial modification of Part I of the application dossier, at the latest, at

the same time as the submission of Part II of the application dossier to at least

one of the Member States concerned.

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The Part II of the application dossier shall be assessed in accordance with

Article 7 and the Member State concerned shall notify the decision on clinical

trial in accordance with Article 8.

In those Member States concerned where the sponsor does not apply for an

authorisation limited to aspects covered by Part II of the assessment report

within two years, the application on the aspects covered by Part I of the

assessment report shall be deemed to have lapsed.

2. When the sponsor submits a substantial modification of Part I of the

application dossier with regard to clinical trial that is subject to a request

referred to in paragraph 1 and has been authorised or authorised subject to

conditions by at least one Member State concerned, all Member States

concerned that received the initial application shall participate in the

assessment of that substantial modification in accordance with Article 18 or 22

as appropriate.’

(11) Article 14 is amended as follows:

(a) paragraph 1 is replaced by the following:

‘1. Where the sponsor wishes to extend an authorised clinical trial to another

Member State (additional Member State concerned), the sponsor shall

submit an application dossier to that Member State through the EU

portal.

The application dossier may be submitted only after the notification date

of the first initial authorisation decision by at least one Member State

concerned.’

(b) paragraph 3 is replaced by the following:

‘3. The additional Member State concerned shall notify the sponsor, through

the EU portal, within 47 days from the date of submission of the

application dossier referred to in paragraph 1 of this Article, by way of

one single decision as to whether the clinical trial is authorised, whether

it is authorised subject to conditions, or whether the authorisation is

refused. Article 8(2), (3), (4) and (5) apply to the decision of the

additional Member State concerned.’

(c) paragraph 4 is deleted;

(d) paragraph 5 to 8 are replaced by the following:

‘5. Within 42 days following the submission date referred to in paragraph 1,

the additional Member State concerned may communicate to the

reporting Member State and the other Member States concerned any

considerations through the EU portal.’

(e) paragraphs 6, 7 and 8 are replaced by the following:

‘6. Between the submission date referred to in paragraph 1 and the expiry of

the period referred to in paragraph 3, only the reporting Member State

may request additional information from the sponsor concerning the

aspects covered in Part I of the assessment report, taking into account the

considerations referred to in paragraph 5.

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For the purpose of obtaining and reviewing this additional information

from the sponsor in accordance with the third and fourth subparagraphs,

the reporting Member State may extend the period referred to in the first

subparagraph of paragraph 3 by a maximum of 28 days.

The sponsor shall submit the requested additional information within the

period set by the reporting Member State, which shall not exceed 14 days

from receipt of the request.

Upon receipt of the additional information the reporting Member State,

the additional Member State concerned and all other Member States

concerned shall review any additional information provided by the

sponsor together with the original application and shall share any

unaddressed considerations relevant to the application. The coordinated

review shall be performed within a maximum of seven days from the

receipt of the additional information and the further consolidation shall

be performed within a maximum of seven days from the end of the

coordinated review. The reporting Member State shall take due account

of the considerations of the Member States concerned and shall record

how the considerations have been dealt with.

Where the sponsor does not provide additional information within the

period set by the reporting Member State in accordance with the third

subparagraph, the application shall be deemed to have lapsed in the

additional Member State concerned.

The request for additional information and the additional information

shall be submitted through the EU portal

7. The additional Member State concerned shall assess, for its territory, the

aspects covered in Part II of the assessment report and submit Part II

assessment report, including its conclusions, through the EU portal, to the

sponsor.

Within period referred to in paragraph 3, additional Member State may

request, through the EU portal, with justified reasons, additional

information from the sponsor regarding aspects covered in Part II of the

assessment report as far as its territory is concerned.’

8. For the purpose of obtaining and reviewing the additional information

referred to in paragraph 6 or 7 the additional Member State concerned

may extend the period referred to in paragraph 5 by maximum of 28

days.

The sponsor shall submit the requested additional information within the

period set be the additional Member State concerned, which shall not

exceed 14 days from the receipt of the request.

Upon receipt of the additional information, the Member State concerned

shall compete its assessment within a maximum of 14 days.

Where the sponsor does not provide additional information within the

period set by the additional Member State concerned in accordance with

second subparagraph, the application shall be deemed to have lapsed in

the additional Member State concerned.’

(f) paragraphs 9 and 10 are deleted;

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(g) paragraphs 11 and 12 are replaced by the following:

‘11. Where the additional Member State concerned has not notified the

sponsor of its decision within the period referred to in paragraph 3, or in

case that period has been extended in accordance with paragraph 6 or 8

and where that additional Member State concerned has not notified the

sponsor of its decision within the extended period, the conclusion on Part

I of the assessment report shall be deemed to be the decision of that

additional Member State concerned on the application for authorisation

of the clinical trial.”

12. A sponsor shall not submit an application dossier in accordance with this

Article where a procedure for a substantial modification of Part I of the

assessment report, set out in Chapter III, is pending as regards that

clinical trial.’

(12) the following Article 14a is inserted:

’Article 14a

Appointment of a new reporting Member State

1. The reporting Member State may initiate the procedure for an appointment of a

new reporting Member State if:

(a) the reporting Member State has notified its decision refusing the

authorisation of the clinical trial; or

(b) the clinical trial is no longer taking place in the reporting Member State.

2. The procedure can only be launched after the clinical trial has been authorised

in at least one Member State concerned.

3. The reporting Member State shall notify the sponsor and other Member States

concerned of its intention to cease to be a reporting Member State.

4. The Member States concerned shall declare their willingness to become new

reporting Member State. The selection of new reporting Member State shall

follow the rules established Article 5a (4) and (5).

5. Following the initiation of the procedure for the appointment of a new

reporting Member State, the initial reporting Member State shall continue to

carry out its tasks until all of the ongoing assessments and records are

completed and the respective final assessment reports are submitted to the EU

portal.

6. The new reporting Member State shall become responsible for the assessment

of any application related to Part I of the assessment report, including an

application based on Article 14, that has been submitted after it has been

notified as the reporting Member State to the sponsor and all Member States

concerned by the EU portal.’

(13) the following Chapter IIa is inserted:

‘Chapter IIa

SPECIAL AUTHORISATION PROCEDURES

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Article 14b

Accelerated procedure for the authorisation of multinational clinical trials in the context of

public health emergencies

1. During a recognised public health emergency at Union level pursuant to Article

23 of Regulation (EU) 2022/2371 of the European Parliament and of the

Council, Member States shall apply an accelerated procedure for the

authorisation of multinational clinical trials for medicinal products intended for

the treatment, prevention or medical diagnosis of the disease or condition

which are directly related to the public health emergency.

2. To address an emergence or development of a serious cross-border threat to

health as defined in Article 3(1) of Regulation 2022/2371 that is likely to lead

to the recognition of a public health emergency at Union level in accordance

with Article 23(1) of Regulation (EU) 2022/2371, Member States shall apply

an accelerated procedure for the authorisation of multinational clinical trials

when this procedure is declared applicable in accordance with the criteria in

paragraph 3 of this Article. The application of the accelerated procedure shall

ensure the availability of medicinal products in order to prevent or swiftly

contain the emerging serious cross-border health threat, to provide timely

treatment options grounded in scientifically robust evidence or to facilitate

medical diagnosis of the disease or condition directly related to the specific

serious cross-border health threat.

3. The Commission shall, by means of implementing acts, lay down the detailed

criteria and the processes for declaring applicability of the accelerated

authorisation procedure to address an emergence or development of serious

cross-border threat to health that is likely to lead to the recognition of a public

health emergency at Union level in accordance with Article 23 (1) of

Regulation (EU) 2022/2371, .

The criteria for declaring applicability of an accelerated authorisation

procedure shall at least include the epidemiological situation and its dynamics

as well as the availability of treatment, prevention and diagnostics options

addressing the emerging serious cross-border threat to health. The process of

declaring applicability of the accelerated authorisation procedure shall involve

consultations with relevant Union agencies, expert groups and advisory bodies

in the field of public health and clinical trials.

The implementing acts referred to in the first subparagraph shall be adopted in

accordance with the examination procedure referred to in Article 88.

4. When submitting the application for the clinical trial authorisation during a

public health emergency as referred to in paragraph 1 or when the accelerated

procedure referred to in paragraph 2 is declared applicable to address an

emerging serious cross-border health threat, pursuant to the procedure referred

to in paragraph 3, the sponsor shall indicate whether the investigational

medicinal products are intended for the treatment, prevention or medical

diagnosis of a disease or a condition directly related to the specific serious

cross-border threat to health. The reporting Member State shall confirm

whether the accelerated procedure is applicable to the clinical trial application.

5. The Commission shall adopt delegated acts in accordance with Article 89 to

supplement this Regulation by setting out the procedures for an accelerated

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authorisation of multinational clinical trials, including timelines, criteria for

evaluating whether a clinical trial qualifies for an accelerated procedure and an

integrated ethical review, and by laying down simplified requirements for the

application dossier.

Article 14c

Combined studies

1. This Article applies to combined studies in which a clinical trial is combined

with a performance study of an in vitro diagnostic medical device that is

subject to authorisation pursuant to Article 58(1) of Regulation (EU) 2017/746,

or is combined with a clinical investigation of a medical device that is subject

to authorisation according to Article 62 of Regulation (EU) 2017/745.

2. By way of derogation from Article 5, the sponsor of a combined study referred

to in paragraph 1, which is to be conducted in one or more Member States, may

submit a single application for authorisation.

3. The single application referred to in paragraph 2 shall be submitted

electronically through the EU Portal to all Member States in which the

combined study is to be conducted (‘Member States concerned’). Where a

combined study has more than one sponsor, the sponsors shall designate one

coordinating sponsor.

4. The Member States concerned shall assess the single application by means of a

coordinated assessment procedure under the direction of a reporting Member

State chosen from among the Member States concerned. If a combined study

involves only one Member State, that Member State shall be the reporting

Member State.

5. The coordinated assessment procedure shall include the assessment by the

competent authorities and review by ethics committees. During the assessment

procedure, the Member States concerned may only raise considerations related

to the following:

(a) the grounds referred to in Article 14a(5) of this Regulation, Article 78(8)

of Regulation (EU) 2017/746 or Article 74(8) of Regulation (EU)

2017/745; or

(b) issues that would lead to ethics committee of the Member State

concerned issuing a negative opinion.

6. Where the conclusion of the reporting Member State as regards the area of

coordinated assessment is that the conduct of the combined study is acceptable,

or acceptable subject to compliance with specific conditions, that conclusion

shall be deemed to be the conclusion of all Member States concerned.

Notwithstanding the first subparagraph of this paragraph, a Member State

concerned may disagree with the conclusion of the reporting Member State

concerning the area of coordinated assessment but only on one of the following

grounds, provided that the corresponding consideration was raised during the

assessment process and the Member State concerned has substantiated

comments that were not sufficiently addressed:

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(a) participation in the combined study would lead to a subject receiving an

inferior treatment than in normal clinical practice in the Member State

concerned;

(b) infringement of its national law;

(c) with regard to the assessment of the medical device or in vitro medical

device, grounds referred to in Article 78(8) of Regulation 2017/746 or

Article 74(8) of Regulation (EU) 2017/745, respectively

7. Where a Member State concerned disagrees with the conclusion on the basis of

paragraph 5, it shall communicate its disagreement, together with a detailed

justification, through the EU Portal, to the Commission, to all other Member

States concerned, and to the coordinating sponsor referred to in paragraph 2.

8. Each Member State concerned shall issue a single decision as to whether the

combined study is authorised, whether it is authorised subject to conditions, or

whether authorisation is refused and shall notify the coordinating sponsor

referred to in paragraph 2.

9. The Commission shall, by means of a delegated act in accordance with Article

89, amend or supplement, as necessary, the provisions of Chapters II to V, VII,

XIII, XIV and XVI and Articles 71 and 72 of this Regulation in order to:

(a) enable a streamlined procedure for an authorisation of combined studies,

including the coordinated assessment of initial applications, coordinated

assessment of the request for substantial modifications and additions of

Member State concerned;

(b) set the requirements applicable during the conduct of the combined

studies, including as regards to the specific safety reporting requirements;

(a) clarify the responsibilities of the combined studies’ sponsors and

investigators;

(b) ensure supervision;

(c) determine the functionalities of the EU portal and EU database necessary

to support application of this Article.

10. When doing so, the Commission shall take into consideration, where relevant,

provisions of Chapter VI and Annex XV of Regulation (EU) 2017/745 or

Chapter VI and Annexes XIII and XIV of Regulation (EU) 2017/746

concerning the investigational device(s) or device(s) for performance study

which are covered by the combined study, as applicable.

Article 14d

Persons assessing the applications

Article 9 applies to assessments made under this Chapter.’

(14) Article 16 is replaced by the following:

‘Article 16

Submission of application

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In order to obtain an authorisation, the sponsor shall submit an application dossier to

the Member States concerned through the EU portal. The date on which the sponsor

submitted the application for an authorisation of a substantial modification is referred

to within this Chapter as the submission date.’;

(15) the following Article 16a is inserted:

‘Article 16a

Parallel substantial modification

1. The sponsor may submit to the reporting Member State, through the EU portal,

an application for a parallel substantial modification regarding aspects covered

by Part I of the assessment report, prior to the notification of a decision on an

ongoing assessment of a substantial modification in accordance with Article

19(1) or Article 23(1).

2. The sponsor may submit to the same Member State concerned, through the EU

portal, an application for a parallel substantial modification of an aspect

covered by Part II of the assessment report prior to the notification of a

decision on an ongoing assessment of a substantial modification in accordance

with Article 20(5) or Article 23(1) by the same Member State concerned.

3. The reporting Member State or Member state concerned, as applicable, shall

accept the application for a parallel substantial modification if the parallel

substantial modification concerns distinct and independent aspects of the

application dossier and may be assessed concurrently by the same Member

State concerned or reporting Member State.

4. When scope of the application for the parallel substantial modification covers

both Part I and Part II of the assessment report, the sponsor shall seek the

agreement of both, the reporting Member State and the relevant Member States

concerned. The relevant Member State concerned may oppose the agreement if

the substantial modification concerns aspects of Part II covered by an ongoing

assessment.’

(16) Article 17 is amended as follows:

(a) paragraphs 1 and 2 are replaced by the following:

‘1. The reporting Member State for the authorisation of the substantial

modification shall be the reporting Member State for the initial

authorisation procedure.

2. Within four days from the submission date, the reporting Member State

shall validate the application and notify the sponsor through the EU

portal as to whether:

(a) the substantial modification concerns an aspect covered by Part I of

the assessment report;

(b) the application dossier is complete in accordance with Annex II;

and

(c) in case of parallel substantial modification to Part I, whether such a

parallel substantial modification is acceptable taking into account

the requirements of Article 16a.

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When applicable, in the context of a substantial modification of Part I,

the Member State concerned shall verify whether the translation or

translations in the national language or languages in accordance with the

requirements of Articles 26 and 69 has or have been submitted as a

substantial modification of Part II. Article 21 applies to the assessment of

the accuracy of translations.’

(b) paragraph 4 is replaced by the following:

‘4. Where the reporting Member State finds that the application does not

concern an aspect covered by Part I of the assessment report or that the

application dossier is not complete or, where applicable, that the parallel

substantial modification is not acceptable, it shall inform the sponsor

thereof though the EU portal and shall set a maximum of four days for

the sponsor to comment on the application of to complete the application

dossier though the EU portal.

The reporting Member State shall notify the sponsor within 14 days from

the submission date, as to whether or not the application complies with

the requirements set out in paragraph 2, points (a), (b), and when

applicable point (c).

Where the reporting Member State has not notified the sponsor within the

period referred to in the second subparagraph, the substantial

modification applied for shall be deemed to concern an aspect covered by

Part I of the assessment report, the application dossier shall be deemed to

be complete and, when applicable, the parallel substantial modification

shall be deemed to be acceptable taking into account the requirements of

Article 16a.

Where the sponsor has not provided comments or completed the

application dossier within the period referred to in the first subparagraph,

the application shall be deemed to have lapsed in all the Member States

concerned.’

(17) Article 18 is amended as follows:

(a) paragraphs 3 and 4 are replaced by the following:

‘3. The reporting Member State shall submit, through the EU portal, the final

assessment report including its conclusions, to the sponsor and to the

other Member States concerned within 28 days from the submission date.

For the purpose of this Article and of Articles 19 and 23, the reporting

date shall be the date on which the final assessment report is submitted to

the sponsor and the other Member States concerned.

4. For clinical trials involving more than one Member State the assessment

process of substantial modification shall include three phases:

(a) an assessment phase performed by the reporting Member State

within 21 days from the submission date. The assessment phase

shall end when the reporting Member State circulates the draft

assessment report;

(b) a review phase performed within three days from the end of the

assessment phase, involving all the Member States concerned, and;

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(c) a coordination phase performed within four days from the end of

the review phase.

During the assessment phase, the reporting Member State shall develop a

draft assessment report and circulate it to all the Member States

concerned.

During the review phase, all Member States concerned shall review the

application on the basis of the draft assessment report and shall share

considerations for their Member State that are relevant to the application.

Considerations may only be raised on:

– one or more grounds referred to in Article 19(2) of this Regulation.

– on matters that would lead the ethics committee issuing negative

opinion.

During the consolidation phase, the reporting Member State shall take

due account of the considerations of the other Member States concerned

when finalizing the assessment report and shall record how the

considerations have been addressed. The reporting Member State shall

submit the final assessment report to the sponsor and all the other

Member States concerned by the reporting date.’

(b) paragraph 5 is deleted;

(c) paragraph 6 is replaced by the following:

‘6. Between the validation date and the reporting date, only the reporting

Member State may request additional information from the sponsor,

taking into account the considerations referred to in paragraph 4.

For the purpose of obtaining and reviewing this additional information

from the sponsor in accordance with the third and fourth subparagraph,

the reporting Member State may extend the period referred to in the first

subparagraph of paragraph 3 by a maximum of 14 days.

The sponsor shall submit the requested additional information within the

period set by the reporting Member State. This period shall not extend

beyond seven days from the receipt of the request.

Upon receipt of the additional information, the Member States concerned

shall review any additional information provided by the sponsor and shall

share any unaddressed considerations relevant to the application. The

review shall be performed within a maximum of three days from the

receipt of the additional information and further consolidation shall be

performed within a maximum of seven days from the receipt of

additional information from the sponsor. When finalising the assessment

report, the reporting Member State shall take due account of the

considerations of the other Member States concerned and shall record

how the considerations have been dealt with.’;

(18) Article 19 is amended as follows:

(a) paragraphs 1 and 2 are replaced by the following:

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‘1. Each Member State concerned shall notify the sponsor through the EU

portal as to whether the substantial modification is authorised, whether it

is authorised subject to conditions, or whether authorisation is refused.

Notification shall be done by way of a single decision within five days

from the reporting date.

Where the conclusion of the reporting Member State is that the

substantial modification is acceptable or acceptable subject to

compliance with specific conditions, that conclusions shall be deemed to

be the conclusions of the Member State concerned.

A substantial modification subject to condition may be implemented

unless the Member State concerned specified that the condition is

suspensive. Unless otherwise specified, the fulfilment of the condition

does not require a submission of a request for another substantial

modification.

Notwithstanding the first subparagraph, a Member State concerned may

disagree with that conclusion of the reporting Member State only on the

following grounds, provided that the consideration was raised during the

process pursuant to Article 18(4) and it considers that it was not

sufficiently addressed:

(a) when it considers that participation in the clinical trial would lead

to a subject receiving an inferior treatment than in normal clinical

practice in the Member State concerned;

(b) infringement of its national law as referred to in article 90.

2. Where the Member State concerned disagrees with the conclusion on the

basis of the second subparagraph, it shall communicate its disagreement,

together with a detailed justification, through the EU portal, to the

Commission, to all Member States and to the sponsor.

A Member State concerned shall refuse to authorise a substantial

modification if it disagrees with the conclusion of the reporting Member

State as regards Part I of the assessment report on any of the grounds

referred to in the second paragraph or where an ethics committee has

issued a negative opinion which, in accordance with the law of that

Member State concerned, is valid for the entire Member State. That

Member State shall provide for an appeal procedure in respect of such

refusal.’

(19) Article 20 is amended as follows:

(a) paragraphs 1 and 2 are replaced by the following:

‘1. Within four days from the submission of the application dossier, the

Member State concerned shall notify the sponsor though the EU portal of

the following:

(a) whether the substantial modification concerns an aspect covered by

Part II of the assessment report;

(b) whether the application dossier is complete in accordance with

Annex II;

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(c) in case of parallel modification to Part I, whether the submission is

acceptable taking into account the requirements of Article 16a.

‘2. Where the Member State concerned has not notified the sponsor within

the period referred to in paragraph 1, the substantial modification applied

for shall be deemed to concern an aspect covered by Part II of the

assessment report and the application dossier shall be deemed to be

complete and, when applicable, the parallel substantial modification shall

be deemed to be acceptable taking into account the requirements of

Article 16a.’

(b) in paragraph 3, the two first subparagraphs are replaced by the following:

‘Where the Member State concerned finds that the substantial modification

does not concern an aspect covered by Part II of the assessment report or that

the application dossier is not complete, or, where applicable, that the parallel

substantial modification is not acceptable, it shall inform the sponsor thereof

through the EU portal and shall set a maximum of five days for the sponsor to

comment on the application or to complete the application dossier through the

EU portal.

Within 14 days from the submission date the reporting Member State shall

notify the sponsor as to whether or not the application complies with the

requirements set out in paragraph 1 points (a), (b), and if applicable, (c).’

(c) in paragraph 5, the second and third subparagraphs are replaced by the

following:

‘Notification shall be done by way of a single decision within 28 days from the

submission date.

A substantial modification subject to condition may be implemented unless the

Member State concerned specified that the condition is suspensive. Unless

otherwise specified, a fulfilment of the condition does not require a submission

of a request for another substantial modification.’

(d) in paragraph 6, the second, third and fourth subparagraphs are replaced by the

following:

‘For the purpose of obtaining and reviewing this additional information from

the sponsor, the Member State concerned may extend the period referred to in

the paragraph 5, second subparagraph, by a maximum of 14 days.

The sponsor shall submit the requested additional information within the period

set by the Member State concerned, which shall not exceed seven days from

the receipt of the request.

Upon receipt of the additional information, the Member State concerned shall

complete its assessment within a maximum seven days.’;

(20) in Article 21, paragraph 1 is replaced by the following:

‘1. Where a substantial modification relates to aspects covered by Parts I and II of

the assessment report, the application for an authorisation of that substantial

modification shall be validated in accordance with Articles 17 and 20.’;

(21) Article 22 is amended as follows:

(a) paragraph 1 is replaced by the following:

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‘1. Each Member State concerned shall assess, for its own territory, the

aspects of the substantial modification which are covered by Part II of the

assessment report and submit, through the EU portal, that report,

including its conclusion, to the sponsor within 28 days from the

submission date. If the reporting Member State requested additional

information regarding aspects covered by Part I of the assessment report

as per Article 21(2) in conjunction with Article 18(6), or when a Member

State concerned requests additional information from the sponsor

regarding Part II aspects of the application, Member States concerned

may extend this period by 14 days.’

(b) paragraph 2 is deleted;

(c) paragraph 3 is replaced by the following:

‘3. The sponsor shall submit the requested additional information within the

period set by the Member State concerned, which shall not exceed seven

days from the receipt of the request.

Upon receipt of the additional information, the Member State concerned

shall complete its assessment within a maximum of seven days from the

submission of the requested information by the sponsor.

Where the sponsor does not provide the requested additional information

within the period set by the Member State concerned the application shall

be deemed to have lapsed in that Member State.

The request for additional information and the additional information

shall be submitted through the EU portal.’

(22) Article 23 is amended as follows:

(a) in paragraph 1, the third subparagraph is replaced by the following:

‘A substantial modification subject to condition may be implemented unless

the Member State concerned specified that the condition is suspensive. Unless

otherwise specified, a fulfilment of the condition does not require a submission

of a request for another substantial modification.’

(b) in paragraph 2, the second subparagraph, is replaced by the following:

’Notwithstanding the first subparagraph, a Member State concerned may

disagree with the conclusion of the reporting Member State only on the

following grounds, provided that the consideration was raised during the

process pursuant to Article 18(4) and it considers that it was not sufficiently

addressed:

(a) when it considers that participation in the clinical trial would lead to a

subject receiving an inferior treatment than in normal clinical practice in

the Member State concerned;

(b) infringement of its national law as referred to in Article 90.’

(23) Article 25 is amended as follows:

(a) paragraph 1 is amended as follows:

(i) in the first subparagraph, point (e) is replaced aby the following:

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‘(e) justification as to why the clinical trial is a minimal-intervention or

low-intervention clinical trial, in cases where this is claimed by the

sponsor.’;

(ii) the second subparagraph is replaced by the following:

‘The list of required documentation and information for Part I is set out

in Part I of Annex I. The list of required documentation for Part II is set

out in Part II of Annex I.’;

(b) the following paragraphs 1a, 1b and 1c are inserted:

‘1a. The requirements for Part I may be adapted for minimal-intervention or

low-intervention clinical trials.”

‘1b. The sponsor shall use harmonised templates, where such templates are

available, for the submission of documents for Part II of the application

dossier necessary for the authorisation of the clinical trial, in accordance

with the requirements described in Article 7(1) of this Regulation.

1c. To draw up and update, when necessary, harmonised templates to be

used by sponsors, the Commission shall be empowered to adopt

implementing acts in accordance with Article 88. The harmonised

templates may include standardised sections for documents referred to in

Article 7(2) and in Annex I.’

(c) the following paragraph 2a is inserted:

’2a. The requirements referred to in paragraph 2 may be adapted for minimal-

intervention and low-intervention clinical trials.’

(d) the following paragraphs 8 and 9 are added:

‘8. An application dossier for an authorisation of a clinical trial or for an

authorisation of a substantial modification may rely on health data

accessed under Chapter IV of Regulation (EU) 2025/327 of the European

Parliament and of the Council*

9. National competent authorities and ethics committees shall ensure that

the persons validating or assessing the initial application and substantial

modification requests only documents which are listed in Part I and Part

II of Annex I and Annex II.’

* Regulation (EU) 2025/327 of the European Parliament and of the

Council of 11 February 2025 on the European Health Data Space and

amending Directive 2011/24/EU and Regulation (EU) 2024/2847 (OJ L,

2025/327, 5.3.2025. ELI: http://data.europa.eu/eli/reg/2025/327/oj).

(24) the following Chapters IVa and IVb are inserted:

‘Chapter IVa

INVESTIGATIONAL MEDICINAL PRODUCT CORE DOSSIER

Article 27a

Establishment of an investigational medicinal product core dossier

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1. At the time of submission of a clinical trial application referred to in Articles 5

and 11 the sponsor may request through the EU portal the establishment of an

investigational medicinal product core dossier. To this end, the sponsor shall

provide data and information referred to in point (Ga) of Part I of Annex I.

2. The sponsor shall submit the request for the establishment of the

investigational medicinal product core dossier to all Member States concerned

of the initial trial. The sponsor may extend this request to other Member States

than the Member States concerned. The reporting Member State of the initial

clinical trial shall become the depositary Member State.

3. The depositary Member State shall verify the completeness and suitability of

the core dossier for the purposes of the initial clinical trial. At the latest by the

time when the conclusion of the assessment of Part I is due in accordance with

Article 6(3) the depositary Member State shall notify the sponsor and the other

core dossier competent Member States through the EU portal of the

establishment of the investigational medicinal products core dossier where the

assessment is positive.

4. The investigational product core dossier shall be relied upon by the reporting

Member State and the Member States concerned in the process of authorising

the initial clinical trial referred to in paragraph 1.

5. Once established, the investigational medicinal product core dossier shall be

referred to in all subsequent applications concerning the clinical trial in the

context of which the investigational medicinal products core dossier was

established and any other corresponding clinical trial.

Article 27b

Maintenance and changes of the investigational medicinal products core dossier

1. The sponsor shall keep the investigational medicinal product core dossier

updated and shall review it at least once per year. When the sponsor identifies a

necessity to update the investigational products core dossier, paragraph 2

applies.

2. When new information, relevant to maintain the suitability and completeness

of an established investigational product core dossier becomes known to the

sponsor, the sponsor shall submit to the depositary Member State, through the

EU portal, a request for a change of the investigational medicinal product core

dossier.

3. In case of a new application for an authorisation of a new corresponding

clinical trial, the reporting Member State of that clinical trial together with the

depositary Member State shall assess the suitability of the investigational

product core dossier for the purpose of the authorisation of the trial application,

that is;

(a) whether the investigational product core dossier is complete as regards

the information on the characteristics and knowledge about the

investigational medicinal products;

(b) if appropriate, the compliance with the requirements concerning the

manufacturing and import of investigational medicinal products set out in

Chapter IX;

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(c) whether the investigator’s brochure and the IMPD is adequate and

complete for the scope of use as proposed by the sponsor in the

application in accordance point Ga, Part I of Annex I.

The reporting Member State of the corresponding clinical trial shall

communicate the results of its assessment to the depositary Member State.

If the investigational product core dossier does not contain all the information

necessary for the authorisation of the clinical trial, the reporting Member State

may request the sponsor to change the investigational product core dossier.

The sponsor shall in such situations request a change of the investigational

medicinal product core dossier in accordance with paragraph 2.

4. After receiving the request for a change to the core dossier, independently of

whether a change is submitted in the context of an assessment of an application

related to a corresponding clinical trial or independently, the depositary

Member State shall verify whether the core dossier, once changed, will

continue to fulfil the requirements listed in paragraph 3 points (a), (b) and (c).

The Member State concerned with the core dossier shall not duplicate the

assessment of the depositary Member State. The depositary Member State may

consult the Member State concerned as appropriate.

5. If a request for a core dossier change is submitted in the context of an ongoing

assessment related to a corresponding clinical trial, the timeline for change of

the core dossier shall allow for timely approval of the clinical trial.

6. The sponsor shall assess whether a change to the investigational product core

dossier makes it necessary to submit a substantial modification in

corresponding clinical trials that are ongoing.

Article 27c

Procedural aspects related to the establishment and maintenance of the investigational

medicinal products core dossier

The Commission shall set out the detailed rules governing the submission of a

request for the establishment of an investigational product core dossier, its

assessment and maintenance by means of implementing acts, including the rules for

cooperation between the core dossier competent Member States and the change of

depositary Member State. Those implementing acts shall be adopted in accordance

with the examination procedure referred to in Article 88.”

Chapter IVb

REGULATORY SANDBOXES AND USE OF AI

Article 27d

Regulatory sandbox

1. The Commission may, pursuant to the procedure set out in paragraph 7,

establish and operate a regulatory sandbox at Union level that provides a

controlled and time-limited framework to enable, under real-world conditions,

the testing of innovative approaches in clinical trials to which the full

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application of certain requirements of this Regulation is not possible or

appropriate and which therefore may require adaptations.

2. The regulatory sandbox under this Regulation may encompass approaches to

the authorisation and conduct of the clinical trials and where appropriate,

maybe be implemented in coordination and synergies with the regulatory

sandboxes established pursuant to Regulation (EU) 2024/1689 with full

involvement of competent authorities supervising the sandbox under

Regulation (EU) 2024/1689 and in accordance with the relevant procedures

and rules for participating in those AI regulatory sandboxes.

3. The activities within a regulatory sandbox shall take place pursuant to a

specific plan, for eligible clinical trials, which may be conducted under

enhanced regulatory oversight of the Member States concerned. The plan shall

clearly identify the requirements of this Regulation that are temporarily

adapted or derogated from in the sandbox and that may relate to, as necessary,

to source data and documentation requirements, recruitment and informed

consent procedures, monitoring and reporting requirements, trial design rules,

investigational medicines handling rules, safety reporting rules, site

requirements. The plan shall also identify the roles and responsibilities of

sponsors, investigators, and manufacturers.

4. A regulatory sandbox may be established only if the following conditions are

met:  

(a) it is not possible to authorise or conduct a clinical trial in full compliance

with the requirements of this Regulation due to innovative approaches in

the clinical trial or due to the specificity of the investigational medicinal

product;  

(b) the approaches referred to in point (a) are expected to contribute to at

least one of the following objectives: 

(i) increasing the robustness of the data generated in the trial;

(ii) considerably decreasing clinical trial length, and increasing the

efficiency of the clinical trial;

(iii) enabling new technologies and approaches in the development of

medicinal products that have the potential to positively and

distinctively contribute to better prevention, diagnosis, and

treatment, as well as increase adherence to treatment plans or

improve the efficiency of the provision of health care;  

 (c) the sandbox provides safeguards to ensure the safety, well-being, and

fundamental rights of clinical trial participants, data robustness, and

maintained integrity of the clinical trials within the sandbox.

5. The regulatory sandbox shall not affect the supervisory or corrective powers of

the Member States concerned and shall operate under the direct supervision of

the competent authorities in the Member State concerned for activities that take

place on its territory.

6. Before setting up a sandbox, the Commission shall request an opinion of the

CTAG. 

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7. The Commission may establish a regulatory sandbox by means of

implementing acts, after taking into consideration opinions referred to in

paragraph 6. Those implementing acts shall be adopted in accordance with the

examination procedure referred to in Article 88.

8. Member States shall notify the Commission of any risk to health and safety or

fundamental rights or integrity and robustness of data identified during the

operation of a sandbox. In these cases, the Commission may, by means of

implementing acts, suspend or revoke a regulatory sandbox.

8. Without prejudice to Article 114(1) of [Regulation (EU) …/… of the European

Parliament and the Council [reference to be added after adoption cf.

COM(2023) 193 final], where in the context of a regulatory sandbox under

Article 113 of Regulation (EU) …/… of the European Parliament and the

Council [reference to be added after adoption cf. COM(2023) 193 final] is

considered that new regulatory approaches in clinical trial are necessary for the

product development, the Commission may consider to establish a regulatory

sandbox under this Regulation to complement the regulatory sandbox

established under Regulation (EU) …/… of the European Parliament and the

Council [reference to be added after adoption cf. COM(2023) 193 final].

Article 27e

Use of Artificial Intelligence in Clinical Trials

1. For those clinical trials where the sponsor plan to use AI models or systems,

the sponsor shall evaluate the benefits and risks related to patient safety and

data robustness of the use of the AI in the context of a specific clinical trial for

a specific purpose taking into account the guidelines laid down in Article 37 of

Regulation [...] [Biotech Act].

2. The sponsor shall provide information in the protocol on the specific purpose

of the use of AI models or systems and the description of the process in the

context of the specific clinical trial.

3. When the investigation of a medicinal product in a clinical trial is combined

with a performance study of an AI in vitro diagnostic medical device or a

clinical investigation of an AI medical device, the provisions of Article 14 on

coordinated assessment for authorising combined studies shall apply.

4. In cooperation with the CTAG and, where appropriate, the Medical Device

Coordination Group, the Artificial Intelligence Board, the Agency shall

develop guidelines referred to in paragraph 1 of this Article.

** Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND

OF THE COUNCIL laying down Union procedures for the authorisation and

supervision of medicinal products for human use and establishing rules

governing the European Medicines Agency, amending Regulation (EC) No

1394/2007 and Regulation (EU) No 536/2014 and repealing Regulation (EC)

No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No

1901/2006, COM/2023/193final

(25) Article 28 is amended as follows:

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(a) paragraph 2 is deleted.

(b) in paragraph 3, the last sentence is deleted.

(26) in Article 29(1), the following subparagraph is added:

‘The communication in the context of an interview between the investigator and the

subject or the investigator and the subject and its legally designated representative, as

applicable, may be done remotely through use of electronic means. The record of the

informed consent procedure may have an electronic form and shall be signed relying

on electronic identification means complying with Regulation (EU) No 910/2014 of

the European Parliament and of the Council* or the equivalent standards.

* Regulation (EU) No 910/2014 of the European Parliament and of the Council of

23 July 2014 on electronic identification and trust services for electronic transactions

in the internal market and repealing Directive 1999/93/EC, OJ L 257,

28.8.2014.ELI: http://data.europa.eu/eli/reg/2014/910/oj.’’

(27) in Article 30(3), point (c) is replaced by the following:

‘(c) the clinical trial is a minimal-intervention clinical trial;’

(28) in Article 31(1), point (e) is deleted;

(29) in Article 32 (1), point (e) is deleted;

(30) in Article 33, the following second paragraph is inserted:

’Women who become pregnant or begin breastfeeding while participating in a

clinical trial shall not be automatically excluded from participation in the clinical

trial.’

(31) in Article 41, the following paragraph 5 is added:

’5. Reporting requirements of adverse events and serious adverse events for

minimal-intervention and low-intervention clinical trials shall be simplified by

applying a risk-based approach. Any such adaptation should be clearly stated

and justified in the protocol by the sponsor.:

(32) in Article 48, point (a) is replaced by the following:

‘(a) whether the clinical trial is a minimal-intervention or low-intervention clinical

trial;’:

(33) the following Article 50a is inserted:

’Article 50a

Delivery of investigational and auxiliary medicinal products through a dispensing pharmacy,

an authorised person or directly to the subject

When justified in the protocol, the delivery of investigational medicinal products and

auxiliary medicinal products to the clinical trials subjects may be ensured at a

distance under the supervision of the investigator.

In case of a minimal-intervention and a low-intervention clinical trial, the

distribution of the investigational medicinal products can be ensured in a Member

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State where the clinical trial has been authorised, under the responsibility of the

investigator, through the dispensing pharmacies or by persons authorised to supply

medicinal products to thesubject.

The protocol and investigator’s brochure shall describe the arrangements for direct

delivery to subjects or through dispensing pharmacies or persons authorised to

supply to the patients, including the roles and responsibilities of all parties involved

and procedures for secure handling, storage.

The direct delivery to subjects shall comply with the guidelines referred to in

paragraph 1 of Article 63a.’:

(34) in Article 51(1), first subparagraph is replaced by the following:

’Investigational medicinal products shall be traceable. They shall be stored, returned

and/or destroyed as appropriate and proportionate to ensure the safety of the subject

and the reliability and robustness of the data generated in the clinical trial, in

particular, taking into account whether the investigational medicinal product is an

authorised investi­gational medicinal product, and whether the clinical trial is a

minimal-intervention or low-inter­vention clinical trial.’;

(35) in Article 53(2), the first sentence is replaced by the following:

’The sponsor shall submit to the Member States concerned, through the EU portal,

inspection reports of third country authorities concerning the clinical trial and

relevant to subject safety .’

(36) in Article 57, the first subparagraph is replaced by the following:

’The sponsor and the investigator shall keep a clinical trial master file. The clinical

trial master file shall at all times contain the essential documents relating to that

clinical trial which allow verification of the conduct of a clinical trial and the quality

of the data generated, taking into account all characteristics of the clinical trial,

including in particular whether the clinical trial is a minimal-intervention or low-

intervention clinical trial.’;

(37) Article 61 is amended as follows:

(a) paragraph 6 is replaced by the following:

‘6. Member States shall make the processes set out in paragraph 5 subject to