Pöördumine

UN City, Marmorvej 51 Tel.: +45 45 33 70 00 Email: [email protected] DK-2100 Copenhagen Ø Denmark

Fax: +45 45 33 70 01 Website: https://www.who.int/europe

WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTÉ

WELTGESUNDHEITSORGANISATION ВСЕМИРНАЯ ОРГАНИЗАЦИЯ ЗДРАВООХРАНЕНИЯ

Date: 18 June 2025 Ms Helen Sõber Adviser European Union Affairs and International Co- operation Department Ministry of Social Affairs Suur-Ameerika 1 10122 Tallinn Estonia

REGIONAL OFFICE FOR EUROPE BUREAU RÉGIONAL DE L’EUROPE

REGIONALBÜRO FÜR EUROPA ЕВРОПЕЙСКОЕ РЕГИОНАЛЬНОЕ БЮРО

Head office:

UN City, Marmorvej 51, DK-2100 Copenhagen Ø, Denmark

Tel.: +45 45 33 70 00; Fax: +45 45 33 70 01 Email: [email protected]

Website: https://www.who.int/europe

Our reference: Notre référence: Unser Zeichen: См. наш номер:

Your reference: Votre référence: Ihr Zeichen: На Ваш номер:

Dear Ms Sõber, I have the honour to share the revised Terms of Reference (TOR) for National Influenza Centres (NICs) that replaces the NIC TOR (2017). This includes a new annex (Annex 1) which details the ongoing benefits available and provided to Member States through the Global Influenza Surveillance and Response System (GISRS). The updates apply to the human seasonal component only, with the objective to improve clarity on the scope and purpose of sharing seasonal influenza virus materials with WHO Collaborating Centres (WHO CCs) of GISRS. The continued sharing of influenza virus materials is critical for risk assessment and in the prevention and control of emerging influenza viruses.

These updates in the revised NIC TOR are based on extensive consultations with key stakeholders, including representatives from Ministries of Health, Directors of pilot and non-pilot NICs, Directors of WHO CCs, Nagoya Protocol focal points, and Convention on Biological Diversity: Access and Benefit Sharing (ABS) focal points. We kindly request the following:

1. acknowledgment of receipt of this letter and confirmation of the continued participation of the

National Influenza Centre (NIC) in your country under the revised NIC Terms of Reference (TOR), in consultation, as appropriate, with relevant national stakeholders; and

2. information on your current national Nagoya Protocol and ABS position, if applicable, regarding page 4, paragraphs 9 & 10 of the NIC TOR.

The Global Influenza Programme, WHO Headquarters would appreciate receiving your response within 60 working days of receipt of this correspondence. Kindly send your reply to Dr Dmitriy Pereyaslov, e-mail: [email protected] with copy to Regional Focal Point Dr Karen Nahapetyan, email: [email protected], and NIC Director in your country. WHO counts on your continuous support to the NIC in your country in fulfilling the WHO NIC TOR as part of GISRS surveillance, preparedness, and response operations at national, regional, and global levels.

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I would like to avail myself of this opportunity to thank you for the continued fruitful collaboration. Sincerely yours, Ihor Perehinets Regional Emergency Director Encls: Global Influenza Surveillance and Response System National Influenza Centres Terms of Reference Copy for information to: Ms Agne Nettan-Sepp, Head, European Union Affairs and International Co-operation Department, Ministry of Social Affairs, Suur-Ameerika 1, 10129 Tallinn, Estonia H.E. Ms Riia Salsa-Audiffren, Ambassador Representative of the Republic of Estonia, Permanent Mission of the Republic of Estonia to the United Nations Office and other international organizations in Geneva, Chemin du Petit-Saconnex 28A, CH-1209 Genève, Switzerland H.E. Mr Andre Pung, Ambassador Extraordinary and Plenipotentiary, Embassy of the Republic of Estonia, Frederiksgade 19, 4th floor, 1265 Copenhagen K, Denmark Ms Kristina Köhler, Liaison Officer, WHO Country Office, Estonia, Paldiski Road 81, 10617 Tallinn, Estonia Johanna Kristina Tamm, Laboratory for Communicable Diseases, Health Board Health Board, Paldiski mnt 81 Tallinn 10614 Estonia

Global Influenza Surveillance and Response System National Influenza Centres

Terms of Reference

30 May 2024 Page 1 of 15

I. Introduction National Influenza Centres (NICs)1 together with World Health Organization Collaborating Centres for Influenza (WHO CCs),2 WHO Essential Regulatory Laboratories (ERLs)3 and H5 Reference Laboratories4 form the Global Influenza Surveillance and Response System (GISRS) coordinated by the WHO Global Influenza Programme (GIP).5 Established in 1952, the then Global Influenza Surveillance Network became GISRS following the adoption of resolution WHA64.5 by the Sixty-fourth World Health Assembly in May 2011.6 GISRS is the primary network and resource for global influenza surveillance and control, continuously monitoring the evolution of seasonal,a pandemic and emerging zoonotic influenza viruses in the interests of public health. NICs and their host countries receive benefits through GISRS to support national and global public health surveillance and response activities (Annex 1). These activities result in the generation of surveillance information, the timely detection of influenza viruses, and the sharing of representative influenza virus isolates and/or influenza virus-positive clinical specimens with GISRS WHO CCs. NICs are institutions authorized and designated by their national authority and subsequently recognized by WHO for the purpose of participating in the work of GISRS under the WHO NIC Terms of Reference (TOR). An NIC may have additional obligations under the national authority of its host country. WHO recognition of a laboratory as an NIC within GISRS requires that a country accepts and agrees to comply with the following TOR.

II. Membership of GISRS is the result of a stringent, multi-step process that includes:

1. Official request by a national authority to WHO.

2. Collaboration between the national authority and WHO to assess whether the laboratory’s capacities, processes and procedures meet the TOR required by WHO.

3. National authority acceptance to participate in GISRS pursuant to the TOR, which includes the sharing of influenza viruses and/or influenza virus- positive clinical specimens with GISRS WHO CCs, and the sharing of relevant surveillance data with the WHO GIP.

a Seasonal influenza is an acute respiratory infection caused by influenza viruses which circulate in all parts of the world among humans. Currently circulating in humans are influenza A(H1N1), A(H3N2) and B influenza viruses – https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal).

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4. Issuance of an official letter of recognition by WHO.

5. Periodic review by WHO of the laboratory’s continued capacities to meet the required standards, as set forth in the NIC TOR, to ensure that influenza surveillance is maintained.

III. General roles and responsibilities NICs undertake the following general roles and responsibilities:

1. serve as the reference laboratory for influenza in their country;

2. serve as a technical resource on influenza-related matters for their national authority;

3. serve as a key point of contact with WHO on issues related to influenza in their country;

4. share with GISRS WHO CCs, in a timely manner, seasonal influenza virus isolates and/or influenza virus-positive clinical specimens in accordance with national Access and Benefit Sharing (ABS) guidelines;

5. agree to the use and sharing of influenza virus isolates and/or influenza virus-positive clinical specimens by GISRS WHO CCs, ERLs and H5 Reference Laboratories for risk assessment in accordance with their corresponding WHO TOR;

6. share influenza virus sequence data7 and, where available, accompanying metadatab, c through publicly accessible databases;

7. adhere to applicable national and international biosafety standards8 for working with influenza viruses;

8. adhere to applicable national and international regulations on the transport of dangerous goods (Class/division 6.2)9 when shipping influenza virus isolates and/or influenza virus-positive clinical specimens;

9. meet the quality requirements of national or international quality standards, as applicable, and participate in the WHO External Quality Assessment Programme (EQAP); and

10. maintain a high level of technical proficiency by participating in training provided by GISRS and other sources.

b On the assumption that the sharing of metadata complies with national policy and legislation. c Descriptions of metadata used by databanks are provided in the report of the PIP Advisory Group Technical Working Group on the Sharing of Influenza Genetic Sequence Data. June 2016 (https://cdn.who.int/media/docs/default-source/pip-framework/pip-framework-advisory- group/twg_doced1d1fb3-f99e-4797-82f0-60a357a37aee.pdf?sfvrsn=7efec205_1&download=true).

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NICs handle several types of influenza virus isolates and/or influenza virus-positive clinical specimens which are for the purposes of these TOR classified as follows:

1. Human seasonal influenza viruses.

2. Pandemic influenza preparedness (PIP) biological materials (BM), including influenza viruses with human pandemic potential (IVPP).10

3. Other influenza viruses from animal or environmental specimens that are not classified as “human seasonal influenza viruses” or PIP BM.10

IV. Additional roles and responsibilities NICs undertake the following additional roles and responsibilities When working with human seasonal influenza viruses

1. NICs collect respiratory specimens either through an established network of physicians, health care centres or other sentinel sites, and/or through soliciting influenza virus-positive clinical specimens from laboratories providing diagnostic services. Patients included in surveillance should preferably meet the syndromic case definition11 of influenza-like illness (ILI), acute respiratory infection (ARI) or severe acute respiratory infection (SARI). NICs are encouraged to include specimens representative of all age groups in the surveillance system.

2. Depending on available resources, NICs identify seasonal influenza viruses using molecular detection methods and/or virus culture and/or immunological methods.

3. NICs differentiate between influenza Type A and Type B viruses and attempt to identify the subtype of influenza A viruses and the lineage of influenza B viruses. For assistance with diagnostic testing, NICs can obtain updated reagents and laboratory protocols from GISRS WHO CCs through WHO.

4. NICs report timelyd defined virological surveillance information to their national authorities, and then either directly to the WHO online FluNet12 platform of RespiMarte or indirectly to a regional platform for uploading to WHO FluNet. Epidemiological information, if available, should be reported

d Results for any given week should be reported the following week at a time determined by WHO regional offices and/or headquarters. Already submitted results should be updated when more detailed results (for example, subtype determination) become available. In order to provide global updates on the current situation, reports should be submitted by Thursday 12:00 UTC each week. e RespiMart (developed from FluMart) is a platform to facilitate the exchange, harmonization, consolidation and storage of surveillance data on respiratory viruses with epidemic and pandemic potential, including influenza viruses, RSV and SARS-CoV-2. RespiMart provides a single platform for sharing aggregated and case-based data from different applications and/or data sources thereby allowing for integrated analysis and reporting – https://www.who.int/tools/RespiMart.

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to the RespiMart WHO FluID platform13 – either by the NIC or national focal point as designated by the host country. Reporting should be done weekly during the months when seasonal influenza is commonly observed, but preferably throughout the year.

5. NICs immediately report to their national authorities and to WHO any observation of unusual influenza activity in their country.

6. NICs immediately share with GISRS WHO CCs influenza A virus isolates and/or influenza virus-positive clinical specimens without well-defined results or those that cannot be subtyped using the updated reagents available through GISRS. Such findings should be reported to their national authority according to national and/or international rules and regulations, and where applicable, the International Health Regulations (2005).14

7. NICs share representative recent seasonal influenza virus isolates and/or influenza virus-positive clinical specimens in a timely manner with a GISRS WHO CC of their choice for further characterization on the understanding that the sharing of such materials among GISRS WHO CCs and ERLs, in accordance with international ethical guidelines, is essential for: (a) virus characterization and risk assessment; (b) informing WHO influenza virus vaccine composition recommendations; (c) developing reference materials; and (d) implementing the WHO EQAP for GISRS and other influenza laboratories. NICs note the relevant WHO guidance on the frequency and timing of the shipping of influenza virus isolates and/or influenza virus- positive clinical specimens to GISRS WHO CCs.15

8. NICs provide relevant virological, clinical and epidemiological information on the representative virus isolates and/or influenza-positive clinical specimens shipped to GISRS WHO CCs.

9. NICs agree, in accordance with national regulations and protocols, that if a seasonal virus shared with a GISRS WHO CC is recommended for development as a candidate vaccine virus (CVV) such a virus may be developed by a GISRS WHO CC as a CVV,f and that such a CVV may be shared with vaccine manufacturers, upon their request, for consideration as a component in the development and production of a seasonal influenza vaccine.

10. As members of GISRS, NICs have access to the benefits available and provided by GISRS as outlined in Annex 1.g

f Candidate vaccine viruses are developed by GISRS WHO CCs with the support of GISRS partner laboratories. g Benefits include contributions acquired from industry under the Pandemic Influenza Preparedness (PIP) Framework, under section 6.14.3, which are used to improve pandemic influenza preparedness and response, strengthen protection against pandemic influenza by improving and strengthening WHO GISRS, conduct disease burden studies, and strengthen laboratory and surveillance capacity, particularly in developing countries (Article 3).

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When working with influenza viruses that are classified as PIP BM TOR are described in Annex 5 of the Pandemic Influenza Preparedness (PIP) Framework (reproduced in Annex 2). NICs share IVPP according to relevant WHO guidance materials.16 When working with other influenza viruses from animal or environmental specimens that are not classified as human seasonal influenza viruses or PIP BM Occasionally, NICs may receive influenza viruses that do not fall into the categories of human seasonal influenza viruses or PIP BM – for example, viruses from animal or environmental specimens.

1. NICs must follow applicable national and/or international biosafety requirements and good microbiology laboratory practice to avoid cross- contamination with viruses of human origin. Such material should preferably be handled in facilities away from those where human specimens and viruses are investigated.

2. NICs share virus samples with GISRS WHO CCs of their choice to support GISRS risk assessment following national and international rules and regulations. It is the responsibility of the NICs to ensure that appropriate permits and other national/international documents and approvals are in place to facilitate virus sharing.

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V. References

1 National Influenza Centres. 28 August 2023. Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/national-influenza- centres). 2 WHO Collaborating Centres and their Terms of Reference. Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/who-collaboration- center-erl). 3 WHO Essential Regulatory Laboratories (ERLs) list of laboratories. Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/who- erls). 4 WHO H5 Reference Laboratories and the Terms of Reference (TOR). Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/h5- reference-laboratories). 5 Global Influenza Programme [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza-programme). 6 Sixty-fourth World Health Assembly: Geneva, 16–24 May 2011: Resolutions and decisions. Annexes. Geneva: World Health Organization; 2011. Resolution WHA64.5 (https://iris.who.int/handle/10665/106547?locale-attribute=ru&locale=es&mode=full). 7 Next-generation sequencing of influenza viruses. General information for national influenza centres. Geneva: World Health Organization; 2020 (https://cdn.who.int/media/docs/default- source/influenza/global-influenza-surveillance-and-response-system/related- documents/ngs_guidance_for_nics.pdf). 8 Laboratory biosafety manual. Fourth edition and associated monographs. Geneva: World Health Organization; 2020 (https://iris.who.int/handle/10665/337956). 9 Recommendations on the transport of dangerous goods: model regulations, 23rd revised edition. New York, Geneva: United Nations; 2023 (https://unece.org/transport/dangerous-goods/un-model- regulations-rev-23). 10 Pandemic Influenza Preparedness (PIP) Framework for the sharing of influenza viruses and access to vaccines and other benefits. Second edition. Geneva: World Health Organization; 2021 (https://www.who.int/publications/i/item/9789240024854). 11 End-to-end integration of SARS-CoV-2 and influenza sentinel surveillance: revised interim guidance, 31 January 2022. Geneva: World Health Organization; 2022 (https://iris.who.int/handle/10665/351409). 12 FluNet Summary [website]. Geneva: World Health Organization (https://www.who.int/tools/flunet/flunet-summary). 13 FluID [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza- programme/surveillance-and-monitoring/fluid). 14 International Health Regulations (2005). Third edition. Geneva: World Health Organization; 2016 (https://www.who.int/publications/i/item/9789241580496). 15 Operational guidance for sharing seasonal influenza viruses with WHO Collaborating Centres (CCs) under the Global Influenza Surveillance and Response System (GISRS). Geneva: World Health Organization; 2017 (WHO/WHE/IHM/GIP/2017.6; https://apps.who.int/iris/handle/10665/259400). 16 Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework. Geneva: World Health Organization; 2017 (WHO/WHE/IHM/GIP/2017.3; https://iris.who.int/handle/10665/259402).

Global Influenza Surveillance and Response System National Influenza Centres

Terms of Reference

30 May 2024 Page 7 of 15

Annex 1

List of material and non-material benefits of GISRSh

As a member of the Global Influenza Surveillance and Response System (GISRS) and in accordance with the National Influenza Centres Terms of Reference, National Influenza Centres (NICs) are provided with, and have access to, a range of benefits, some of which are provided on request.i Such benefits support seasonal and zoonotic influenza surveillance, capacity strengthening, and other influenza prevention and control activities in countries, and facilitate collective GISRS actions to mitigate the public health risks associated with influenza outbreaks.

Material benefits include 1. Reagents and virusesj, k

a. Annually updated laboratory reagents for the following influenza virus assays: polymerase chain reaction (PCR) singleplex and multiplex assays; haemagglutination inhibition assays (HIA); indirect fluorescent antibody (IFA) test; and sequencing reagents for Sanger or next-generation sequencing assays.

b. Primers/probes for the molecular detection of non-influenza respiratory viruses of public health importance, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV)l for countries implementing epidemiological and virological surveillance of such viruses as recommended for GISRS integrated surveillance.

c. Updated diagnostic reference control viruses.

d. Annually updated vaccine antigens for developing potency test reagents.

e. Tissue culture media for influenza virus isolation.

h This document is intended to be a “living document” and may be updated as appropriate. i For the detailed list of benefits and currently available reagents contact the WHO Global Influenza Programme (GIP) at: [email protected]. j Diagnostic reagents and reference viruses are provided through GISRS initiatives. There may be some limit restrictions depending upon the activity in which an NIC participates. For additional information on reagents contact: [email protected]. k For information on these, contact WHO GIP at: [email protected]. l RSV reagents are available to GISRS member countries enrolled in global RSV surveillance.

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f. High-growth reassortant viruses developed by reassorting laboratories, and prototype influenza candidate vaccine viruses (CVVs) developed by GISRS WHO Collaborating Centres (WHO CCs).m

g. Annual proficiency panels for participation in the WHO External Quality Assessment Programme (EQAP) for the molecular detection of seasonal and zoonotic influenza viruses, and where applicable:

• proficiency panels for participation in the WHO EQAP for the molecular detection of non-influenza respiratory viruses of public health importance such as SARS-CoV-2 and RSV;

• proficiency panels for participation in external quality assessments of virus isolation in cell culture and embryonated chicken eggs, and identification of the haemagglutinin subtype of viral isolates by haemagglutination inhibition testing and/or microneutralization assay;

• proficiency panels for participation in external quality assessments of antiviral susceptibility testing; and/or

• proficiency panels for participation in external quality assessments of influenza virus gene sequencing.

h. Materials required as described in WHO Guidance on regulations for the transport of infectious substances for shipping of influenza virus isolates and/or influenza virus-positive clinical specimens through the WHO Shipping Fund Project to facilitate the sharing of influenza viruses within GISRS.n, o, p

Non-material benefits include

1. Epidemiological and virological public health information and tools, including

a. Global, regional and national epidemiological and virological information sharingq by geographical groupings of countries, areas and territories on influenza, SARS-CoV-2, and RSV (where available) through the reporting by national sentinel and non-sentinel surveillance systems to the WHO surveillance data platform RespiMart. This will include information on the geographical areas most affected, the level of activity according to epidemiological week and severity of cases.

b. Access to epidemiological and virological surveillance technical updates and to situation reports for: (a) seasonal influenza;r (b) influenza at the animal- human interface; (c) influenza viruses with human pandemic potential (IVPP); (d) SARS-CoV-2; (e) RSV; and (f) as applicable, other emerging respiratory

m The development of high-growth CVVs is a complex process, involving collaboration between laboratories involved in developing reassortants and GISRS WHO CCs. Two technologies are currently used: classical reassortment and reverse genetics. n Shipping & logistics: https://www.who.int/initiatives/global-influenza-surveillance-and-response- system/virus-sharing/shipping-and-logistics-activities. o Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework. Geneva: World Health Organization; 2017 (https://www.who.int/publications/i/item/operational-guidance-on-sharing-influenza-viruses). p Operational guidance on sharing seasonal influenza viruses with WHO Collaborating Centres (CCs) under the Global Influenza Surveillance and Response System (GISRS). Geneva: World Health Organization; 2017 (https://www.who.int/publications/i/item/WHO-WHE-IHM-GIP-2017.6). q For respiratory virus updates see: https://www.who.int/teams/global-influenza- programme/surveillance-and-monitoring/influenza-updates. r FluNet [website]. Geneva: World Health Organization (https://www.who.int/tools/flunet).

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viruses of public health significance. Such technical updates better equip countries to prepare for and respond to future respiratory virus epidemics and pandemics.

c. Analyses and reports from GISRS WHO CCs coordinated by WHO Global Influenza Programme (GIP) and detailing the genetic, antigenic and antiviral- susceptibility characteristics of viruses circulating in the country and shared with GISRS WHO CCs.

d. Updated laboratory protocols for the surveillance, detection and characterization of seasonal and pandemic influenza viruses for:

i. molecular detection of seasonal and pandemic influenza viruses

ii. antiviral-susceptibility testing

iii. genetic characterization (sequencing)

iv. antigenic characterization

v. serological detection of influenza viruses

vi. virus isolation procedures.

e. Tools and other resources to help countries monitor their epidemiological and virological influenza situation, perform risk assessments, and promptly exchange information with GISRS, including:

i. global epidemiological surveillance standards for influenza;s ii. data analysis tools provided through the RespiMart platform – such as

FluNett and FluID;u iii. the WHO Epidemic and Pandemic Influenza Severity Assessment

(PISA) tool;v iv. the WHO Tool for Influenza Pandemic Risk Assessment (TIPRA);w v. the WHO Influenza Virus Traceability Mechanism (IVTM);x vi. the WHO document A manual for estimating disease burden associated

with seasonal influenza;y vii. protocols for investigating non-seasonal influenza and other emerging

acute respiratory diseases;z and

s See: Global epidemiological surveillance standards for influenza. Geneva: World Health Organization; 2013 (https://www.who.int/publications/i/item/9789241506601). t FluNet [website]. Geneva: World Health Organization (https://www.who.int/tools/flunet). u FluID [online platform]. Geneva: World Health Organization (https://www.who.int/teams/global- influenza-programme/surveillance-and-monitoring/fluid). v Pandemic influenza severity assessment (PISA). A WHO Guide to assess the severity of influenza in seasonal epidemics and pandemics. Geneva: World Health Organization; 2017 (https://www.who.int/publications/i/item/pandemic-influenza-severity-assessment-(-pisa)-a-who-guide- to-assess-the-severity-of-influenza-in-seasonal-epidemics-and-pandemics). w Tool for influenza pandemic risk assessment (TIPRA). Version 2 Release. Geneva: World Health Organization; 2020 (https://www.who.int/publications/i/item/tool-for-influenza-pandemic-risk- assessment-(tipra)-2nd-edition). x Influenza Virus Traceability Mechanism (IVTM 2.0) [website]. Geneva: World Health Organization (https://extranet.who.int/ivtm2/). y A manual for estimating disease burden associated with seasonal influenza. Geneva: World Health Organization; 2015 (https://www.who.int/publications/i/item/9789241549301). z Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases. Geneva: World Health Organization; 2018 (https://www.who.int/publications/i/item/WHO-WHE-IHM- GIP-2018.2).

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viii. Influenza Investigations & Studies (Unity Studies) standardized template protocols.aa

f. Assessments of the public health risks posed by evolving and emerging influenza virus strains through the use of standardized and consistent approaches to outbreak investigations, in partnership with GISRS collaborators.

g. Recommendations on risk management measures, including those related to influenza vaccines and antiviral drugs.

h. Access to established GISRS online and, when possible, in-person platforms to share experiences and information, and to interact with other GISRS laboratories.bb

2. Training, mentoring, and capacity strengthening (both epidemiological and

laboratory) through institutional capacity-building based on participation, collaboration and cooperation with WHO headquarters, regional/country offices, GISRS WHO CCs and other GISRS-associated entities and partners. This includes networking, participation in GISRS meetings, twinning projects and/or joint tasks, and the provision of technical support for troubleshooting, implementing diagnostic procedures and surveillance protocols.cc

3. Access to technical support for genomic sequencing and/or bioinformatics from

GISRS WHO CCs and GISRS-associated entities and partners for countries without established sequencing capacities, or for the validation of sequencing results obtained by NICs.

4. Access to technical support for inputting data and the analysis of genetic

sequence data through appropriate publicly accessible databases such as the EpiFlu™ database of the GISAID Global Data Science Initiativedd and databases in the International Nucleotide Sequence Database Collaboration (INSDC).

5. Access to outputs, including estimations of health care burden, pooled vaccine

effectiveness data, PISA summaries for countries and TIPRA reports. 6. Direct and free-of-charge real-time access to advanced expertise and support in

GISRS WHO CCs, WHO Essential Regulatory Laboratories (ERLs) and H5 Reference Laboratories for seasonal and pandemic viruses.

aa Influenza investigations & studies (Unity Studies) [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza-programme/surveillance-and-monitoring/influenza- investigations-studies-unity). bb These include the EZcollab platform (https://ezcollab.who.int/), the GISRS Information Centre and the GISRS Discussion Forum. cc Some contributions for the support of GISRS are made through the PIP Framework. Countries benefit additionally from distinct contributions from GISRS industry partners for specific activities/projects including the Global influenza hospital surveillance network (GIHSN) and the Partnership for Influenza Vaccine Introduction (PIVI). dd GISRS industry partners provide some contributions towards the functioning and updating of the global and publicly accessible genetic sequence database platforms for seasonal and zoonotic influenza, SARS-CoV-2, and RSV.

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7. Collaborative research initiatives with other GISRS membersee with acknowledgement made of the research contributions of national scientific presentations and publications.ff

8. Inclusion of the name of the institution, its Director and contact details in the list of

NICs formally recognized by WHO and available at: https://www.who.int/initiatives/global-influenza-surveillance-and-response- system/national-influenza-centres

For questions on GISRS benefits please contact: [email protected]

ee Support for research activities is received from GISRS partners including vaccine manufacturers. Areas of research include clinical trials, evaluation of new manufacturing platforms, use of adjuvants, improved vaccine formulations and knowledge-based studies to support improved vaccine coverage in all age cohorts. For additional information contact GISRS at [email protected]. ff WHO actively seeks the participation of scientists from GISRS laboratories and GISRS member countries in scientific research on clinical specimens and/or influenza and other respiratory viruses and invites active engagement in the preparation of manuscripts for presentation and publication. Contributors will be appropriately acknowledged in line with guidance such as that published by the International Committee of Medical Journal Editors.

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Annex 2

Extract (pp 49–52) from Annex 5 of the Pandemic Influenza Preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits: National Influenza Centres. Terms of Reference related to work with Pandemic Influenza Preparedness biological materials.gg

gg https://iris.who.int/bitstream/handle/10665/341850/9789240024854-eng.pdf?sequence=1

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UN City, Marmorvej 51 Tel.: +45 45 33 70 00 Email: [email protected] DK-2100 Copenhagen Ø Denmark

Fax: +45 45 33 70 01 Website: https://www.who.int/europe

WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTÉ

WELTGESUNDHEITSORGANISATION ВСЕМИРНАЯ ОРГАНИЗАЦИЯ ЗДРАВООХРАНЕНИЯ

Date: 18 June 2025 Ms Helen Sõber Adviser European Union Affairs and International Co- operation Department Ministry of Social Affairs Suur-Ameerika 1 10122 Tallinn Estonia

REGIONAL OFFICE FOR EUROPE BUREAU RÉGIONAL DE L’EUROPE

REGIONALBÜRO FÜR EUROPA ЕВРОПЕЙСКОЕ РЕГИОНАЛЬНОЕ БЮРО

Head office:

UN City, Marmorvej 51, DK-2100 Copenhagen Ø, Denmark

Tel.: +45 45 33 70 00; Fax: +45 45 33 70 01 Email: [email protected]

Website: https://www.who.int/europe

Our reference: Notre référence: Unser Zeichen: См. наш номер:

Your reference: Votre référence: Ihr Zeichen: На Ваш номер:

Dear Ms Sõber, I have the honour to share the revised Terms of Reference (TOR) for National Influenza Centres (NICs) that replaces the NIC TOR (2017). This includes a new annex (Annex 1) which details the ongoing benefits available and provided to Member States through the Global Influenza Surveillance and Response System (GISRS). The updates apply to the human seasonal component only, with the objective to improve clarity on the scope and purpose of sharing seasonal influenza virus materials with WHO Collaborating Centres (WHO CCs) of GISRS. The continued sharing of influenza virus materials is critical for risk assessment and in the prevention and control of emerging influenza viruses.

These updates in the revised NIC TOR are based on extensive consultations with key stakeholders, including representatives from Ministries of Health, Directors of pilot and non-pilot NICs, Directors of WHO CCs, Nagoya Protocol focal points, and Convention on Biological Diversity: Access and Benefit Sharing (ABS) focal points. We kindly request the following:

1. acknowledgment of receipt of this letter and confirmation of the continued participation of the

National Influenza Centre (NIC) in your country under the revised NIC Terms of Reference (TOR), in consultation, as appropriate, with relevant national stakeholders; and

2. information on your current national Nagoya Protocol and ABS position, if applicable, regarding page 4, paragraphs 9 & 10 of the NIC TOR.

The Global Influenza Programme, WHO Headquarters would appreciate receiving your response within 60 working days of receipt of this correspondence. Kindly send your reply to Dr Dmitriy Pereyaslov, e-mail: [email protected] with copy to Regional Focal Point Dr Karen Nahapetyan, email: [email protected], and NIC Director in your country. WHO counts on your continuous support to the NIC in your country in fulfilling the WHO NIC TOR as part of GISRS surveillance, preparedness, and response operations at national, regional, and global levels.

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I would like to avail myself of this opportunity to thank you for the continued fruitful collaboration. Sincerely yours, Ihor Perehinets Regional Emergency Director Encls: Global Influenza Surveillance and Response System National Influenza Centres Terms of Reference Copy for information to: Ms Agne Nettan-Sepp, Head, European Union Affairs and International Co-operation Department, Ministry of Social Affairs, Suur-Ameerika 1, 10129 Tallinn, Estonia H.E. Ms Riia Salsa-Audiffren, Ambassador Representative of the Republic of Estonia, Permanent Mission of the Republic of Estonia to the United Nations Office and other international organizations in Geneva, Chemin du Petit-Saconnex 28A, CH-1209 Genève, Switzerland H.E. Mr Andre Pung, Ambassador Extraordinary and Plenipotentiary, Embassy of the Republic of Estonia, Frederiksgade 19, 4th floor, 1265 Copenhagen K, Denmark Ms Kristina Köhler, Liaison Officer, WHO Country Office, Estonia, Paldiski Road 81, 10617 Tallinn, Estonia Johanna Kristina Tamm, Laboratory for Communicable Diseases, Health Board Health Board, Paldiski mnt 81 Tallinn 10614 Estonia

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Terms of Reference

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I. Introduction National Influenza Centres (NICs)1 together with World Health Organization Collaborating Centres for Influenza (WHO CCs),2 WHO Essential Regulatory Laboratories (ERLs)3 and H5 Reference Laboratories4 form the Global Influenza Surveillance and Response System (GISRS) coordinated by the WHO Global Influenza Programme (GIP).5 Established in 1952, the then Global Influenza Surveillance Network became GISRS following the adoption of resolution WHA64.5 by the Sixty-fourth World Health Assembly in May 2011.6 GISRS is the primary network and resource for global influenza surveillance and control, continuously monitoring the evolution of seasonal,a pandemic and emerging zoonotic influenza viruses in the interests of public health. NICs and their host countries receive benefits through GISRS to support national and global public health surveillance and response activities (Annex 1). These activities result in the generation of surveillance information, the timely detection of influenza viruses, and the sharing of representative influenza virus isolates and/or influenza virus-positive clinical specimens with GISRS WHO CCs. NICs are institutions authorized and designated by their national authority and subsequently recognized by WHO for the purpose of participating in the work of GISRS under the WHO NIC Terms of Reference (TOR). An NIC may have additional obligations under the national authority of its host country. WHO recognition of a laboratory as an NIC within GISRS requires that a country accepts and agrees to comply with the following TOR.

II. Membership of GISRS is the result of a stringent, multi-step process that includes:

1. Official request by a national authority to WHO.

2. Collaboration between the national authority and WHO to assess whether the laboratory’s capacities, processes and procedures meet the TOR required by WHO.

3. National authority acceptance to participate in GISRS pursuant to the TOR, which includes the sharing of influenza viruses and/or influenza virus- positive clinical specimens with GISRS WHO CCs, and the sharing of relevant surveillance data with the WHO GIP.

a Seasonal influenza is an acute respiratory infection caused by influenza viruses which circulate in all parts of the world among humans. Currently circulating in humans are influenza A(H1N1), A(H3N2) and B influenza viruses – https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal).

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4. Issuance of an official letter of recognition by WHO.

5. Periodic review by WHO of the laboratory’s continued capacities to meet the required standards, as set forth in the NIC TOR, to ensure that influenza surveillance is maintained.

III. General roles and responsibilities NICs undertake the following general roles and responsibilities:

1. serve as the reference laboratory for influenza in their country;

2. serve as a technical resource on influenza-related matters for their national authority;

3. serve as a key point of contact with WHO on issues related to influenza in their country;

4. share with GISRS WHO CCs, in a timely manner, seasonal influenza virus isolates and/or influenza virus-positive clinical specimens in accordance with national Access and Benefit Sharing (ABS) guidelines;

5. agree to the use and sharing of influenza virus isolates and/or influenza virus-positive clinical specimens by GISRS WHO CCs, ERLs and H5 Reference Laboratories for risk assessment in accordance with their corresponding WHO TOR;

6. share influenza virus sequence data7 and, where available, accompanying metadatab, c through publicly accessible databases;

7. adhere to applicable national and international biosafety standards8 for working with influenza viruses;

8. adhere to applicable national and international regulations on the transport of dangerous goods (Class/division 6.2)9 when shipping influenza virus isolates and/or influenza virus-positive clinical specimens;

9. meet the quality requirements of national or international quality standards, as applicable, and participate in the WHO External Quality Assessment Programme (EQAP); and

10. maintain a high level of technical proficiency by participating in training provided by GISRS and other sources.

b On the assumption that the sharing of metadata complies with national policy and legislation. c Descriptions of metadata used by databanks are provided in the report of the PIP Advisory Group Technical Working Group on the Sharing of Influenza Genetic Sequence Data. June 2016 (https://cdn.who.int/media/docs/default-source/pip-framework/pip-framework-advisory- group/twg_doced1d1fb3-f99e-4797-82f0-60a357a37aee.pdf?sfvrsn=7efec205_1&download=true).

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NICs handle several types of influenza virus isolates and/or influenza virus-positive clinical specimens which are for the purposes of these TOR classified as follows:

1. Human seasonal influenza viruses.

2. Pandemic influenza preparedness (PIP) biological materials (BM), including influenza viruses with human pandemic potential (IVPP).10

3. Other influenza viruses from animal or environmental specimens that are not classified as “human seasonal influenza viruses” or PIP BM.10

IV. Additional roles and responsibilities NICs undertake the following additional roles and responsibilities When working with human seasonal influenza viruses

1. NICs collect respiratory specimens either through an established network of physicians, health care centres or other sentinel sites, and/or through soliciting influenza virus-positive clinical specimens from laboratories providing diagnostic services. Patients included in surveillance should preferably meet the syndromic case definition11 of influenza-like illness (ILI), acute respiratory infection (ARI) or severe acute respiratory infection (SARI). NICs are encouraged to include specimens representative of all age groups in the surveillance system.

2. Depending on available resources, NICs identify seasonal influenza viruses using molecular detection methods and/or virus culture and/or immunological methods.

3. NICs differentiate between influenza Type A and Type B viruses and attempt to identify the subtype of influenza A viruses and the lineage of influenza B viruses. For assistance with diagnostic testing, NICs can obtain updated reagents and laboratory protocols from GISRS WHO CCs through WHO.

4. NICs report timelyd defined virological surveillance information to their national authorities, and then either directly to the WHO online FluNet12 platform of RespiMarte or indirectly to a regional platform for uploading to WHO FluNet. Epidemiological information, if available, should be reported

d Results for any given week should be reported the following week at a time determined by WHO regional offices and/or headquarters. Already submitted results should be updated when more detailed results (for example, subtype determination) become available. In order to provide global updates on the current situation, reports should be submitted by Thursday 12:00 UTC each week. e RespiMart (developed from FluMart) is a platform to facilitate the exchange, harmonization, consolidation and storage of surveillance data on respiratory viruses with epidemic and pandemic potential, including influenza viruses, RSV and SARS-CoV-2. RespiMart provides a single platform for sharing aggregated and case-based data from different applications and/or data sources thereby allowing for integrated analysis and reporting – https://www.who.int/tools/RespiMart.

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to the RespiMart WHO FluID platform13 – either by the NIC or national focal point as designated by the host country. Reporting should be done weekly during the months when seasonal influenza is commonly observed, but preferably throughout the year.

5. NICs immediately report to their national authorities and to WHO any observation of unusual influenza activity in their country.

6. NICs immediately share with GISRS WHO CCs influenza A virus isolates and/or influenza virus-positive clinical specimens without well-defined results or those that cannot be subtyped using the updated reagents available through GISRS. Such findings should be reported to their national authority according to national and/or international rules and regulations, and where applicable, the International Health Regulations (2005).14

7. NICs share representative recent seasonal influenza virus isolates and/or influenza virus-positive clinical specimens in a timely manner with a GISRS WHO CC of their choice for further characterization on the understanding that the sharing of such materials among GISRS WHO CCs and ERLs, in accordance with international ethical guidelines, is essential for: (a) virus characterization and risk assessment; (b) informing WHO influenza virus vaccine composition recommendations; (c) developing reference materials; and (d) implementing the WHO EQAP for GISRS and other influenza laboratories. NICs note the relevant WHO guidance on the frequency and timing of the shipping of influenza virus isolates and/or influenza virus- positive clinical specimens to GISRS WHO CCs.15

8. NICs provide relevant virological, clinical and epidemiological information on the representative virus isolates and/or influenza-positive clinical specimens shipped to GISRS WHO CCs.

9. NICs agree, in accordance with national regulations and protocols, that if a seasonal virus shared with a GISRS WHO CC is recommended for development as a candidate vaccine virus (CVV) such a virus may be developed by a GISRS WHO CC as a CVV,f and that such a CVV may be shared with vaccine manufacturers, upon their request, for consideration as a component in the development and production of a seasonal influenza vaccine.

10. As members of GISRS, NICs have access to the benefits available and provided by GISRS as outlined in Annex 1.g

f Candidate vaccine viruses are developed by GISRS WHO CCs with the support of GISRS partner laboratories. g Benefits include contributions acquired from industry under the Pandemic Influenza Preparedness (PIP) Framework, under section 6.14.3, which are used to improve pandemic influenza preparedness and response, strengthen protection against pandemic influenza by improving and strengthening WHO GISRS, conduct disease burden studies, and strengthen laboratory and surveillance capacity, particularly in developing countries (Article 3).

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When working with influenza viruses that are classified as PIP BM TOR are described in Annex 5 of the Pandemic Influenza Preparedness (PIP) Framework (reproduced in Annex 2). NICs share IVPP according to relevant WHO guidance materials.16 When working with other influenza viruses from animal or environmental specimens that are not classified as human seasonal influenza viruses or PIP BM Occasionally, NICs may receive influenza viruses that do not fall into the categories of human seasonal influenza viruses or PIP BM – for example, viruses from animal or environmental specimens.

1. NICs must follow applicable national and/or international biosafety requirements and good microbiology laboratory practice to avoid cross- contamination with viruses of human origin. Such material should preferably be handled in facilities away from those where human specimens and viruses are investigated.

2. NICs share virus samples with GISRS WHO CCs of their choice to support GISRS risk assessment following national and international rules and regulations. It is the responsibility of the NICs to ensure that appropriate permits and other national/international documents and approvals are in place to facilitate virus sharing.

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V. References

1 National Influenza Centres. 28 August 2023. Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/national-influenza- centres). 2 WHO Collaborating Centres and their Terms of Reference. Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/who-collaboration- center-erl). 3 WHO Essential Regulatory Laboratories (ERLs) list of laboratories. Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/who- erls). 4 WHO H5 Reference Laboratories and the Terms of Reference (TOR). Geneva: World Health Organization (https://www.who.int/initiatives/global-influenza-surveillance-and-response-system/h5- reference-laboratories). 5 Global Influenza Programme [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza-programme). 6 Sixty-fourth World Health Assembly: Geneva, 16–24 May 2011: Resolutions and decisions. Annexes. Geneva: World Health Organization; 2011. Resolution WHA64.5 (https://iris.who.int/handle/10665/106547?locale-attribute=ru&locale=es&mode=full). 7 Next-generation sequencing of influenza viruses. General information for national influenza centres. Geneva: World Health Organization; 2020 (https://cdn.who.int/media/docs/default- source/influenza/global-influenza-surveillance-and-response-system/related- documents/ngs_guidance_for_nics.pdf). 8 Laboratory biosafety manual. Fourth edition and associated monographs. Geneva: World Health Organization; 2020 (https://iris.who.int/handle/10665/337956). 9 Recommendations on the transport of dangerous goods: model regulations, 23rd revised edition. New York, Geneva: United Nations; 2023 (https://unece.org/transport/dangerous-goods/un-model- regulations-rev-23). 10 Pandemic Influenza Preparedness (PIP) Framework for the sharing of influenza viruses and access to vaccines and other benefits. Second edition. Geneva: World Health Organization; 2021 (https://www.who.int/publications/i/item/9789240024854). 11 End-to-end integration of SARS-CoV-2 and influenza sentinel surveillance: revised interim guidance, 31 January 2022. Geneva: World Health Organization; 2022 (https://iris.who.int/handle/10665/351409). 12 FluNet Summary [website]. Geneva: World Health Organization (https://www.who.int/tools/flunet/flunet-summary). 13 FluID [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza- programme/surveillance-and-monitoring/fluid). 14 International Health Regulations (2005). Third edition. Geneva: World Health Organization; 2016 (https://www.who.int/publications/i/item/9789241580496). 15 Operational guidance for sharing seasonal influenza viruses with WHO Collaborating Centres (CCs) under the Global Influenza Surveillance and Response System (GISRS). Geneva: World Health Organization; 2017 (WHO/WHE/IHM/GIP/2017.6; https://apps.who.int/iris/handle/10665/259400). 16 Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework. Geneva: World Health Organization; 2017 (WHO/WHE/IHM/GIP/2017.3; https://iris.who.int/handle/10665/259402).

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Annex 1

List of material and non-material benefits of GISRSh

As a member of the Global Influenza Surveillance and Response System (GISRS) and in accordance with the National Influenza Centres Terms of Reference, National Influenza Centres (NICs) are provided with, and have access to, a range of benefits, some of which are provided on request.i Such benefits support seasonal and zoonotic influenza surveillance, capacity strengthening, and other influenza prevention and control activities in countries, and facilitate collective GISRS actions to mitigate the public health risks associated with influenza outbreaks.

Material benefits include 1. Reagents and virusesj, k

a. Annually updated laboratory reagents for the following influenza virus assays: polymerase chain reaction (PCR) singleplex and multiplex assays; haemagglutination inhibition assays (HIA); indirect fluorescent antibody (IFA) test; and sequencing reagents for Sanger or next-generation sequencing assays.

b. Primers/probes for the molecular detection of non-influenza respiratory viruses of public health importance, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV)l for countries implementing epidemiological and virological surveillance of such viruses as recommended for GISRS integrated surveillance.

c. Updated diagnostic reference control viruses.

d. Annually updated vaccine antigens for developing potency test reagents.

e. Tissue culture media for influenza virus isolation.

h This document is intended to be a “living document” and may be updated as appropriate. i For the detailed list of benefits and currently available reagents contact the WHO Global Influenza Programme (GIP) at: [email protected]. j Diagnostic reagents and reference viruses are provided through GISRS initiatives. There may be some limit restrictions depending upon the activity in which an NIC participates. For additional information on reagents contact: [email protected]. k For information on these, contact WHO GIP at: [email protected]. l RSV reagents are available to GISRS member countries enrolled in global RSV surveillance.

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f. High-growth reassortant viruses developed by reassorting laboratories, and prototype influenza candidate vaccine viruses (CVVs) developed by GISRS WHO Collaborating Centres (WHO CCs).m

g. Annual proficiency panels for participation in the WHO External Quality Assessment Programme (EQAP) for the molecular detection of seasonal and zoonotic influenza viruses, and where applicable:

• proficiency panels for participation in the WHO EQAP for the molecular detection of non-influenza respiratory viruses of public health importance such as SARS-CoV-2 and RSV;

• proficiency panels for participation in external quality assessments of virus isolation in cell culture and embryonated chicken eggs, and identification of the haemagglutinin subtype of viral isolates by haemagglutination inhibition testing and/or microneutralization assay;

• proficiency panels for participation in external quality assessments of antiviral susceptibility testing; and/or

• proficiency panels for participation in external quality assessments of influenza virus gene sequencing.

h. Materials required as described in WHO Guidance on regulations for the transport of infectious substances for shipping of influenza virus isolates and/or influenza virus-positive clinical specimens through the WHO Shipping Fund Project to facilitate the sharing of influenza viruses within GISRS.n, o, p

Non-material benefits include

1. Epidemiological and virological public health information and tools, including

a. Global, regional and national epidemiological and virological information sharingq by geographical groupings of countries, areas and territories on influenza, SARS-CoV-2, and RSV (where available) through the reporting by national sentinel and non-sentinel surveillance systems to the WHO surveillance data platform RespiMart. This will include information on the geographical areas most affected, the level of activity according to epidemiological week and severity of cases.

b. Access to epidemiological and virological surveillance technical updates and to situation reports for: (a) seasonal influenza;r (b) influenza at the animal- human interface; (c) influenza viruses with human pandemic potential (IVPP); (d) SARS-CoV-2; (e) RSV; and (f) as applicable, other emerging respiratory

m The development of high-growth CVVs is a complex process, involving collaboration between laboratories involved in developing reassortants and GISRS WHO CCs. Two technologies are currently used: classical reassortment and reverse genetics. n Shipping & logistics: https://www.who.int/initiatives/global-influenza-surveillance-and-response- system/virus-sharing/shipping-and-logistics-activities. o Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework. Geneva: World Health Organization; 2017 (https://www.who.int/publications/i/item/operational-guidance-on-sharing-influenza-viruses). p Operational guidance on sharing seasonal influenza viruses with WHO Collaborating Centres (CCs) under the Global Influenza Surveillance and Response System (GISRS). Geneva: World Health Organization; 2017 (https://www.who.int/publications/i/item/WHO-WHE-IHM-GIP-2017.6). q For respiratory virus updates see: https://www.who.int/teams/global-influenza- programme/surveillance-and-monitoring/influenza-updates. r FluNet [website]. Geneva: World Health Organization (https://www.who.int/tools/flunet).

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viruses of public health significance. Such technical updates better equip countries to prepare for and respond to future respiratory virus epidemics and pandemics.

c. Analyses and reports from GISRS WHO CCs coordinated by WHO Global Influenza Programme (GIP) and detailing the genetic, antigenic and antiviral- susceptibility characteristics of viruses circulating in the country and shared with GISRS WHO CCs.

d. Updated laboratory protocols for the surveillance, detection and characterization of seasonal and pandemic influenza viruses for:

i. molecular detection of seasonal and pandemic influenza viruses

ii. antiviral-susceptibility testing

iii. genetic characterization (sequencing)

iv. antigenic characterization

v. serological detection of influenza viruses

vi. virus isolation procedures.

e. Tools and other resources to help countries monitor their epidemiological and virological influenza situation, perform risk assessments, and promptly exchange information with GISRS, including:

i. global epidemiological surveillance standards for influenza;s ii. data analysis tools provided through the RespiMart platform – such as

FluNett and FluID;u iii. the WHO Epidemic and Pandemic Influenza Severity Assessment

(PISA) tool;v iv. the WHO Tool for Influenza Pandemic Risk Assessment (TIPRA);w v. the WHO Influenza Virus Traceability Mechanism (IVTM);x vi. the WHO document A manual for estimating disease burden associated

with seasonal influenza;y vii. protocols for investigating non-seasonal influenza and other emerging

acute respiratory diseases;z and

s See: Global epidemiological surveillance standards for influenza. Geneva: World Health Organization; 2013 (https://www.who.int/publications/i/item/9789241506601). t FluNet [website]. Geneva: World Health Organization (https://www.who.int/tools/flunet). u FluID [online platform]. Geneva: World Health Organization (https://www.who.int/teams/global- influenza-programme/surveillance-and-monitoring/fluid). v Pandemic influenza severity assessment (PISA). A WHO Guide to assess the severity of influenza in seasonal epidemics and pandemics. Geneva: World Health Organization; 2017 (https://www.who.int/publications/i/item/pandemic-influenza-severity-assessment-(-pisa)-a-who-guide- to-assess-the-severity-of-influenza-in-seasonal-epidemics-and-pandemics). w Tool for influenza pandemic risk assessment (TIPRA). Version 2 Release. Geneva: World Health Organization; 2020 (https://www.who.int/publications/i/item/tool-for-influenza-pandemic-risk- assessment-(tipra)-2nd-edition). x Influenza Virus Traceability Mechanism (IVTM 2.0) [website]. Geneva: World Health Organization (https://extranet.who.int/ivtm2/). y A manual for estimating disease burden associated with seasonal influenza. Geneva: World Health Organization; 2015 (https://www.who.int/publications/i/item/9789241549301). z Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases. Geneva: World Health Organization; 2018 (https://www.who.int/publications/i/item/WHO-WHE-IHM- GIP-2018.2).

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viii. Influenza Investigations & Studies (Unity Studies) standardized template protocols.aa

f. Assessments of the public health risks posed by evolving and emerging influenza virus strains through the use of standardized and consistent approaches to outbreak investigations, in partnership with GISRS collaborators.

g. Recommendations on risk management measures, including those related to influenza vaccines and antiviral drugs.

h. Access to established GISRS online and, when possible, in-person platforms to share experiences and information, and to interact with other GISRS laboratories.bb

2. Training, mentoring, and capacity strengthening (both epidemiological and

laboratory) through institutional capacity-building based on participation, collaboration and cooperation with WHO headquarters, regional/country offices, GISRS WHO CCs and other GISRS-associated entities and partners. This includes networking, participation in GISRS meetings, twinning projects and/or joint tasks, and the provision of technical support for troubleshooting, implementing diagnostic procedures and surveillance protocols.cc

3. Access to technical support for genomic sequencing and/or bioinformatics from

GISRS WHO CCs and GISRS-associated entities and partners for countries without established sequencing capacities, or for the validation of sequencing results obtained by NICs.

4. Access to technical support for inputting data and the analysis of genetic

sequence data through appropriate publicly accessible databases such as the EpiFlu™ database of the GISAID Global Data Science Initiativedd and databases in the International Nucleotide Sequence Database Collaboration (INSDC).

5. Access to outputs, including estimations of health care burden, pooled vaccine

effectiveness data, PISA summaries for countries and TIPRA reports. 6. Direct and free-of-charge real-time access to advanced expertise and support in

GISRS WHO CCs, WHO Essential Regulatory Laboratories (ERLs) and H5 Reference Laboratories for seasonal and pandemic viruses.

aa Influenza investigations & studies (Unity Studies) [website]. Geneva: World Health Organization (https://www.who.int/teams/global-influenza-programme/surveillance-and-monitoring/influenza- investigations-studies-unity). bb These include the EZcollab platform (https://ezcollab.who.int/), the GISRS Information Centre and the GISRS Discussion Forum. cc Some contributions for the support of GISRS are made through the PIP Framework. Countries benefit additionally from distinct contributions from GISRS industry partners for specific activities/projects including the Global influenza hospital surveillance network (GIHSN) and the Partnership for Influenza Vaccine Introduction (PIVI). dd GISRS industry partners provide some contributions towards the functioning and updating of the global and publicly accessible genetic sequence database platforms for seasonal and zoonotic influenza, SARS-CoV-2, and RSV.

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7. Collaborative research initiatives with other GISRS membersee with acknowledgement made of the research contributions of national scientific presentations and publications.ff

8. Inclusion of the name of the institution, its Director and contact details in the list of

NICs formally recognized by WHO and available at: https://www.who.int/initiatives/global-influenza-surveillance-and-response- system/national-influenza-centres

For questions on GISRS benefits please contact: [email protected]

ee Support for research activities is received from GISRS partners including vaccine manufacturers. Areas of research include clinical trials, evaluation of new manufacturing platforms, use of adjuvants, improved vaccine formulations and knowledge-based studies to support improved vaccine coverage in all age cohorts. For additional information contact GISRS at [email protected]. ff WHO actively seeks the participation of scientists from GISRS laboratories and GISRS member countries in scientific research on clinical specimens and/or influenza and other respiratory viruses and invites active engagement in the preparation of manuscripts for presentation and publication. Contributors will be appropriately acknowledged in line with guidance such as that published by the International Committee of Medical Journal Editors.

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Annex 2

Extract (pp 49–52) from Annex 5 of the Pandemic Influenza Preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits: National Influenza Centres. Terms of Reference related to work with Pandemic Influenza Preparedness biological materials.gg

gg https://iris.who.int/bitstream/handle/10665/341850/9789240024854-eng.pdf?sequence=1

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