Report of the meeting with industry to discuss common activities for deployment of pandemic influenza response products: Geneva, Switzerland, 3-4 October 2019 and Rio de Janeiro, Brazil, 24 October 2019

REPORT OF THE MEETING WITH INDUSTRY TO DISCUSS COMMON ACTIVITIES FOR DEPLOYMENT OF PANDEMIC INFLUENZA RESPONSE PRODUCTS Geneva, Switzerland 3−4 October 2019 and Rio de Janeiro, Brazil 24 October 2019 Report of the meeting with industry to discuss common activities for deployment of pandemic influenza response products: Geneva, Switzerland, 3-4 October 2019 and Rio de Janeiro, Brazil, 24 October 2019 ISBN 978-92-4-000831-1 (electronic version) ISBN 978-92-4-000830-4 (print version) © World Health Organization 2020 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non- commercial purposes, provided the work is appropriately cited, as indicated below. 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This publication contains the report of the meeting with industry to discuss common activities for deployment of pandemic influenza response products and does not necessarily represent the decisions or policies of WHO. iii Contents Executive summary ................................................................................................................... iv Highlighting the importance of global partnerships for effective pandemic influenza vaccine deployment ................................................................................................................................. 1 Setting the scene: 10 years after the H1N1 pandemic, where are we now? .............................. 1 Overview of WHO’s operational framework for deployment of pandemic influenza vaccines2 Overview of regulatory processes and responsibilities .............................................................. 4 Overview of the WHO prequalification process and requirements, including labelling, languages and packaging ........................................................................................................... 5 Overview of the PIP Framework and SMTA2 mechanism ....................................................... 6 Challenges associated with pandemic vaccine production: response during the start of a pandemic .................................................................................................................................... 7 Logistical considerations during a pandemic ............................................................................. 8 Further actions and conclusions ................................................................................................. 9 Annex 1. Further actions: starting our collaborative work ...................................................... 10 Annex 2. List of bottlenecks and activities with regard to CVV and post-CVV development from the 3rd informal consultation to address challenges and bottleneck in vaccine response at the start of an influenza pandemic ....................................................................................... 17 Annex 3. Agenda and list of participants ................................................................................. 18 Annex 4. Selection of key proposed action points from the 2011 Main operational lessons learnt from the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative ............ 23 iv Executive summary Preparedness and readiness for responding to a global pandemic influenza requires the engagement of many stakeholders. To ensure the effective and efficient allocation and deployment of pandemic influenza products to the populations most in need, manufacturers of such products play a critical role in the entire supply chain. Under the auspices of the Pandemic Influenza Preparedness Framework, the World Health Organization (WHO) organized two consultations with relevant industry representatives. The meetings provided an opportunity to exchange information on existing preparedness activities, to review challenges for pandemic vaccine production and deployment pathways and to identify areas where WHO and industry partners need to work together, including in the planning of future simulation exercises involving industry. During the pandemic the main processes associated with the access, allocation and deployment of pandemic influenza vaccines are divided into three main categories (see also figure above): Category 1) Request, allocation and acceptance of pandemic influenza vaccines from WHO; Request, allocation and acceptance of pandemic influenza vaccines from WHO WHO DG invites Member States (MS) to solicit WHO secured pandemic influenza vaccines MS express interest to WHO DG to receive WHO secured vaccines and provides necessary documentation WHO reviews application (against eligibility criteria including technical NDVP specifications) WHO communicates decision to allocate pandemic influenza vaccines and plans allocation accordingly MS obtain the necessary approvals for in country receipt and use of pandemic influenza vaccines Manufacturer vaccine release, transport and reaching of in-country clearance at port of entry Vaccines are being shipped to the MS as per applicable contractual agreements Distribution of in-country vaccine from port of entry to point of administration Consignee of shipment receives the pandemic influenza vaccines and associated products, that have been bundled, performs all necessary custom clearance procedures and sends the Vaccine Arrival Report to WHO MS performs activities associated with distribution of vaccines, vaccination campaign, monitoring and evaluation as described in the NDVP MS share with WHO the lessons learned, and key data related to the deployment response following end of pandemic v Category 2) Manufacturer vaccine release, transport and reaching of in-country clearance at port of entry; and Category 3) Distribution of in-country vaccine from port of entry to point of administration. During the meetings, participants reviewed the three main categories, discusses and agreed on a list of actions to address gaps and improving these processes. The key areas of activity resulting from these initial discussions are summarized below: • Share, review and support the WHO Operational Framework for Access, Allocation and Deployment of Pandemic Influenza Vaccine. • Engage in table-top simulation exercises relating to specific technical domains. • Map countries’ regulatory status and existing pathways that could be applicable to pandemic vaccine use. • Sensitize various manufacturers regarding the prequalification process – including clarifications on prequalification fast-track processes and the languages that should be present on labels and package inserts. • Collect data relevant to logistics to support WHO with planning activities in this area. • Clarify how SMTA2 Standard Material Transfer Agreements would come into effect in the event of a pandemic being declared. 1 Highlighting the importance of global partnerships for effective pandemic influenza vaccine deployment The workshop highlighted the complexity of pandemic influenza deployment operations and the importance of collective work involving industry partners, including vaccine and antiviral manufacturers as well as freight forwarders, under the auspices of the Pandemic Influenza Preparedness (PIP) Framework adopted by WHO Member States in 2011. Challenges observed in the 2009 pandemic influenza vaccine deployment response were stressed, including the fact that vaccine access and availability was considered “too little and too late” for low-resource countries. A key achievement of the PIP Framework has been the signing of 13 Standard Material Transfer Agreements 2 (SMTA2), which are legally binding contracts between WHO and influenza vaccine manufacturers, to secure approximately 10% of their future real-time pandemic vaccine production for the next pandemic. This, together with mechanisms to assist the allocation of vaccines, will ensure wider access and more equitable distribution of pandemic vaccines to countries in need. The need for closer collaboration between pandemic influenza responders was emphasized as one of the critical elements for a robust and efficient global pandemic response. The meeting on 3−4 October 2019 in Geneva, Switzerland, brought together several stakeholders: 1) industry – represented by seven companies which are part of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA); 2) representatives of the IFPMA Secretariat and of BIO; 3) representatives of two freight forwarding companies; and 4) WHO staff from different units across the Organization, notably Influenza Preparedness and Response, Global Influenza Programme, Pandemic Influenza Preparedness Framework, Support for Response, Regulatory Systems Strengthening, Prequalification, and Operations and Support for Logistics.1 A smaller-scale meeting took place with participants from four vaccine manufacturers that are members of the Developing Countries Vaccine Manufacturers Network (DCVMN) on 24 October 2019 in Rio de Janeiro, Brazil. WHO provided an overview of the main conclusions of the meeting held in Geneva. The participants offered positive feedback on the areas of work identified and expressed willingness to be engaged in future meetings on the subject. Setting the scene: 10 years after the H1N1 pandemic, where are we now? This session was divided into two parts, with presentations from both WHO and manufacturers. Both presentations highlighted the achievements in strengthening pandemic preparedness capacities since the last (2009) H1N1 influenza pandemic, and stressed ways to foster global collaboration towards a more effective deployment process. WHO underlined that pandemic influenza is one of the 10 main threats to global health, and introduced participants to the Global Influenza Strategy 2019−2030. The strategy has two main outcomes: 1) better global tools through coordination of research and innovation, and 2) stronger country capacities. The presentation also introduced the guidance and tools available to support countries in strengthening their pandemic preparedness and highlighted achievements from the deployment and regulatory outputs of the PIP Framework. Areas of 1 See Annex 3 for the list of participants. 2 additional work to improve the pandemic response were identified, including: 1) early detection of the pandemic; 2) timely sharing of the pandemic virus strain for vaccine production; 3) candidate vaccine virus (CVV) development; and 4) regulatory readiness. Industry stressed the need for stronger collaboration with WHO and the importance of well- established systems for seasonal vaccination to increase the capacity and efficiency for pandemic influenza vaccine production. The imbalance between supply and demand for seasonal and pandemic influenza production capacity was highlighted. One method of increasing production capacity for pandemic influenza vaccine is to foster demand for sustainable seasonal influenza programmes. Manufacturers stated that there is a critical need for clearly defined triggers and communication to support manufacturers’ decisions regarding the switch from seasonal to pandemic vaccine production; this is because the switch to pandemic vaccine production will have an impact on seasonal vaccine commitments to countries. Industry signaled a potential concern that the Nagoya Protocol may result in delayed access to seasonal viruses. WHO and the industry discussed the importance of conducting simulation exercises (SimEX) to test the different aspects of a pandemic response. Additionally, it was highlighted that countries should be prepared to detect and assess Adverse Events Following Immunization (AEFI). The point was raised that although the focus of this meeting was on the deployment of vaccine in a pandemic, strong mechanisms and close collaboration regarding antivirals and diagnostics are also needed. Overview of WHO’s operational framework for deployment of pandemic influenza vaccines Participants were introduced to a draft operational framework for access, allocation and deployment of pandemic vaccines, which was based on the lessons learned from the 2009 WHO deployment initiative.2 The framework, which will be shared with industry partners for comments and feedback, aims to establish a common understanding of roles, responsibilities and standard operating procedures for all the stakeholders involved in the pandemic vaccine allocation and deployment cascade. 2 Main operational lessons learnt from the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative. Geneva: World Health Organization; 2011 (https://www.who.int/influenza_vaccines_plan/resources/h1n1_vaccine_deployment_initiaitve_moll.pdf, accessed 20 November 2019). 3 Figure 1. Global allocation and deployment cascade for WHO-secured pandemic influenza vaccines The presentation highlighted some of the recommended actions3 that should be taken to advance the readiness of pandemic influenza vaccine, including establishing a cross-function, cross-region communication channel involving all stakeholders to facilitate information- sharing and to support the timely and effective efforts of the different actors during deployment of pandemic vaccine. Industry representatives suggested: 1) to highlight that the in-country vaccine allocation decisions, which may be based on recommendations from the Strategic Advisory Group of Experts (SAGE) on Immunization, should be planned before the operational allocation by WHO and 2) to include the regulatory release of vaccines, which created a bottleneck in 3 A list of recommended actions can be found in Main operational from the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative. Geneva: World Health Organization; 2011 (https://www.who.int/influenza_vaccines_plan/resources/h1n1_vaccine_deployment_initiaitve_moll.pdf, accessed 20 November 2019). Request, allocation and acceptance of pandemic influenza vaccines from WHO WHO DG invites Member States (MS) to solicit WHO secured pandemic influenza vaccines MS express interest to WHO DG to receive WHO secured vaccines and provides necessary documentation WHO reviews application (against eligibility criteria including technical NDVP specifications) WHO communicates decision to allocate pandemic influenza vaccines and plans allocation accordingly MS obtain the necessary approvals for in country receipt and use of pandemic influenza vaccines Manufacturer vaccine release, transport and reaching of in-country clearance at port of entry Vaccines are being shipped to the MS as per applicable contractual agreements Distribution of in-country vaccine from port of entry to point of administration Consignee of shipment receives the pandemic influenza vaccines and associated products, that have been bundled, performs all necessary custom clearance procedures and sends the Vaccine Arrival Report to WHO MS performs activities associated with distribution of vaccines, vaccination campaign, monitoring and evaluation as described in the NDVP MS share with WHO the lessons learned, and key data related to the deployment response following end of pandemic 4 2009, between the manufacturer production and packaging in Figure 1. WHO explained that, before its allocation decision, vaccine-requesting countries will be required to submit documents4 to demonstrate their readiness and capacity to deploy vaccines and implement a vaccination campaign quickly. Among those documents, the National Deployment and Vaccination Plan (NDVP),5 will provide a detailed approach to in-country vaccine allocation. WHO is currently working with countries to develop/update 1) NDVPs; 2) influenza pandemic preparedness plans; 3) national action plans for health security (NAPHSs); 4) to strengthen their overall core capacities under the International Health Regulations (IHR); and identify links between these documents as well as (5) enhance regulatory preparedness. Overview of regulatory processes and responsibilities The presentation on regulatory processes and responsibilities offered participants an overview of WHO initiatives to strengthen national regulatory capacities for 1) the regulatory oversight of pandemic influenza products through pre- and post-market phases, and 2) for the adoption of regulatory pathways that accelerate regulatory approval of pandemic influenza products. Actions taken are based on the following lessons learned from the 2009 pandemic: 1) challenges posed by rigid regulation and legal frameworks; 2) different regulatory requirements in different countries; 3) the lengthy regulatory process to register/approve a product; and 4) unclear roles and responsibilities. Participants were introduced to the WHO Global Benchmarking Tool (GBT)6 which is used to evaluate the maturity level of national regulatory systems on a scale of 1 (existence of some elements of a regulatory system) to 4 (operating at an advanced level of performance and continuous improvement). As of October 2019, 144 countries were categorized as maturity levels 1 and 2, indicating that they did not have an adequate regulatory system able to assess the quality, safety and efficacy of medical products. As of October 2019, 50 countries were classified as having reached maturity levels 3 or 4. Through the GBT, WHO is identifying strengths and areas for improvement, facilitating the formulation of an institutional development plan (IDP) to build on strengths and to address identified gaps, prioritizing IDP interventions, and monitoring progress and achievements. As many countries will not have the capacity to move to maturity level 3 in coming years, WHO is promoting “smart regulation” (such as reliance and recognition) as a preferable regulatory pathway to approve pandemic vaccines in these countries.7 Reliance is the process of reviewing the marketing authorization report/decision issued by a mature national regulatory 4 Countries eligible for, and interested in accessing, WHO-donated vaccines are required to send a letter of intent, a letter of agreement (Country Recipient Agreement, or CRA) and an NDVP. 5 Guidance on development and implementation of a national deployment and vaccination plan for pandemic influenza vaccines. Geneva: World Health Organization; 2012 (https://apps.who.int/iris/bitstream/handle/10665/75246/9789241503990_eng.pdf?sequence=1, accessed 20 November 2019). 6 WHO Global Benchmarking Tool (GBT) for evaluation of national regulatory systems. Geneva: World Health Organization (https://www.who.int/medicines/regulation/benchmarking_tool/en/, accessed 20 November 2019). 7 Regulatory pathways include full review, fast-track, strain-change procedure, reliance and recognition. See: WHO Expert Committee on Biological Standardization, Sixty-seventh report. Geneva: World Health Organization; 2017. WHO Technical Report Series, No. 1004. Annex 7: Guidelines on regulatory preparedness for provision of marketing authorization of human pandemic influenza vaccines in non-vaccine-producing countries, p. 469. Available at: http://apps.who.int/medicinedocs/documents/s23326en/s23326en.pdf, accessed 20 November 2019). 5 authority (NRA) or through WHO prequalification, while recognition is the direct acceptance of the marketing authorization decision of another NRA or the WHO prequalification process without further evaluation. In the alert and pandemic phases, these regulatory options would be the least time-consuming for certain NRAs with lower maturity levels but would still ensure that a high-quality assessment of the pandemic product has been performed before licensing. The session also stressed industry’s role in speeding up processes and documents for regulatory approval. In this regard, two actions were proposed, namely: 1) when aware of the regulatory requirements of specific countries, manufacturers could expedite the delivery of documents, and 2) WHO and manufacturers could agree on a minimum set of documents that should be provided to NRAs. During the discussion session, participants highlighted the importance of establishing robust surveillance systems that can look at the quality and programmatic aspects of the use of pandemic vaccine. Moreover, they emphasized the need for clarification on the status of pandemic influenza strains under the Nagoya Protocol legislation. Overview of the WHO prequalification process and requirements, including labelling, languages and packaging Participants learned about WHO’s prequalification principles, routes and processes. The importance of collaborative registration procedures (CRP) and joint assessments were also stressed. The objectives of CRP include: 1) to facilitate the assessment and accelerate national registration of prequalified products, and 2) to accelerate the registration of health products that have already received approval from a “stringent regulatory authority”. The procedure was used to speed up the prequalification and approval of MenAfriVac vaccine in several African countries in 2010. With regard to influenza vaccines, the WHO prequalification team highlighted the prequalification considerations linked to the various types of vaccines and the corresponding complexities in terms of quality, stability, clinical and nonclinical investigations, programmatic suitability, labelling and packaging, batch release, prequalification application and procedure, and biosafety considerations. The prequalification team offered the following definitions that may be relevant for the different types of vaccines: 1) pandemic vaccine used in the pandemic outbreak; 2) prototype, which is a pandemic influenza vaccine developed and licensed before a pandemic, using a model virus strain; 3) pre-pandemic, which is a licensed vaccine that is produced and stockpiled in anticipation of a pandemic, with a strain that could be the agent of a future pandemic; and 4) seasonal influenza vaccine (which might be subjected to a virus strain change in the event of a pandemic in order to match the pandemic virus). There was a robust discussion about international packaging requirements for prequalification, including language, labelling QR codes and any anticipated labelling requirements for vaccines released to WHO. Manufacturers’ representatives highlighted the challenge of issuing different labelling documents that might be needed to comply with local NRA requirements. Further collaborative work on harmonized labelling information is needed. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) can serve as a resource for achieving greater harmonization for pandemic products. 6 Discussion points in this session included: • Genetically modified organisms (GMO) and special requirements as part of the prequalification process: it was clarified that the WHO prequalification process is a scientific assessment, and that vaccines that are submitted to WHO prequalification approval need first to be licensed by the NRA in the country where the manufacturer is located. Consequently, any such considerations will be dependent on local NRA requirements. • Time-limited risk-based assessments for pandemic vaccine: WHO’s prequalification team is developing clear procedures for time-limited risk-based assessment. This approach is suitable for special situations such as licensed vaccines for emergency use (i.e. fractional dose), vaccines that would follow the emergency use and assessment listing (EUAL) and products such as snake antivenom. • The impact of new technology or new production processes on regulatory issues: further discussion is needed between WHO, manufacturers and regulatory authorities to ensure greater clarity on the impact that engaging in such reviews would have on the regulators. • Regional regulatory champions: WHO started a process to map national regulatory capacities for pandemic influenza vaccine, with the aim of identifying regulators who could support NRAs that require assistance. In the Americas Region, there are reference authorities that work on the harmonization of regulatory requirements and try to reach agreement on the acceptance of vaccines and the waiver of regulatory requirements. In the European Region, there is a well-functioning regulatory network in which, if the vaccine is licensed in one country, all other countries will rely on this decision. In the South-East Asian Region, WHO is supporting the establishment of a mechanism for joint registration. The African Region has previously conducted joint registration of products. Despite all these mechanisms, it is important to note that the final decision on which pathway to use for vaccine licensing is determined by the country concerned. • Prequalification of seasonal vaccines and strain change: vaccines that have been prequalified are expected to be updated regularly with a strain change. • There is a need to clarify the payment requirements for prequalification assessment of pandemic influenza vaccine. Overview of the PIP Framework and SMTA2 mechanism This session provided an overview of the PIP Framework and its two benefit-sharing mechanisms – 1) the Partnership Contribution, which is an annual financial contribution to WHO from influenza vaccine, diagnostic and pharmaceutical manufacturers that use the Global Influenza Surveillance and Response Network (GISRS),8 and 2) the Standard Material Transfer Agreement 2 (SMTA2), which is a legally binding advance supply agreement signed between WHO and an influenza product manufacturer that receives PIP biological materials 8 GISRS is a system that has fostered global confidence and trust for over half a century through effective collaboration and sharing of viruses, data and benefits based on Member States’ commitment to a global public health model. Additional information is available at: https://www.who.int/influenza/gisrs_laboratory/en/, accessed 20 November 2019). 7 from the GISRS. As of October 2019, 13 SMTA2s had been signed between WHO and influenza vaccine manufacturers. After signature, SMTA2s are to be reviewed every 4 years to ensure they are up-to-date and operational when the next pandemic occurs. In general, companies commit under the agreement to supply WHO with approximately 10% of their real-time pandemic influenza vaccine production during the next pandemic. This session provided an opportunity for interactive discussions on how to operationalize SMTA2 commitments and on clarifying some of the technical supply terms and requirements. Participants were asked to reflect on and discuss relevant deployment terms such as regulatory, prequalification, delivery, packaging and labelling. As a result, a list of SMTA2 supply terms that need further clarification, as well as activities that need further collaboration between WHO and industry partners and within different WHO units, has been developed and will be shared with participants. Challenges associated with pandemic vaccine production: response during the start of a pandemic This session provided an overview of the pandemic vaccine response components in national plans for pandemic preparedness and risk assessment, the global triggers to initiate pandemic vaccine production, and the challenges associated with vaccine response during the start of a pandemic. • According to an assessment of 57 national plans for pandemic preparedness and risk management, most countries consider the pandemic declaration by WHO’s Director- General as the trigger for a fully fledge pandemic response comprising pharmaceutical and non-pharmaceutical interventions. The distinction between the “public health emergency of international concern” (PHEIC) and the pandemic declaration was highlighted. Whereas a PHEIC declaration has clearly established criteria and procedures, the pandemic declaration process lacks clear criteria. Participants were reminded that the current WHO pandemic phase continuum – interpandemic, alert, pandemic, transition – is based on risk assessment and is distinct from the PHEIC declaration, and that the current process of WHO declaration of a pandemic is based on the experience and lessons learned from the influenza pandemic of 2009. Considerations for critical WHO action on initiating an influenza vaccine response, including the selection of the pandemic strain and the move from seasonal to pandemic vaccine production during the start of a pandemic, would include: • the epidemiological characteristics of the pandemic; • characteristics and risk assessment of the pandemic influenza virus through the GISRS; • declaration of a PHEIC in line with the IHR (2005); • declaration of an influenza pandemic by WHO’s Director-General in consultation with subject expert groups (i.e. SAGE and GISRS); • a suitable pandemic CVV and subsequently reagents available through GISRS. Meeting participants reviewed the outcomes of informal WHO consultations to address challenges and bottlenecks in vaccine response at the start of an influenza pandemic. 8 Information and analysis on risks, opportunities and challenges that vaccine manufacturers might face in different pandemic scenarios is ongoing. WHO is considering various approaches to engage experts from private entities on technical bottlenecks surrounding the potential switch from seasonal to pandemic vaccine production, including CVV development and post-CVV development.9 Critical clarification points that emerged in group discussion included: • whether intellectual property rights of live-attenuated vaccines apply to pandemic vaccines; • a pandemic alert signal that pre-hints a pandemic declaration by the Director-General of WHO so that production sites can prepare for moving from seasonal to pandemic vaccine production; • WHO criteria for a pandemic declaration; • proper communication channels to inform all partners of evolving activities through each pandemic phase; • biocontainment requirements. Logistical considerations during a pandemic The presentation by the Operations, Support and Logistics team gave an overview of WHO’s regional structure and the supply chain structure. The presentation explained how WHO would operate in the event of an influenza pandemic. Further clarity was provided on the relationship between WHO and UNICEF during a pandemic and the fact that WHO can utilize the benefits of the UNICEF freight forwarder agreements. There was also an explanation of why WHO would like to be able to choose between “free carrier” FCA and “carriage and insurance paid” (CIP) Incoterms rather than the “ex-works” (EXW) Incoterms terms agreed in some of the SMTA2s. For some countries where it is possible to ship directly, CIP may be the appropriate Incoterm. However, for many of the countries that will be supplied with donated product via WHO, suitable direct flights with cold chain capabilities may be scarce, there may be a lack of cold chain infrastructure in the country and problems of airport congestion or closure linked to a pandemic emergency may occur. Consequently, WHO would anticipate moving donated product via a staging location (either an international location which can serve the majority of countries, or a regional location if there is a cluster of countries that can easily be served). The staging area will allow WHO to bring together the donated product with syringes, safety boxes and any other items and then distribute them to the affected countries once they are assured that cold chain capacity is available for the shipment. WHO will share the suggested Incoterm and potential alternatives by writing to the manufacturers. 9 A list of bottlenecks and activities related to CVV and post-CVV development can be found in Annex 2 of this report. 9 The presentation highlighted the importance of a continuously updated database containing the main logistics data (e.g. manufacturers’ hubs, product characteristics in terms of weight, volume, size) for an effective and efficient match of supply and demand during a pandemic. Further actions and conclusions Following the presentations and discussions during the meeting, participants were invited to identify critical activities that should be carried out by the end of 2020.10 These were also presented at the meeting in Rio de Janeiro on 24 October to members of the DCVMN. There was concurrence on the areas of work identified. Participants in both meetings expressed willingness to be engaged in future meetings on the subject. In conclusion, participants praised the level of interaction and articulated that the meeting and further actions will foster collaboration between WHO and industry towards better pandemic preparedness. 10 The list of activities can be found in Annex 1 of this report. 10 Annex 1. Further actions: starting our collaborative work During the WHO meeting with industry partners to discuss common activities for deployment of pandemic influenza response products held on 3-4 Oct 2019, action items have been developed where WHO and industry partners have to collaborate to address the major operational lessons learned of the 2009 H1N1 influenza pandemic and the provisions of the PIP framework. The action items are listed in the table below and are organized around the critical path of global allocation and deployment operations for WHO-secured pandemic influenza products. In short, these milestones are: Countries make requests to WHO to access pandemic influenza products WHO reviews requests and decides allocation Countries accept allocation decisions and conditions WHO places order to manufacturers to release product Packing and shipping of products Pandemic influenza products and associated supplies arrive in country 11 Milestone in the critical path of deployment operations Activity detail What would success look like/ activities needed to achieve this. Time frame Who will contribute Before countries make requests to WHO to access pandemic influenza vaccines Obtain clarification on the need for intellectual property (IP) for pandemic use products: would the IP rights be waived for pandemic use by manufacturers and would the waiver cover only the pandemic period so that, once it transitions into seasonal influenza, the legal status will change. What would be the legal and regulatory implications for the use of reverse genetic material? Obtaining the response within the proposed time frame. Q1 2020 Industry 12 Before countries make requests to WHO to access pandemic influenza vaccines A joint simulation exercise should be organized around understanding one or more of the following: • potential triggers for the production switch; • different scenarios or ways of activating certain response steps for the early pandemic stages; • exercising the pandemic antiviral components; • understanding communication pathways. The results of the survey being conducted by the WHO Global Influenza Programme on risks associated with the switch from vaccine manufacturers could serve as the basis for the way forward. The simulation table-top exercise should consider real-time activities that may happen in different scenarios based on specific stakeholders’ responses, with a particular emphasis on the alert activities. Potentially consider using pandemic spread patterns from the London School of Hygiene and Tropical Medicine (LSHTM) Cambridge experiment through the Contagion App (the Haslemere spread dataset). Potential Q4 2020 WHO and industry 13 Before countries make requests to WHO to access pandemic influenza vaccines & WHO reviews requests and decides allocation Disseminate the considerations which will be entered in the Operational Framework for Access, Allocation and Deployment of Pandemic Influenza Vaccine and gather feedback on this. Following finalization of the operational framework, engage is a simulation exercise to test certain elements. Q3 2020 with prior potential engagements to gather feedback throughout Q1 and Q2. WHO Countries accept allocation decisions and conditions Country Recipient Agreement (CRA) sensitization and checklist on the requirements to ensure readiness to engage with this legal instrument to be presented to countries. The associated documentation is developed and piloted with selected Member States. TBD WHO Countries make requests to WHO to access pandemic influenza vaccines Mapping of the countries’ regulatory status and existing pathways which could be applicable to pandemic vaccine use/status of granting use based solely on prequalification certificate. Currently partially available. This mapping exercise could facilitate a greater understanding of regulatory harmonization trends/ harmonized documentation required for licensing which will inform future discussions. Q3 2020 WHO 14 WHO places order with manufactures Look at options to clearly describe the SMTA2 requirement for manufacturers to supply pandemic vaccine to WHO in “real time”. Identify a common understanding of the term “real time” and how it can be described in a rolling supply context. As part of this activity, identify how the Forecasting and Ordering table in the SMTA2s can be improved/modified. Q1 2020 WHO WHO places order with manufactures Sensitize/facilitate various manufacturers regarding the prequalification process. There is already a prequalification programme on sensitization and industry could be notified about when these events occur. This would include clarifications on the prequalification fast-track option. Consider drafting a document on how the prequalification process would work in the pandemic phase. Revisit the 2009 document on this and update it if needed. The updated document may also provide clarifications on whether a product that has been licensed as a single- dose pre-filled syringe presentation might be considered for prequalification as it is or following a change towards a multi-dose vial presentation. Ongoing WHO 15 Packing and shipping of products Seek input on the clarity/specificity of certain supply terms in the SMTA2 and share revised delivery terms. WHO will draft a document outlining those supply terms in the SMTA2 that require further clarification. The document will also include a revised incoterm clause and rationale for the change to the delivery terms. The document will be shared with industry associations for feedback and resulting amendments to already concluded SMTA2s will be accomplished through the SMTA2 4-year review process. Q1 2020 WHO Packing and shipping of products Designate a focal point from each manufacturer logistics team to communicate with the WHO Deployment and Operational Support and Logistics (OSL) team with a view to streamlining communications on these topics. Engage in a data collection exercise relevant to logistics to support WHO with planning activities. There is a complete database with the required information from the targeted manufacturers which will allow OSL to articulate a pandemic logistics strategy. Return of WHO data collection sheet within 4 weeks of receipt. Industry 16 Packing and shipping of products Engage in a table-top simulation exercise which may imply modulating specific technical domains and having a staged approach, depending on availability of manufacturers and other partners. Have a set agenda and enough time to consider the implications of securing dedicated time from the operational staff. Ensure this is a jointly-designed exercise. The first step would be to develop a concept note on this and share it with partners. Table-top exercise to take place in Q2 2020. WHO Packing and shipping of products It is still to be clarified which languages should be present on the labels and the package insert. Is there a specific WHO language pack (e.g. 6 WHO official languages) or is it acceptable as long it is English (US, UK, other type)? The implications of these clarifications should be further considered in relation to contractual obligations and the need to have a real- time 10% supply. Q2 2020 (tentative) WHO Packing and shipping of products Submitting the issue of a harmonized labelling information for pandemic influenza vaccines for consideration by ICH and, if accepted, cooperating to achieve this goal. Request deemed admissible and placed on the ICH agenda. Issuing labelling information harmonized worldwide. Q2 2020 WHO 17 Annex 2. List of bottlenecks and activities with regard to CVV and post-CVV development from the 3rd informal consultation to address challenges and bottleneck in vaccine response at the start of an influenza pandemic CVV development Post-CVV development 18 Annex 3. Agenda and list of participants Agenda Meeting with industry partners to discuss common activities for deployment of pandemic influenza response products Day One Session name Presenters 09:00 - 09:30 Registration 09:30 - 09:45 Welcome Sylvie Briand, IHM 9:45 - 10:30 Setting the scene - 10 years after the H1N1 pandemic: Where are we now? Ann Moen, IHM/IPR Industry 10:30 - 11:00 Coffee break 11:00 - 11:30 Overview of WHO Operational Framework for Deployment of Pandemic Influenza Vaccines Tim Nguyen, WHO/SFR 11:30 - 12:30 Overview of regulatory processes and responsibilities Alireza Khadem, RHT/RSS 12:30 - 13:30 Lunch 13:30 - 15:00 Overview of WHO prequalification process and requirements including labelling, languages and packaging Discussion Carmen Rodriguez Hernandez Alain Georges L. Fauconnier EMP/PQT 15:00 - 15:30 Coffee break 15:30 - 16:00 Overview of PIP Framework and SMTA 2 mechanism Anne Huvos, IHM/PIP 16:00 - 17:00 Operationalizing SMTA2 commitments Anne Huvos, IHM/PIP 17:00 End of Day 1 Chair of Day 1 19 Day two Session name Presenters 08:45 - 09:15 Recap of Day 1 Chair of Day 2 09:15 - 10:45 Challenges associated with pandemic vaccine production Wenqing Zhang, IHM/GIP 10:45 - 11:15 Coffee break 11:15 - 12:15 Logistics during a pandemic Antoine Delaitre, EMO/OSL 12:15 - 13:15 Lunch 13:15 - 15:00 Starting our collaborative work – where to begin Tim Nguyen, IHM/SFR 15:00 - 15:30 Coffee break 15:30 - 16:30 Next steps Tim Nguyen, IHM/SFR 16:30 - 17:00 Final comments and close of meeting Anne Huvos, Tim Nguyen and Wenqing Zhang IHM Industry partners Phyllis Arthur Vice President Infectious Diseases and Diagnostics Policy BIO Paula Barbosa Vaccines Policy Manager IFPMA Sean Batten Supply Chain Product Leader Influenza Sanofi PasteurAstraZeneca, Matthew Downham Associate Director Biopharmaceuticals Development (Influenza Vaccines) AstraZeneca Aeron Hurt Principal Global Medical Director Influenza Roche Mickael Julie Deputy Director Pandemic Influenza Project Sanofi Pasteur 20 Igor Krasilnikov Deputy Director International Relations St Petersburg Institute of Vaccine Melchior Kuo Intern IFPMA Laurence Lambremont Technical Life Cycle Management Influenza GSK Kathleen Laya Director Pandemic Response Lead GSK Sam Lee Senior Director Pandemic and New Influenza Product Strategy Sanofi Pasteur Ole Lyngshede Lund Scan Global Logistic Steve Moloney Director Global Planning Seqirus Sonja Rollenhagen International Pandemic Influenza Strategy Leader Roche Christensen Søren Kuehne + Nagel / CPH MS-ER Beverly Taylor Head Influenza Scientific Affairs and Pandemic Readiness Seqirus Ted Tsai Head Immunization Science and Policy Takeda WHO Headquarters Sylvie Briand Director Infectious Hazard Management WHO Headquarters Ann Moen Chief Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters Claudia Alfonso Scientist Regulatory Systems Strengthening Essential Medicines and Health Products WHO Headquarters Jennifer Barragan Fromme Technical Officer Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters 21 André Buell Office Assistant High Threat Pathogens Infectious Hazard Management WHO Headquarters Antoine Delaitre Logistician Operations Support and Logistics Emergency Operations WHO Headquarters Alain Georges L. Fauconnier Scientist Prequalification Team Regulation of Medicines and other Health Technologies WHO Headquarters Ioana Ghiga Technical Officer Support for Response Infectious Hazard Management WHO Headquarters Shoshanna Goldin Technical Officer Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters Sarah Hess Technical Officer Infectious Hazard Management WHO Headquarters Alexandra Hill Technical Officer High Threat Pathogens Infectious Hazard Management WHO Headquarters Anne Marie Huvos Manager Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters Alireza Khadem Broojerdi Scientist Regulatory Systems Strengthening Essential Medicines and Health Products WHO Headquarters Alexandra Kontic Technical Officer (Legal) Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters Viviane Melo Bianco Consultant Support for Response Infectious Hazard Management WHO Headquarters Paul Molinaro Chief Operations Support and Logistics Emergency Operations WHO Headquarters 22 Tim Nguyen Team Leader Support for Response Infectious Hazard Management WHO Headquarters Razieh Ostad Ali Dehaghi Technical Officer Regulatory Systems Strengthening Essential Medicines and Health Products WHO Headquarters Carmen A. Rodriguez Hernandez Scientist Prequalification Team Regulation of Medicines and other Health Technologies WHO Headquarters Jose Rovira Vilaplana Technical Officer High Threat Pathogens Infectious Hazard Management WHO Headquarters Gina Samaan Team Leader Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters Derek Short Consultant Operations Support and Logistics Emergency Operations WHO Headquarters Wenqing Zhang Manager Influenza Preparedness and Response Infectious Hazard Management WHO Headquarters 23 Annex 4. Selection of key proposed action points from the 2011 Main operational lessons learnt from the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative 1. Reach agreement with all stakeholders on an overall framework of activities, roles and responsibilities relating to vaccine deployment during a pandemic for all actors in that framework. Periodically review the framework and assess where it needs to be updated or revised. 2. Prepare in advance and maintain a framework for legal agreements with donor governments and manufacturers (explaining issues such as indemnification, and how to deal with ownership and title transfer) to expedite legal agreements during future pandemic events. 3. Review pandemic epidemiological trends and the timeline of pandemic vaccine deployment activities to assess how best to align the latter with the former, with a particular focus placed on anticipating emerging changes and mitigating their impact. 4. Regularly engage major global stakeholders in readiness training for future pandemics, including simulation exercises for pandemic vaccine deployment. 5. Investigate if and how regulatory processes for pandemic vaccines can be shortened at global and national levels during a pandemic. 6. Investigate the possibility of a better-harmonized licensing approach for vaccines during a pandemic. 7. Identify and agree upon a standard, minimal set of product/regulatory documentation that would be provided for each shipment of donated vaccines or ancillary products during a pandemic. 8. Evaluate current global cold-chain capacity and, where necessary, identify approaches for ensuring sufficient surge capacity to handle large volumes of vaccine during a pandemic. 9. Align country NDPs with overall national pandemic preparedness and response plans, and with health-sector and intersectoral strategies and plans/budgets. 10. Study the interplay between pandemic and seasonal influenza vaccination and evaluate how best to advise countries in this regard. 11. Establish a cross-function, cross-region communication channel that involves all stakeholders to facilitate information sharing and to support the timely and effective efforts of the different actors during pandemic vaccine deployment. 12. Document the process of pandemic H1N1 vaccine deployment to serve as a basis for deployment planning during future pandemics