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Report of the Second WHO Informal Consultation held in Geneva, SwitzerlandInfluenza Vaccine Response during the Start of a Pandemic
21 July - 22 July 2016
Ordering code: WHO/HSE/PED/GIP/EPI/2017.1
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i
Influenza Vaccine Response during the Start of a Pandemic
ContentsExecutive Summary i
1. Introduction and Scope of Meeting 1
2. Reports of key international pandemic influenza preparedness activities 2
3. Organization of the Consultation 5
4. Refinement of the process for pandemic vaccine response 5
5. Principles and bottlenecks in making the switch from seasonal to pandemic vaccine production 6
6. Key Outcomes of the Meeting and Next Steps 13
7. References 14
8. Abbreviations 14
9. Acknowledgements 15
10. Annexes 15
1. Scenarios2. Draft operational framework for pandemic vaccine response3. Timelines of pandemic vaccine production4. Process of the WHO vaccine response to an influenza pandemic or a potential pandemic5. Further activities: the “Parking Lot”6. List of Participants
Report of the Second WHO Informal Consultation held in Geneva, Switzerland – 21 July - 22 July 2016
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
Executive Summary
i
In June 2015, the World Health Organization (WHO) held an Informal Consultation to bring together key stakeholders to address questions associated with vaccine response at the start of an influenza pandemic and, in particular, the strategic problems associated with switching from seasonal influenza vaccine production to pandemic vaccine production (switch). The 2015 Consultation clarified some of the complexities associated with the switch and identified key actions and challenges. However, several gaps remained in both knowledge and planning.
A second Informal Consultation was held by WHO in June 2016. The main goal of the 2016 consultation was to work to bridge these gaps by better understanding the complexities of the early stages of pandemic vaccine development; elaborating the principles that could guide the decision to switch; obtaining a better understanding of the evidence or data needed to support the decision-making process; and prioritizing the technical actions needed to overcome any bottlenecks in pandemic vaccine production.
The main outcomes of the meeting were:• The decision to switch is complex and multi-
faceted and will involve nearly all parts of the influenza community. An integrated approach could be achieved by establishing an international expert group tasked with making such a recommendation to WHO.
• Greater clarity and transparency is needed in the decision-making process, which will be enhanced by elaborating the principles involved in making such a decision. Several principles were proposed during the Consultation.
• National and international decision makers should be made aware of the complex issues associated with the decision to switch.
• As identified during the first consultation, there are several potential technical bottlenecks which could severely interfere with pandemic vaccine development. These were discussed and solutions were proposed. The next steps would be to convene expert groups in order to address potential solutions in greater depth.
• The feasibility of establishing a publicly funded small scale GMP pilot lot vaccine production facility should be explored. The facility could be used in the early stages of pandemic vaccine development by assessing CVV yield; assessing biosafety; producing pilot lots of vaccine for evaluation of process yield and for clinical evaluation; supplying antigen for potency reagents; and establishing diagnostic capacity.
• Three charts were finalized during the consultation (the operational framework for pandemic vaccine response; timelines of pandemic vaccine production; process of the WHO vaccine response to an influenza pandemic or a potential pandemic). These are intended for inclusion in the final version of the PIRM Framework document.
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
1. Introduction and Scope of the Meeting
1
In June 2013, WHO published a revision of the pandemic influenza preparedness and response guidance entitled Pandemic Influenza Risk Management (PIRM) — WHO interim guidance (ref 1). The WHO PIRM framework provides flexibility to countries for risk-based national response, including pandemic influenza vaccine response. In order to ensure rapid and adequate production anddeployment of pandemic influenza vaccines, taking into consideration seasonal epidemicswhich may be severe and occur concurrently at the start of a pandemic, there is apressing need to review the whole process from identification of the pandemic virus through to vaccines being available for use.
In June 2015, the first WHO Informal Consultation was held (http://www.who.int/influenza/resources/publications/influenzavaccineresponse_meeting01/en/) in order to bring together key stakeholders to address questions associated with pandemic vaccine response at the start of an influenza pandemic and to identify and discuss the strategic problems around switching from seasonal influenza vaccine production to pandemic vaccine production.
The Consultation clarified some of the enormous complexities at national, regional and global levels with the various public and private partners involved and an “operational framework for pandemic vaccine response was drafted”. While a common understanding of an effective pandemic vaccine response was established at the first Consultation, key
challenges were also identified including: risk assessment; availability of candidate vaccine viruses (CVVs) and reagents; clinical trials; regulatory procedures; bottlenecks involved in production of seasonal vaccines and in the switch to pandemic vaccine production; and programmatic issues involved in vaccine “roll out”. Also adding to the complexity was the possible need for the use of seasonal vaccines at the start of a pandemic.
One of the key recommendations from the first WHO Consultation was that WHO, through its advisory bodies, shall recommend the start of pandemic influenza vaccine production based on risk assessment. It was also recommended that the PIRM be updated from the earlier “interim” 2013 version and finalized based on the outcome of the WHO Consultation.
The Second Informal Consultation was held in June 2016. Its main objectives were to:
• Better understand the complexities and strategies for pandemic vaccine response at the start of a pandemic through discussion of different pandemic scenarios;
• Elaborate the principles that will guide the decision to switch from production of seasonal vaccine to pandemic vaccine;
• Better understand the evidence or data needed to support the decision-making process;
• Prioritize the technical actions needed to overcome any bottlenecks in pandemic vaccine production; and
• Finalize the draft “operational framework for a pandemic vaccine response” and use this to finalize the WHO PIRM Framework.
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT2
This information considerably helped the discussions in 2015, but needed updating for the second consultation in 2016. In addition there were other activities that need some explanation in order that participants could fully contribute to the second consultation.
2.1 The key players in WHO decision- making at the start of pandemic influenza vaccine production
WHO will engage all expertise inside and outside of the organization needed for the decision making, including but not limited to the following WHO programmes and advisory bodies:• Global Influenza Programme including
WHO Global Influenza Surveillance and Response System (GISRS) and PIP Framework Secretariat
• Initiative for Vaccine Research including GAP
• Technologies Standards and Norms including vaccine regulation
• Global Capacities, Alert and Response including IHR
• Strategic Advisory Group of Experts (SAGE) on Immunization
• IHR Emergency Committee
2.2 Pandemic Influenza Risk Management (PIRM)
As reported in the first consultation, the WHO published in 2013 a revision of the influenza preparedness and response guidance, entitled “Pandemic Influenza Risk Management (PIRM) – WHO interim guidance”. The PIRM Framework provides high-level guidance on risk management of pandemic influenza, but
It was emphasized that both the first and the second consultations were designed specifically to address issues and difficulties in producing pandemic vaccines at the start of a pandemic and not to address other different but possibly related issues surrounding pandemic vaccine production and use.
Thirty-eight participants from 24 countries were drawn from WHO Collaborating Centres (WHO CCs), National Influenza Centers (NICs), WHO Essential Regulatory Laboratories (ERLs), academic research community, National Regulatory Authorities (NRAs), national/regional public health agencies, vaccine manufacturers, International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), Developing Countries Vaccine Manufacturers Network (DVVMN) and other stakeholders.
2. Reports of key international pandemic influenza preparedness activities
At the start of the first consultation, background information was provided to bring all participants up to date on some key international pandemic influenza preparedness activities:• WHO Pandemic Influenza Risk Management
(PIRM) Framework (ref 1)• The International Health Regulations
(IHR) 2005 (ref 2)• The Pandemic Influenza Preparedness
(PIP) Framework (ref 3)• The WHO Global Action Plan for Influenza
Vaccines (GAP) (ref 4)
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT | 3
the section on pandemic influenza vaccines still needs completion. The two WHO consultations on Influenza Vaccine Response during the Start of a Pandemic should enable the PIRM Framework to be completed with the inclusion of the operational framework and the practical issues associated with pandemic vaccine development and, in particular, those associated with switching from seasonal vaccine to pandemic vaccine production.
2.3 Tool for Pandemic Influenza Risk Assessment (TIPRA) (http://www.who.int/influenza/areas_of_ work/human_animal_interface/tipra/en/)
One of the main components of the PIRM Framework is the country-specific risk assessment of the pandemic potential of a newly detected influenza virus, taking into account the global risk assessment conducted by WHO. TIPRA provides the means by which countries, regions and WHO (at a global level) can conduct standardized hazard assessment. TIPRA attempts to answer questions such as, “what is the risk of sustained human-to-human transmission of the virus; specifically, what is the likelihood and what is the likely impact?”. There are 11 steps in the TIPRA process and during its development, it has been tested several times in simulation exercises before Version 1 was launched in May 2016 (http://apps.who.int/iris/bitstream/10665/250126/1/WHO-OHE-PED-GIP-2016.3.pdf).
2.4 Global Action Plan for Influenza Vaccines (GAP)
As reported during the first consultation, the Global Action Plan for Influenza Vaccines (GAP) is a comprehensive strategy to reduce the global shortage of influenza vaccines for seasonal epidemics and pandemic influenza in all countries
through three major approaches:1. Increase in seasonal vaccine use.2. Increase in vaccine production capacity.3. Research into more effective vaccines. Another important component is sustainability of any improvements made.
GAP started in 2006 and there has been considerable progress since then, with nine approved new vaccines (6 pandemic and 3 seasonal vaccines) with some of the vaccines being prequalified for possible UN use. GAP will end in 2016, when there will be a review taking account of opinions from stakeholders around the world (http://www.who.int/influenza_vaccines_plan/en/).
2.5 Standard Material Transfer Agreements 2 (SMTA2) (http://www.who.int/influenza/pip/ benefit_sharing/smta2/en/)
Under the PIP Framework, a non-GISRS institution that receives PIP biological materials from a GISRS laboratory is required to complete a Standard Material Transfer Agreement 2 (SMTA2) with WHO. The SMTA2 is a legally-binding contract to ensure that manufacturers of vaccines, antivirals and diagnostic products and research institutions that receive PIP biological materials share with WHO some of the benefits arising from their access to the PIP biological materials. Possible benefits include pandemic influenza vaccines, antiviral medicines and other pandemic related products or technologies.
In terms of vaccine manufacturers, WHO strategy was first to reach agreement with manufacturers that had prequalified vaccines and had export experience. At the
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT4
time of the second consultation, WHO had concluded or was in formal negotiation with seven large vaccine manufacturers and was in informal negotiations with two other manufacturers having prequalified vaccines. For manufacturers of diagnostic materials, WHO was in formal negotiations with two large manufacturers and a number of smaller manufacturers. Forty-seven academic and research institutions from around the world had already signed SMTA2s and 19 had agreed to provide some benefits. In addition, WHO will be consulting widely to examine the various options for effective deployment of influenza vaccines.
2.6 The IFPMA perspective on the initiation of pandemic vaccine production
Before the PIRM Framework was adopted, vaccine manufacturers had a clear signal to start pandemic vaccine production when WHO had declared pandemic phase 6 of the former WHO pandemic guidance was declared by WHO. At present, the PIRM Framework gives responsibility to countries and regions for pandemic response based on its own risk assessment, but the World Health Assembly clearly noted that the initiation of pandemic vaccine production is the responsibility of vaccine manufacturers (ref 6), leading to considerable uncertainty surrounding the decision to initiate pandemic vaccine production. Given the interconnected nature of vaccine manufacturers and countries, they need:
• A clear international signal of when to switch from seasonal to pandemic vaccine production;
• Clear identification of roles and responsibilities of key stakeholders involved in the decision-making process; and
• Clarity and transparency in the decision-making process.
2.7 The USA plan to mitigate vaccine mismatch risk
During the 2014-2015 northern hemisphere influenza season, there was late emergence of an influenza A (H3N2) virus which led to a vaccine mismatch and reduction in vaccine effectiveness (http://ecdc.europa.eu/en/publications/Publications/RRA-InfluenzaA-H3N2-Dec-2014.pdf http://www.nature.com/articles/srep15279). As a result of a USA government enquiry, the HHS organized an interagency consultation to try to develop a plan to mitigate the risk of a vaccine mismatch. There are elements of this plan that have synergy with improving the decision-making process for a pandemic vaccine switch, e.g. improving CVV and reagent availability and improving the yield of high-growth reassortants. The proposal from the consultation is that the USA decision on seasonal vaccine strains could be in stages, with the possibility of one vaccine strain decision being delayed until April 15th.
The most relevant message from the USA consultation is to take steps to be better prepared to make a vaccine strain change, whether it be seasonal or pandemic.
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT | 5
3. Organization of the Consultation
After hearing the progress reports described above and in order to stimulate discussion to address the main objectives of the consultation, participants were provided with two different scenarios (Annex 1) for initiating a pandemic vaccine response during the early stages of a pandemic. Participants were tasked with assessing the type of data needs and the principles involved in making decisions about vaccine production following the emergence of a pandemic virus while seasonal influenza virus was still circulating and causing illness.
The discussions were enriched by the varied backgrounds and experiences of the participants and representatives from vaccine manufacturers. In addition, as with the first consultation, the discussions were aided by an external facilitator. The pandemic scenario discussions were invaluable for formulating ideas as participants moved on to the next tasks during the meeting and for different stakeholders to understand the challenges involved of various players. It was noticeable that during the second consultation, participants had a clearer understanding of the need for risk assessment and the procedures for producing a pandemic vaccine than they had one year earlier. Consequently, one of the tasks identified for participants during the second consultation was to identify the key principles and the data required for a decision to recommend the start of pandemic vaccine production so that key stakeholders will also be able to understand and follow the recommendation with more ease and with greater transparency.
The second focus of the consultation was to refine the description of the pandemic vaccine process, which was drafted during the first consultation. Three tables outlining the process were finalized by input from all participants.
The third activity was to build on earlier experience from the first consultation and identify principles that should be applied to decisions made to switch from seasonal to pandemic vaccine production and to address the various technical bottlenecks in pandemic vaccine production so that possible solutions could be identified.
During the first consultation, areas of concern that were outside the scope of the meeting but still needed attention were listed in a “parking lot”. Supplementary items identified during the second consultation were added to the list. (Annex 5).
Finally, the key outcomes and next steps were identified.
4. Refinement of the process for pandemic vaccine response
As noted above, three pandemic vaccine process charts were finalized during the consultation:• Operational framework for pandemic
vaccine response (i.e. who takes the actions?). (Annex 2)
• Timelines of pandemic vaccine production (i.e. when are actions taken?). (Annex 3)
• Process of the WHO vaccine response to influenza pandemic or potential pandemics (i.e. how are actions taken?). (Annex 4)
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT6
The outcomes of the consultation will be referenced in the PIRM Framework document in order to better describe the complexities and interactions of different stakeholders in making a pandemic vaccine available.
It was particularly challenging to develop accurate and realistic timelines for pandemic vaccine production as so many of the activities had an impact on other activities. For example, if there are delays in producing a CVV, there will also be delays in vaccine clinical trials, vaccine production and ultimately in vaccine availability. The timelines developed during the two consultations therefore reflect pandemic vaccine production during ideal circumstances. If some activities do not go well, they may take longer and this is indicated in the hatched areas of the chart.
5. Principles and bottlenecks in making the switch from seasonal to pandemic vaccine production
Participants were invited to discuss and make proposals for the types of evidence, expertise and principles needed to make a decision to switch from producing seasonal vaccine to pandemic vaccine. Inevitably there are some aspects of the vaccine production process which could cause potential bottlenecks and delay vaccine availability and some of these were raised during the first consultation.
At the second consultation, participants were encouraged to develop proposals for solutions to the bottlenecks and identify who should be responsible for taking each issue forward.
It was noted, however, that these proposals only reflect the opinions of the participants during the consultation and the actual solutions may be different after further discussed among expert groups drawn together by WHO.
5.1 Principles
There are many challenges in switching from production of seasonal vaccine to pandemic vaccine and, as elaborated during the first consultation, they are:
• A switch that is too early may compromise the production of seasonal vaccine with possibly severe public health consequences.
• A switch that is too late could have significant public health consequences, particularly if the pandemic is severe.
• Influenza vaccine production facilities cannot produce seasonal and pandemic vaccines at the same time. If the decision to start pandemic vaccine production is made when a facility is in the middle of producing seasonal vaccine, the facility has to stop seasonal vaccine production and switch to pandemic vaccine production. In addition, many areas lack influenza vaccine production capacity.
• Risk assessment involves the virological, epidemiological and clinical aspects of the emerging pandemic as well as assessment of the risk of stopping seasonal vaccine production potentially resulting in not having enough seasonal vaccine for vulnerable people.
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT | 7
• Few countries have a revised pandemic preparedness plan in place that includes country-specific risk assessment, risk management and vaccine response procedures.
With these challenges in mind, participants identified the following key principles in making a decision to start pandemic vaccine production:
• Any decision will be made on incomplete data. The amount and quality of data available in the early stages of a pandemic are likely to be different from those available in the later stages.
• There should be some built-in flexibility in order to review the decision to switch or not to switch as new data arise. But once the decision to switch is made, it will not be realistic to switch back immediately.
• There are different components to the advice and evidence needed:
o Technical (e.g. evidence, data). o Philosophical (e.g. ethics, transparency).o Structural (e.g. governance, expert advice).
• The declaration of a pandemic does not automatically trigger a switch to pandemic vaccine production. For example, a pandemic vaccine may be produced against the threat from a newly emerging, highly pathogenic virus, although it may not have reached pandemic proportions. Conversely, it may not be considered appropriate to produce a pandemic vaccine
if a pandemic has been declared, yet the virus causes only mild infections while ongoing seasonal influenza infections are severe and widespread. Considerations such as time of year, the geography of seasonal and pandemic virus circulation, and availability of CVVs will also play a role.
• The WHO recommendation should maximize global health and be guided by expert opinion.o The risks of mortality, morbidity and
economic consequences should be considered in order to minimize serious impact.
o The impact of not having enough seasonal vaccine available in case of a switch should be considered.
• Any decision or recommendation should be evidence-based and the process should be transparent and defensible. o There should be clarity of roles and
responsibilities for individuals and organizations making decisions.
o The information assessed should include a global map of influenza manufacturing capacity and relevant timelines for vaccine production.
• Different vaccine formulations should be an option (e.g. monovalent pandemic and monovalent seasonal vaccine; monovalent pandemic and bivalent seasonal vaccine) and these options should be evaluated by experts.
• The structure of the WHO Expert committee tasked with making recommendations on the start of
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT8
pandemic vaccine production should be representative and include groups such as manufacturers.
• There should be clear, understandable and rapid communication of any decision or recommendation, equally accessible by all stakeholders.
5.2 Bottlenecks
As identified during the first consultation, there are several potential technical bottlenecks that could severely interfere with pandemic vaccine development. Each bottleneck was discussed by participants with a view to identifying the data needed to solve the problems and, where possible, to identify how the problem could be solved and by whom.
BOTTLENECK DATA NEEDED SOLUTIONS
Lack of suitable BSL3/GMP laboratories for early small scale work
Not enough labs producing CVVs especially from highly pathogenic (hp) viruses
Not enough high containment labs for making LAIV CVVs
Uncertainty of CVV status in terms of implications related to the Nagoya Protocol or PIP Framework*
Uncertainty about manufacturers’ obligations to share synthetic seed viruses and shipping requirements
Delays in access to CVVs
• Review number of suitable labs available
• None identified
• Review number of suitable labs available
• None identified
• None identified
• None identified
• Dedicated publicly funded pilot BSL3/GMP labs
• WHO to identify and establish more pandemic CVV labs
• Dedicated publicly funded pilot BSL3/GMP labs
• WHO to obtain clarification
• Manufacturers to start dialogue with WHO
• Manufacturers to obtain import permits (including GMO CVV) in advance; obtain agreement(s) with courier(s)
CVV Production/Availability
* After the Consultation, clarification has been obtained that CVVs are included within PIP Framework, i.e. not covered by Nagoya Protocol
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
BOTTLENECK DATA NEEDED SOLUTIONS
Identification of the type of safety tests needed; availability of wt virus comparator; the need for ferret safety tests
Continued need for chicken pathogenicity tests of CVVs derived from hp viruses
Slow decision on biosafety and USDA Select Agent status; biosafety status could be country-specific
Uncertainty about biosafety status of synthetic CVVs especially with USDA Select Agent status
• WT virus risk assessment• Criteria for attenuation
and biosafety and utility of safety tests
• Historical review of chicken test data
• Review in vitro test data
• Information on pathogenicity
• Sequence especially HA/NA gene segments and including both egg and cell isolates
• Information on pathogenicity
• Sequence especially HA/NA gene segments and including both egg and cell isolates
• WHO to review guidance on safety testing of CVVs
• USDA to remove requirement for chicken pathogenicity test or remove hp influenza viruses from Select Agent status
• All CVV labs aiming to work with hp viruses should register with USDA in advance
• WHO to lead and coordinate bio-safety assessment and to speed up assessment
• WHO to provide feedback on IFPMA ‘white paper’ on CVV biocontainment
• Better coordination of CVV labs• Better communication between
CVV labs and manufacturers• CVV labs to standardize release
documents for CVVs• Future use of synthetic HA/NA CVVs
• Manufacturers to clarify status with human and agricultural safety authorities
• WHO to coordinate accumulation of data and liaison with human and agricultural safety authorities
Biocontainment for Wild Type Pandemic Virus and CVV
9
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT10
BOTTLENECK DATA NEEDED SOLUTIONS
BOTTLENECK DATA NEEDED SOLUTIONS
Low yielding CVV; slow evaluation of CVV yield
Low downstream yield from CVV (i.e. vaccine processing)
Not enough CVVs to select one with high yield
Genetic/protein instability during downstream processing
Delay in availability of clinical trial vaccine lots, specifically related to vaccine potency assays
Delay due to GMO issues
Delay due to country-specific vaccine lot release
Delay in clinical trial protocol review
Delay in serology assays
• Small scale yield in eggs and cells
• Small scale processing yield
• None identified
• Genetic/amino acid sequencing
• Data from SRID and alternative potency assays
• Certificate of analysis
• Lot release data
• None identified
• Robustness and reproducibility of assays
• CVV labs and manufacturers to optimize rapid small scale yield assessment techniques
• Better high yield donor viruses• Dedicated publicly funded pilot
BSL3/GLP labs
• CVV labs and manufacturer to optimize rapid small scale yield and processing assessment techniques
• Dedicated publicly funded pilot BSL3/GMP labs
• WHO to identify and establish more possible pandemic CVV labs
• Sequence optimization to improve yield and stability
• WHO and ERLs to review and recommend alternative potency assays
• None identified
• WHO ERLs to coordinate pandemic vaccine lot release globally
• Harmonize clinical trial procedures
• Improvement, standardization and acceptance of assays
Yield and Manufacturing of CVVs
Clinical Trials for the First Pandemic Vaccines
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT | 11
BOTTLENECK DATA NEEDED SOLUTIONS
BOTTLENECK DATA NEEDED SOLUTIONS
Delays in reagent supply will delay vaccine lot release and vaccine supply
• Availability of antigen and antiserum for use in reagent production
• Biosafety status of antigen• Which CVV is being used?• Suitability of existing
reagents, i.e. are new ones really needed?
• Review of regulatory requirements in different countries
• A basic set of criteria for seasonal and pandemic vaccine prequalification
• Requirements for donated vaccines in an emergency
• Confirmation of whether country NRAs meet published criteria for functionality
• Robustness of pandemic vaccine capability in countries
• Review of data on vaccine effectiveness
• Labelling requirements for emergency use of pandemic vaccine
• Review of pandemic vaccine lot release requirement in different countries
• Reagent supply needs better coordination and harmonization
• Alternative validated potency tests• Early start of antiserum production
(before CVV availability) • Allow use of heterologous reagent• Consider making panel of reagents
at risk
• Cross communication between regulatory authorities
• WHO to introduce prequalification for seasonal and pandemic influenza vaccines
• Continue to support regional regulatory harmonization in low and middle income countries
• M S to establish or strengthen NRAs:o Regulatory systems o Marketing Authorization
• Agreement on criteria for assessment of vaccine effectiveness
• Harmonization of labels and package inserts for pandemic vaccines
• Harmonization of pandemic vaccine lot release
Timing of SRID Reagents for Vaccine Potency Testing
Regulatory Harmonization
Lack of mutual recognition of regulatory procedures leading to delays in vaccine supply
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
BOTTLENECK DATA NEEDED SOLUTIONS
BOTTLENECK DATA NEEDED SOLUTIONS
Delay in making a risk assessment of whether or not to make a vaccine switch
If pre-filled syringes are used, filling is slower and uses more antigen; if multidose vials are used, thiomersal will be used and this limits its use
• Potential impact of new virus versus that of seasonal virus, including: o Epidemiologyo Severityo Modellingo Impacto Ability to manufacture
vaccine
• Update of risk assessment as more data becomes available
• Criteria used by countries for selecting final presentation
• Formulation requirements to ensure required shelf life
• An understanding of the need for prefilled syringes for some groups, e.g. pregnant women, children
• Develop decision-making process including data, data source, data collecting channels, analytical methods, and communication channels.
• WHO to prepare formal output from risk assessments
• Review of risk assessment
methodology
• Evaluate different delivery methods
• Education on benefits of use of multidose vials
• Use USA model of a fill/finish network to optimize global filling capacity
Risk Assessment
Fill and Finish Capacity
12
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
� There is a need for an integrated approach to the decision to switch or not to switch as there are many components to the decision process and they will involve nearly all parts of the influenza community. Such an integrated approach could be achieved by bringing together an international expert group tasked with making such a recommendation. The expert group should follow the principles as outlined during this consultation and should meet occasionally to work through switch scenarios in order to establish an effective working relationship.
� There is a need for greater clarity and transparency in the decision-making process and the elaboration during this consultation of the principles involved in making the decision will be a considerable help.
� As a result of the scenario exercises and resulting discussions, participants were now much better informed about the complex nature of the switch process and thus would be better equipped to make a recommendation and implement the decision. However, it is less likely that key national and international decision makers are fully aware of these issues. A critical outcome of the two consultations is to bring this information to key decision makers both within and outside of WHO.
� A main focus of the second consultation was to propose solutions to bottlenecks and problems that would interfere with making a timely switch and making pandemic vaccine available quickly. The next steps would be to follow up these proposals including identifying leading entities and convening expert groups in order to bring solutions closer. It was agreed at the consultation that small working groups, organized by WHO, would take this forward.
� One important outcome was the identification of solutions to the potential bottleneck where manufacturers are uncertain about clear signals being received concerning the need to escalate pandemic vaccine production (Bottleneck: Risk Assessment; Operational Flowchart: 1 Risk Assessment and Communications).
� One proposal that was placed in the “parking lot” during the first consultation was to establish a publicly funded small scale GMP pilot lot vaccine production facility. This proposal was repeated several times during the second consultation so that it was now regarded as one of the key outcomes. The facility could be used to assess CVV yield, assess biosafety, produce pilot lots of vaccine for evaluation of process yield, assess supply of antigen for potency reagent, establish diagnostic capacity and for training purposes. The facility would need to be in continuous use, e.g. as a training facility in non-pandemic period. Then in a pandemic emergency it would be used for influenza vaccine evaluation.
The main outcomes of the second consultation were:
6. Key Outcomes of the Consultation and Next Steps
13
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
8. Abbreviations
BLA Biologics License Application (USA regulatory mechanism)
BSL2+ Biosafety level 2+
CVV Candidate Vaccine Virus
DCVMN Developing Countries Vaccine Manufacturers Network
ERL WHO Essential Regulatory Laboratory
EUA Emergency Use Authorization (USA regulatory mechanism)
GAP WHO Global Action Plan for Influenza Vaccines
GISRS WHO Global Influenza Surveillance and Response System
6. Implementation of the International Health Regulations (2005) Report of the Review Committee on the Functioning of the International Health Regulations (2005) in relation to Pandemic (H1N1) 2009.
1. Pandemic Influenza Risk Management (PIRM) – WHO interim guidance
2. The International Health Regulations (IHR) 2005
3. The Pandemic Influenza Preparedness (PIP) Framework for the sharing of influenza viruses and access to vaccines and other benefits
7. References
http://www.who.int/influenza/preparedness/ pandemic/GIP_PandemicInfluenzaRisk ManagementInterimGuidance_Jun2013.pdf
http://whqlibdoc.who.int/publica-tions/2011/9789241503082_eng.pdf
http://apps.who.int/gb/ebwha/pdf_files/WHA64/A64_10-en.pdf
http://whqlibdoc.who.int/hq/2006/WHO_IVB_06.13_eng.pdf
http://whqlibdoc.who.int/publica-tions/2008/9789241580410_eng.pdf?ua=1
http://www.who.int/influenza/pip/smta2_eng.pdf?ua=1
� Following finalization of the operational framework for pandemic vaccine response, it will now be possible to finalize the PIRM Framework document. Following that, there should be consultation with member states on its implementation and periodically it should be reviewed and updated.
� As the expert working group progresses as mentioned above, WHO may consider organizing a third consultation on the same topic.
Further activities recognized during the first and second consultations and not considered directly within the scope of the consultations are listed in the “parking lot” (Annex 5).
14
4. Global Action Plan for Influenza Vaccines (GAP) to increase global influenza production capacity and supply
5. Standard Material Transfer Agreement 2 (SMTA2) outside the WHO global influenza surveillance and response system (GISRS)
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
Annexes
1. Scenarios2. Draft operational framework for pandemic
vaccine response3. Timelines of pandemic vaccine production4. Process of the WHO vaccine response to an
influenza pandemic or a potential pandemic5. Further activities: the “parking lot”6. List of Participants
12 15
GMO Genetically Modified Organism
GMP Good Manufacturing Practice
HHS USA Department of Health and Human Services
hp Highly pathogenic
IHR International Health Regulations (2005)
IFPMA International Federation of Pharmaceutical Manufacturers & Associations
IND Investigational New Drug (USA regulatory mechanism)
LAIV Live Attenuated Influenza Vaccine
MS WHO Member States
NIC WHO National Influenza Centre
NRAs National Regulatory Authorities
NRLs National Regulatory Laboratories
PIP Pandemic Influenza Preparedness
PIRM Pandemic Influenza Risk Management
RG Reverse Genetics
SAGE Strategic Advisory Group of Experts on immunization
9. Acknowledgements
The World Health Organization (WHO) wishes to acknowledge the contributions of all experts who participated in the preparation and in particular:
Derek Ellis (Canada), Susan Perry (Canada) and John Wood (United Kingdom) for peer review of the report.
SRID Single Radial Immunodiffusion
SMTA2 Standard Material Transfer Agreements 2
TIPRA Tool for Influenza Pandemic Assessment
WHO CCs WHO Collaborating Centres
wt Wild type
USA United States of America
USDA United States Department of Agriculture
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
ANNEX 1 – Scenarios
Scenario 1(Note: In discussing this scenario, note that the WHO GISRS network is continuously assessing and respond-ing to the risk of existing and emerging influenza viruses and that the WHO mechanisms including IHR and SAGE are functioning efficiently).
Week 1 GISRS has detected 12 human cases of H6N9 infection in the Netherlands during the month of December. The virus, originally detected in aquatic birds has acquired mutations in HA usually associated with mammalian adaptation.
Question 1 a) Do any additional communications need to be made? b) Do any additional actions need to be taken and by whom?
Week 2One hundred further cases of human H6N9 infection have been detected within the same region. All infections are clinically not as severe as those associated with seasonal H3N2 virus that is causing widespread human infection. An H6N9 CVV was prepared by GISRS one year earlier.
Question 2 a) Do extra CVVs need to be made? b) Do any additional actions need to be taken and by whom?
Week 6Within a month over 800 cases of H6N9 human infection have occurred across several countries. Cases were across all age groups.
Question 3 a) Is there a need to advance the development for a pandemic vaccine now? And if so, how far down
the development pathway should it go and by whom? b) Will national/regional contracts of seasonal vaccines be affected by activating pandemic APAs; if so,
how? c) When should pandemic vaccine production start? For all manufacturers or some - if only some, what
are the principles or assumption to consider when making this decision. Who decides what? d) Are there issues around seasonal versus pandemic vaccine availability? Are there any implications for
those needing seasonal vaccine?
Question 4 (Concluding Question): a) In this scenario, what would you recommend with regard to pandemic vaccine production vs.
seasonal vaccine production? b) On what basis is this recommendation to be made? Who are the stakeholders making the
recommendation? How should the recommendations be communicated?
16
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
ANNEX 1 – Scenarios
Scenario 2(Note: In discussing this scenario, note that WHO GISRS network is continuously assessing influenza isolates and novel viruses and that IHR and WHO expert committees such as SAGE are regularly informed).
Week 1 GISRS has detected the emergence of an antigenically drifted H3N2 in New Guinea.
Week 5The drifted H3N2 virus has spread to Fiji and Northern Australia, and the WHO VCM for the Southern Hemisphere has recommended the inclusion of the drifted H3N2 virus in the seasonal vaccine. There is evidence that infections are clinically severe with many patients being hospitalized.
Question 1 a) Do any additional communications need to be made? b) Do any additional actions need to be taken and by whom?
Week 6GISRS has detected 10 human cases of H10N2 virus in New guinea. One patient was hospitalised.
Week 7There is evidence of spread of H10N2 virus within the region but infections are clinically not as severe as the variant H3N2 virus infections. All age groups are affected.
Question 2 WHO (GISRS) is now ready to distribute CVVs to vaccine manufacturers for pandemic vaccine preparatory activities. a) When are manufacturers able to work with these CVV’s to produce clinical lots? b) Does working with CVVs and the production of clinical lots interfere with the production of seasonal vaccine?
Week 10 Within a month 1500 cases of H10N2 human infection have occurred across several countries and H3N2 infections continue to occur. All age groups were affected by both viruses.
Question 3 a) Should countries and stakeholders be informed on the progress of developing pandemic vaccine; and if so, how? b) How does WHO communicate with countries, industry and regulators? c) Would the presence of the N2 in the southern hemisphere vaccine provide any cross protective immunity and how would this influence
any decision to produce H10N2 vaccine?
Question 4 a) Is there a need to advance the development for a pandemic vaccine now? And if so, how far down the development pathway
should it go and by whom? b) Will national/regional contracts of seasonal vaccines be affected by activating pandemic APAs; if so, how? c) When should pandemic vaccine production start? For all manufacturers or some - if only some, what are the principles or assumption to consider
when making this decision. Who decides what? d) Are there issues around seasonal versus pandemic vaccine availability? Are there any implications for those needing seasonal vaccine? e) If both the H3 and H10 viruses were resistant to neuraminidase inhibitors, would this affect any of your decisions?
Weeks 12 - 15Within 3 months over 49 countries reported the spread of influenza, with many patients needing medical attention and some needing intensive care. Over 100,000 cases were reported with a 0.4% mortality rate. There were reports of severe challenges for the health care systems in most countries. There was also an increase in reports of absenteeism in front line health care workers. Laboratory tests on some 9200 samples showed that about 50% were of the new novel type A virus and nearly 50% were the new variant H3.
Question 5 (Concluding Question): a) In this scenario, what would you recommend with regard to pandemic vaccine production vs. seasonal vaccine production? b) Would your recommendation change in the face of increased morbidity and mortality which was over and above the normal seasonal
expectation. c) On what basis is this recommendation to be made? Who are the stakeholders making the recommendation? How should the recommendations
be communicated? d) In the situation of H3 dominating in some regions and H10 in others, what would your recommendations be?
17
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
AN
NEX
2 –
Dra
ft o
pera
tiona
l fra
mew
ork
for
pand
emic
vac
cine
res
pons
e
Activ
ities
Coordinating Entities
Deliv
erab
les o
r Out
puts
Chan
nels
to
Com
mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
s
to g
o fo
rwar
d or
not
with
the
prod
uctio
n of
pan
dem
ic v
acci
ne
– to go forward or not with the production of pandemic vaccine 1
Activ
ities
Coordinating Entities
Chan
nels
to
Com
mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
sOu
tcom
es
Dossi
er ro
ute
WHO
, man
ufac
ture
rs, na
tiona
l an
d reg
ional
(e.g.
EMA)
re
gulat
ing au
thor
ities
WHO
, Reg
ulato
rsAp
prov
al/no
appr
oval
Enha
nced
/fast-
track
ed ap
prov
al pr
oces
s
See #
1 belo
w
Guide
lines
Web
site
Wor
ksho
ps to
crea
te
unde
rstan
ding o
f the
pr
oces
ses
Emer
genc
y rou
teW
HO, m
anuf
actu
rers,
natio
nal
and r
egion
al (e
.g. EM
A)
regu
lating
auth
oriti
es
WHO
, Reg
ulato
rsAp
prov
al/no
appr
oval
Enha
nced
/fast-
track
ed ap
prov
al pr
oces
s
See #
2 belo
w
Guide
lines
Web
site
Wor
ksho
ps to
crea
te
unde
rstan
ding o
f the
pr
oces
ses
Regu
lator
y ove
rsigh
t to
assu
re th
e qua
lity o
f pa
ndem
ic va
ccine
s
Exiti
ng lo
t rele
ase l
abs
includ
ing W
HO ER
Ls an
d NR
A lab
s
Regu
lator
y Ne
twor
k/W
HODe
velop
men
t of a
form
al ne
twor
k of
relea
se la
bora
torie
s to e
nhan
ce
avail
abilit
y of p
ande
mic
vacc
ine
Clear
set o
f assa
ys to
stre
amlin
e pr
oces
s
See #
3 belo
w
Web
sites
, wor
ksho
ps,
writt
en st
anda
rds,
mem
bersh
ip cri
teria
Risk
man
agem
ent,
safet
y m
onito
ring,
signa
l det
ectio
n
Vacc
ine eff
ectiv
enes
s qu
antifi
catio
n of a
dver
se
effec
ts, ex
posu
re da
ta
Bene
fit /
risk a
ssessm
ent
Healt
h car
e wor
kers,
re
gulat
ors,
publi
c hea
lth
imm
uniza
tion p
rogr
ams,
man
ufac
ture
rs
Natio
nal R
egula
tory
Au
thor
ities
Impr
oved
safet
y asse
ssmen
t an
d mon
itorin
g sys
tem
Incre
ased
use o
f too
ls
(mod
els, e
tc.)
See #
4 belo
w
HCW,
publi
c hea
lth
orga
nizat
ions,
man
ufac
ture
rs
Distr
ibutio
n and
co
mm
unica
tions
Pand
emic
Vacc
ine
Deplo
ymen
t Plan
Healt
h aut
horit
ies
SAGE
Healt
h and
loc
al au
thor
ities
SAGE
Distr
ibutio
n,
avail
abilit
y, ea
rly AD
RsHe
alth a
utho
rities
an
d NRA
s ERL
s via
telec
onfer
ence
or em
ail
or ot
her c
hann
els
Registration Process &Pre-qualification Process
Pharmaco-vigilance
Vaccine Rollout
Lot Release5
Activ
ities
Coordinating Entities
Chan
nels
to
Com
mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
sOu
tcom
es
Prod
uctio
n of A
ntige
n
WHO
ERLs
and m
anuf
actu
rers
WHO
ERLs
Avail
abilit
y of c
alibr
ated
reag
ents
WHO
ERL w
ebsit
es an
d W
HO w
ebsit
e, an
d WHO
ch
aired
telec
onfer
ence
s (TC
)
Prod
uctio
n of A
ntise
rum
Inte
rnat
ional
calib
ratio
n stu
dies
WHO
ERLs
WHO
ERLs
Calib
rate
d rea
gent
sW
HO ER
Ls vi
a TC o
r em
ail
or ot
her c
hann
els, re
agen
t tra
cking
table
and o
ther
ch
anne
ls as
appr
opria
teSt
ructu
red f
eedb
ack f
rom
m
anuf
actu
rers
on us
e of r
eage
nts
WHO
ERLs
NR
AsW
HO ER
Ls an
d m
anuf
actu
rers
Pote
ntial
inte
nsifi
catio
n of s
easo
nal
prod
uctio
n prio
r to t
he po
tent
ial st
art
of pa
ndem
ic va
ccine
prod
uctio
n
Man
ufac
ture
rsIn
dividu
al m
anuf
actu
rers
Pote
ntial
ly inc
reas
ed vo
lume o
f se
ason
al va
ccine
sDi
rect
com
mun
icatio
n fro
m m
anuf
actu
rers
to cu
stom
er co
untri
es,
upda
tes t
o WHO
Cessa
tion o
f sea
sona
l vac
cine
prod
uctio
n W
HO, N
ation
al Au
thor
ities
, an
d man
ufac
ture
rsW
HO, N
ation
al Au
thor
ities
, and
m
anuf
actu
rers
Read
iness
for p
ande
mic
vacc
ine
man
ufac
turin
gDi
rect
com
mun
icatio
n fro
m m
anuf
actu
rers
to cu
stom
er co
untri
es,
upda
tes t
o WHO
Ongo
ing
risk a
sses
smen
t on
the
need
for p
ande
mic
vacc
ine
WHO
, IHR
EC, G
ISRS
, SAG
E an
d ot
her s
ubje
ct ex
pert
sW
HOW
HO w
ebsit
e, ot
her
med
ia ch
anne
ls as
ap
prop
riate
Star
t of p
ande
mic
vacc
ine pr
oduc
tion
WHO
, man
ufac
ture
rsM
anuf
actu
rers
and
regu
lator
s In
itiat
ion of
pand
emic
vacc
ine
prod
uctio
nIFP
MA to
WHO
(upd
ates
wi
th pr
oprie
tary
pr
otec
tions
);m
anuf
actu
rers
to
custo
mer
coun
tries
Vacc
ine pr
oduc
tion
Man
ufac
ture
rsM
anuf
actu
rers
Build
mon
obulk
stoc
k of
pand
emic
strain
Upda
tes f
rom
IFPM
A to
WHO
, and
man
ufac
ture
rs to
custo
mer
coun
tries
Vacc
ine fo
rmula
tion
Man
ufac
ture
rs, W
HOM
anuf
actu
rers
Pand
emic
Vacc
ineUp
date
s fro
m IF
PMA t
o W
HO, a
nd m
anuf
actu
rers
to cu
stom
er co
untri
es
Fillin
g/Pa
ckag
ingM
anuf
actu
rers,
cu
stom
er co
untri
esM
anuf
actu
rers,
cu
stom
er co
untri
es
and W
HO
Corre
ct pr
opor
tions
of m
ultido
se
vials,
syrin
ges,
etc.
IFPMA
to W
HOIn
dustr
y to C
usto
mer
Seasonal Vaccine Production
Reagent Calibration & Supply
Reagent Preparation
Pandemic Vaccine Production
RISK
ASS
ESSM
ENT
&
COM
MUN
ICAT
IONS
REGI
STRA
TION
CLIN
ICAL
EVA
LUAT
ION
Activ
ities
Coordinating Entities
Chan
nels
to
Com
mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
sOu
tcom
es
Star
t with
CVVs
and
Seed
Lot
Man
ufac
ture
rs, re
gulat
ors,
relev
ant n
ation
al au
thor
ityM
anuf
actu
rers
and R
egula
tors
Influ
enza
vacc
ine lo
ts su
itable
for h
uman
use
that
can b
e gro
wn to
hig
h yiel
ds
WHO
plat
form
s, e.g
. we
bsite
, pre
ss re
lease
, te
lecon
feren
ces –
regu
lar
and e
mer
genc
y as
appr
opria
te
Evalu
ate G
rowt
h Pr
oper
ties
Man
ufac
ture
rsM
anuf
actu
rers
and R
egula
tors
Yield
data
Telec
onfer
ence
s of W
HO,
IFPMA
and i
nvolv
ed
man
ufac
ture
rs an
d oth
er
entit
ies as
appr
opria
te
Anim
al St
udies
Man
ufac
ture
rs’ se
nior
man
agem
ent,
natio
nal/
globa
l coo
rdina
ting
entit
ies, e
.g. BA
RDA
(Biom
edica
l Adv
ance
d Re
sear
ch &
Dev
elopm
ent
Auth
ority
) to d
o/fu
nd/
coor
dinat
e ext
ra tr
ials
Man
ufac
ture
rs an
d Reg
ulato
rsAp
prov
al fro
m re
levan
t re
gulat
orW
HO pl
atfo
rms,
e.g.
webs
ite, p
ress
relea
se,
telec
onfer
ence
s – re
gular
an
d em
erge
ncy a
s ap
prop
riate
Rapid
com
mun
icatio
ns
with
man
ufac
ture
rs,
fund
ers,
custo
mer
coun
tries
an
d oth
er en
tities
as
appr
opria
te
Prec
linica
l stu
dies
Ethic
s com
mitt
ee
appr
ovals
Stud
ies in
adult
s
Paed
iatric
stud
ies
Regu
lator
y eva
luatio
n of
vacc
ine sa
fety
Man
ufac
ture
rs, ac
adem
ia,co
mm
ercia
l clin
ical
trial
units
, nat
ional/
inter
natio
nal e
ntiti
es,
such
as U
S NIH
/CDC
Man
ufac
ture
rs,
regu
lator
s, na
tiona
l/ int
erna
tiona
l en
tities
such
as
US N
IH/C
DC
Evalu
ation
of va
ccine
sa
fety
Com
mun
icatio
n at
globa
l plat
form
to al
l sta
keho
lders,
inclu
ding
regu
lator
s and
othe
r na
tiona
l aut
horit
ies,
mod
eller
s and
othe
r en
tities
as ap
prop
riate
Sero
logy w
ith
appr
opria
te ex
pert
advic
e and
over
sight
at
all st
ages
Ethic
s com
mitt
ee,
regu
lator
y aut
horit
ies,
man
ufac
ture
rs, ac
adem
ia,
com
mer
cial c
linica
l tri
al un
its, n
ation
al/
inter
natio
nal e
ntiti
es,
such
as U
S NIH
/CDC
Fund
ers,
com
mer
cial
labor
ator
ies
involv
ed in
cli
nical
trials
, m
anuf
actu
rers
Corre
lates
of pr
otec
tion;
va
ccine
form
ulatio
n;
vacc
inatio
n stra
tegy
Com
mun
icatio
n at
globa
l plat
form
inclu
ding
webs
ite, p
ress
relea
ses,
and
telec
onfer
ence
s.
Rapid
dire
ct co
mm
unica
tion w
ith
man
ufac
ture
rs an
d fun
ders
Clinical Lot Production Clinical Trials3
Not
es1.
Fo
rwar
d lo
okin
g ou
tcom
es w
ould
be
esta
blis
hmen
t of g
loba
l gui
delin
es a
nd
com
mon
regu
lato
ry p
roce
sses
to s
uppo
rt fa
st tr
acki
ng/c
heap
er d
evel
opm
ent c
osts
.2.
A
ppro
val p
roce
ss p
rinci
ples
to in
clud
e: c
larit
y, tr
ansp
aren
cy, m
utua
l rec
ogni
tion,
rapi
d ac
cess
.3.
Ea
ch W
HO
regi
on s
houl
d ha
ve s
uch
labo
rato
ries.
Mut
ual r
ecog
nitio
n pr
oced
ures
to b
e de
velo
ped.
Re
cogn
ized
sta
ndar
ds a
nd in
spec
tions
are
nee
ded,
EU
can
be
seen
as
as a
mod
el.
4.
Incr
ease
d co
nfide
nce
amon
g H
CW a
nd p
ublic
. Ens
ure
case
defi
nitio
ns a
re a
vaila
ble
for A
EFIs
.
4PR
ODUC
TION
CVV
DEVE
LOPM
ENT
CVV
DEVE
LOPM
ENT
RISK
ASS
ESSM
ENT
& CO
MM
UNIC
ATIO
N
REGI
STRA
TION
PROD
UCTI
ON
OPE
RATI
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AL
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ORK
FO
R PA
ND
EMIC
VAC
CIN
E RE
SPO
NSE
VERS
ION
30.
09.2
016
Virolo
gical
Risk
Asse
ssmen
tW
HO, G
ISRS,
affec
ted c
ount
ries,
OFFL
U, an
imal
secto
rs,
acad
emic
instit
ution
s
WHO
Upda
ted r
isk as
sessm
ent b
ased
on
virus
char
acte
rizat
ion an
d spe
cial
studie
s
WHO
web
site,
scien
tific
publi
catio
ns as
appr
opria
te
Epide
miol
ogica
l M
onito
ring a
nd
Risk
Asse
ssmen
t
WHO
, GISR
S and
asso
ciate
d ep
idem
iolog
ic ins
titut
ions i
n aff
ecte
d cou
ntrie
s, re
giona
l co
ordin
ating
entit
ies, e
.g. EC
DC
WHO
Early
descr
iption
s of t
he em
ergin
g ep
idem
iolog
ical p
atte
rn of
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ia
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nels
as ap
prop
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ratio
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emic
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perts
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ratio
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site,
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ls as
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opria
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ALUA
TION
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Bi
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se A
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sear
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ww
.fluc
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u/G
ACV
S W
HO
Glo
bal A
dviso
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omm
ittee
on
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AP
WH
O G
loba
l Act
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for I
nflue
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Nat
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Pa
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Re
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men
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tail
criti
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teps
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cludi
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prod
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seas
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vacc
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to p
ande
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vacc
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Coordinating Entities
Chan
nels
to
Com
mun
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th
e Out
com
esPa
rtici
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sOu
tcom
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Wild
Type
Viru
sW
HO CC
s,
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sorti
ng La
bs
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CCs,
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asso
rting
Labs
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CCs,
Re
asso
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La
bs
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CCs,
Re
asso
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La
bs
Pote
ntial
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Pote
ntial
CVVs
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web
site,
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em
ail di
stribu
tion,
IFPM
A te
lecon
feren
ces a
nd ot
her
chan
nels
as ap
prop
riate
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web
site,
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em
ail di
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tion,
IFPM
A te
lecon
feren
ces a
nd ot
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chan
nels
as ap
prop
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sorta
nt
RG Re
asso
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CCs,
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asso
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Labs
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CCs,
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asso
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La
bs
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ntial
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web
site,
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ail di
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opria
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Evalu
ation
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CCs,
ERLs
, m
anuf
actu
rers
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with
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HO CC
s, IFP
MA, a
nd
man
ufac
ture
rs
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opria
tene
ss of
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VVs f
or
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ufac
turin
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onfer
ence
s of W
HO, IF
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and i
nvolv
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anuf
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ther
entit
ies as
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prop
riate
Asse
ssmen
t of B
SL
Leve
l for L
arge
Sc
ale Pr
oduc
tion
WHO
Expe
rt Gr
oup o
n Bi
ocon
tainm
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OIE/
FAO
WHO
Requ
ired
cont
ainm
ent l
evels
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web
site,
telec
onfer
ence
s of
WHO
, IFPM
A, N
ation
al Re
gulat
ory A
utho
rity (
NRA)
, inv
olved
man
ufac
ture
rs an
d ot
her e
ntiti
es as
appr
opria
te
18
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
AN
NEX
2 –
Dra
ft o
pera
tiona
l fra
mew
ork
for
pand
emic
vac
cine
res
pons
e
OPE
RATI
ON
AL
FRA
MEW
ORK
FO
R PA
ND
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VAC
CIN
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titie
s
to g
o fo
rwar
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with
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prod
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pan
dem
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acci
ne
Risk Assessment & Communications –– to go forward or not with the production of pandemic vaccine 1RI
SK A
SSES
SMEN
T
& CO
MM
UNIC
ATIO
NS
Virolo
gical
Risk
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ssmen
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ISRS,
affec
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coun
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LU, a
nimal
secto
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isk as
sessm
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ased
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char
acte
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s
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web
site,
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catio
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prop
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miol
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onito
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titut
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mic
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ken
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web
site,
sci
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licat
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prop
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rity A
ssessm
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cted c
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C
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Upda
ted s
ever
ity as
sessm
ent
WHO
web
site,
scien
tific
publi
catio
ns as
ap
prop
riate
Decla
ratio
n of P
HEIC
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, IHR E
mer
genc
y Co
mm
ittee
(EC)
, GISR
S and
ot
her s
ubjec
t exp
erts
WHO
WHO
D-G
’s dec
larat
ion of
PHEIC
an
d issu
ance
of te
mpo
rary
re
com
men
datio
ns
WHO
web
site,
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r m
edia
chan
nels
as
appr
opria
te
Decla
ratio
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emic
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m h
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ww
.fluc
op.e
u/G
ACV
S W
HO
Glo
bal A
dviso
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ittee
on
Vacc
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Safe
tyG
AP
WH
O G
loba
l Act
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Plan
for I
nflue
nza
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bal I
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iseas
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reve
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labo
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ntre
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Ess
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Labo
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ry*
USA
regu
lato
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echa
nism
CLIN
ICAL
EVAL
UATI
ON
19
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
OPE
RATI
ON
AL
FRA
MEW
ORK
FO
R PA
ND
EMIC
VAC
CIN
E RE
SPO
NSE
CVV
DEVE
LOPM
ENT
CVV
DEVE
LOPM
ENT
RISK
ASS
ESSM
ENT
& CO
MM
UNIC
ATIO
N
REGI
STRA
TION
PROD
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ON
CLIN
ICAL
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UATI
ON
Activ
ities
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Chan
nels
to
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mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
sOu
tcom
es
CVV Development Bio- containment
CVV Assessment and Evaluation2
Wild
Type
Viru
sW
HO CC
s,
Reas
sorti
ng La
bs
WHO
CCs,
Re
asso
rting
Labs
WHO
CCs,
Re
asso
rting
La
bs
WHO
CCs,
Re
asso
rting
La
bs
Pote
ntial
CVVs
Pote
ntial
CVVs
WHO
web
site,
WHO
em
ail di
stribu
tion,
IFPM
A te
lecon
feren
ces a
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her
chan
nels
as ap
prop
riate
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web
site,
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em
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CCs,
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La
bs
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web
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bsW
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CCs,
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anuf
actu
rers
WHO
with
W
HO CC
s, IFP
MA, a
nd
man
ufac
ture
rs
Appr
opria
tene
ss of
the C
VVs f
or
man
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turin
g
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onfer
ence
s of W
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nvolv
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ssmen
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FAO
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cont
ainm
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evels
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web
site,
telec
onfer
ence
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WHO
, IFPM
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ation
al Re
gulat
ory A
utho
rity (
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, inv
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ntiti
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OSSA
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rug
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e Ev
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onso
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ww
.fluc
op.e
u/G
ACV
S W
HO
Glo
bal A
dviso
ry C
omm
ittee
on
Vacc
ine
Safe
tyG
AP
WH
O G
loba
l Act
ion
Plan
for I
nflue
nza
Vacc
ines
GIS
RS
Glo
bal I
nflue
nza
Surv
eilla
nce
& Re
spon
se S
yste
mG
MO
G
enet
ical
ly M
odifi
ed O
rgan
ismG
MP
Goo
d M
anuf
actu
ring
Prac
tice
HCW
H
ealth
Car
e W
orke
rIH
R In
tern
atio
nal H
ealth
Reg
ulat
ions
(200
5)IF
PMA
In
tern
atio
nal F
eder
atio
n of
Pha
rmac
eutic
al
Man
ufac
ture
rs &
Ass
ocia
tions
IND
In
vest
igat
iona
l New
Dru
g*
NCL
s N
atio
nal C
ontr
ol L
abor
ator
ies
NRA
s N
atio
nal R
egul
ator
y Au
thor
ities
OIE
W
orld
Org
aniz
atio
n fo
r Ani
mal
Hea
lthPH
EIC
Pu
blic
Hea
lth E
mer
genc
y of
Inte
rnat
iona
l Con
cern
PIP
Pand
emic
Influ
enza
Pre
pare
dnes
sPI
RM
Pand
emic
Influ
enza
Risk
Man
agem
ent
RG
Reve
rse
Gen
etic
sSA
GE
Stra
tegi
c Ad
viso
ry G
roup
of E
xper
ts o
n Im
mun
izat
ion
SRID
Si
ngle
Rad
ial I
mm
unod
iffus
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TIPR
A
Tool
for I
nflue
nza
Pand
emic
Risk
Ass
essm
ent
VRB
PAC
US
Vacc
ines
and
Rel
ated
Bio
logi
cal P
rodu
cts A
dviso
ry C
omm
ittee
US
NIH
/CD
C U
S N
atio
nal I
nstit
utes
of H
ealth
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tres
for D
iseas
e
Cont
rol a
nd P
reve
ntio
nW
HO
CCs
W
HO
Col
labo
ratin
g Ce
ntre
sW
HO
ERL
s W
HO
Ess
entia
l Reg
ulat
ory
Labo
rato
ry*
USA
regu
lato
ry m
echa
nism
20
AN
NEX
2 –
Dra
ft o
pera
tiona
l fra
mew
ork
for
pand
emic
vac
cine
res
pons
e
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
RISK
ASS
ESSM
ENT
& CO
MM
UNIC
ATIO
N
PROD
UCTI
ON
CLIN
ICAL
EVAL
UATI
ON
OPE
RATI
ON
AL
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ORK
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R PA
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mun
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esPa
rtici
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titie
sOu
tcom
es
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t with
CVVs
and
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Lot
Man
ufac
ture
rs, re
gulat
ors,
relev
ant n
ation
al au
thor
ityM
anuf
actu
rers
and R
egula
tors
Influ
enza
vacc
ine lo
ts su
itable
for h
uman
use
that
can b
e gro
wn to
high
yie
lds
WHO
plat
form
s, e.g
. web
site,
pres
s re
lease
, tele
conf
eren
ces –
regu
lar
and e
mer
genc
y as a
ppro
priat
e
Evalu
ate G
rowt
h Pr
oper
ties
Man
ufac
ture
rsM
anuf
actu
rers
and R
egula
tors
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data
Telec
onfer
ence
s of W
HO, IF
PMA a
nd
involv
ed m
anuf
actu
rers
and o
ther
en
tities
as ap
prop
riate
Anim
al St
udies
Man
ufac
ture
rs’ se
nior
man
agem
ent,
natio
nal/g
lobal
coor
dinat
ing en
tities
, e.g.
BA
RDA (
Biom
edica
l Adv
ance
d Re
sear
ch &
Dev
elopm
ent
Auth
ority
) to d
o/fu
nd/
coor
dinat
e ext
ra tr
ials
Man
ufac
ture
rs an
d Reg
ulato
rsAp
prov
al fro
m re
levan
t re
gulat
orW
HO pl
atfo
rms,
e.g. w
ebsit
e, pr
ess
relea
se, t
eleco
nfer
ence
s – re
gular
an
d em
erge
ncy a
s app
ropr
iate
Rapid
com
mun
icatio
ns w
ith
man
ufac
ture
rs, fu
nder
s, cu
stom
er
coun
tries
and o
ther
entit
ies as
ap
prop
riate
Prec
linica
l stu
dies
Ethic
s com
mitt
ee
appr
ovals
Stud
ies in
adult
s
Paed
iatric
stud
ies
Regu
lator
y eva
luatio
n of
vacc
ine sa
fety
Man
ufac
ture
rs, ac
adem
ia,co
mm
ercia
l clin
ical t
rial u
nits,
natio
nal/i
nter
natio
nal e
ntiti
es
such
as U
S NIH
/CDC
, eth
ics
com
mitt
ees
Man
ufac
ture
rs,
regu
lator
s, na
tiona
l/ int
erna
tiona
l en
tities
such
as
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IH/C
DC
Evalu
ation
of va
ccine
sa
fety
Com
mun
icatio
n at g
lobal
platfo
rm to
all
stak
ehold
ers,
includ
ing re
gulat
ors
and o
ther
natio
nal a
utho
rities
, m
odell
ers a
nd ot
her e
ntiti
es as
ap
prop
riate
Sero
logy w
ith
appr
opria
te ex
pert
advic
e and
over
sight
at
all st
ages
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s com
mitt
ee, re
gulat
ory
auth
oriti
es, m
anuf
actu
rers,
ac
adem
ia, co
mm
ercia
l cli
nical
trial
units
, nat
ional/
int
erna
tiona
l ent
ities
, su
ch as
US N
IH/C
DC, re
sear
ch
entit
ies, e
.g. FL
UCOP
Fund
ers,
com
mer
cial
labor
ator
ies
involv
ed in
cli
nical
trials
, m
anuf
actu
rers
regu
lator
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Corre
lates
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otec
tion;
va
ccine
form
ulatio
n;
vacc
inatio
n stra
tegy
Com
mun
icatio
n at g
lobal
platfo
rm
includ
ing w
ebsit
e, pr
ess r
eleas
es,
and t
eleco
nfer
ence
s.
Rapid
dire
ct co
mm
unica
tion w
ith
man
ufac
ture
rs an
d fun
ders
Clinical Lot Production Clinical Trials3CV
V DE
VELO
PMEN
T REGI
STRA
TION
GL
OSSA
RY
AD
R Ad
vers
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rug
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ollo
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mun
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Bi
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icen
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pplic
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osaf
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Ca
ndid
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ine
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sD
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elop
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trie
s Vac
cine
Man
ufac
ture
rs N
etw
ork
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C Eu
rope
an C
entr
e fo
r Dise
ase
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entio
n an
d Co
ntro
lEM
A
Euro
pean
Med
icin
es A
genc
yEU
A
Emer
genc
y U
se A
utho
rizat
ion*
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O
Food
and
Agr
icul
ture
Org
aniz
atio
n of
the
UN
FLU
COP
EU re
sear
ch c
onso
rtiu
m h
ttp:
//w
ww
.fluc
op.e
u/G
ACV
S W
HO
Glo
bal A
dviso
ry C
omm
ittee
on
Vacc
ine
Safe
tyG
AP
WH
O G
loba
l Act
ion
Plan
for I
nflue
nza
Vacc
ines
GIS
RS
Glo
bal I
nflue
nza
Surv
eilla
nce
& Re
spon
se S
yste
mG
MO
G
enet
ical
ly M
odifi
ed O
rgan
ismG
MP
Goo
d M
anuf
actu
ring
Prac
tice
HCW
H
ealth
Car
e W
orke
rIH
R In
tern
atio
nal H
ealth
Reg
ulat
ions
(200
5)IF
PMA
In
tern
atio
nal F
eder
atio
n of
Pha
rmac
eutic
al
Man
ufac
ture
rs &
Ass
ocia
tions
IND
In
vest
igat
iona
l New
Dru
g*
NCL
s N
atio
nal C
ontr
ol L
abor
ator
ies
NRA
s N
atio
nal R
egul
ator
y Au
thor
ities
OIE
W
orld
Org
aniz
atio
n fo
r Ani
mal
Hea
lthPH
EIC
Pu
blic
Hea
lth E
mer
genc
y of
Inte
rnat
iona
l Con
cern
PIP
Pand
emic
Influ
enza
Pre
pare
dnes
sPI
RM
Pand
emic
Influ
enza
Risk
Man
agem
ent
RG
Reve
rse
Gen
etic
sSA
GE
Stra
tegi
c Ad
viso
ry G
roup
of E
xper
ts o
n Im
mun
izat
ion
SRID
Si
ngle
Rad
ial I
mm
unod
iffus
ion
TIPR
A
Tool
for I
nflue
nza
Pand
emic
Risk
Ass
essm
ent
VRB
PAC
US
Vacc
ines
and
Rel
ated
Bio
logi
cal P
rodu
cts A
dviso
ry C
omm
ittee
US
NIH
/CD
C U
S N
atio
nal I
nstit
utes
of H
ealth
/Cen
tres
for D
iseas
e
Cont
rol a
nd P
reve
ntio
nW
HO
CCs
W
HO
Col
labo
ratin
g Ce
ntre
sW
HO
ERL
s W
HO
Ess
entia
l Reg
ulat
ory
Labo
rato
ry*
USA
regu
lato
ry m
echa
nism
21
AN
NEX
2 –
Dra
ft o
pera
tiona
l fra
mew
ork
for
pand
emic
vac
cine
res
pons
e
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
OPE
RATI
ON
AL
FRA
MEW
ORK
FO
R PA
ND
EMIC
VAC
CIN
E RE
SPO
NSE
Activ
ities
Coordinating Entities
Chan
nels
to
Com
mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
sOu
tcom
es
Prod
uctio
n of A
ntige
nW
HO ER
Ls an
d m
anuf
actu
rers
WHO
ERLs
Avail
abilit
y of c
alibr
ated
re
agen
tsW
HO ER
L web
sites
and W
HO
webs
ite, a
nd W
HO ch
aired
te
lecon
feren
ces (
TCs)
Prod
uctio
n of A
ntise
rum
Inte
rnat
ional
calib
ratio
n stu
dies
WHO
ERLs
WHO
ERLs
Calib
rate
d rea
gent
sW
HO ER
Ls vi
a TCs
or em
ail or
ot
her c
hann
els, re
agen
t tra
cking
table
and o
ther
ch
anne
ls as
appr
opria
teSt
ructu
red f
eedb
ack f
rom
m
anuf
actu
rers
on us
e of r
eage
nts
WHO
ERLs
NR
AsW
HO ER
Ls, a
nd
man
ufac
ture
rs
Pote
ntial
inte
nsifi
catio
n of s
easo
nal
prod
uctio
n prio
r to t
he po
tent
ial
start
of pa
ndem
ic va
ccine
prod
uctio
n
Man
ufac
ture
rsIn
dividu
al m
anuf
actu
rers
Pote
ntial
ly inc
reas
ed vo
l-um
e of s
easo
nal v
accin
esDi
rect
com
mun
icatio
n fro
m
man
ufac
ture
rs to
custo
mer
co
untri
es, u
pdat
es to
WHO
Cessa
tion o
f sea
sona
l vac
cine
prod
uctio
n W
HO, N
ation
al Au
thor
ities
, an
d man
ufac
ture
rs
WHO
, Nat
ional
Auth
oriti
es, a
nd
man
ufac
ture
rs
Read
iness
for p
ande
mic
vacc
ine m
anuf
actu
ring
Dire
ct co
mm
unica
tion f
rom
m
anuf
actu
rers
to cu
stom
er
coun
tries
, upd
ates
to W
HO
Ongo
ing
risk a
sses
smen
t on
the
need
for p
ande
mic
vacc
ine
WHO
, IHR
EC, G
ISRS
, SA
GE an
d ot
her
subj
ect e
xper
ts
WHO
WHO
web
site,
othe
r med
ia
chan
nels
as ap
prop
riate
Star
t of p
ande
mic
vacc
ine pr
oduc
tion
WHO
, man
ufac
ture
rs,
NCLs
Man
ufac
ture
rs an
d reg
ulato
rs In
itiat
ion of
pand
emic
vacc
ine pr
oduc
tion
IFPMA
to W
HO (u
pdat
es w
ith
prop
rieta
ry pr
otec
tions
);m
anuf
actu
rers
to cu
stom
er
coun
tries
Vacc
ine pr
oduc
tion
Man
ufac
ture
rs, N
CLs
Man
ufac
ture
rsBu
ild m
onob
ulk st
ock o
f pa
ndem
ic str
ainUp
date
s fro
m IF
PMA t
o WHO
, an
d man
ufac
ture
rs to
custo
mer
co
untri
es
Vacc
ine fo
rmula
tion
Man
ufac
ture
rs, W
HO,
NCLs
Man
ufac
ture
rsPa
ndem
ic Va
ccine
Upda
tes f
rom
IFPM
A to W
HO,
and m
anuf
actu
rers
to cu
stom
er
coun
tries
Fillin
g/Pa
ckag
ingM
anuf
actu
rers,
cu
stom
er co
untri
esNC
Ls
Man
ufac
ture
rs,
custo
mer
coun
tries
an
d WHO
Corre
ct pr
opor
tions
of
mult
idose
vials
, syr
inges
, et
c.
IFPMA
to W
HOIn
dustr
y to C
usto
mer
Seasonal Vaccine Production
Reagent Calibration & Supply
Reagent Preparation Pandemic Vaccine Production4
PROD
UCTI
ON
Reco
mm
end
that
pro
duct
ion
of p
ande
mic
vacc
ine
com
men
ce, b
ased
on ri
sk
asse
ssm
ent.
This
may
enta
il cr
itica
l ste
ps in
cludi
ng
switc
hing
from
pro
duct
ion
of
seas
onal
vacc
ine t
o pan
dem
ic va
ccin
e
CVV
DEVE
LOPM
ENT
RISK
ASS
ESSM
ENT
& CO
MM
UNIC
ATIO
N
REGI
STRA
TION
PROD
UCTI
ON
CLIN
ICAL
EV
ALUA
TION
GL
OSSA
RY
AD
R Ad
vers
e D
rug
Reac
tion
AEF
I Ad
vers
e Ev
ent F
ollo
win
g Im
mun
izat
ion
BLA
Bi
olog
ics L
icen
se A
pplic
atio
n*
BSL2
+ Bi
osaf
ety
leve
l 2+
CVV
Ca
ndid
ate
Vacc
ine
Viru
sD
CVM
N
Dev
elop
ing
Coun
trie
s Vac
cine
Man
ufac
ture
rs N
etw
ork
ECD
C Eu
rope
an C
entr
e fo
r Dise
ase
Prev
entio
n an
d Co
ntro
lEM
A
Euro
pean
Med
icin
es A
genc
yEU
A
Emer
genc
y U
se A
utho
rizat
ion*
FA
O
Food
and
Agr
icul
ture
Org
aniz
atio
n of
the
UN
FLU
COP
EU re
sear
ch c
onso
rtiu
m h
ttp:
//w
ww
.fluc
op.e
u/G
ACV
S W
HO
Glo
bal A
dviso
ry C
omm
ittee
on
Vacc
ine
Safe
tyG
AP
WH
O G
loba
l Act
ion
Plan
for I
nflue
nza
Vacc
ines
GIS
RS
Glo
bal I
nflue
nza
Surv
eilla
nce
& Re
spon
se S
yste
mG
MO
G
enet
ical
ly M
odifi
ed O
rgan
ismG
MP
Goo
d M
anuf
actu
ring
Prac
tice
HCW
H
ealth
Car
e W
orke
rIH
R In
tern
atio
nal H
ealth
Reg
ulat
ions
(200
5)IF
PMA
In
tern
atio
nal F
eder
atio
n of
Pha
rmac
eutic
al
Man
ufac
ture
rs &
Ass
ocia
tions
IND
In
vest
igat
iona
l New
Dru
g*
NCL
s N
atio
nal C
ontr
ol L
abor
ator
ies
NRA
s N
atio
nal R
egul
ator
y Au
thor
ities
OIE
W
orld
Org
aniz
atio
n fo
r Ani
mal
Hea
lthPH
EIC
Pu
blic
Hea
lth E
mer
genc
y of
Inte
rnat
iona
l Con
cern
PIP
Pand
emic
Influ
enza
Pre
pare
dnes
sPI
RM
Pand
emic
Influ
enza
Risk
Man
agem
ent
RG
Reve
rse
Gen
etic
sSA
GE
Stra
tegi
c Ad
viso
ry G
roup
of E
xper
ts o
n Im
mun
izat
ion
SRID
Si
ngle
Rad
ial I
mm
unod
iffus
ion
TIPR
A
Tool
for I
nflue
nza
Pand
emic
Risk
Ass
essm
ent
VRB
PAC
US
Vacc
ines
and
Rel
ated
Bio
logi
cal P
rodu
cts A
dviso
ry C
omm
ittee
US
NIH
/CD
C U
S N
atio
nal I
nstit
utes
of H
ealth
/Cen
tres
for D
iseas
e
Cont
rol a
nd P
reve
ntio
nW
HO
CCs
W
HO
Col
labo
ratin
g Ce
ntre
sW
HO
ERL
s W
HO
Ess
entia
l Reg
ulat
ory
Labo
rato
ry*
USA
regu
lato
ry m
echa
nism
22
AN
NEX
2 –
Dra
ft o
pera
tiona
l fra
mew
ork
for
pand
emic
vac
cine
res
pons
e
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
CVV
DEVE
LOPM
ENT
RISK
ASS
ESSM
ENT
& CO
MM
UNIC
ATIO
N
REGI
STRA
TION
PROD
UCTI
ON
OPE
RATI
ON
AL
FRA
MEW
ORK
FO
R PA
ND
EMIC
VAC
CIN
E RE
SPO
NSE
Not
es1.
M
anuf
actu
rers
are
enc
oura
ged
to li
cens
e va
ccin
es a
ppro
ved
for e
mer
genc
y us
e.2.
Fo
rwar
d lo
okin
g ou
tcom
es w
ould
be
esta
blis
hmen
t of g
loba
l gui
delin
es a
nd c
omm
on re
gula
tory
pro
cess
es to
sup
port
fast
trac
king
/che
aper
dev
elop
men
t cos
ts.
3.
App
rova
l pro
cess
prin
cipl
es to
incl
ude:
cla
rity,
tran
spar
ency
, mut
ual r
ecog
nitio
n, ra
pid
acce
ss.
4.
Each
WH
O re
gion
sho
uld
have
suc
h la
bora
torie
s. M
utua
l rec
ogni
tion
proc
edur
es to
be
deve
lope
d.
Reco
gniz
ed s
tand
ards
and
insp
ectio
ns a
re n
eede
d, E
U c
an b
e se
en a
s as
a m
odel
.5.
In
crea
sed
confi
denc
e am
ong
HCW
and
pub
lic. E
nsur
e ca
se d
efini
tions
are
ava
ilabl
e fo
r AEF
Is.
Activ
ities
Coordinating Entities
Chan
nels
to
Com
mun
icate
th
e Out
com
esPa
rtici
patin
g En
titie
sOu
tcom
esDo
ssier
rout
e
See #
1 belo
w
WHO
, man
ufac
ture
rs,
natio
nal a
nd re
giona
l (e
.g. EM
A) re
gulat
ing
auth
oriti
es
WHO
, Re
gulat
ors
Appr
oval/
no ap
prov
al
Enha
nced
/fast-
track
ed
appr
oval
proc
ess
See #
2 belo
w
Guide
lines
Web
site
Wor
ksho
ps to
crea
te
unde
rstan
ding o
f the
pr
oces
ses
Emer
genc
y rou
teW
HO, m
anuf
actu
rers,
na
tiona
l and
regio
nal (e
.g.
EMA)
regu
lating
auth
oriti
es
WHO
, Re
gulat
ors
Appr
oval/
no ap
prov
al
Enha
nced
/fast-
track
ed
appr
oval
proc
ess
See #
3 belo
w
Guide
lines
Web
site
Wor
ksho
ps to
crea
te
unde
rstan
ding o
f the
pr
oces
ses
Regu
lator
y ove
rsigh
t to
assu
re th
e qua
lity o
f pa
ndem
ic va
ccine
s.
Exiti
ng lo
t rele
ase l
abs
includ
ing W
HO ER
Ls an
d NC
Ls
Regu
lator
y Ne
twor
k/W
HO
Deve
lopm
ent o
f a fo
rmal
netw
ork o
f rele
ase
labor
ator
ies to
enha
nce
avail
abilit
y of p
ande
mic
vacc
ine
Clear
set o
f assa
ys to
str
eam
line p
roce
ss
See #
4 belo
w
Web
sites
, wor
ksho
ps,
writt
en st
anda
rds,
mem
bersh
ip cri
teria
Risk
man
agem
ent,
safet
y mon
itorin
g, sig
nal
dete
ction
Vacc
ine eff
ectiv
enes
s qu
antifi
catio
n of a
dver
se
effec
ts, ex
posu
re da
ta
Bene
fit /
risk a
ssessm
ent
Healt
h car
e wor
kers,
re
gulat
ors,
publi
c hea
lth
imm
uniza
tion p
rogr
ams,
man
ufac
ture
rs
Natio
nal
Regu
lator
y Au
thor
ities
, W
HO
Impr
oved
safet
y asse
ssmen
t an
d mon
itorin
g sys
tem
Incre
ased
use o
f too
ls
(mod
els, e
tc.)
See #
5 belo
w
HCW,
publi
c hea
lth
orga
nizat
ions,
man
ufac
ture
rs,
inter
natio
nal e
xcha
nge o
f sa
fety d
ata/
signa
ls via
WHO
/SA
GE/G
ACVS
Distr
ibutio
n and
co
mm
unica
tions
Pand
emic
Vacc
ine
Deplo
ymen
t Plan
Healt
h aut
horit
ies
SAGE
Healt
h and
loc
al au
thor
ities
SAGE
Distr
ibutio
n,
avail
abilit
y, ea
rly AD
RsHe
alth a
utho
rities
and N
CLs
ERLs
via T
Cs or
or ot
her
chan
nels
Registration Process &Pre-qualification Process
Pharmacovigilance Vaccine RolloutLot Release5
REGI
STRA
TION
CLIN
ICAL
EV
ALUA
TION
GL
OSSA
RY
AD
R Ad
vers
e D
rug
Reac
tion
AEF
I Ad
vers
e Ev
ent F
ollo
win
g Im
mun
izat
ion
BLA
Bi
olog
ics L
icen
se A
pplic
atio
n*
BSL2
+ Bi
osaf
ety
leve
l 2+
CVV
Ca
ndid
ate
Vacc
ine
Viru
sD
CVM
N
Dev
elop
ing
Coun
trie
s Vac
cine
Man
ufac
ture
rs N
etw
ork
ECD
C Eu
rope
an C
entr
e fo
r Dise
ase
Prev
entio
n an
d Co
ntro
lEM
A
Euro
pean
Med
icin
es A
genc
yEU
A
Emer
genc
y U
se A
utho
rizat
ion*
FA
O
Food
and
Agr
icul
ture
Org
aniz
atio
n of
the
UN
FLU
COP
EU re
sear
ch c
onso
rtiu
m h
ttp:
//w
ww
.fluc
op.e
u/G
ACV
S W
HO
Glo
bal A
dviso
ry C
omm
ittee
on
Vacc
ine
Safe
tyG
AP
WH
O G
loba
l Act
ion
Plan
for I
nflue
nza
Vacc
ines
GIS
RS
Glo
bal I
nflue
nza
Surv
eilla
nce
& Re
spon
se S
yste
mG
MO
G
enet
ical
ly M
odifi
ed O
rgan
ismG
MP
Goo
d M
anuf
actu
ring
Prac
tice
HCW
H
ealth
Car
e W
orke
rIH
R In
tern
atio
nal H
ealth
Reg
ulat
ions
(200
5)IF
PMA
In
tern
atio
nal F
eder
atio
n of
Pha
rmac
eutic
al
Man
ufac
ture
rs &
Ass
ocia
tions
IND
In
vest
igat
iona
l New
Dru
g*
NCL
s N
atio
nal C
ontr
ol L
abor
ator
ies
NRA
s N
atio
nal R
egul
ator
y Au
thor
ities
OIE
W
orld
Org
aniz
atio
n fo
r Ani
mal
Hea
lthPH
EIC
Pu
blic
Hea
lth E
mer
genc
y of
Inte
rnat
iona
l Con
cern
PIP
Pand
emic
Influ
enza
Pre
pare
dnes
sPI
RM
Pand
emic
Influ
enza
Risk
Man
agem
ent
RG
Reve
rse
Gen
etic
sSA
GE
Stra
tegi
c Ad
viso
ry G
roup
of E
xper
ts o
n Im
mun
izat
ion
SRID
Si
ngle
Rad
ial I
mm
unod
iffus
ion
TIPR
A
Tool
for I
nflue
nza
Pand
emic
Risk
Ass
essm
ent
VRB
PAC
US
Vacc
ines
and
Rel
ated
Bio
logi
cal P
rodu
cts A
dviso
ry C
omm
ittee
US
NIH
/CD
C U
S N
atio
nal I
nstit
utes
of H
ealth
/Cen
tres
for D
iseas
e
Cont
rol a
nd P
reve
ntio
nW
HO
CCs
W
HO
Col
labo
ratin
g Ce
ntre
sW
HO
ERL
s W
HO
Ess
entia
l Reg
ulat
ory
Labo
rato
ry*
USA
regu
lato
ry m
echa
nism
23
AN
NEX
2 –
Dra
ft o
pera
tiona
l fra
mew
ork
for
pand
emic
vac
cine
res
pons
e
| Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT
AN
NEX
3 –
Tim
elin
es o
f pa
ndem
ic v
acci
ne p
rodu
ctio
n
19
VERS
ION
26.
10.2
016
TIM
ELIN
E O
F PA
ND
EMIC
VAC
CIN
E PR
OD
UC
TIO
N
1
2
3 4
5 6
7 8
9 10
11
12
13
14
15
16
17
18
19
20
21
2
2
23
24
ACTI
VITI
ES
ACTI
ONS
WEE
K NU
MBE
R SI
NCE W
HO R
ECOM
MEN
DATI
ON O
F PAN
DEM
IC VI
RUS
(gen
etic
sequ
ence
upl
oad)
ENTI
TIES
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
COM
MEN
TS A
ND P
OTEN
TIAL
ISSU
ES
Lin
eLin
eLin
e
14
Us
ed by
EU an
d cou
ntrie
s/NRA
s tha
t foll
ow th
e EMA
. Assu
mes
that
the m
anuf
actu
ring
proc
ess f
or th
e em
ergin
g pan
dem
ic vir
us w
ill be
the s
ame a
s tha
t for
seas
onal
vacc
ine vi
ruse
s. Ea
rly di
scus
sions
with
NRA
esse
ntial
.
15
Emer
genc
y use
appr
oval
may
be gi
ven p
rior t
o fina
l regis
tratio
n. Ea
rly di
scus
sions
wi
th N
RA es
sent
ial.
16
All m
anuf
actu
rers
shou
ld ide
ally s
eek r
egist
ratio
n of t
he va
ccine
not o
nly m
ock d
ossie
r app
rova
l an
d/or
emer
genc
y use
.
17
This
is th
e bat
ch re
lease
proc
ess.
Faste
r alte
rnat
ive te
sts su
ch as
ELISA
tests
could
also
be us
ed
in ad
dition
to SR
ID to
asse
ss po
tenc
y. En
doto
xin te
sts ar
e esse
ntial
as ar
e oth
er lo
t rele
ase
requ
irem
ents.
. Abo
ut 4
to 6
days
are n
eede
d.
18
AEFI
mon
itorin
g by t
he N
RA an
d oth
er sp
ecial
ist gr
oups
, web
-bas
ed re
porti
ng an
d sen
tinel
mon
itorin
g. Th
is wo
uld oc
cur b
eyon
d the
14 w
eek m
ark.
19
Distr
ibutio
n by p
rogr
amm
e man
ager
s to s
ites.
Roll-
out p
riorit
y to b
e det
erm
ined a
ccord
ing
to th
e pan
dem
ic pla
n. To
cont
inue b
eyon
d the
wee
k 14 m
ark.
CV
Vs ar
e sele
cted b
y the
WHO
CCs.
RG re
asso
rtant
s will
take
abou
t 19 d
ays,
classi
cal
reas
sorta
nts a
bout
21 da
ys. S
ynth
etic
seed
s may
also
be an
optio
n. Sa
fety t
estin
g TBD
, but
if th
e CVV
is de
rived
from
a hig
hly p
atho
genic
viru
s, it
will n
eed t
o be e
valua
ted f
or ex
clusio
n fro
m “S
elect
Agen
t” sta
tus i
n the
USA
and i
f the
CVV i
s der
ived b
y rev
erse
gene
tics i
t will
need
to
com
ply w
ith EU
GM
O re
gulat
ions.
CVVs
are g
ener
ally N
OT di
stribu
ted u
ntil S
teril
ity Te
st co
mple
te &
at le
ast a
1-wa
y HI b
ut in
a pa
ndem
ic sit
uatio
n the
y cou
ld be
distr
ibute
d pen
ding
HI an
d ste
rility
data
. WHO
will
give c
lear g
uidan
ce on
bioc
onta
inmen
t and
a ris
k asse
ssmen
t of
seve
rity,
trans
miss
ibilit
y and
epide
miol
ogy a
ssocia
ted w
ith th
e em
ergin
g viru
s.
2 Ch
eckin
g gen
e seq
uenc
es, g
ene c
onste
llatio
n and
perfo
rming
one a
nd tw
o way
tests
.
4
Poor
yield
s migh
t res
ult in
delay
s in v
accin
e sup
ply to
larg
e pop
ulatio
ns.
5 Es
sent
ial to
begin
a cli
nical
trial
if req
uired
(pha
se 1)
. Som
e cou
ntrie
s will
requ
ire a
clinic
al tri
al if t
he em
ergin
g pan
dem
ic su
btyp
e has
little
or no
clini
cal d
ata.
HA co
nten
t and
dosin
g sch
edule
will
not b
e kno
wn fo
r a ne
w su
btyp
e. Ad
ults a
nd ol
der a
dults
shou
ld be
inclu
ded i
n th
e tria
l. It i
s exp
ecte
d tha
t a ha
lf dos
e x 2
would
be gi
ven t
o chil
dren
as fo
r sea
sona
l vac
cine.
6 Th
e ear
ly sta
ges o
f plan
ning a
nd re
cruitm
ent w
ill ha
ve ta
ken p
lace e
arlie
r tha
n this
.
7
Base
line s
erolo
gy an
d the
n at 2
and 4
wee
ks af
ter in
jectio
n.
8
ADRs
need
to be
mon
itore
d esp
ecial
ly in
the fi
rst pa
rt of
the c
linica
l tria
l and
then
in th
e field
as
a pha
rmac
ovigi
lance
stud
y dep
endin
g on t
he N
RA. T
his w
ould
occu
r bey
ond t
he 14
wee
k mar
k.
9
Th
e pro
ducti
on of
a m
onov
alent
vacc
ine ca
n tak
e plac
e ear
ly wi
th ex
pecte
d lot
relea
se la
ter.
Man
ufac
ture
rs ne
ed to
supp
ly an
tigen
to ER
Ls as
soon
as po
ssible
for r
eage
nt pr
epar
ation
.
11/1
2
The p
rodu
ction
of sh
eep s
era i
s crit
ical a
nd a
majo
r bot
tlene
ck in
the p
roce
ss.
13
Idea
lly th
e 4 W
HO ER
Ls w
ould
calib
rate
the r
eage
nts.
But i
f tim
e is o
f the
esse
nce,
the r
eage
nt
can b
e cali
brat
ed lo
cally
to sa
ve ti
me,
e.g., b
etwe
en th
e ERL
and t
he m
anuf
actu
rer o
r ano
ther
co
mpe
tent
labo
rato
ry, th
e opt
ion to
prep
are a
nd ca
libra
te on
e set
of re
agen
ts to
redu
ce th
e wo
rkloa
d of c
ross
calib
ratio
n, an
d alte
rnat
ive te
sts su
ch as
ELISA
tests
to be
cons
idere
d pen
ding
relev
ant N
RA ap
prov
al.
COM
MEN
TS A
ND P
OTEN
TIAL
ISSU
ES
CO
MM
ENTS
AND
POT
ENTI
AL IS
SUES
1, 2,
3 and
4
{Th
is tim
eline
is in
idea
l circ
umsta
nces
whe
n eve
ryth
ing go
es w
ell. If
som
e acti
vities
do no
t go w
ell, t
hey m
ay ta
ke lo
nger
and t
his is
indic
ated
in th
e hat
ched
area
s of t
he ch
art.
Due t
o the
inte
r-rela
tedn
ess o
f man
y of t
he ac
tiviti
es, a
delay
in on
e acti
vity w
ould
delay
othe
rs in
the t
imeli
ne.
Prog
ram
me
man
ager
sVa
ccin
e D
istr
ibut
ion
Vacc
ine
avai
labl
e fo
r dep
loym
ent
Reas
sort
ing
Labs
WH
O C
Cs a
nd R
eass
ortin
g La
bs
Man
ufac
ture
rs
ERLs
Regu
lato
ry A
utho
ritie
s
Reas
sort
ant d
evel
opm
ent
Reas
sort
ant e
valu
atio
n
Reas
sort
ant a
sses
smen
tD
evel
opm
ent
Clin
ical
tria
ls
Vacc
ine
Prod
uctio
n
Reag
ents
Regu
latio
n
Lot r
elea
sePh
arm
acov
igile
nce
Dev
elop
men
t of C
VVs
for d
istr
ibut
ion
CVVs
cha
ract
eriz
atio
n in
clud
ing
safe
ty a
nd s
hipp
ing
Bios
afet
y/G
MO
app
rova
lCV
Vs Y
ield
and
gro
wth
cha
ract
eris
tics
Clin
ical
lot p
rodu
ctio
n Re
crui
tmen
t and
Exe
cutio
nSe
rolo
gyA
DR
mon
itorin
g A
ntig
en p
rodu
ctio
nVa
ccin
e Fo
rmul
atio
n/Pa
ckag
ing/
Dis
trib
utio
nPr
epar
atio
n of
pur
ified
HA
(for
she
ep im
mun
isat
ion)
Prod
uctio
n of
reag
ents
Calib
ratio
ns a
nd s
uppl
y of
reag
ents
Stra
in v
aria
tion
in m
ock
doss
ier
Emer
genc
y us
e ap
prov
alRe
gist
ratio
n pr
oces
sSR
ID a
nd E
ndot
oxin
test
s, co
ld c
hain
revi
ewA
EFI m
onito
ring
24
Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
ANNEX 4 – Process of the WHO vaccine response to an influenza pandemic or a potential pandemic
20
PROCESS FOR WHO PANDEMIC VACCINE RESPONSE TO INFLUENZA PANDEMICS/POTENTIAL PANDEMICS
DETECTION OF A NOVEL
VIRUS IN HUMANS
Preliminary global RA by GISRS including epidemiology, transmissibility and severity of
the disease associated with the virus
Selection of candidate viruses by GISRS
Biosafety assessment of CVVs by WHO
Further virus characterization by WHO CCs
IHR notification. Assessment of CVVs
by WHO and WHO CCs
Assessment of need for HGR development
Need to develop
Potentially significant to public health?
Development of high-growth reassortants by GISRSand other laboratories
Initiation of the development of potency reagents by GISRS
Distribution of high-growth reassortants
Yield evaluation by manufacturers and GISRS
RA on further vaccine development
Assessment if results warrant
production/use of pandemic/
pre-pandemic vaccines
Availability of potency reagents by GISRS
Clinical trials if needed
National/regional licensing/stockpiling as appropriate
Continuous update to SAGE; updates to member states, and other stakeholders as appropriate
WHO declaration of pandemic
Large-scale production/ release of vaccines for use by country/region
YES
NO
GLOSSARY
CVV Candidate Vaccine Virus
GISRS WHO Global Influenza Surveillance and Response System
HGRHigh growth reassortant
IHR International Health Regulations (2005)
RA Risk Assessment
SAGE WHO Strategic Advisory Group of Experts on Immunization
WHO CC WHO Collaborating Centre of GISRS
WHO ERL WHO Essential Regulatory Laboratory
Review of the use of pandemic/ pre-pandemicand seasonal vaccines by WHO, SAGE and other experts
Further vaccine
development/ licensing/
stockpiling
WHO recommendation on pandemic vaccine production and use
Y E S
YES
NO
VERSION 30.09.2016
Continuous assessment by WHOs IHR, SAGE and subject experts, as well as industry and stakeholders on:
1. Epidemiology, including severity assessment
2. Virology
3. Biosafety assessment
4. The status of seasonal vaccine production
5. The need for pandemic or pre-pandemic vaccines
6. The risks associated with switch from seasonal to pandemic production
7. The risks associated with switch back to seasonal vaccine production
NO
NO
YES
(a) HGR(s)(b) alternative
vaccine viruses?
1 Need a decision whether CVV is covered by Nagoya Protocol
1
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ANNEX 5Further Activities: the “Parking Lot”
The “parking lot” was a list of comments relevant to the informal consultation but not considered in depth. Some of the Parking Lot comments and proposals from the first Consultation have now been incorporated into Section 5.2 Bottlenecks of this report. The remaining Parking Lot items could be considered as part of forward agendas in future meetings. New proposals from the 2016 consultation are in italics.
Key proposals
Communication• Improve sharing of information including
genetic, sequence and epidemiological data.• Review how WHO communicates to
stakeholders in an emergency.
Research • Promote Gain of Function research.• Further surveillance information on the
spread of pandemic viruses and seasonal viruses concurrently. What is the likelihood of a pandemic virus displacing seasonal viruses?
Future meetings• Hold a specific consultation on research
and development of current and future pandemic vaccines.
Other activities• Finalize the risk assessment tool (TIPRA).• Update national pandemic preparedness
plans.• Consider adding administration procedures
in pandemic plans.
• What preservatives are to be recommended for pandemic vaccines?
• If an adjuvant is needed for pandemic vaccine and not all manufacturers have access to an effective adjuvant, what plans are in place to share adjuvants?
• What is the process to stop pandemic vaccine production?
Further proposals• Harmonize vaccine distribution, shipping,
logistics, and cold chain.• Include recombinant, cell based and
live vaccines in future consultations on pandemic vaccine response.
• Review new technology platforms to speed up production of current vaccines.
• Review the need and progress of potentially more effective vaccine, including adjuvanted and universal vaccines.
• Post-release observational vaccine effectiveness studies, especially among elderly vaccines, should be undertaken.
• Behavioural analysis: how do people actually behave in a pandemic? E.g., politicians, medical profession and the public.
• Pharmacovigilence should be strengthened globally.
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ANNEX 6 List of Participants
Dr Ian BarrWHO Collaborating Centre for Reference and Research on Influenza Peter Doherty Institute for Infection and Immunity 792 Elizabeth St, MelbourneVictoria 3000Australia
Dr William CracknellR&D Influenza OperationsbioCSL45 Poplar Road3052 - Parkville, VictoriaParkvilleAustralia
Dr Armen DonabedianInfluenza Division/Biomedical Advanced Research and Development Authority (BARDA)/HHS/ASPRDepartment of Health and Human Services330 Independence Avenue SW, Rm G640Washington, DC 20201USA
Dr Matthew DownhammManufacturing Science & TechnologyAstraZeneca OperationsRenaissance Way, Boulevard Industry ParkLiverpool L24 9JWUK
Mr Derek EllisConversArt Consulting1 Inwood DriveOttawa, Ontario K2M2A4Canada
Dr Othmar EngelhardtWHO Essential Regulatory LaboratoryDivision of VirologyNational Institute for Biological Standards and Control (NIBSC)Blanche Lane, South MimmsPotters BarHertfordshireEN6 3QGUK
Dr Bruce GellinNational Institutes of Health (NIH)National Vaccine Program Office (NVPO)U.S. Department of Health and Human Services200 Independence Avenue, S.W.Washington, DC 20201USA
Dr Kari JohansenExpert Influenza and other Vaccine Preventable DiseasesSurveillance and Response Support UnitEuropean Center for Disease Prevention and ControlSE 171 83 StockholmStockholmSweden
Dr Jacqueline KatzWHO Collaborating Centre for Surveillance Epidemiology and Control of InfluenzaCenters for Disease Control and Prevention (CDC)Influenza BranchMS G16, 1600 Clifton RoadAtlanta GA 30333USA
Dr Sam LeeSanofi PasteurPandemic & New Influenza ProductsDiscovery DriveSwiftwater, PA 18370-0187USA
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Dr John McCauleyCrick Worldwide Influenza CentreThe Francis Crick InstituteMill Hill LaboratoryThe Ridgeway, Mill HillLondon NW7 1AAUK
Dr Heidi MeyerPaul-Ehrlich-Institut International CooperationRegulatory Services HessenGermany
Dr Hartmut NedebockPandemic Influenza ResponseGlaxoSmithKline Vaccines20, Avenue Fleming, Building W231300 WavreBelgium
Dr Elisabeth NeumeierManufacturing Sciences & PLCMGlaxoSmithKline BiologicalsNL der SB Pharma GmbH & Co. KGZirkusstraße 40, 01069 DresdenGermany
Daniel NormandeauConversArt Consulting1651 promenade Autumn Ridge DriveOttawa, Ontario K1C 6Y1Canada Dr Bram PalacheInfluenza VacccinesAbbott BiologicalsC. J. van Houtenlaan 361381 CP - WeespThe Netherlands
Dr Pasi PenttinenDisease Programme for Influenza and other Respiratory VirusesEuropean Centre for Disease Prevention and Control (ECDC)Tomtebodavägen 11a171 83 StockholmSweden
Dr Jean-Luc SionEuropean CommissionDG SANTEUnit C3 Health ThreatsHITEC 02/95L-2920-Luxembourg Kirchberg
Dr Stepanie SonnbergScientist504 S. Rosa RdSuite 200Madison, WI 53719 USA
Dr Beverly TaylorTechnology and Scientific AffairsNovartisGaskill Road, SpekeLiverpool, L24 9GRUK
Dr Theodore TsaiTakeda Vaccines40 Landsdowne StCambridge, MA 02139USA
Dr John Martin WatsonDepartment of Health510, Wellington House133-144 Waterloo RoadSD1 8UG - LondonUK
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Influenza Vaccine Response during the Start of a Pandemic – 2nd WHO Informal Consultation REPORT |
Dr Richard WebbyWHO Collaborating Centre for Studies on the Ecology of Influenza in AnimalsSt Jude Childrens Research HospitalDepartment Virology & Molecular Biology332 N. Lauderdale StMemphis TN 38105, USA
Dr Jerry WeirDivision of Viral ProductsCenter for Biologics Evaluation and ResearchFood and Drug Administration10903 New Hampshire AvenueSilver Spring, MD 20993USA
Dr John WoodDivision of VirologyNational Institute for Biological Standards and Control (NIBSC)Blanche Lane, South Mimms EN6 3QG - Potters Bar, HertsUK
Ms Margarita Xydia-CharmantaVaccines PolicyInternational Federation of Pharmaceutical Manufactures & AssociationsChemin des MinesP.O. Box 1951211 Geneva 20Switzerland
Dr Seyed Mohsen ZahraeiCentre for Disease Control Water & Food Borne Diseases DepartmentMinistry of Health and Medical EducationTehranIslamic Republic of Iran
WHO SECRETARIAT
Claudia Alfonso HQ/HIS/EMP/RHT/RSS
Hien Doan WHO/HQ/HSE/GIP
Martin Friede HQ/HIS/EMP/PHI
Gary Grohmann WHO/HQ/HSE/GIP
Joachim Hombach HQ/FWC/IVB/IVR
Marie-Paul Kieny HQ/HIS/HIA
Sasha Kontic HQ/HSE/PED/HIP
Philippe Lambach HQ/FWC/IVB/IVR
Justin Ortiz HQ/IVB
Laszlo Palkonyay HQ/HIS/EMP/RHT/PQT
Gina Samaan HQ/HIP
Guido Torelli HQ/HIS/EMP/PHI
Katelijn Vandemaele WHO/HQ/HSE/GIP
Wenqing Zhang WHO/HQ/HSE/GIP
Tiequn Zhou HQ/HIS/EMP/RHT/TSN
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