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Section A: Summary
This report presents a detailed briefing on pandemic influenza in response
to the June 2018 Board request as part of the Vaccine Investment Strategy
(VIS) 2018. It includes a review of the landscape, gap analysis and
preliminary assessment of potential options for Gavi engagement.
The Board is asked to approve a learning agenda (with financial implications
of approximately US$ 4 million from 2019-2022), to be developed with
WHO, on the use of routine immunisation of healthcare workers with
seasonal influenza vaccines to strengthen countries’ pandemic
preparedness.
Section B: Detailed Briefing on Pandemic Influenza
Introduction
1.1 The Gavi Board approved an approach and set of evaluation criteria for
considering vaccine investments for epidemic preparedness and response
in June 2018, within the overarching Vaccine Investment Strategy (VIS)
2018.
1 This approach comprises three steps: firstly, identification, with
WHO, of vaccines for consideration; secondly, development of a ‘living
assessment’ as vaccine development progresses; and finally, a full
investment case for Board consideration. Progression through each stage
is determined by pre-defined triggers.
2
1.2 Given that pandemic influenza meets the ‘trigger’ for an investment case3
,
the Board requested the Secretariat, in consultation with WHO and experts,
to prepare an extensive briefing on pandemic influenza preparedness and
bring a related investment case if appropriate.
4 As pandemic influenza is an
outlier in terms of both the exceptional global threat that it poses and the
1 https://www.gavi.org/about/governance/gavi-board/minutes/2018/6-june/minutes/07---vaccineinvestment-strategy---short-list/
2 A ‘living assessment’ would be developed once preliminary safety and immunogenicity data is
available for the vaccine (Phase 2a/b). An investment case would be developed once there is a
defined pathway to vaccine licensure in the short-term (e.g., 1 year), major public health need or
update of a WHO use recommendation.
3 Based on the availability of licensed product(s) and WHO recommendation
4 The focus of this briefing is on pandemic influenza, however seasonal influenza is important for
pandemic preparedness as demand for seasonal influenza supports global manufacturing capacity.
SUBJECT: PANDEMIC INFLUENZA PREPAREDNESS
Agenda item: 13
Category: For Decision
Report to the Board
28-29 November 2018
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extent of current risk mitigation efforts, this briefing draws from the
evaluation framework, but also includes more detail on the role of WHO and
the broader pandemic preparedness and response landscape.
1.3 Gavi’s role in pandemic influenza has been discussed at multiple points in
the past. Following the 2005 H5N1 pandemic, the Board recommended that
Gavi focus on safeguarding routine immunisation in an influenza pandemic
and increasing uptake of vaccines that contribute to secondary infections in
a pandemic (e.g., pneumococcal). During the 2009 H1N1 pandemic, WHO
did not propose a specific role for Gavi in the response, and following the
pandemic WHO initiated a number of activities to improve preparedness.
This analysis reconsiders Gavi’s potential role in pandemic influenza
preparedness based on assessment of current needs and gaps and in the
context of Gavi’s comparative advantage relative to other actors.5,6
1.4 Based on extensive consultations
7 and a gap analysis, the Secretariat
focused the briefing on consideration of the potential impact of: a)
reserving/subsidising production capacity and b) market signals for new
vaccine technology to improve pandemic vaccine supply; establishing
routine immunisation in priority groups to improve vaccine delivery in a
pandemic. Please refer to Appendix 1 for additional detail beyond what is
summarised in this report.
Disease risk and burden
2.1 Influenza viruses pose a global threat because they are highly diverse,
evolve rapidly in human and animal hosts, and can cause disease of varying
severity (including secondary bacterial infections which may require
antibiotics and contribute to antimicrobial resistance). Annually, the
circulation of seasonal influenza viruses causes 3-5 million cases of severe
illness and between 290,000 and 650,000 respiratory deaths. Influenza
pandemics occur with the emergence of a new influenza sub-type to which
the human population has limited immunity and which is able to spread
efficiently between human hosts. Together with classic public health
measures, vaccines play a critical role in reducing the severity and
transmission of both seasonal and pandemic influenza.
2.2 As exemplified by the 1918 pandemic, which killed between 50 and 100
million people, influenza pandemics represent a major global threat in terms
5 Gavi has also considered support for routine influenza immunisation in the past, focusing on
impact on seasonal influenza rather than pandemic preparedness. Most recently, in Phase 2 of the
VIS 2018, routine immunisation in pregnant women was assessed but not considered to merit a
case for investment based on low projected mortality and morbidity impact.
6 This briefing focuses on pandemic preparedness. In the event of a pandemic, Gavi would work
with WHO and partners to support the response in Gavi-supported countries through existing
policies (e.g., reprogramming of HSS through the Fragility, Emergencies, Refugees Policy) or other
efforts.
7 The VIS 2018 Phase 3 country consultations included 96 survey responses and 28 discussions
with stakeholders from 17 countries. The VIS Steering Committee provided technical and strategic
guidance, and experts were consulted on specific topic areas.
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of morbidity, mortality and impact on health systems and economies. The
1918 pandemic killed almost as many South Africans as Americans and was
considered the worst natural disaster in the country’s history. The single
patient group most likely to die was pregnant women with a death rate of
23-71%. Analyses show that the impact of pandemics is disproportionately
high in low income countries, exacerbated by weak health systems and
limited access to interventions for prevention and treatment.
8 A modelling
analysis of a potential future pandemic projects that 96% of deaths would
occur in non-OECD countries. To put the overall risk of influenza pandemics
in perspective, a recent study estimates that a severe influenza pandemic
could have a death toll 2500 times higher than the 2013-2016 Ebola virus
disease outbreak.
Current landscape and strategic context
3.1 As the agency responsible for leading global pandemic influenza
preparedness and response efforts, WHO oversees a number of activities
to: strengthen pandemic and epidemic preparedness (such as the
International Health Regulations and the Joint External Evaluation 9
);
support the development of global and national influenza programmes (such
as the Global Influenza Programme, Global Influenza Surveillance and
Response System, National Pandemic Preparedness plans); and
strengthen supply security and access to both seasonal and pandemic
influenza vaccines (such as the Global Action Plan for Influenza Vaccines
2006-2016, and the Pandemic Influenza Preparedness [PIP] Framework).
A new SAGE Working Group on Influenza Vaccines has been established
and is expected to report in 2019/2020.
3.2 Alliance and broader partners are also engaged in specific efforts to support
pandemic influenza preparedness and response that complement WHO’s
activities. For example, the US Centers for Disease Control and Prevention
(CDC) and One Health Partners play a role in influenza surveillance and the
links between human, animal and environmental health; the Taskforce for
Global Health’s Partnership for Influenza Vaccine Introduction (PIVI)
programme supports establishment of seasonal influenza programmes in
MICs; UNICEF and PAHO procure influenza vaccine for routine
immunisation in developing countries; the Bill & Melinda Gates Foundation,
Sabin and others are supporting R&D for next generation/universal
influenza vaccine candidates; and the World Bank, through its Pandemic
Emergency Financing Facility, has a role in financing for pandemic
response. Further information on the current landscape of activities and
roles and responsibilities of different actors is provided in Appendix 1.
3.3 WHO is currently developing a new ‘Global Influenza Strategy 2018-2030’
(expected by Q1 2019, see Appendix 2 for draft summary) which
consolidates existing efforts, focusing on three strategic priorities:
8 Risk mitigation efforts include surveillance (GISRS), risk assessment of new/ emerging strains
(PISA), data and sample sharing, and capacity for rapid pandemic vaccine production.
9 Within the JEE process, 16 of 19 indicators are focused on, or relate to, influenza.
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I. strengthening pandemic preparedness and response for influenza;
II. expanding seasonal influenza prevention and control policies and
programmes to protect the vulnerable (highlighting health care
workers and/or other high-risk groups); and,
III. promoting research and innovation to address unmet public health
needs.
3.4 This briefing has been developed in close consultation with WHO, reflecting
both their guidance and experience from existing programmes and the new
strategy. The analysis considers how Gavi’s efforts could be integral to
addressing these priorities, including contributing to equity and
sustainability, addressing the bottlenecks described in the 2009 pandemic
and expanding WHO’s external partnerships.
Timely supply of pandemic vaccine
4.1 The 2011 PIP Framework secures, in real time, up to an estimated 425
million doses of vaccine for WHO to distribute in an influenza pandemic to
countries without access. 10 However, limitations of current vaccine
technology constrains the potential impact of the PIP supply agreements.
Since vaccine viruses have to be matched to the pandemic strain, vaccine
cannot be produced in advance and stockpiled. In addition, the speed of
vaccine production is slow relative to pandemic spread: it can take ~5
months or longer for the first dose of pandemic vaccine to be produced.
4.2 Using WHO ideal assumptions for vaccine production speed, the Secretariat
analysed the availability of PIP doses relative to the evolution of a pandemic
based on data from the 2009 H1N1 pandemic.
11 In an ’optimistic’ scenario,
only up to ~30 million doses would be available prior to the hypothetical
pandemic peak. This is enough to cover the smallest priority group in PIP
countries, healthcare workers, but no others. The majority of doses would
become available later in the pandemic when the mortality/morbidity impact
of vaccination would be substantially less.
4.3 One approach to increase the timely availability of pandemic vaccine would
be for Gavi to pay manufacturers a fee to hold part of their production and/or
to subsidise expanded production to increase total global volume. While this
would leverage the Alliance’s market shaping expertise, the estimated costs
to reserve sufficient capacity for all high priority groups in Gavi-eligible
countries are high: ~US$ 400-US$ 850 million per year to reserve vaccine
production, excluding the costs of pandemic doses, vaccine delivery and
production capacity expansion. There is also significant risk that the yield
would be less than projected or additional doses would be required. Based
on the assessment of costs and risks, the VIS Steering Committee (SC) and
PPC supported the view that Gavi should not further explore this approach.
10 WHO PIP Framework website (last accessed August 2018); personal communication with WHO;
includes both donated vaccine and vaccine available at affordable pricing
11 2009 was widely considered to be a ‘best-case’ scenario given the subtype, speed of
transmission, disease severity and geographic source. See Appendix 2 for additional detail on
assumptions.
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4.4 Alternatively, Gavi could provide financial incentives (e.g., similar to an
Advance Market Commitment) for new technologies such as novel
platforms and cross-protective vaccines, which could reduce vaccine
production time or enable pre-pandemic stockpiling. Based on expert
consultation, this is not recommended at this time given uncertain
timeframes and the limited value of a signal given barriers are likely to be
technical or scientific rather than due to lack of investment. However, the
Secretariat will continue to monitor the landscape including the development
of potential alternatives to vaccines in a pandemic.12
Timely delivery of pandemic vaccine
5.1 Even with timely availability of pandemic vaccine through PIP, lack of
national systems for regulatory approval and vaccine delivery may delay
administration of vaccines in priority groups. This could also limit the future
impact of next generation influenza vaccines. A 2011 External Review for
WHO13 emphasised the lack of national capacity to accept, approve and
distribute pandemic vaccine to priority groups in the 2009/2010 pandemic.
As an indicator of countries’ limited capacity to utilise pandemic vaccine, in
2009 only 78 million of 120 million donated doses were delivered to
countries.14
5.2 One solution is to strengthen routine immunisation programmes for delivery
of seasonal influenza vaccine, since key activities for routine immunisation
provide the foundation for pandemic response.15 Preliminary analysis of the
2009/2010 pandemic by WHO/CDC found that countries with functional,
public seasonal influenza programmes were over twice as likely to get
influenza vaccine before the end of the pandemic as countries without.
5.3 Given the systems impact, a strategy for routine immunisation in one priority
group would likely accelerate vaccine delivery to all high priority groups in a
pandemic. Of the priority groups for seasonal influenza immunisation, there
is a strong case for focusing on healthcare workers: contribution to
maintaining health systems; relatively low cost given the small cohort size16;
link with the Universal Health Care 2030 agenda; and ethical principles of
justice, given their increased risk. There is also evidence that healthcare
workers’ acceptance of influenza vaccine influences community vaccine
confidence and uptake. A delivery platform would also enable more efficient
immunisation of healthcare workers against other vaccine preventable
diseases (e.g., hepatitis B) and emerging diseases (e.g. Ebola).
12 Novel vaccines and antibodies offering cross strain protection or long-term protection and new
vaccine, platform and delivery technologies were explored. New therapeutics were not explored.
13 2011 Report of the Review Committee on the Functioning of the International Health Regulations
(2005) in relation to Pandemic Influenza A (H1N1) 2009
14 In order to receive doses countries had to provide information to WHO on planning for regulatory
approval and vaccine delivery
15 E.g., regulatory approval, policy development, surveillance, delivery platform, pharmacovigilance
16 For the period of 2020-2035, the total cost of vaccine procurement for routine immunisation of
healthcare workers in Gavi-eligible countries would be ~US$ 56 million compared with
~US$ 991 million for pregnant women. This excludes costs for establishing the platform and
delivery.
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Learning agenda for routine immunisation of healthcare workers
6.1 While routine immunisation in a priority group has significant potential for
impact by improving vaccine delivery in a pandemic, there are a number of
outstanding issues and open questions. In consultations, country
stakeholders anticipated challenges to establishing routine immunisation
programmes for healthcare workers. They highlighted the need for:
regulatory processes; approaches to define and register the population;
development of immunisation policy for adults; and evidence-based
approaches to increase vaccine acceptance. There are also questions as to
how this approach could best support accelerated vaccine delivery in a
pandemic and strengthen epidemic preparedness beyond influenza.
6.2 A learning agenda would enable key knowledge and evidence gaps to be
addressed and could also inform consideration of any further investment.
This would be developed in close collaboration with WHO, in support of the
2018-2030 Global Influenza Strategy objectives, and with other partners
working in influenza and epidemic preparedness. Based on preliminary
discussions, the learning agenda might include: review of existing policies
and programmes for healthcare worker immunisation/occupational health;
regulatory processes; policy requirements for the healthcare worker
population, including consideration of sub-populations such as pregnant
women; approaches to identifying and following-up healthcare workers,
recognising that they may be a diverse population; use of vaccine and
requirements for timely delivery; and an overarching evaluation programme
to understand barriers, facilitators, links with other investments in epidemic
preparedness and alignment with other Gavi investments/programmes.
Country selection would take into account factors such as vulnerability to
outbreaks, size of national healthcare worker population and any previous
investment in influenza vaccine delivery (such as PIVI). Learning agenda
studies may be focus on sub-national populations. Partners have indicated
that Gavi’s role in supporting vaccine use and focus on strengthening
immunisation systems would be a substantial contribution to broader global
efforts.
6.3 The scope of the learning agenda, the evaluation approach and alignment
with the broader influenza public health research agenda would be explored
with partners. Where appropriate, the learning agenda would leverage
existing tools and learnings from other efforts (e.g., the work of PIVI to
promote seasonal influenza immunisation in MICs).
Implications
7.1 Financial implications: The costs associated with the learning agenda are
estimated to be approximately US$ 4 million from 2019-202217. For 2019,
resources will be managed within the existing approved budget, while for
17 Of the US$ 4 million, US$ 2 million is for 2019-2020, of which US$ 1 million is for 2019.
Projections assume costs associated with vaccine procurement; adaptation of existing tools;
technical assistance to support policy and programme development; meetings; and development
of evaluation tools.
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2020 and beyond, resourcing would be addressed as part of the regular
budgeting process.
7.2 Gender implications: Both seasonal and pandemic influenza cause
disproportionate morbidity and mortality burden in pregnant women. Given
that the majority of healthcare workers in low income countries are female
it will also be important in the learning agenda to consider how the needs of
the sub-population that are also pregnant would be addressed. The
recommendation in the PREVENT guidelines as to the ‘presumptive
inclusion of pregnant women’ in vaccine research and delivery programmes
should be considered in the context of pandemic influenza preparedness
and the development of a healthcare worker immunisation programme. 18
Section C: Actions requested of the Board
The Gavi Alliance Programme and Policy Committee recommends to the Gavi
Alliance Board that it:
a) Approve the development of a learning agenda to assess the feasibility and
impact of routine influenza immunisation of healthcare workers to support
epidemic and pandemic influenza preparedness;
b) Note the financial implications associated with the above approval for
2019-2022 are expected to be approximately US$ 4 million, comprised of
approximately US$ 1 million in 2019 (which the Secretariat will strive to absorb
from the Board-approved Partners’ Engagement Framework (PEF) budget for
that year), US$ 1 million in 2020 and US$ 2 million in 2021-2022.
Annexes
Annex A: Implications/Anticipated impact
Additional information available on BoardEffect
Appendix 1: Pandemic Influenza Detailed Briefing
Appendix 2: Summary of Draft WHO Global Strategy for Influenza 2018-2030
Additional reference materials online:
VIS internet page: http://www.gavi.org/about/strategy/vaccine-investmentstrategy/
18 Draft Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT)
guidelines (in preparation); personal communication |