and McCauley, 2018). Avian influenza fears led to a frantic period of vaccine development and global preparations for pandemic influenza, during which issues of equitable access to vaccines and benefits from research on influenza viruses made some stakeholders question the legitimacy of GISN/GISRS, which reached a peak when Indonesia refused to share its H5N1 virus samples with WHO because it believed that it would not receive equitable access to the benefits derived from them (Fidler, 2010). The persistent H5N1 threat called for a wider appreciation of vaccine operations and benefits, as governments began to stockpile vaccines and antivirals, and led to “greater government scrutiny of the fairness of the global system” (Hay and McCauley, 2018).

In March and April 2009, a novel strain of H1N1 spread in Mexico and the United States (WHO, 2012). This ultimately led to the first influenza pandemic of the twenty-first century, which is estimated to have caused 151,000–575,000 deaths (Rockman et al., 2020). Early reports of H1N1 outbreaks activated information-sharing networks among the numerous WHO surveillance units, and the GISRS backbone responded well, in terms of assessing epidemiological information provided by the NICs and characterizing the virus’ antigenic and genetic characteristics at the WHO CCs. The U.S. Centers for Disease Control and Prevention (CDC) officially reported the first cases of H1N1 to WHO on April 18, 2009. On April 29, 2009, WHO convened an emergency committee under the authority of the IHR to make recommendations on whether a pandemic should be declared (Kamradt-Scott et al., 2018). As the cases increased at more than 200 locations around the world, preparations for vaccine production and other responses began. A suitable candidate vaccine virus (CVV) was selected relatively quickly (Ampofo et al., 2012); by late spring, the seasonal vaccine production cycle was nearly at its end and manufacturers were able to begin preparations for dealing with H1N1 (WHO, 2012).

Although it obtained quick surveillance data for H1N1 influenza, WHO did not officially declare a global pandemic until June 11, 2009. Soon thereafter, it launched the WHO Pandemic Influenza A (H1N1) Vaccine Deployment Initiative, which it later deemed to be the “first coordinated global response to an influenza pandemic” (WHO, 2012). Under this initiative, WHO coordinated the support of governments, foundations, and manufacturers to facilitate access to pandemic influenza vaccines in low- and middle-income countries (LMICs). Eventually, millions of vaccine doses, syringes, safety boxes, and other items were donated, and substantial financial and logistical support was pledged.

Despite this novel deployment coordination structure, the H1N1 experience is generally considered to offer a cautionary tale for the challenges of upscaling production of global influenza vaccines and deploying them during a pandemic. Box 2-1 summarizes major gaps in terms of international

coordination for producing and distributing vaccines. Production was not triggered quickly because the switch from seasonal to pandemic vaccine production was poorly coordinated and did not occur until after many seasonal vaccines were already delivered. High-income countries (HICs),

including the United States, set up procurement contracts with manufacturers and began receiving vaccines as early as October 2009. But the majority of vaccines were mostly rolled out after the peak of the pandemic in the fall; by then, demand was low, many doses were wasted, and many low-income

countries received less than planned. The egg-based vaccine also showed generally poor efficacy, which exacerbated issues with public confidence and markets.

Fidler (2010) offered a particularly biting analysis of equity during the 2009–2010 pandemic: “in terms of vaccines for 2009-H1N1, donations from manufacturers and developed countries were not the product of real negotiations, given that WHO and developing countries had little leverage to influence developed countries other than rhetoric about equity, justice, and solidarity.” In the end, wealthy countries

These countries ensured that they had sufficient vaccine to cover their populations when pledging donations, and some—including the United States—postponed donations when they were not politically expedient.

Apart from its role with vaccine production and distribution, WHO faced criticism over the timing of its declaration of a pandemic (a necessary step to initiate the “switch”) and its decision to remove pandemic influenza guidance from its website. Three independent panels found no evidence that WHO had engaged in inappropriate conduct but also recommended significant changes for its responses to health emergencies (Cohen and Carter, 2010; Flynn, 2010; Kamradt-Scott et al., 2018; WHO, 2011).

EXPANDING AND ENHANCING INFLUENZA SURVEILLANCE SINCE 2009

The governance and financing challenges during the 2009 H1N1 pandemic stimulated negotiations that led to the launch of the Pandemic Influenza Preparedness (PIP) Framework in 2011. This framework is a formal, but nonbinding, agreement between WHO member states to improve PPR, with a focus on equity and benefit sharing. Under its governance, when countries share influenza viruses with pandemic potential (IVPP) with GISRS, they are entitled to access specific benefits, including timely access to vaccines, derived from these viruses in a pandemic. The PIP Framework agreement only covers IVPP strains. Pharmaceutical companies who use virus data from GISRS for products (such as vaccines or antivirals) provide in-kind donations or discounted product doses to WHO for deployment during a pandemic and also partner contributions, which are used to bolster capabilities for PPR (such as surveillance) for low-income countries

participating in GISRS. Chapter 3 includes more details about areas of success and persisting gaps in the PIP Framework.

Governance structures such as the PIP Framework and the Nagoya Protocol on Access to Genetic Resources to the Fair and Equitable Sharing of Benefits Arising from Their Utilization of the Convention on Biological Diversity (discussed further in Chapter 3) have yet to be tested in an influenza pandemic. The world can now produce more vaccines than in 2009 but has not yet developed governance or coordination mechanisms to solve serious issues of vaccine access and equity, including the “switch,” poor market-based incentives for producing pandemic vaccines, and deployment and delivery.

Like access and benefit sharing, governance structures for the surveillance and monitoring of zoonotic influenza have evolved significantly since 2009. In 2004, the OIE/FAO Joint Network of Expertise on Animal Influenza (OFFLU) was founded during the peak of the H5N1 (avian influenza) crisis. WHO joined forces with the World Organisation for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) in 2006, with the launch of the Global Early Warning System for Major Animal Diseases, including Zoonosis (GLEWS). This became an early One Health mechanism, linking together the three organizations for event-based disease surveillance. The 2009 H1N1 pandemic provided momentum for OFFLU, and in 2010, the three organizations published a Tripartite Concept Note on “Sharing responsibilities and coordinating global activities to address health risks at the animal-human-ecosystems interface” (FAO-OIE-WHO, 2010). They named avian influenza as a major priority for this alliance along with rabies and antimicrobial resistance (Dauphin, 2015; FAO-OIE-WHO, 2013). Through OFFLU, representatives of the veterinary and animal health sector have taken part in biannual WHO consultations on influenza virus surveillance data since 2011 that analyze surveillance data and provide recommendations on viral strains to use for influenza vaccines in the upcoming season. In this way, OFFLU participates in GISRS (routine influenza surveillance) and provides data collected from OIE/FAO Reference Centers and national animal health laboratories to WHO. Creating pre-pandemic CVVs for human vaccines relies heavily on this zoonotic virus data (Dauphin, 2015; Mackenzie et al., 2014).

In recent years, momentum has been building for extending the GISRS and GLEWS event-based surveillance or creating “GLEWS+” and “GISRS+.” GLEWS+ is designed as a cross-sectoral mechanism for conducting joint risk assessments for influenza and other zoonotic pathogens (FAO-OIE-WHO, 2013). The GISRS+ proposal is currently in its infancy at WHO. In WHO discussions during June 2021, it was suggested as a mechanism to build on and expand GISRS surveillance capabilities based on capacities developed and gaps identified during COVID-19 (see Figure 2-1). GISRS+

would function as the integrated system for surveillance and monitoring of respiratory viruses with epidemic and pandemic potential (WHO, 2021).

The GISRS+ proposal underscores the fact that GISRS structures have been leveraged during the COVID-19 response and can be expanded for other respiratory viruses. The laboratory network underpinning GISRS would expand, as would capacity building and training opportunities. Deciding which structures to extend (such as creating additional WHO CCs and how they will relate to GISRS) or redesign for other respiratory viruses (such as in the PIP Framework) will require a formal coordination mechanism. WHO is considering mechanisms required to support GISRS+ as a formal health governance structure.

A SNAPSHOT OF CURRENT INFLUENZA VACCINE GOVERNANCE STRUCTURES AND FRAMEWORKS

The WHO GISRS and PIP Framework form a major piece of the multilateral ecosystem for influenza surveillance and control. However, the wider “regime complex” or global ecosystem for influenza pandemic vaccines is much more complex and extends far beyond WHO’s normative power. Box 2-2 provides a nonexhaustive overview of some of the major organizations and programs involved in global and regional influenza policy and governance (NASEM, 2018; Schroeder, 2018; WHO, 2019) based on whether they involve multilateral, bilateral, or regional coordination; international regulations; public–private partnerships (PPPs); industry partnerships; and civil society organization (CSO) partnerships. The structures highlighted demonstrate the often-blurred boundaries around seasonal and pandemic influenza vaccines and vaccination.

The list of organizations and programs in Box 2-1 reflects the 2019 Conference Report “Shaping meeting to explore the value of a coordinated work plan for epidemic and pandemic influenza vaccine preparedness,” which called for a systematic effort to map the wide range of national, regional, and global actors that make up the influenza vaccine ecosystem (Ruscio et al., 2020). While this undertaking is beyond the scope of this short consensus study, it is an important next step. Our abridged analysis of major influenza governance structures reinforces that meeting’s finding that strengthening influenza vaccine PPR must be “guided by an alliance of international stakeholders, to include, among others, governmental and nongovernmental organization representation, civil society representatives, vaccine manufacturers, international organizations, and health security and influenza experts” (Ruscio et al., 2020, p. 3179).

3. pandemic clinical trials in adults and children may also inform the vaccination regimen required to induce a sufficient immune response for a novel influenza subtype, particularly next-generation viruses. This would reduce the response time for vaccine distribution if a similar subtype causes a future pandemic (Rockman et al., 2020).
4. Building effective seasonal vaccination programs: Because influenza viruses are highly prone to mutating, seasonal vaccines are strain based, and vaccination must be against the predominant circulating strains each year. WHO states that the need for annual vaccination, coupled with varying and often low vaccine efficacy, continues to contribute to influenza vaccine hesitancy. Both vaccine distribution and use also reflect major disparities. Recent data show that 47 percent of the global population (residents of countries in the Eastern Mediterranean, South-East Asian and African WHO regions) received only 5 percent of annually distributed vaccines. Countries and the global community must understand and address barriers that affect influenza vaccine distribution, uptake, import, and regulation to strengthen seasonal programs and improve the market for them if pandemic capacity is to be kept “warm” by seasonal vaccination.
5. Performing national pandemic planning: WHO developed pandemic influenza risk management guidance to encourage countries to develop national pandemic preparedness plans. In early 2018, WHO also published a checklist to help countries develop or update their plans. As of September 2018, however, few countries had updated their plans, and 101 countries did not have plans or had none publicly available. Without plans, countries would be hampered in terms of deploying vaccines during a pandemic (WHO, 2017).

In 2021, the Center for Infectious Disease Research and Policy (CIDRAP) took a step toward highlighting precisely how new technologies may be developed and harnessed for influenza. As discussed further in Chapter 4, its influenza vaccines R&D roadmap describes programs, policies, and financing that may accelerate progress for universal or broadly protective influenza vaccines. CIDRAP again underscores the importance of multi-sector and multi-actor collaboration for influenza governance; it is funded by the Wellcome Trust and advised by a steering group, composed of representatives of WHO, the Sabin Vaccine Institute, The Rockefeller Foundation, the Wellcome Trust, the Bill & Melinda Gates Foundation, and the Global Funders Consortium for Universal Influenza Vaccine Development (CIDRAP, 2021a).

The newest evolution of influenza governance may ultimately be through a pandemic treaty or instrument. The general concept of an international treaty on pandemic preparedness was put forward by the president of

the European Commission in December 2020 and has been endorsed by the European Union, the WHO director-general, and 26 heads of state, although the United States has expressed a preference for a nonbinding agreement (Viñuales et al., 2021). In May 2021, the World Health Assembly reached a consensus to hold a special session in November, during which an international treaty or instrument on pandemic preparedness will be debated (CIDRAP, 2021b; Gostin et al., 2021). This proposal follows the general pattern of reactivity; it is a product of COVID-19 reflections that individual organizations and governments cannot adequately prepare for pandemic threats alone. This argument was taken up by the Independent Review Panel for Pandemic Preparedness and Response (IPPPR). In its May 2021 report, it recommended stronger leadership and better coordination for pandemic preparedness through a more independent WHO, creation of a Global Health Threats Council, and a pandemic treaty.

The pandemic treaty may best be viewed as a recognition that a future global health crisis response system needs to go beyond embracing the IHR and WHO as the global health coordination agency. Much work needs to be done on whether it would be modeled along the lines of the Paris Climate Change Treaty or the Geneva Conventions and what it would require under the auspices of a Global Health Threats Council and institutions such as the G20. More work will be required to determine its core functions and boundaries. For instance, some have argued that it should focus on “deep prevention” to reduce the risk of pathogen spillover from humans to animals (drawing on inspiration from the global governance of nuclear, environmental, and financing system risks) (Viñuales et al., 2021). Others have put forward concrete end points, such as establishing a global agency, similar to WHO, that can coordinate governments, launch large-scale operations, enforce international rules, assess health systems, and provide objective technical advice to countries (Moon and Kickbusch, 2021).

The pandemic treaty debate goes beyond the boundaries of this study on influenza governance. What we are interested in is how to best to ensure that the successful governance structures and frameworks used for influenza inform proposals being advanced by the plethora of groups and studies and that the specific requirements of pandemic influenza are given due weight as a highly hazardous pathogen. Our argument is that the global influenza system may well be the most well established and functioning among those extant systems for pandemic preparedness (e.g., GISRS for surveillance, the PIP Framework for ABS, GAP for vaccine manufacturing capacity building, and IFPMA IVS to provide a link to market generation). Some of these global arrangements and agreements can be made much more visible and prominent as examples that can either effectively withstand geopolitical tensions and sovereignty control or effectively operate sufficiently under the radar at R&D, technical, production, and trade levels.