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7 The Development of the PIP Framework: Global Lessons on Equity and Fairness for Pandemic Preparedness S ession 1, part C of the workshop highlighted global lessons on equity and fairness related to pandemic preparedness. Panelists focused on illustrating such lessons through discussions about the virus-sharing controversy that emerged during the 2006 H5N1 avian influenza outbreak and that catalyzed the development of the Pandemic Influenza Prepared- ness (PIP) Framework. Makarim Wibisono, professor at the Indonesian Defense University, offered his perspective on the Indonesian govern- mentâs decision to withhold virus samples from the World Health Orga- nization (WHO) based on issues about inequitable access to the benefits derived from those samples. John E. Lange, senior fellow for global health diplomacy at the United Nations (UN) Foundation discussed his experi- ences as part of the U.S. delegation in the virus-sharing controversy and contributed his perspectives on the events that led to the development of the PIP Framework. Steven Solomon, principal legal officer at WHO, described the technical process behind the PIP Frameworkâs negotiations, and Anne Huvos, manager of the PIP Framework Secretariat at WHO, provided an overview of the challenges to and opportunities for the PIP Framework moving forward. The discussion was moderated by Keiji Fukuda, director and clinical professor, School of Public Health, The University of Hong Kong. 91
92 LESSONS LEARNED FROM A CENTURY OF OUTBREAKS CONTEXT FOR THE DEVELOPMENT OF THE PIP FRAMEWORK: PERSPECTIVE FROM INDONESIA Makarim Wibisono, professor at the Indonesian Defense Univer- sity, provided insight into the Indonesian governmentâs decision to with- hold virus samples from WHO during the countryâs H5N1 outbreak. He explained that the first outbreaks of H5N1 occurred in China between 1996 and 2003; H5N1 then spread rapidly to Southeast Asia and was first detected in domestic poultry in Indonesia in 2003. It was not diagnosed in humans in the country until July 2005, at which point it spread swiftly from western Java (WHO, 2014). In addition to its devastating effect on domestic and wild bird populations, H5N1 caused 115 deaths among 141 confirmed human cases by April 2009 (WHO, 2014). A cluster of cases in Sumatra induced public panic because it was unclear if transmission had occurred among humans rather than from animals to humans. This incited Indonesian media outlets and politicians to begin questioning the ability of the Indonesian Ministry of Health to contain the virus. During the outbreak, the Indonesian government initially complied with the Global Influenza Surveillance Network (GISN) regulations related to sharing the H5N1 virus. Established by WHO in 1952, the GISN requires affected countries to send samples of their virus to WHO Collaborating Center libraries and is the precursor to the current Global Influenza Surveillance and Response System (GISRS). The laboratory then identifies the candidate vaccine virus (CVV) and disseminates those findings to pharmaceutical companies for vaccine manufacturing. Wibisono said that despite Indonesiaâs willingness to share virus samples with the GISN, the country experienced great difficulty accessing the H5N1 vaccines that those samples helped produce. A delegation led by the minister of health in Indonesia traveled to WHO to seek a stockpile of the vaccine. The delegation was informed that WHO did not have processes in place to supply drugs directly to countries. Wibisono described that the delegation was advised to approach the manufacturer of the antiviral oseltamivir, but the manufacturer informed that the government of Indonesia would have to wait 2 years to receive the medication because the product was sold out based on advance purchase commitments. In response, the Indonesian minister of health announced in December 2006 that Indonesia would no longer share its H5N1 virus samples with WHO Collaborating Centers.1 The minister of health said that the GISN process was inequitable because vaccines produced from samples shared by developing countries were less likely to be available to those countriesâ populations. 1 Indonesia resumed sharing the H5N1 virus in March 2007 after a 2-day, high-level technical meeting organized by WHO that included representatives from approximately 20 countries. See https://www.who.int/mediacentre/news/releases/2007/pr09/en (accessed February 26, 2019).
THE DEVELOPMENT OF THE PIP FRAMEWORK 93 CONTEXT FOR THE DEVELOPMENT OF THE PIP FRAMEWORK: PERSPECTIVE FROM THE UNITED STATES John E. Lange, senior fellow for global health diplomacy at the UN Foundation, provided the U.S. perspective during the virus-sharing controversy and the events that led to the eventual development of the PIP Framework. He noted that high-level political engagement by the U.S. government was a boon to the H5N1 response, as illustrated by the creation of the International Partnership for Avian and Pandemic Influenza in September 2005. When Indonesiaâs minister of health announced Indonesiaâs refusal to share viruses with WHO Collaborating Centers in December 2006, high-level U.S. government officials expressed concern about the potential for that decision to precipitate a catastrophic influenza pandemic if additional countries stopped sharing viruses. Lange said that immediate sharing of samples is important because timing is critical in an emerging pandemic situation. Samples need to be delivered as quickly as possible to WHO Collaborating Centers and then to manufacturers to produce a vaccine, he explained. In May 2007, WHO passed a resolution at the World Health Assembly to create a process for discussions that would lead to the PIP Framework 4 years later (WHO, 2007b). That process included bilateral discussions between the Indonesian government and the U.S. government, both of which had different perceptions about those discussions (Supari, 2008). Indonesian representatives were focused on ensuring equitable access to the vaccines produced by the virus samples they provide, while the U.S. representatives were focused on public health and the immediate need to share virus samples for global benefit. Lange reported that the subtext of the discussions from the U.S. perspective, however, was a tension between using the vaccine for domestic purposes or helping developing countries. These deliberations sparked critical U.S. media coverage of the Indonesian governmentâs claim to âviral sovereigntyâ2 (Holbrooke and Garrett, 2008). Lange noted that in response to such critique, Wibisono wrote an article on the Convention on Biological Diversity, arguing that countries have sovereignty over their biological materialsâincluding pathogens found in their territoriesâand that countries could mandate benefit sharing in return for access to influenza virus samples (Wibisono, 2008). The negotiation process around this issue took years to resolve and was challenging, Lange remarked, but it was ultimately concluded successfully in May 2011 with the passage of the World Health Assembly Resolution 64.5 and the develop- ment of the PIP Framework. 2 Viralsovereignty was described as the idea that âdeadly viruses are the sovereign property of individual nations even though they cross borders and could pose a pandemic threat to all the peoples of the worldâ (Holbrooke and Garrett, 2008).
94 LESSONS LEARNED FROM A CENTURY OF OUTBREAKS PROCESS OF DEVELOPING THE PIP FRAMEWORK Steven Solomon, principal legal officer at WHO, explained that member states had collaboratively decided that a framework was needed to ensure rapid and robust virus sharing in a framework that equalized the value of sample sharing and of benefits sharingâresulting in the mandate in 2007 that Lange described earlier. Solomon said the process of developing the PIP Framework took 4 years, but such processes tend to be lengthier in order to ensure that the product of the process is reached by consensus. He also commented that 4 years is a relatively swift negotiation period considering that 194 member states are involved. WHO and the World Health Assembly both operate on the basis of consensus, which does not mean that no country has concerns, but he clarified that no country objects strongly enough to block the adoption of the framework. As a resolution of the World Health Assembly, the PIP Framework is not a legally binding document on the whole. However, it does have some legally binding elements under international and domestic law, such as contracts with vaccine manufacturers. Solomon explained that in 2011 the World Health Assembly re-entered the process to consider the product of the work by the member states it had mandated. At that point, the issue blocking consensus was a debate over the Nagoya Protocol,3 which was still being negotiated. The Nagoya Protocolâs implications for pathogen sharing (including influenza) were beginning to be recognized, which led to disagreement about whether the PIP Frame- work should reference the Nagoya Protocol. Solomon noted that the issue continues to this day; the World Health Assembly will convene in 2019 to consider the implications of the Nagoya Protocol for the PIP Framework, and negotiations could continue for several more years. POTENTIAL CHALLENGES AND OPPORTUNITIES FOR THE PIP FRAMEWORK Anne Huvos, manager of the PIP Framework Secretariat at WHO, described how the PIP Framework contributes at an international level and what challenges remain for it. Ultimately, the PIP Framework was the product of a 4-year investment by WHO member states to resolve two criti- cal issues for public health security: (1) ensuring that countries continue to share influenza viruses with pandemic potential for risk assessment and for developing pandemic vaccines, and (2) ensuring greater equitable access 3 As described in Chapter 3, the Nagoya Protocol is a supplementary agreement to the Convention on Biological Diversity. It provides a transparent legal framework for the effective implementation of the fair and equitable sharing of benefits that arise from the use of genetic resources. For more information on the Nagoya Protocol, see https://www.cbd.int/abs/about/ (accessed February 11, 2019).
THE DEVELOPMENT OF THE PIP FRAMEWORK 95 to future pandemic vaccines by all countries based on public health need, irrespective of development status or other financial considerations. Huvos remarked that the idea for the PIP Framework originated in 2003 in response to fears that the reemergence of avian influenza would cause a devastating pandemic. However, the spark that drove the framework- creation process was developing countriesâ loss of trust in the global system for virus sharing and access to vaccines. The governments of developing countries felt that the WHO-coordinated system of virus sharing was inequitable and failed to provide reasonable protection for their people. The initiation of the PIP Framework discussions marked the start of the trust-rebuilding process among countries. Ultimately, the process facilitated the resumption of virus sharing in the years after the PIP Framework was adopted. Huvos said that the PIP Framework also represents a successful approach to partnership with the private sector. More than $163 million in partner- ship contributions have been collected from individual manufacturers, and those funds have been used to strengthen pandemic preparedness capaci- ties and to gradually build a response fund for the next pandemic (WHO, 2018e). WHO has also signed multiple contracts to secure approximately 10 percent of future pandemic vaccine production and therefore will be able to send vaccines to countries in need during the next pandemic. Â urrently, Â C this represents about 400 million doses of vaccines, and this number will likely increase if manufacturing technologies continue to improve and the next pandemic does not occur soon (WHO, 2017b). Several global challenges may threaten the success of the PIP Frame- work (see Box 7-1). One challenge, Huvos noted, is how to deal with sharing genetic sequence data under the framework. Given the nature of the contracts signed as a part of the PIP Framework, the increasing use of genetic sequence data could potentially impede WHOâs access to vaccines and to other critical pandemic response products. Contracts must be signed by any entity that receives physical PIP biological materials from GISRS. However, if a product is manufactured only with genetic sequence data, WHO cannot require the manufacturer to sign a contract to share its prod- uct. This issue is currently hypothetical for vaccines because of the regula- tory processes in place, but the PIP Framework could be compromised if those regulatory and manufacturing processes evolve. The second challenge Huvos identified was the adoption of the Nagoya Protocol. The basic premise of this protocol is that anyone who wishes to access a countryâs genetic resources must provide agreed-upon benefits in return to that country. The treaty currently has nearly 110 parties that are in the process of developing their own national implementation laws, which can and do differ substantially by country. The Nagoya Protocol recog- nizes that some genetic resources are already covered by other access- and
96 LESSONS LEARNED FROM A CENTURY OF OUTBREAKS BOX 7-1 Some Challenges and Concerns About the Pandemic Influenza Preparedness (PIP) Framework Although the development of the PIP Framework has been a significant achievement, several concerns and challenges remain, according to David Fidler, professor of law at Indiana University Bloomington (see Chapter 3), and Anne Huvos, manager of the PIP Framework Secretariat at the World Health Organiza- tion (WHO): â¢ The PIP Framework covers influenza viruses with pandemic potential but not seasonal influenza viruses or other pathogens. â¢ The timely and adequate sharing of viruses has generally declined since 2013. â¢ The increasing use of genetic sequence data could potentially impede WHOâs access to vaccines and to other critical pandemic-response products. â¢ The potential impact of the Nagoya Protocol on the balance of virus sharing and benefit sharing in the PIP Framework is unclear and could disrupt the global system, which relies on the timely, rapid, and broad sharing of viruses to develop effective seasonal influenza vaccines. â¢ The PIP Framework has not yet been tested in response to a serious influenza pandemic. SOURCES: Fidler presentation, November 26, 2018; Huvos presentation, November 28, 2018. benefit-sharing instruments, and this is considered acceptable if those instruments are consistent with the Nagoya Protocol. For instance, if the PIP Framework for influenza viruses with pandemic potential is deemed to be an access- and benefit-sharing instrument that is consistent with Nagoya standards, then the Nagoya Protocol will not apply to influenza viruses with pandemic potential. Huvos explained that the Nagoya Protocol would apply to sharing and to accessing seasonal influenza viruses because those viruses are not covered by the PIP Framework. Potential conflicts between the Nagoya Protocol and the PIP Framework might disrupt the global system, which relies on the timely, rapid, and broad sharing of viruses to develop effective seasonal influenza vaccines. Huvos said that moving forward with the PIP Framework will require robust communication strategies that emphasize the public health impor- tance of the framework for all countries and for their populations. In 2017, the World Health Assembly requested that WHO analyze the implications of genetic sequence data with regard to the Nagoya Protocol on the PIP Framework. The resulting analysis sketched several options for each of
THE DEVELOPMENT OF THE PIP FRAMEWORK 97 those issues, such as adapting GISRS or developing one or more broader instruments to cover all pathogens. Huvos argued that WHOâs most impor- tant task is to avoid repeating the mistakes of the past, which WHO could accomplish by acting transparently, inclusively, and iteratively to maintain the trust of all its partners. DISCUSSION Keiji Fukuda, director and clinical professor, School of Public Health, The University of Hong Kong, observed that the PIP Framework emerged as a solid solution to a difficult situation in a way that balanced two important and noncompeting values while satisfying the member states and other stakeholders who substantially contributed to the discussions. He said the PIP Framework is unique because âit goes beyond merely stating principles to actually acting on it. I think that is why, for so many people, the PIP Framework remains a touchstone about what we should be aspiring to.â The importance of achieving a collective global benefit as well as fairness and equity for individual parties, he reflected, will need to be struck in order to facilitate future multilateral global cooperation related to pandemics and other global health issues. However, he cau- tioned that although developing the PIP Framework was a great achieve- ment, time does not stand still; other global frameworks and technologies are being developed and therefore necessitate discussions to negotiate how they fit with each other and to identify how they impact day-to-day work on preparedness. The loss of the PIP Framework would be a major step backward, he argued, because its implementation has improved the avail- ability of vaccines and antivirals, garnered some continuous funding, and helped countries develop needed structures to support surveillance and other public health necessities. Applying the PIP Model to Future Negotiations Fukuda asked panelists if the process used to negotiate the PIP Framework is an applicable model for the future. Wibisono said that the PIP process is a new and important model of international relations for addressing global challenges. The discussions were unique because they involved active participation from all stakeholders in order to achieve a difficult task: reaching consensus on adaptable solutions. Lange said that this new model may be useful for facilitating international cooperation without a cumbersome treaty process. He remarked, âThe beauty of the PIP Framework is that it is not a treaty; it is a resolution that was passed by the World Health Assembly, which has ended up as a standard of materials transfer agreement and a contract . . . and it has worked.â
98 LESSONS LEARNED FROM A CENTURY OF OUTBREAKS Solomon said the model would be useful for ensuring legitimacy and credibility in discussions aimed at building trust and ensuring equity, which require long-term investments in transparency, inclusiveness, and broad understanding among all stakeholders. Huvos said that the PIP model may be useful for future discussions, but some aspects may be hard to replicate. She explained that preparedness for influenza is a unique microcosm of mutually supporting interests: Governments need vaccines to protect their people, countries need to share their viruses in order to have a good vaccine, and industries need to make vaccines and to derive some revenue. Unlike many emerging diseases, influenza is already recognized as an important concern in many countriesâ public health systems. Huvos suggested that the core principles of the PIP modelâequity, fairness, partnership, and transparencyâare replicable elements. Some of the platforms and mechanisms for seasonal influenza and for pandemic preparedness may also be replicable in other discussions. Frameworks for Other Pathogens Suerie Moon, director of the Global Health Centre of The Graduate Institute of International and Development Studies, asked if frameworks similar to PIP will be needed for pathogens other than influenza. If so, she asked how to gather the requisite political startup energy to develop that type of framework in the absence of a crisis such as the one that catalyzed the PIP Framework. Solomon responded that new frameworks that apply to all pathogens will be required. However, a crisis will probably be needed to instigate the process unless countries come to realize that the global health benefit of rapid sharing can only be gained through a multilateral regime like the PIP Framework. He added that, in his experience, many health ministers believe that the problem of pathogen sharing has been solved by the PIP Framework since failures to share other types of pathogens have not yet had a negative global impact. Huvos remarked that the PIP Frameworkâs narrow scope only covers pandemic influenza vaccines, so the first priority should be to create a framework to share seasonal influenza viruses before moving on to non-influenza pathogens. A crisis is emerging in which seasonal influenza viruses are not being shared in time for consid- eration at seasonal vaccine composition meetings. As a result, she said the seasonal virus sharing system will likely deteriorate as the Nagoya Protocol is implemented in more countries. Wibisono noted that the PIP Framework has helped expand countriesâ capacities to produce the seasonal influenza vaccine. Arnold Monto, professor of public health in the Department of Epidemiology at the University of Michigan, added that member states will not advocate for a seasonal influenza framework until they recognize the importance of seasonal influenza vaccines. One example of this importance
THE DEVELOPMENT OF THE PIP FRAMEWORK 99 is the fact that pandemic influenza vaccines cannot be produced without an existing system for producing seasonal influenza vaccines, he said. Implications of Genetic Sequence Data and Emerging Technologies Eva Harris, professor of infectious diseases and vaccinology at Uni- versity of California, Berkeley, elaborated on earlier remarks that genetic sequence data can jeopardize the PIP Framework. For example, companies might be able to avoid signing the contract on the technicality that genome sequence data are not biological material per se because they are derived from biological material. Peter Daszak, president of EcoHealth Alliance, asked how the capability to reverse engineer an entire virus could be addressed from a legal perspective. A single base pair in a genetic sequence could be tweaked to make it an essentially different organism, which would create another series of legal and regulatory problems. Fukuda remarked that this multiplicity of conceptual and legal issues people had raised about the Nagoya Protocol are complex because the protocol was developed with an environmental focus while the PIP Framework was developed with a public health focus. Trust and mistrust are still fundamental issues, he added, despite the years-long efforts during the negotiations to identify mistrust and find a solution for it. The PIP Framework was considered successful because all participants were instrumental in reaching a final agreement, but these emerging issues have exposed a lingering level of mistrust. He warned that mistrust needs to be confronted before it burgeons again because every time a potentially dangerous new pathogen is identified, the same issues ariseâwho owns the virus, what will happen to it, which agreements will need to be made, and whether consent will be needed. Fukuda predicted that another lengthy process of deliberations will be required to resolve issues raised by genetic sequence data and by other emerging technologies such as artificial intelligence and big data.