The fourth session of the workshop, which focused on overcoming barriers and forging partnerships, was moderated by Alan Tennenberg, chief medical officer, Global Public Health, Johnson & Johnson. The session’s objectives were to discuss novel strategies to enhance existing or stimulate new cross-sectoral collaborations and public–private partnerships, as well as to identify promising approaches to ensure the sustainability of innovative interventions. The session featured two panels, the first of which explored strategies for breaking down barriers and fostering new forms of partnership to enable innovation.
During the first panel, Colonel Matthew Hepburn, joint product lead, U.S. Army, discussed strategies for enabling biotechnologies through partnerships. Rahima Dosani, global health market access advisor, Center for Innovation and Impact, U.S. Agency for International Development (USAID), described her organization’s approach to fostering new partnerships to enable innovation. Rajeev Venkayya, president, Global Vaccine Unit, Takeda Pharmaceuticals, remarked on opportunities for partnership models to address unmet needs in global health, particularly in low- and middle-income countries (LMICs). Tennenberg remarked that multisectoral collaboration is the only way to effectively counter the global health challenges being faced today. No sector can face these challenges alone, he said, but great things are possible when each sector brings its unique attributes to the table. However, lack of trust and poorly aligned objectives can threaten the success of those partnerships. He asked the panelists to consider how those barriers can be overcome to “beat back the pathogens at the gate.”
Matthew Hepburn described a process for enabling biotechnologies through partnerships—“from information to injection.” He leads a newly formed and integrated effort called the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND).1 The project focuses on the advanced development of biomedical products to solve infectious diseases and chemical, biological, radiological, and nuclear threats. Its aim is to develop medical solutions by enabling biotechnologies to facilitate rapid response during crises against future threats.
He explained that JPEO-CBRND is not responsible for the entire development of a product through its life cycle; rather, it works with partners with government, academia, and the private sector to accelerate products at steady state. He suggested that colleagues in the private sector and academia should consider JPEO-CBRND as an enabler of next-generation technology, rather than another entity seeking funds for product development. He added that JPEO-CBRND should receive the first call from the Secretary of Defense in a situation that warrants a medical solution to address an outbreak or threat for which there is no vaccine or therapeutic agent—or only preclinical products—that needs to be rolled out to thousands of people in a short period of time.
Strategies for Enabling Biotechnologies Through Partnerships
Hepburn pointed out that the mission of JPEO-CBRND is different from the mission of an organization such as the Biomedical Advanced Research and Development Authority (BARDA), which is tasked with protecting 350 million Americans. Instead, JPEO-CBRND’s role is to be an early firebreak providing rapid deployment of vaccines or therapeutics while the larger national and international responses are gearing up. To do so, JPEO-CBRND concentrates on adopting next-generation technology and working through integrated partnerships from start to finish. Hepburn stated that the guiding premise of JPEO-CBRND is that during a crisis, the focus needs to be on the four components that have been reorganized within the U.S. Department of Defense (DoD) to accomplish this mission: (1) characterizing a threat, (2) selecting technology, (3) manufacturing a product, and (4) testing and distributing the product.
Characterizing the threat through global sample identification and sample characterization is carried out through partnerships as well as investments in biodetection assays and international sequencing programs, said
Hepburn. Through partnership with groups such as the U.S. Centers for Disease Control and Prevention and other groups in DoD, JPEO-CBRND aims to be at the forefront of making sequences available and understanding the emerging pathogen threat. He noted that academic centers tend to make sequencing information about pathogens available for antibody and vaccine discovery only after they publish the data. Hepburn maintained that this practice is not acceptable, because information about translating from sequence in real time is necessary for the medical product discovery process. JPEO-CBRND hopes to accomplish this in real time through integration and partnerships.
The next step is to select technology and accelerate product development. Hepburn explained that this step is intentionally referred to as “technology selection” rather than “discovery,” because JPEO-CBRND focuses on partnerships to support existing products rather than reinventing the wheel. If no appropriate products are readily available, then JPEO-CBRND invests in automated antibody discovery. He highlighted a program run by the Defense Advanced Research Projects Agency (DARPA) called the Pandemic Prevention Platform, which invests in rapid antibody discovery against future pathogens. He remarked that this field is ripe and has reduced the timeline from years to weeks in terms of discovering a host of antibodies that could be useful against future pathogen threats. The challenge of selecting only a few from among the thousands of antibodies discovered to take into advanced development has the potential to be addressed by artificial intelligence and machine learning, he added.
The third component is manufacturing products and technology transfer through current good manufacturing practices, said Hepburn. DoD invested in an advanced development and manufacturing facility in Florida after the H1N1 pandemic in 2009, he continued. The facility is privately owned, but it is linked with a network at BARDA to provide surge capacity in a crisis. Hepburn said that as soon as JPEO-CBRND has a product available—even while the discovery process is still ongoing—the product immediately goes to the front of the line for manufacturing and production at the facility.
The fourth component is to test products for safety and efficacy prior to distribution, said Hepburn. The capacity to conduct clinical trials is being built out further with DoD’s aim to improve the ability to have mobile and global outbreak clinical trial capabilities. As an example, Hepburn commended the Congolese volunteers and colleagues from the National Institutes of Health and the World Health Organization, who demonstrated that a randomized controlled trial can be conducted in Ebola treatment units in a conflict zone during a crisis, dispelling the notion that clinical trials are not feasible during an outbreak. He highlighted the need to adopt next-generation technologies, including electronic data capture and continuous physiologic monitoring. He added that DoD needs these next-generation
technologies to deliver prolonged field care for its worldwide deployed force.
Building on Hepburn’s discussion of the importance of partnerships, Rahima Dosani described USAID’s overall approach to private-sector partnerships, provided examples of successful partnerships, and suggested a set of best practices for creating and sustaining effective cross-sectoral partnerships.
USAID’s Approach to Private-Sector Engagement
Private-sector engagement is critical to USAID’s global health work to combat microbial threats, said Dosani (USAID, 2019a,b). Cross-sectoral partnerships are needed because the public sector cannot address those threats on its own. Traditional grant funding will not be sufficient to meet the health-related United Nations Sustainable Development Goals (SDGs) given the $134 billion investment gap for health-related SDGs in LMICs, which is expected to triple to $371 billion in the next 10 years (Stenberg et al., 2017). She described the private sector as a significant source of incredible networks, systems, and technical expertise, as well as an increasingly significant source of providing services in LMICs. For example, in many countries, the majority of people who seek care for fevers do so in the private sector (Ansah et al., 2016). Collaborations with the private sector offer contributions in technical expertise, networks, strategic systems, and flexibility, she added.
USAID’s perspective is that the future of development will primarily be enterprise driven and reliant on private-sector collaboration, said Dosani. Business as usual will not end the need for assistance; private-sector engagement is needed to foster collaboration with the private sector, make catalytic use of USAID resources, seek market-based solutions for greater sustainability, and mobilize private capital for scale. She shared several private-sector engagement principles developed by USAID:
- To engage early and often with private-sector actors and other partners to design and implement strategies and projects of shared value;
- To incentivize and value private-sector engagement throughout planning and programming to adapt continuously to new evidence, opportunities, or circumstances;
- To expand the use of USAID approaches and tools that unlock the potential of the private sector; and
- To build and act on the evidence of what works and what does not work.
Over USAID’s long history of building partnerships, it has found that private-sector partnerships can catalyze health goals to scale to be efficient, cost-effective, and sustainable, said Dosani. Increasing scale enables programs to reach more of the target population by drawing on private-sector resources and expertise or by accessing private-sector channels (USAID, 2019b). Greater efficiency involves operating more efficiently or cost-effectively by adapting private-sector expertise, skills, or tools. Private-sector partnerships also improve cost-effectiveness by achieving procurement savings from more competitive markets that facilitate access to health products and open or expand markets for commercial actors. Program sustainability can be enhanced by using handover strategies, revenue-generating business models, and commercially viable, local private-sector partners. To illustrate these advantages, Dosani shared three examples of USAID’s successful private-sector partnerships, which have evolved through various stages of success and lack thereof (see Box 6-1).
Practices to Create and Sustain Effective Cross-Sectoral Partnerships
Using the example of work by the Aspen Management Partnership for Health (AMP Health) to increase the leadership capacity of government ministries of health, Dosani highlighted a set of best practices for creating and sustaining effective cross-sectoral, private-sector partnerships. The first is that private-sector engagement can take many forms and should be iterative; the second is that interests should be aligned and each partner’s unique assets should be leveraged; and the third is that progress should be measured early to track impact, and lessons from mistakes should be used to inform and evolve the partnership over time.
Spectrum of Private-Sector Engagement Options
Dosani explained that a spectrum of private-sector engagement options exists, with different types of engagement involving different amounts of risk and investment. In a government-led engagement, government is the driver in leveraging private-sector resources and expertise; this type of engagement may or may not be aligned with commercial interests or core business operations. In co-creation, the government is a co-creator engaged with the private sector jointly identifying challenges and designing programming to address shared interests; this includes the co-creation of market-based approaches. In private-sector-led engagement, the government is the facilitator in providing assistance in addressing private-sector constraints and risks; these engagements may be built on for-profit and market-based approaches to challenges.
She noted that private-sector engagements are iterative and do not necessarily lead to formal, full-on partnerships. For example, a private-sector entity can be engaged to co-create a target product profile, test products during research and development, or consider how to bring a product or service to scale. Partnerships start with light touch engagement during an early stage of exploration and can move into a curated stage where engagement is refined, with each partner having set work streams with defined goals. If a strong model of partnership is identified, the proof-of-concept stage includes a pilot project to test the value and impact of collaboration. In the case that a best model of partnership has been identified and piloted—with clear value and impact for all collaborators—then the model can be further tested through scale in other environments or countries. Areas for consideration at each stage of partnership include the potential impact and time until execution, the assessment of risk, the level of government effort, and the level of commitment from the private sector. She added that the same considerations apply at each stage of engagement, but the bar for risk and certain impact gets higher as progress is made.
Aligning Interests and Finding Shared Value
Dosani’s second best practice for private-sector engagement was to align interests and find shared value. The engagement archetype ought to be based on shared interests. In the first stage of exploration, she remarked, the goals for the public sector are achieving effective coverage, quality, cost-efficiency, and sustainability; for the private sector, the goals are growth, risk diversification, public relations with the government and community, and having a healthy workforce. She highlighted four different project archetypes: corporate philanthropy, corporate social responsibility, shared interest, and investment. In the execution phase, private-sector engagement activities should be designed to achieve shared interests and make a health impact. In the supporting-to-scale phase, long-term commitment from both the government and the partner should be confirmed. At each stage, Dosani advised questioning whether the appropriate approach is being used.
Dosani linked these practices to the partnership with AMP Health, which has a diverse set of partners that has catalyzed exponential rather than linear results. Through a range of public, private, and nonprofit partnerships, it has been successful in teaching many new skills and approaches in the past 4 years. She pointed out that AMP Health places management partners within a certain team for at least 2 years to help build the capacity of its teams. It has successfully aligned the interests of the three pharmaceutical companies that have supported them; this enables teams to make better and more strategic choices about resource allocation, which aligns in the best interests of the pharmaceutical companies as well. This holistic, team-based approach includes management partners, but also extends to in-country workshops and live learning, distance learning, one-on-one executive coaching, focus work streams, and leadership labs.
AMP Health also rigorously evaluates its impact, she said. This is conducted through the following:
- Regular measurement of an individual’s development of leadership and management capabilities;
- Regular measurement of team effectiveness;
- Keeping scorecards of leadership and management best practices, tools, and processes used by high-functioning teams;
- Tracking and describing concurrent health system evolution; and
- Undertaking qualitative measurement of the leadership and management journey.
Adapting and Evolving Partnership Models
Dosani highlighted the importance of learning from failure and continuously adapting and evolving partnership models. For instance, AMP Health
has evolved and made organizational changes in response to past mistakes. Specifically, after an initial partnership in Kenya, AMP Health decided not to continue work with the community health team at the Ministry of Health because of devolution and political challenges. As the political landscape changed, AMP Health realized that it was not an adapting and enabling context for its work. AMP Health is completely demand driven and only works in countries and departments within ministries of health where there is a direct government request for partnership. Instead of providing traditional technical assistance, it focuses on building the capacity of entire teams. It supports ministries of health longitudinally, guided by the idea that achieving long-lasting behavior change and building capacity takes time and commitment beyond short funding cycles, she added.
Rajeev Venkayya drew on his range of experiences with the Coalition for Epidemic Preparedness Innovations (CEPI) as a grant recipient from major international funding bodies, and as a contract recipient from BARDA to reflect on some of the opportunities and challenges in forging private-sector partnerships to address unmet global health needs. Venkayya remarked that the partnership model needed to conduct mission-driven research to address major unmet needs in global health in LMICs is complex. The industry has a long track record of developing products for developed markets, but innovation is needed to encourage the development of products for those markets that are not as attractive for private-sector entities.
He clarified that there is industry interest in supporting the needs of developing markets, but companies are accountable to stockholders and investors and need to demonstrate that the capital invested in product development will have a return that is competitive with other opportunities. These companies have expertise in developing these types of products that need to be developed for LMICs in order to create a greater probability of success, he added.
Opportunities for Partnership to Strengthen the Vaccine Clinical Development Cycle
Venkayya considered strategies for optimizing and strengthening the partnership model around the clinical development cycle for vaccines, from candidate vaccines to licensed vaccines that can be used in the field. For many diseases faced in LMICs—such as Lassa fever, Middle East respiratory syndrome (MERS), Nipah virus, and chikungunya—there is no shortage of vaccine candidates. In CEPI’s efforts to find partners, it has found many
entities interested in developing these vaccines, but fewer who have experience in taking vaccines all the way through to development and licensure. He said that compared to the early stages of vaccine development, CEPI and other large industry partners can play a more substantial role during the later stages of vaccine development.
During the later stages, vaccine development is a risky, capital-intensive, and lengthy process because the high bar for safety and efficacy requires large clinical trials that can pick up low or infrequently occurring adverse effects that need to be identified before large-scale deployment of a vaccine. For example, the dengue vaccine program is currently being evaluated in a phase 3 trial that has enrolled 20,000 children across 8 countries. The hope is that this trial may have enough dengue patients to demonstrate a statistically significant effect of the vaccine in groups of individuals that require it.
Further challenges relate to demonstrating efficacy, particularly when the population that will be exposed to the infectious agent is unknown and huge populations need to be immunized in order to ensure that certain numbers are exposed to the threat and placebo in the vaccine group. In addition to those barriers, the chemistry, manufacturing, and controls requirements around process development and validation drive the substantial expense and time associated with vaccine development, he said.
Venkayya suggested that a strategy to address barriers related to expense and timelines of vaccine development is to determine correlates of protection—meaning, identifying factors that will accurately predict the protection and the deployment of the vaccine into large populations. This would be helpful for vaccines against dengue, chikungunya, and other emerging infectious diseases. Another opportunity is to develop pathways that are predictable enough to allow the licensure of vaccines without large-scale efficacy trials. Sometimes called “accelerated review pathways,” these rely primarily on preclinical and clinical data that demonstrate certain levels of antibodies that correlate with protection in animal models, which will then lead to licensure with substantial postmarketing commitments. He added that this type of pathway would also unlock efficiencies and reduce costs in vaccine development. Venkayya maintained that the burden should not be placed on regulators alone. Companies have a role to play because they understand what is required to develop their products, and they should provide regulators with ideas about how to reconsider the regulatory pathway to licensure.
Challenges in Engaging the Private Sector to Address Global Health Needs
Venkayya described how CEPI is tackling the issue of unmet needs in global health by engaging the private sector. The challenge for large compa-
nies considering involvement in these types of programs goes beyond technical risk to substantial market risks. These include whether there will be the epidemiology to support uptake of the vaccine if it is successfully developed and licensed as well as vaccine hesitancy concerns. Other risks relate to the margin differences among low-, middle-, and high-income countries, which are associated with tiered pricing, which fundamentally change the risk and investment dynamic in companies. He highlighted push funding as an easy solution demonstrated by CEPI, the Bill & Melinda Gates Foundation, and product development partnerships. Push funding decreases the risk for companies and incentivizes them to accept the opportunity cost of deploying their resources from more predictable programs to one that has a different risk and investment profile, he noted. For instance, BARDA is providing Takeda Pharmaceuticals with cost reimbursement that allows the company to address public health challenges, such as Zika.
Ideological Concerns in Private-Sector Partnerships
Venkayya noted that there are ideological issues in the ecosystem around public–private partnerships to achieve product development goals: concern and trepidation that public funds are going to companies that are perceived to have significant resources to develop products for the public good, but that those products will not be accessible after they are developed. He surmised that this fear may be driven by situations in which the pricing of products for HIV has made them inaccessible. However, he said that the companies who seek out engagement with entities like CEPI are doing so because they genuinely want to address public health problems.
Venkayya sees social media and other media as mechanisms of accountability to apply pressure to companies that have taken public funds to develop a product for the public good but do not act appropriately. He described this as an “insurance policy” to ensure that groups like CEPI are partnering with companies that will do what is necessary from an access standpoint. He added that the most important element of a strong partnership between industry and funding entities is trust, which spans the dimensions of competency, honesty, and benevolence (Grayson, 2016). For example, BARDA has confidence that Takeda knows what it is doing, that it can deliver on a product, that it will be transparent, and that it is in the partnership in order to do the “right thing.” Venkayya suggested that these dimensions need to be rigorously applied to all partnerships and private-sector engagements.
Tennenberg remarked that CEPI is a strong example of partnership between multiple stakeholders to tackle public health needs and asked about
how the organization came into existence. Venkayya said that it involved the efforts of hundreds of people and organizations such as the National Academies of Sciences, Engineering, and Medicine. The 2014 Ebola epidemic was a driver of CEPI, because there were vaccines in the pipeline but no framework with which to evaluate the vaccines quickly in the field. CEPI took on the challenge of looking at the highest epidemic threats in the world and investing in a pipeline to bring vaccine candidates up to phase 2A or 2B, so that phase 3–ready compounds could be deployed into the field with appropriate clinical trials when an epidemic emerges. He noted that this was the original model, but it would be very complex to follow this template in reality, so he expects modifications going forward.
Venkayya added that CEPI has been successful in implementing a broad range of partnerships that have contributed to a broad range of vaccine candidates in the pipeline. Brian Bird said he previously worked on developing a vaccine for Rift Valley fever that was recently selected by CEPI for further development in their human pipeline. He remarked that CEPI brought a wealth of expertise to the technical side of the process that was also beneficial from a funding agency’s perspective. He suggested applying this type of collaborative approach to antimicrobial resistance and other seemingly intractable problems.
Tennenberg pointed out the “elephant in the room” of large health care companies needing to answer to shareholders, remaining accountable to the business plan, and maintaining their top and bottom lines. He asked for strategies to motivate companies to be involved in projects with a return on investment that will be lower than other opportunities. Hepburn said that when he was at DARPA, the model was to invest in the best people in the world to solve the problem, whether they were domestic, international, a small biotechnical company, a university, or part of cost-share partnerships with large pharmaceutical companies. He saw the advantages and disadvantages of working with each type of group, but a common issue was that the U.S. government does not negotiate very well for grants or cost-share partnerships. He suggested that negotiation should aim to achieve practical mutual benefit rather than the government simply providing money. He noted that the U.S. government has improved over the past decade in adopting new and different ways to contract these types of investments with small biotechnical and large pharmaceutical companies.
In cases where the opportunity cost for a company would be excessive, he suggested that the government should consider what else it can offer from its toolbox, such as adopting next-generation technology for clinical trials or cost sharing on testing a mutually beneficial vaccine using DoD’s global network of clinical trials. Hepburn added that DoD and the U.S. Food and Drug Administration (FDA) have a strong relationship, which has been codified in public law, that works for the unique needs related to military
medicine and infectious diseases. He suggested the potential for cost-share partnerships on vaccines with DoD and FDA, because private-sector input into regulatory policy is critical.
Dosani remarked that the return on investment is not necessarily as low as it is assumed to be—for instance, the development impact bond with the UBS Optimus Foundation and Merck has up to an 8 percent return—and there is a broad spectrum of ways these types of investments can provide good returns. Furthermore, negotiations to determine what both parties want out of the partnership may reveal that employees are interested in investing in social causes rather than financial interests. She added that negotiations with private-sector companies should seek to understand their interests and show that there is shared value in improving the company’s operations as well.
Venkayya underscored the importance of being flexible and sophisticated in understanding what a partner specifically values. With respect to ideological issues around access, he noted that the Bill & Melinda Gates Foundation’s global access policy was pioneering in its focus on getting products for populations in LMICs, which has now expanded to ensure that poor populations in middle- and upper-income countries are also benefiting from the investment. He added that allowing private entities to capture value in other markets with a platform that a funder has helped to develop or reduce risk is an example of how flexibility can engage the private sector while allowing the funder to achieve its aims as well.
Keiji Fukuda, director and clinical professor, The University of Hong Kong School of Public Health, commented on the difficulty in establishing public–private partnerships and asked how interests should be aligned among multiple partners in the context of a lack of trust and differing motives. He noted that although there are ad hoc partnerships and larger-scale entities such as CEPI, a larger ecosystem of partnership does not yet exist, perhaps owing to the focus on the private-sector side rather than the benefits of leadership, governance, and legitimacy that the public-sector side has to offer. Venkayya responded that CEPI still needs to make progress in engaging with large private-sector companies in vaccine development programs, but it is providing the elements of public-sector leadership, governance, and legitimacy. He suggested that this could be codified into a more predicable framework or structure through a coalition of like-minded partners, for example, as long as the framework also allows room to bring in external innovation.
Hepburn added that the government can provide leadership and legitimacy in addition to funding. He suggested that leadership at the highest level of government needs to advocate for more resources to support the public sector and develop a stronger ecosystem of partnerships. Dosani added that
the public sector needs to be more intentional in carving out the time to create this type of ecosystem.
George Haringhuizen asked about enabling preparedness and fast response of mobile and global trials and materials data analysis and whether they are creating agreements in advance about access and benefit sharing with other countries. Hepburn replied that progress is being made, and the U.S. government generally does a good job of engaging with international organizations and partner countries in global health responses, but there is more work to be done.
Hepburn said that from a DoD standpoint, partnership with the host country is paramount; data are frequently shared, and they ensure that local partners receive first authorship on academic collaborations. DoD works to ensure that host countries benefit from the clinical trials and products being developed, but the complexity of these negotiations makes them challenging. He added that DoD benefits on a daily basis from opportunities for mutually beneficial military-to-military collaborations with North Atlantic Treaty Organization (NATO) allies and host countries to support health care delivery and public health emergency responses.
Peter Daszak commended the work by CEPI and other emerging initiatives around the pipeline for pathogens, but he noted that they depend on fragile partnerships and funding structures. He asked how USAID addresses sustainability within its public–private partnership initiatives, particularly in the context of political shifts. Dosani responded that ensuring sustainability is an ongoing challenge, given the fragility of partnerships. She added that many partnerships are not sustainable because it is challenging to track and quantify their impact. Starting to track and measure impact early in the process can help to improve sustainability by demonstrating the benefits of the work being done by the partnership.
Venkayya pointed out that CEPI is still an experiment that needs to demonstrate its success; this will take years owing to the timeline for vaccine development, so milestones needed to be added along the way to give donors confidence that it is on track. He was optimistic about CEPI’s success, despite the challenges inherent in product development. For instance, many product development programs are guaranteed to fail, given the low likelihood of a given product making it to the market, and donors need to be willing to tolerate that outcome. He added that leadership and continuous assessment are important in ensuring that donors maintain confidence in the initiative.
Turkan Gardenier, applied statistician, asked about the application of geographical information science technology. Hepburn responded that the approach to clinical trials needs to be adapted to take into account the huge amount of information that is now available by using more sophisticated statistical design and analysis. He suggested that trials could possibly be carried out more quickly and with far fewer participants if cutting-edge data science
and technology were applied—for example, using accurate point-of-care diagnostics to determine which patients have an infection in a therapeutic trial. Transforming the product development process could also reduce costs enormously, he added.
Jay Siegel, retired, asked whether the four-stage process presented by Hepburn was about monoclonal antibody development for therapeutics, passive immunization, or diagnostics. He also asked about the timeline from receiving a new pathogen to having a promising therapeutic and the extent to which partners are involved in the process. Hepburn responded that he used antibody development as the example because it is a promising technology. Furthermore, the pharmaceutical industry has reduced its risk, and there is a set process on how to make, test, manufacture, and license a monoclonal antibody. However, the same vision of rapid product development could be applied to vaccines.
He said that discovery is not the problem at this point—the back end of manufacturing and clinical trials is the primary challenge. He suggested that the best strategy for success during a crisis is minimal change, that is, to do everything by the same process that regulatory agencies are comfortable with at a steady rate. This strategy is starting to be used for antibody production as well as in various vaccine platforms, he noted, and expressed hope that it would streamline manufacturing and regulatory processes.
Jyoti Joshi pointed out that the private sector is not one player, but multiple players that are at different levels with distinct knowledge and expertise. She asked about how to balance concerns about safety in the context of accelerated introductions and review pathways, given that reports of product performance may be delayed in settings with health systems that are already weaker or easily compromised by an outbreak. More broadly, she asked how health systems’ resilience and trust building figure into these conversations.
Venkayya said that when the Bill & Melinda Gates Foundation was introducing the rotavirus vaccine into LMICs, they considered the number of lives lost per day that the introduction of the vaccine was delayed. He suggested applying the same concept to product development timelines and urgency for epidemic diseases. The benefits of shortening timelines through alternative review and licensure pathways need to be weighed against safety concerns, however. This requires a benefit–risk calculation that takes into account management of risk on the safety and efficacy side as well as careful pharmacovigilance and safety monitoring once the product is released.
Accelerated access to the market is contingent on a robust set of postmarketing commitments to evaluate for safety, he added. It is possible to take a risk-based approach to the licensure pathway to accelerate product delivery, while also pacing the rollout to identify safety issues as the product is scaled. Hepburn suggested leveraging the power of next-generation technology, such as cell phones, to capture postmarketing safety data. He
also called for using technology to democratize clinical trial enrollment and the capture of health care information, while ensuring that patients’ private data are protected.
Carolyn Carroll, statistician, asked how to incorporate the risk profile into funding for new vaccines (e.g., the risks associated with Zika and Ebola). Venkayya responded that there are flavors of risk with any vaccine. Zika vaccine development, for example, had significant epidemiological and market risks. For a venture-backed or public company, the value proposition on a risk-adjusted basis of investing in a Zika vaccine is not attractive relative to other places that capital could be allocated. Takeda was willing to make the investment and take the risk because BARDA reduced the risk of the effort by shouldering much of the investment. Takeda still bears opportunity costs and other costs, but it is contributing to the vaccine development for the benefit of public health.
Rick Bright commented on the importance of trust, communication, and transparency in public–private partnerships, both from the bottom up and the top down. He also highlighted the discrepancy in interpreting the return on investment by different partners as the partnership evolves over time. For example, private entities may look at public funding as a gift or grant, while government entities such as BARDA are accountable for getting the full agreed-upon return on investment on behalf of the U.S. taxpayers, which, it is hoped, will benefit global public health as well. He added that BARDA has changed its approach to partnering with private industry to replace rigid, outdated contractual terms and to move toward flexible agreements that allow the government to behave more as a business partner in negotiations and discussions about return on investment.
Bright also highlighted innovation in regulatory sciences led by agencies such as FDA and the European Medicines Agency in terms of future drug production, vaccine development, and diagnostics. Venkayya noted an asymmetry in relationships between a funder and a contract or grant awardee. Awardees may not have the capability to aggregate risks in a sophisticated way and may face pressure to overpromise. He suggested that both sides of a partnership need to be more careful and candid about risks, timelines, and budgets.
Kent Kester remarked on the potential to look across technologies and platforms in the interagency world to focus on public health imperatives, codify best practices, and thus simplify and streamline the development of public–private partnerships. Hepburn said that DoD, USAID, and the U.S. Department of Health and Human Services are working together better than ever before, sharing research capacity and expertise. However, relationships and trust still need to be strengthened. He suggested focusing on building more formalized structures to codify best practices and ensure that this coordination outlasts individual relationships.
Daniel Berman suggested using negotiation and advanced market commitments or service contracts to generate public support for increased investment in partnerships for product development. Venkayya replied that prices should not be negotiated at the preclinical or phase 1 stage of development, because there are so many uncertainties that will have an effect on the price. However, it is possible to negotiate on the principles of how to operate, which CEPI is doing. He added that having donors and investors on the board adds layers of protection that help to ensure the appropriate use of taxpayer dollars and adherence to access provisions. CEPI has also put other mechanisms in place as a fallback to protect donor and taxpayer resources, as well as the populations that CEPI intends to help.
James Lawler, director, Clinical and Biodefence Research, National Strategic Research Institute, University of Nebraska, remarked that the products and technologies developed through these partnerships are not used in a vacuum; therefore, it is important to consider the effect they are actually having in practice. For example, new products being employed to address the Ebola outbreak in the Democratic Republic of the Congo are not having a substantial effect on the case fatality ratio. He suggested a focus on leveraging partnerships and investment to integrate high-quality supportive clinical care in resource-limited settings.
Hepburn acknowledged the tension between a focus on physical product development and adopting a holistic approach to outbreak response. He suggested that clinical trials for product development could be layered on top of an observational study to promote a more comprehensive understanding of health and disease during outbreaks. Eva Harris called for more discussion around governments, industry, and populations in the Global South and their roles as partners.
Dosani responded that USAID is focused on building countries’ self-reliance, so partnerships are done in-country and led, to some extent, by country governments and are supported, rather than controlled at the agency level. The examples she discussed are supported by local governments, local nonprofits, and the local private sector. Andrew Clements, deputy director, Pandemic Influenza and Other Emerging Threats Unit, USAID, commented that in addition to biomedical inventions, there are other valuable preventive measures—such as infection prevention and control, water and sanitation, and livestock value chain biosecurity—that could benefit from partnerships with the private sector.