Supporting MCM Development
Across Threats and Funding Cycles
This final chapter reflects on the discussions of preparedness of the nation as a national security concern; commonalities across three case examples, EVD, pandemic influenza, and coronaviruses; and sustainable strategies and business models for MCM development. Session chairs provided brief highlights from the panel discussions.
PREPAREDNESS AS A
NATIONAL SECURITY IMPERATIVE
The sentiment of the first panel session, and of much of the discussion, was that emerging infectious diseases are a national security concern, Parker of Texas A&M summarized. He expressed concern, however, that national security implications of infectious threats are not being recognized appropriately beyond the public health sector. He commented that infectious disease control has become diluted in the “all hazards preparedness” environment. Responses to emerging infectious disease threats will continue to be reactionary unless better efforts are made during interepidemic periods to advance preparedness. This requires a strong leadership function, Parker stressed. One participant suggested the possibility of having a public health agency, separate from HHS. Emphasizing the need for this, Venkayya of Takeda had noted the current lack of an overarching health security office inside the White House, and called for one with technical experts who also understand policy that could align the efforts of departments and agencies and hold them accountable for delivering results. Parker also noted that there has to be a link to the federal budget. Because diseases readily cross borders,
there is an international dimension that is also critical to national security. Global leadership is needed, both during the interepidemic period and during a crisis, Parker said. Participants discussed the dynamic roles of the United States. and other developed world countries, WHO, and other organizations in public health emergencies of international concern.
RESPONDING TO EMERGING INFECTIOUS
Osterholm of CIDRAP called attention to the need for a real-world understanding of risk, saying there is significant focus on biological assessment of risk, with less attention to social, political, and economic factors. For example, the fastest-growing areas of the world are the developing cities of the developing world, he said. How does transportation out of the Middle East impact the potential movement of the MERS virus? The extent of the 2014 Ebola outbreak was likely less due to changes to the virus, and more a result of changes in Africa and the world, he commented, again reiterating the importance of considering behavioral risks. Another challenge is that the world has become dependent on “just-in-time” delivery systems. Infectious diseases can disrupt supply chains and international trade. Any break in the supply chain can then disrupt access to critical medicines, and there are few stockpiles or reserves that can be deployed to backfill the gaps. In assessing risk and responses, Osterholm noted that there is a need for candor in discussing the data and defining what is really needed. The intent is not to lay blame for what may or may not have happened in past responses, but to develop a path forward to a safer world.
There was much discussion across all panels about prioritizing and funding. Inglesby of the Center for Health Security suggested the need for a dedicated, high-priority emerging infectious disease threats development program in the U.S. government, which would work closely with industry. Currently, he stated, everything is partitioned. There is a biodefense program, a pandemic influenza program, but there is nothing to address emerging infectious disease threats that have not yet reached the emergency threshold status. A dedicated program would mean that new programs do not have to be created when a threat emerges, or that one program does not have to steal staff and resources from another
when a crisis reaches the emergency stage. Such a program could be overseen by BARDA, or BARDA and NIH together, he offered.
Clarity in Language and Development Goals
There is also a need to respond to public and political expectations, clarifying the needs, the processes, and the current status. In this regard, Inglesby also called for clarity of language used. It is often written in journals or the media that there is a new vaccine for MERS, or for Ebola. In fact, it is not a vaccine, but a vaccine candidate, and it will only be a vaccine when it gets through the development system and is approved for use. Osterholm concurred that language is important, and he added that the data used are also very important. Various participants stressed the need for better risk communication strategies so that the media, policy makers, and the public can relate to the real potential implications of outbreaks and interventions, or lack thereof when applicable. Personal stories of how an outbreak can affect daily life can be as powerful in getting the message out as a numerical estimate, which is based on modeling that comes with caveats and is often misunderstood.
Conversations also surrounded the need for more clarity and agreement around rational stopping points in development, as Larsen noted previously. Licensure may not be feasible, but perhaps Phase III–ready assets can be achieved and shelved for use when needed. Mansoura of Novartis cautioned that late-stage development, scale-up, and manufacturing are complicated, and it is important to be aware that there is a 50 percent failure rate even for products that make it to Phase III. Ensuring the public and policy makers understand this statistic as well could help dissuade the thought that a robust pipeline for MCMs is ready and waiting to respond quickly for an array of threats. Across the panel discussions, the point was made that moments of crisis are windows of opportunity for change. Many participants commented that it is important to capture the attention of funders, policy makers, and the public and make the case for sustainable preparedness. Throughout the workshop, participants reiterated that the public health sector is hugely underestimating and not asking enough for what is needed to protect Americans from these threats.
Participants discussed sustainability as it applies to research and development programs; markets for products, partnerships, and networks; and talent and resources. Lessons learned from several examples of live research and development infrastructures were discussed (e.g., VHFC, CPTR). Providing a sustainable market for developers is a persistent challenge, and a variety of push and pull incentives were discussed to help de-risk the investment by companies. One of the themes across the discussions highlighted by several participants was the need to recognize that profit is part of the requirement for companies to be engaged. Similarly, examples described by Rex in Chapter 7 showed that society can underestimate true societal value of MCMs separate from financial value. Rex suggested four long-term goals based on the discussions:
- Fund an active basic science infrastructure. Technology is enabling great things, but there is a need for trained scientists to know what to do with that technology, he said. Maintaining live infrastructures, such as vaccine treatment evaluation units, allows for research and practice.
- Develop a framework for taking programs to stopping points, such as the end of Phase I, or the end of Phase II (i.e., Phase III ready). The notion of stopping partway needs to be examined in some detail, Rex said. There are elements that must be ready at the end of Phase III for registration (e.g., studies of safety, toxicology, carcinogenicity). These elements are not necessarily consecutive, but are layered into the development process. If a program is stopped partway, and some elements are not completed, it may take longer than expected when starting up again if it is necessary to go back and fill in the missing elements.
- Pick a program and complete it. For example, BARDA could select a product for a priority threat that has succeeded in getting to a stopping point, and call for its completion. By virtue of running the drill, Rex said, there will be a product (or not), people who have practiced and learned, and the system will have been tested.
- Encourage/permit multinational funding. For example, Hatchett of BARDA said some companies are working on new anti-
bacterial products and are receiving support from both BARDA and the EU Innovative Medicines Initiative. How can other nations be encouraged to participate in multinational efforts?
Moving forward, Rex recommended that a future Academies workshop consider the economic and societal value of having and not having MCMs. The workshop could delve into understanding the $30 billion that SARS is said to have cost, or how reactionary closing of borders might impact the economy. The workshop could also consider the true feasibility and usefulness of taking product development only partway. He’d like to see education of a broad group of stakeholders as to what is required to take an investigational product from Phase I, to Phase II, to Phase III, and what is the likelihood a product parked at the end of Phase I could eventually become a licensed product. Participants should include representatives of the Department of the Treasury, economists, as well as policy and public health experts, he said. Several participants suggested that co-convening with the Brookings Institution or the American Enterprise Institute could provide a different perspective with important audiences, but it would be essential to maintain the science and health focus.
Acknowledging Past Successes
Participants discussed the existence of success stories and models from which to learn. Project Bioshield, after 10 years and $5.6 billion, has yielded 12 MCMs against CBRN threats, 10 of them licensed. Twenty products supported by BARDA have been licensed since BARDA was created in 2006. The animal rule has been used successfully to approve a monoclonal antibody for the treatment of inhalation anthrax. The solutions that have worked in CBRN, influenza, and global health domains were all adapted to the problems they were seeking to solve in those spaces, offered Abdun-Nabi of Emergent BioSolutions. The solution that is going to work for emerging infectious diseases will likely need to be specifically adapted to that domain, he noted. It can draw on many of the other solutions and tools that have been developed in other spaces, but how they are assembled and used will be unique to the emerging infectious disease space.
Importantly, concluded Hatchett of BARDA, a lesson from the Ebola epidemic response is that responding to emerging infectious diseases must be institutionalized as something that the government values, such
that it sufficiently organizes, funds, and conducts preparedness and response activities. This will need to involve government partnership with industry partners, and ideally, engagement of global partners. Several participants likened the approach and level of organization and commitment that is needed to the Manhattan Project.1 In closing, Mansoura acknowledged the progress made and the successes seen thus far, but cautioned that there is much to be done. We must continue to develop, test, and exercise as we are striving toward next-generation capabilities to address known and unknown infectious diseases that will continue to threaten the national health security of the United States for many years to come.
1The Manhattan Project is the unofficial designation for the former U.S. War Department’s secret program, organized in 1942, to explore the isolation of radioactive isotopes and the production of an atomic bomb. Initial research was conducted at Columbia University in New York City, New York.