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Introduction¹

“As the movement of people, goods, and services across borders increases, our national health security is increasingly dependent on global health security,” states the Office of the Assistant Secretary for Preparedness and Response’s (ASPR’s) National Health Security Strategy,² describing the link between emerging infectious disease threats that may not have available treatments or vaccines, and the security of the world’s health since these diseases also know no boundaries and will easily cross borders. The real and present danger of these emerging infectious diseases is illustrated in the 2013 emergence and persistence of H7N9 as a virus with pandemic potential; the 2014 Ebola virus disease (EVD) outbreak originating in West Africa and leading to isolated cases in several countries around the globe; and the recent surge in cases of Middle East respiratory syndrome coronavirus (MERS-CoV), originating in the Arabian Peninsula with recorded cases now in Asia, Europe, and the United States.

Yet, sustaining public and private investment in the development of medical countermeasures (MCMs) before an emerging infectious disease becomes a public health emergency in the United States has been extremely challenging. Interest and momentum peak during a crisis and wane between events, and there is little interest in disease threats outside the United States until they impact people stateside. In one example, an August 2014 analysis by EcoHealth Alliance, predicted the United States as one of the top three countries that would receive a patient with EVD

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¹The planning committee’s role was limited to planning the workshop. This workshop summary has been prepared by the rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not necessarily endorsed or verified by the Institute of Medicine, and should not be construed as reflecting any group consensus.

²For more on the updated National Health Security Strategy, see http://www.phe.gov/Preparedness/planning/authority/nhss/Pages/global.aspx (accessed July 29, 2015).

as a result of global air travel by an infected individual from West Africa.³ The press release identified five U.S. airports at highest risk based on flight data, but the warning was essentially ignored by the media and decision makers, even though the World Health Organization (WHO) had already declared the outbreak an international public health emergency. Only a few months later would the first Ebola patient in the United States be diagnosed, causing national media coverage and widespread fear among the public and health care workers at all levels. Furthermore, an August 2015 Nature article noted that, while many are hopeful the EVD epidemic in West Africa will usher in a new era of how the world prepares for emerging infectious diseases, many public health officials are afraid that the impetus will fade, as after previous events, once Ebola fades from the limelight (Butler, 2015).

Current operational and business models involving government, the private sector, and academia to build and sustain MCM development capability are limited. Recent decreases in federal funding toward these efforts as well as the shifts from multiyear budgets to annual appropriations from Congress further hamper the ability to sustain capacity between outbreaks. Additionally, many regulations and policies that were developed in response to past events (e.g., severe acute respiratory syndrome, or SARS, in 2003, H1N1 in 2009) do not address potential future needs, or create capabilities and partnerships in a systematic manner. Instead they reactively address past gaps, making it difficult for partners to create broad capabilities able to address unknown future emerging infectious diseases. Although these challenges and others continue to present themselves, successes in MCM development for emerging infectious diseases over the past decade provide important opportunities from which to learn (e.g., the number of products approved and the manufacturing capability needed to support pandemic influenza response). In addition to learning opportunities, these successes in the past decade also provide existing systems that can be leveraged to build better capacity to predict, prepare for, and respond rapidly to emerging infectious disease threats in the future—if maintained at a functioning, operational level.

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³See http://www.ecohealthalliance.org/press/101-ecohealth_alliance_identifies_ebolas_flight_path_to_the_u_s (accessed September 30, 2015).

ACHIEVING RAPID AND NIMBLE MCM CAPABILITY

On March 26 and 27, 2015, the National Academies of Sciences, Engineering, and Medicine, Forum on Medical and Public Health Preparedness for Catastrophic Events; Forum on Drug Discovery, Development, and Translation; and Forum on Microbial Threats co-convened a workshop in Washington, DC, to discuss how to achieve rapid and nimble MCM capability for new and emerging threats. Public- and private-sector stakeholders examined recent efforts to prepare for and respond to outbreaks of EVD, pandemic influenza, and coronaviruses from policy, budget, and operational standpoints. Participants discussed the need for rapid access to MCM to ensure national security and considered strategies and business models that could enhance stakeholder interest and investment in sustainable response capabilities. The objectives for the workshop,⁴ as outlined by the workshop planning committee, are presented in Box 1-1.

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⁴For the full statement of task, see Appendix C.

ORGANIZATION OF THE REPORT

The following report summarizes the presentations from expert speakers and discussions among workshop participants. Chapter 2 highlights some of the persistent, critical gaps in international response capacity, in the context of the 2014 EVD outbreak. Chapter 3 considers preparedness from a national security perspective. Chapters 4, 5, and 6 discuss the challenges of rapid and sustainable development of MCMs in the context of three current threats: EVD, pandemic influenza, and coronaviruses, respectively. Chapter 7 explores business models and strategies for sustainable MCM development, and finally, in Chapter 8, panelists and attendees reflect broadly on the needs and opportunities discussed throughout the workshop.

OVERVIEW OF TOPICS HIGHLIGHTED DURING
PRESENTATIONS AND DISCUSSION⁵

A number of themes emerged across multiple workshop presentations and discussions as participants considered current efforts and future strategies to ensure ready access to MCM for emerging infectious disease threats. The themes and opportunities highlighted below, drawn from the individual presentations and open discussions, are also discussed further in the succeeding chapters.

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⁵Rapporteurs’ summary of main topics and recurring themes from the presentations, discussions, and summary remarks by the meeting and session chairs. Items on this list should not be construed as reflecting any consensus of the workshop participants or any endorsement by the Institute of Medicine or the Forums.

• Emerging infectious disease preparedness viewed as an issue of U.S. national security. There was broad sentiment that emerging infectious diseases are a national security concern. A few participants raised concerns that the current focus on “all hazards preparedness” has diluted attention to infectious disease control, and that the national security implications of infectious disease threats are not given appropriate recognition beyond the public health sector.
• Broader, earlier engagement of stakeholders. Given the far-reaching consequences that can be associated with an outbreak of an emerging infectious disease, many participants highlighted the need to expand the discussion beyond the traditional MCM enterprise stakeholders.
  • John Rex, senior vice president and head of Infection Global Medicines Development, AstraZeneca, called for the involvement of economists, representatives from the Department of the Treasury, and global risk analysts to better understand and convey the potential collateral damage and economic impacts of inaction.
  • Because many, if not most, emerging infectious diseases are zoonotic, many participants noted the value in engaging animal disease surveillance and animal vaccine experts.
  • Although the private sector is clearly a key stakeholder and partner in the MCM enterprise, various participants stressed that the innovative pharmaceutical, biotechnology, and diagnostics industries need to be involved from the start, rather than brought in at some later time after a response strategy has been drafted.
• Practical challenges to ensuring active cooperation. Developing MCMs requires access, cooperation, and accountability. Virus sample sharing is encouraged, but Jeremy Farrar, director of the Wellcome Trust, pointed out that many countries are actually disincentivized to sharing virus samples because they will not be sold back MCMs at an affordable price. A partnership means that both parties will benefit, he said. Nicole Lurie, Assistant Secretary for Preparedness and Response at the Department of Health and Human Services (HHS), also pointed out that few people are publishing their protocols for treatment of EVD, so there has not been nearly enough analysis necessary

• to understand life-saving treatments, let alone information for MCM development. Adding information sharing components as incentives for MCM development can bring more cooperation to the varying sectors involved.

• Transparent prioritization followed by action. Given the vast number of potential infectious disease threats and limited government, industry, and philanthropic budgets, it is clearly not possible to prepare for all eventualities. One participant summarized that “we are either paralyzed to inaction because there are too many threats and we don’t know where to start, or we are too busy dealing with the threat of the moment to address anything else.” Discussion supported the need for holistic threat assessment, considering not only the biological properties of viruses and hosts but also the social or behavioral contexts within which a disease could emerge to become a crisis. Transparency of the process and a clear signal of what is a priority would help partners (i.e., industry) to have some level of confidence in taking action and investing in development.
• The role of industry as a commercial enterprise. Approaches for effectively engaging industry need to be flexible while still company and countermeasure specific. A diverse array of approaches were discussed that could be used to incentivize and de-risk participation in the MCM enterprise (e.g., classic and novel push and pull mechanisms,⁶ a portfolio partnership approach, product development partnerships). To entice and secure company investment, approaches could provide a return on investment or at least be cost neutral, several participants noted. Traditional government contracting mechanisms were described as cumbersome and laborious, and often not suitable for MCM development programs.
• Sustaining interest and investment in MCM development. The market for products and the investment in research and development fluctuate widely with the emerging and waning of an outbreak. Responses to emerging infectious disease threats

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⁶Incentives for the development of MCMs that typically have no guaranteed market are categorized into “push” and “pull” categories. Push incentives lower the costs and risks of development, and pull incentives yield a reward if the product target is met. See more at http://www.nap.edu/catalog/12856/the-public-health-emergency-medical-countermeasures-enterprise-innovative-strategies-to (accessed August 28, 2015).

• will continue to be reactionary unless better efforts are made during interepidemic periods to advance preparedness, noted Gerald Parker, vice president for public health preparedness and response at Texas A&M Health Science Center. Sustaining key capabilities for MCM development over time was a common theme, including maintaining scientific expertise, manufacturing pipelines, and having the networks, partnerships, and relationships for such development. Sustainability challenges and successes can be different for small and large companies.

  • More effective risk communication. Many participants noted the need for better risk communication so the media, policy makers, and the public can understand and relate to the potential implications of outbreaks and interventions, as well as the costs of inaction. A few speakers suggested using the current crisis, while it temporarily has the world’s attention, to make the threats concrete and the planned actions clear.
• The promise of platform technologies. The ability to leverage a licensed manufacturing platform, in a facility approved by the Food and Drug Administration (FDA), has the potential to significantly reduce the time needed for MCM development in response to an emerging infectious disease threat. However, it will take some time for these platform technologies to mature and have the full buy-in of key regulatory agencies. Until then, as Monique Mansoura, Head, Medical Countermeasures & Government Affairs, Americas, at Novartis Influenza Vaccines highlighted, current assumptions and existing capabilities must be tested and exercised in order to provide verifiable assessments of preparedness before an event occurs (e.g., making and testing a vaccine, determining the dose, stockpiling, understanding the stability profile in the stockpile over time).
• A framework to guide decisions on what level of “preparedness” is sufficient. Lurie discussed the need for a better prioritized framework to determine when an MCM is needed versus a more traditional public health measure (e.g., handwashing, masks, vector control). The framework would also help to understand what type of MCMs would be required (e.g., vaccine, therapeutic), and to what stage of development a product should be taken (e.g., seed stocks, pilot lots, stockpiles). Such a decision framework needs to be transparent and easily