Research involving potential pandemic pathogens (PPPs) is essential to protecting global health and security. However, there are biosafety and biosecurity risks associated with undertaking such research that should be adequately considered and appropriately mitigated in order to safely realize the potential benefits. The 2017 Department of Health and Human Services (HHS) Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (HHS P3CO Framework) is intended to guide HHS funding decisions on proposed research that is reasonably anticipated to create, transfer, or use PPPs resulting from the enhancement of a pathogen’s transmissibility or virulence in humans (enhanced PPPs). Enhanced PPP do not include naturally occurring pathogens that are circulating in or have been recovered from nature, regardless of their pandemic potential. This framework describes a robust multidisciplinary, pre-funding review process that considers the potential scientific and public health benefits, biosafety and biosecurity risks, and appropriate risk mitigation strategies to help inform agency decisions.
This framework is responsive to, and in accordance with, the Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight issued by the White House Office of Science and Technology Policy on January 9, 2017 and supersedes the previous Framework for Guiding Department of Health and Human Services Funding Decisions about Research Proposals with the Potential for Generating Highly Pathogenic Avian Influenza H5N1 Viruses that are Transmissible among Mammals by Respiratory Droplets. Adoption of this framework lifted the research funding pause on HHS research that was set forth by the U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses.
Two research projects were reviewed in accordance with the HHS P3CO Framework. Both projects were evaluated through the NIH peer review process in 2013, found to be scientifically meritorious, and funded via mechanisms that allow for the addition of specialized terms and conditions of funding and management of risk. Both projects were subsequently determined to be subject to the Gain-of-Function (GoF) Research Funding Pause, announced in October 2014, resulting in the funds being redirected within the awards to support other non-GoF research. In 2018, the Funding Agency referred both projects, with corresponding risk-benefit analyses and risk mitigation plans, to HHS for review under the new HHS P3CO Framework. The HHS P3CO Review Group included experts in scientific research, biosafety, biosecurity, medical countermeasures, law ethics, public health preparedness and response, biodefense, select agent regulations, and public health policy. Criteria for the HHS P3CO review includes a determination on:
Under the HHS P3CO Framework, the HHS P3CO Review Group determined that, in the case of both research proposals, the research is acceptable for HHS funding with recommended changes to increase the potential benefits while decreasing risks; suggested changes were included as terms and conditions of the awards. Further, it was determined that there are no feasible, equally efficacious alternative methods to address the same question in a manner that poses less risk than the proposed approaches.
Information about these NIH-funded research projects is available on NIH Reporter, an electronic tool that allows users to search a repository of NIH-funded research projects and access publications and patents resulting from NIH funding, and other publicly available sites. Information can also be found at: