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United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential

Effective May 6, 2025

The United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential (“Policy”) is a unified federal oversight framework for conducting and managing certain types of federally funded life sciences research on biological agents and toxins. This Policy addresses oversight of research on biological agents and toxins that, when enhanced, have the potential to pose risks to public health, agriculture, food security, economic security, or national security. It supersedes the 2012 United States Government Policy for Oversight of Life Sciences Dual Use Research of Concern (Federal DURC Policy), the 2014 United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern (Institutional DURC Policy), and the Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (P3CO Framework). This Policy is issued by the Office of Science and Technology Policy (OSTP) in accordance with the directives established by the 2022 National Biodefense Strategy and Implementation Plan, as directed by National Security Memorandum 15, to complete an interagency review of efforts to strengthen responsible conduct for biological research. This Policy has also been issued pursuant to Section 2315 of the Consolidated Appropriations Act, 2023 (42 U.S.C. § 6627) to achieve consistent review and oversight of life sciences research proposed for federal funding that may be reasonably anticipated to involve the creation, transfer, or use of pathogens with enhanced pandemic potential (PEPPs).

The intent of this Policy is to strengthen oversight of life sciences research with biological agents and toxins throughout the research lifecycle by: 

  • Defining an expanded scope of biological agent and toxin research subject to additional oversight by the U.S. government;
  • Providing a unified framework to support the consistent identification and oversight of research proposals subject to this Policy that accounts for safety, security, and ethical considerations; and
  • Delineating the roles and responsibilities of principal investigators, research institutions, and federal departments and agencies that conduct, fund, or oversee research within the scope of this Policy, with an emphasis on institutional oversight and management of this research. 

The purpose of the United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential (“the Policy”) is to establish a unified federal oversight framework for conducting and managing certain types of federally funded life sciences research on biological agents and toxins that may pose risks to public health, agriculture, food security, economic security, or national security.  


Questions regarding the Policy?

Please reach out to the UKY Institutional Contact for Dual Use Research (ICDUR):

Delena (Dee) Mazzetti, MPH, RBP, CBSP

d.mazzetti@uky.edu

(859) 257-1073

Submit Self-Assessment Form

If you believe that your research may fall within scope of Category 1 or Category 2 research, please complete this Self-Assessment Form to notify the University of Kentucky (UK) Institutional Review Entity (IRE).

UKY Self-Assessment Form

Category 1 and Category 2 Research Subject to the Policy

To enable effective implementation, the Policy categorizes the research previously overseen by the 2012 Federal DURC, the 2014 Institutional DURC, and the 2017 P3CO Framework policies into Category 1 and Category 2 research. The Policy also expands the scope of research previously overseen by those policies. As outlined in more detail in Section 5 of the Policy, Category 1 research is subject to oversight by research institutions and federal funding agencies, and Category 2 research is subject to oversight by research institutions, federal funding agencies, and their federal department if applicable due to heightened potential for biosafety and biosecurity risks.   

Any research that meets the definition of both Category 1 and Category 2 research is designated as Category 2 research.  

Category 1 Research

Dual use research of concern (DURC) as defined in the Policy is “life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be misapplied to do harm with no, or only minor, modification to pose a significant threat with potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security.” 

Category 1 research meets three criteria:

  1. it involves one or more of the biological agents and toxins specified in Section 4.1.1;
  2. it is reasonably anticipated to result, or does result, in one of the experimental outcomes specified in Section 4.1.2; and
  3. based on current understanding, the research institution and/or federal funding agency assesses that the research constitutes DURC as specified in Section 4.1.3 of the Policy. 

Biological Agents & Toxins within the Scope of Category 1 Research

  • All Select Agents and Toxins listed in 9 CFR 121.3–121.4, 42 CFR 73.3–73.4, and 7 CFR 331.3 and regulated by USDA and/or HHS.
  • All Risk Group 4 pathogens listed in Appendix B of the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) - Classification of Human Etiologic Agents on the Basis of Hazard.
  • A subset of Risk Group 3 pathogens* listed in Appendix B of the NIH Guidelines - Classification of Human Etiologic Agents on the Basis of Hazard.
  • For biological agents affecting humans that have not been assigned a Risk Group in the NIH Guidelines, refer to the current edition of Biosafety in Microbiological and Biomedical Laboratories (BMBL). In such cases, agents affecting humans that are recommended to be handled at Biosafety Level 3 (BSL-3) or Biosafety Level 4 (BSL-4) per the BMBL guidance are subject to this Policy.
  • Biological agents added during future updates to the Implementation Guidance as specified in Sections 7 and 8. 

*Note: As of the time of release of this Policy, this subset consists of all RG3 pathogens except HIV, HTLV, SIV, Mtb (including mycobacterium bovis), Clade II of MPVX viruses unless containing nucleic acids coding for clade I MPVX virus virulence factors, vesicular stomatitis virus, Coccidioides immitis, C. posadasii, Histoplasma capsulatum, and H. capsulatum var. duboisii. This list may be updated in the Implementation Guidance on a periodic basis.  

Category 1 Experimental Outcomes

  • Increase transmissibility of a pathogen within or between host species;
  • Increase the virulence of a pathogen or convey virulence to a non-pathogen;
  • Increase the toxicity of a known toxin or produce a novel toxin;
  • Increase the stability of a pathogen or toxin in the environment, or increase the ability to disseminate a pathogen or toxin;
  • Alter the host range or tropism of a pathogen or toxin;
  • Decrease the ability for a human or veterinary pathogen or toxin to be detected using standard diagnostic or analytical methods;
  • Increase resistance of a pathogen or toxin to clinical and/or veterinary prophylactic or therapeutic interventions;
  • Alter a human or veterinary pathogen or toxin to disrupt the effectiveness of preexisting immunity, via immunization or natural infection, against the pathogen or toxin; or
  • Enhance the susceptibility of a host population to a pathogen or toxin. 

Category 1 Risk Assessment

Based on current understanding, the research can be reasonably anticipated to provide, or does provide, knowledge, information, products, or technologies that could be misapplied to do harm with no — or only minor — modification to pose a significant threat with potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. 

Category 2 Research

Pathogen with Pandemic Potential (PPP) - is a “pathogen that is likely capable of wide and uncontrollable spread in a human population and would likely cause moderate to severe disease and/or mortality in humans.”   

A pathogen’s capability for “wide and uncontrollable spread in a human population” is a function of the pathogen’s ability to spread in a human population through an efficient means of transmission (e.g., via aerosol, respiratory droplets, direct contact, fomites, etc.). As a general benchmark, “wide and uncontrollable spread” typically refers to pathogens expected to exhibit sustained human-to-human transmission in a population under specific conditions, or an effective reproductive number (Rt) greater than one. Conditions that aid wide and uncontrollable spread include a relative lack of pre-existing population immunity to the pathogen, environmental stability of the pathogen, respiratory route of transmission, and lack of availability of or access to non-medical and medical countermeasures (MCMs) to contain the pathogen. Once a population has been exposed to a pathogen over multiple years or seasonal cycles, the ability for that pathogen to spread disease throughout the human population and cause moderate to severe disease in humans may diminish. However, the absence of one of these conditions alone is insufficient to rule out pandemic potential. For example, Influenza A virus subtype H1N1 (1918) is considered to have pandemic potential because it may be able to spread widely in a population despite the existence of MCMs.  

A pathogen’s capability to cause “moderate to severe disease and/or mortality in humans” may be estimated by comparing case hospitalization rate (CHR) and/or case fatality rates (CFR). These comparisons may not be clear-cut or relevant in every circumstance, but rather can provide a high-level guideline to help PIs, IREs, and federal funding agencies assess which pathogens are included and excluded from the PPP definition.  

While Rt, CHR, and CFR are key tools for determining whether a pathogen is a PPP, it is important to note that these metrics can vary widely based on a range of factors (e.g., levels of population immunity, access to health care, community behaviors, etc.), and relevant data on these metrics may not be available for many pathogens under study in the laboratory. 

Other pathogen characteristics for determining moderate to severe disease potential may include types of symptoms, duration of disease, or long-term symptoms that persist after infection. 

Classification of a pathogen as a PPP can evolve over time, including during the course of a pandemic, due to changing levels of population immunity, development of MCMs, and emergence of variants with differing levels of transmissibility and pathogenicity. Cumulatively, these metrics are meant to help broadly establish a reference class of pathogens that fit in the PPP definition, to help PIs, IREs, and federal funding agencies determine whether a particular pathogen fits the PPP definition based on what is known about the transmissibility and disease characteristics of that pathogen.

Pathogen with Enhanced Pandemic Potential (PEPP) -  is “a type of PPP resulting from experiments that enhance a pathogen’s transmissibility or virulence, or disrupt the effectiveness of pre-existing immunity, regardless of its progenitor agent, such that it may pose a significant threat to public health, the capacity of health systems to function, or national security. Wild-type pathogens that are circulating in or have been recovered from nature are not PEPPs, but may be considered PPPs because of their pandemic potential.” 

“Progenitor agent” within the PEPP definition refers to the starting pathogen of the proposed experiment, which may be a PPP in its wild-type form or a pathogen that is not considered a PPP in its wild-type form, but that when modified meets the definition of a PEPP. 

Eradicated or Extinct PPP - Category 2 oversight is also required for experiments that generate, use, reconstitute, or transfer an eradicated or extinct PPP that may pose a significant threat to public health, the capacity of health systems to function, or national security, regardless of whether the experiment enhances the PPP. Current eradicated and extinct PPPs include Variola major and minor, and Influenza A virus subtypes H1N1 (1918) and H2N2 (1957-1968). Any research with these PPPs is considered Category 2 because of the heightened consequences of biosafety or biosecurity incidents that could occur from directly handling or possessing such pathogens, even without any enhancement to virulence or transmissibility.  

Category 2 research meets three criteria: 

  1. it involves, or is reasonably anticipated to result in, a PPP as specified in Section 4.2.1 of the Policy;
  2. it is reasonably anticipated to result in, or does result in, one or more of the experimental outcomes or actions specified in Section 4.2.2 of the Policy; and
  3. based on current understanding, the research institution and/or federal funding agency assesses that the research is reasonably anticipated to result in the development, use, or transfer of a PEPP or an eradicated or extinct PPP that may pose a significant threat to public health, the capacity of health systems to function, or national security as specified in Section 4.2.3 of the Policy. 

Biological Agents within Scope of Category 2 Research

A Pathogen with Pandemic Potential (PPP), or any pathogen that will be modified in such a way that is reasonably anticipated to result in a PPP. 

Category 2 Research Experimental Outcomes or Actions 

  • Enhance transmissibility of the pathogen in humans;
  • Enhance the virulence of the pathogen in humans;
  • Enhance the immune evasion of the pathogen in humans such as by modifying the pathogen to disrupt the effectiveness of pre-existing immunity via immunization or natural infection; or
  • Generate, use, reconstitute, or transfer an eradicated or extinct PPP, or a previously identified PEPP. 

Category 2 Risk Assessment 

The research can be reasonably anticipated to result in the development, use, or transfer of a PEPP or an eradicated or extinct PPP that may pose a significant threat to public health, the capacity of health systems to function, or national security. 

PIs and IREs should also assess Category 2 research for potential DURC risks as outlined in Section 4.1 of the Policy, and if applicable, include appropriate Category 1 risk mitigation in the draft mitigation plan. 

Principal Investigator Responsibilities

PIs should:

  • Be knowledgeable about and comply with or follow all applicable institutional and U.S. government policies, requirements, and regulations for oversight of biological agent and toxin research.
  • Assess their research throughout the entire lifecycle to identify whether their research may be within the scope of Category 1 or Category 2 oversight.
  • Once PI identifies research potentially subject to Category 1 or Category 2 oversight, notifies the federal funding agency & IRE.
  • Work with IRE to assess risks and benefits & submit risk-benefit assessment & draft risk mitigation plan for review and approval.
  • Conduct Category 1 and Category 2 research according to approved risk mitigation plan.
  • Provide annual progress reports for Category 1 research and semiannual progress reports for Category 2 research.
  • Ensure laboratory personnel are trained, educated, and demonstrated competency of research oversight policies.
  • Communicate Category 1 and Category 2 research in a responsible manner.
 
University of Kentucky PIs must also complete USG Policy for Oversight of DURC and PEPP training. This page will be updated once training is available online.

Review Process

The flowchart below depicts the review and assessment process for Principal Investigators (PIs) from start to finish.



DURC PEPP Review Flowchart