Dual Use Research of Concern (DURC) and Pathogens with Enhanced Pandemic Potential (PEPP)

Dual Use Research is research that is conducted for legitimate purposes, but which could potentially generate knowledge, technologies, or products that could be used for both beneficial and harmful applications. Dual Use Research of Concern(DURC) is a small subset of life science 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, material, or national security.

A 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 type of pathogen with pandemic potential (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.

* “Experiments that enhance a pathogen’s transmissibility” include those that enhance environmental stability of the pathogen or toxin or change the tropism or host range of the pathogen or toxin in a way that enables an increased ability to infect and transmit between humans, among others.

The U.S. Government’s DURC and PEPP Policies establish a national framework to ensure that certain types of life sciences research are conducted responsibly. These policies apply to research involving specific biological agents, toxins, or experiments that could be misused to pose significant threats to public health, agriculture, food security, the environment, economic stability, or national security.

As of May 6, 2025, all federally funded life sciences research must be assessed for its potential to pose such risks. This includes research funded through grants, contracts, cooperative agreements, and other agreements and transactions issued on or after the policy’s effective date. The policies require risk assessments not only at the proposal stage but throughout the entire life cycle of the research project.

Organizations are also encouraged to assess all research that may present biosafety or biosecurity risks, regardless of funding source. This includes in silico studies and the use of computational technologies, such as artificial intelligence, that model or manipulate biological systems.

Principal Investigators (PIs) conducting life sciences research must fulfill the following responsibilities to comply with UMBC and U.S. Government DURC-PEPP oversight requirements:

1. Understand and Comply:
   Be knowledgeable about and comply with all UMBC and U.S. Government policies, requirements, and regulations governing research involving biological agents, toxins, and dual use research concerns.
2. Assess Research Throughout the Lifecycle:
   Evaluate your research at the proposal stage and continuously throughout the research lifecycle to determine whether it is reasonably anticipated to fall within the scope of Category 1 or Category 2 Research. If such research is identified, promptly notify the federal funding agency (if applicable) and the UMBC Biosafety Office.
3. Submit Required Protocols:
   Submit an Institutional Biosafety Committee (IBC) protocol through KUALI for any research involving recombinant or synthetic nucleic acid molecules, infectious agents, select toxins (at any quantity), and/or human materials. All IBC protocols are reviewed for potential Category 1 or Category 2 Research and referred to the Institutional Review Entity (IRE) as needed.
4. Collaborate on Risk Assessment and Mitigation:
   For research identified as Category 1 or Category 2, work with the IRE to assess the risks and benefits and to develop a draft risk mitigation plan. Submit progress reports for Category 1 and/or Category 2 Research to the federal funding agency for ongoing review and evaluation.
5. Follow Approved Mitigation Measures:
   Conduct all Category 1 and Category 2 Research strictly in accordance with the provisions outlined in the approved risk mitigation plan.
6. Ensure Training and Competency:
   Ensure that all laboratory personnel involved in life sciences research under your supervision receive and maintain appropriate education, training, and demonstrated competency regarding DURC-PEPP oversight policies and procedures.
7. Communicate Research Responsibly:
   Communicate findings from Category 1 and Category 2 Research responsibly throughout the research process, not just at publication. All communications must align with the risk mitigation measures approved by the IRE and, if applicable, by the federal funding agency.

“Reasonably anticipated” describes “an assessment of an outcome such that, generally, individuals with scientific expertise relevant to the research in question would expect this outcome to occur with a non-trivial likelihood. It does not require high confidence that the outcome will definitely occur and excludes experiments in which experts would anticipate the outcome to be technically possible, but highly unlikely.”

This definition captures important features of the outcome assessment that are further explained in section B3 of the DURC-PEPP Implementation Guide(link is external):

• “Relevant scientific expertise” refers to the scientific expertise required to anticipate the potential and plausible results of an experiment.
  • Scientists may have differing views on possible and likely outcomes of any particular experiment, so the general assessment of multiple individuals is likely to be more robust than the views of any single individual. The PI is not required to seek assessment from a group of individuals, but rather to use the PI’s individual expertise and experience to consider the range of assessments that individuals with relevant scientific expertise would likely make.
• “Expect this outcome to occur:” While it is impossible to know for certain the result of any experiment in advance, experiments are typically conducted to test specific hypotheses. These hypotheses constitute expectations about the possible results of an experiment, and should be included in the range of results that are “reasonably anticipated” may occur. The PI may consider, if applicable, leveraging existing literature that may have analogous experimental design and/or similar pathogens or toxins to determine potential expectations.
• “Non-trivial likelihood”: A “reasonably anticipated” outcome is not necessarily the most likely outcome, nor is it necessarily an outcome with greater than 50% likelihood. Rather, it is an outcome that has a reasonable, non-negligible chance of occurring. For example, consider an experiment on pandemic influenza that experts anticipate is most likely to result in a loss of function, but that experts also believe could possibly increase transmissibility of the pathogen. An indication of generating a pandemic influenza virus with enhanced transmissibility represents a risk of high consequence to the public if that agent were to be accidentally released. Such a study should therefore undergo Category 2 oversight because, despite the fact that generating a PEPP is not the likeliest outcome, it has a non-trivial likelihood of resulting in a PEPP.
• “Excludes experiments in which an expert would anticipate the outcome to be technically possible, but highly unlikely”: For many experiments it may be possible to imagine a scenario, however unlikely, in which a genetic mutation surprisingly results in an increase in virulence or transmissibility against all reasonable expectations and prior evidence. The purpose of the Policy is to prioritize oversight for experiments that may pose the greatest risks. Technically plausible outcomes with very low likelihoods, as assessed based on pre-existing evidence, are not subject to Category 2 oversight. As per the Policy, if such a result unexpectedly arises during the conduct of research, the study should be halted, immediately be flagged for the IRE and funding entity, and be subject to Category 2 assessment and risk mitigation.

The ICDUR is the Institutional Contact for Dual Use Research and serves as an institutional point of contact for questions regarding compliance with and implementation of the requirements for the oversight of DURC as well as the liaison (as necessary) between the institution and the relevant USG funding agency.

Michael Walsh Director OSP is UMBC ICDUR

The IRE is a committee or designated body within a research institution that reviews proposed or ongoing research to assess whether it falls under Category 1 or Category 2 of the DURC/PEPP policy. The IRE is responsible for conducting risk assessments and determining appropriate actions, including creating and evaluating risk mitigation plans. The IRE ensures that all relevant policies and safety measures are followed for research with potentially high risks.

Category 1 Research

1. It involves one or more of the specified biological agents and/or toxins in the following categories.  See the DURC-PEPP Category 1 List for details.
   1. All Federally Regulated Select Agents and Toxins including those at amounts below the Permissible Toxin Amounts.
   2. All Risk Group 4 pathogens listed in Appendix B of the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines).
   3. A subset of Risk Group 3 pathogens listed in Appendix B of the NIH Guidelines.
   4. For biological agents affecting humans that have not been assigned a Risk Group in the NIH Guidelines, agents affecting humans that are recommended to be handled at BSL3 or BSL4 per the BMBL guidance are subject to the USG DURC-PEPP Policy.

Category 2 research meets three criteria:

1. It involves, or is reasonably anticipated to result in, 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.;
2. It is reasonably anticipated to result in, or does result in, one or more of the following experimental outcomes:
   1. Enhance transmissibility of the pathogen in humans
   2. Enhance the virulence of the pathogen in humans;
   3. 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
   4. Generate, use, reconstitute, or transfer an eradicated or extinct PPP, or a previously identified PEPP.
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.

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

• Human immunodeficiency virus (HIV) types 1 and 2
• Human T cell lymphotropic virus (HTLV) types 1 and 2
• Simian immunodeficiency virus (SIV)
• Mycobacterium tuberculosis, Mycobacterium bovis
• Clade II of MPVX viruses unless containing nucleic acids coding for clade I MPVX virus virulence factors
• Vesicular stomatitis virus
• Coccidioides immitis and Coccidioides posadasii (sporulating cultures; contaminated soil)
• Sporulating cultures of Histoplasma capsulatum, capsulatum var. Duboisii
• Sporulating cultures of Blastomyces (e.g., B. dermatitidis, B. gilchristii)

UMBC will utilize CITI Module on Dual Use Research of Concern (DURC) which provides detailed training on the Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential.  It describes the agents and types of experiments that require oversight. Identifies the responsibilities of principal investigators, federally funded research institutions, federal funding agencies, and institutional contract for dual use research (ICDURC).

• NIH Video Dual Use Research: A Dialogue

• PI Initial Assessment:
  • PI assesses whether research may fall under Category 1 or Category 2 based on biological agents or experimental outcomes.
  • The research institution ensures PIs are aware and comply with this responsibility.
  • Answering the initial three questions in KUALI during the submission process the PI assesses whether research may fall under Category 1 based on biological agents or experimental outcomes. If the PI answers yes to any of the three questions then they are provided a link to a self-assessment where they can determine if the agent could also fall under category 2.
• Proposal Submission:
  • PI submits the research proposal to the federal funding agency, noting potential Category 1 or Category 2 scope.
• Agency Notification:
  • After merit review, the federal funding agency informs the research institution if the proposal is under funding consideration.
• Institutional Review:
  • Institutional Review Entity (IRE) evaluates the PI’s assessment.
  • IRE confirms Category 1 or Category 2 designation through risk assessment.
  • Institution notifies the funding agency of the determination for verification.
• Risk-Benefit Assessment and Mitigation Planning:
  • If within scope, IRE conducts risk-benefit assessments and, with the PI, drafts a risk mitigation plan.
  • PI submits the draft to the funding agency.
• Funding Agency Review and Approval:
  • Category 1: Funding agency evaluates risk-benefit assessments and must approve the mitigation plan before funding.
  • Category 2: Proposal undergoes multidisciplinary review by the funding agency.
    • Review entity advises on risk-benefit, mitigation, and funding.
    • Funding and research cannot proceed without agency approval.
• Mid-Research Discovery:
  • If change in scope is identified during experimentation, PI halts work and notifies the institution and funding agency.
  • IRE conducts assessments per policy procedures.