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

The U.S. Government released in May of 2024, the Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential.pdf (herein referred to as the DURC/PEPP Policy). DURC/PEPP Policy will supersede previous DURC framework policies. The policy includes new oversight roles for researchers, applicants, recipients, and federal funding agencies. The DURC/PEPP Policy addresses the identification and mitigation of biosafety, biosecurity, and information risks associated with manipulation of certain pathogens that could cause significant harm to society.  Updates reflect the evolving nature of scientific and technological risks. As a result, the institution must review all research potentially subject to the policy to determine whether it meets the criteria outlined in the policy for Category 1 (DURC) or Category 2 (PEPP) research. Understanding the definitions is imperative.

Biological Agents are any microorganism (including, but not limited to, bacteria, viruses, fungi, or protozoa), infectious material, or any naturally occurring, bioengineered, or synthesized component of any such microorganism or infectious material, capable of causing:

• Death, disease, or other biological malfunction in a human, an animal, a plant, or another living organism;
• Deterioration of food, water, equipment, supplies, or material of any kind; or Deleterious alteration of the environment.

Dual use research - Research conducted for legitimate purposes that generates knowledge, information, technologies, and/or products that can be utilized for benevolent or harmful purposes.

Dual Use Research of Concern (DURC) - 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. DURC aligns with Category 1 Research.

Gain of Function (GOF) Research - Experiments in which a microorganism is changed, resulting in the acquisition of new, or an enhancement of existing, biological phenotypes. Note that while GOF is a term that still may be occasionally used in the context of dual use research, it has largely been superseded by the terms PEPP and DURC.

Institutional Contact for Dual Use Research (ICDUR) - The official designated by the research institution to serve as an internal resource for application of this Policy as well as the liaison (as necessary) between the institution and the relevant federal funding agency.

Institutional Review Entity (IRE) - The entity established by the research institution to execute the institutional oversight responsibilities for Category 1 and Category 2 Research as described in the USA Policy.

Pathogen with Pandemic Potential (PPP) - 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. 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. PEPP aligns with Category 2 Research.

Reasonably anticipated describes an assessment of outcomes 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 occur but excludes experiments in which experts would anticipate the outcome to be technically possible, but highly unlikely

In the 2024 "US Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential" (USA Policy), two categories of the most concerning research are defined as:

Category 1, also referred to as Dual Use Research of Concern (DURC), and

Category 2, also referred to Pathogen with Enhanced Pandemic Potential (PEPP) research.

To qualify for each category under the policy, a series of three conditions must be met, which are outlined under the  

Category 1 & Category DURC/PEPP Classifications Table section.

	Category 1 Research - DURC	Category 2 Research - PEPP
Condition 1: Agents and/or toxins involved in research	A Select Agent or Toxin (list), including select toxins at exempt quantities.  A Risk Group 4 pathogen as listed in Appendix B of the NIH Guidelines.  A Risk Group 3 pathogen as listed in Appendix B of the NIH Guidelines with the exceptions of:  Human Immunodeficiency Virus (HIV), Human T-Lymphotropic Virus (HTLV), Simian Immunodeficiency Virus (SIV), Mycobacterium tuberculosis, Mycobacterium bovis, Clade II of Monkeypox virus, Vesicular Stomatitis Virus, Coccidioides immitis, Coccidioides posadasii, Histoplasma capsulatum, and Histoplasma capsulatum var. duboisii.	Any 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, also referred to as a Pathogen with Pandemic Potential (PPP). Any pathogen that is modified in such a way that is reasonably anticipated to result in a PPP.
Condition 2: Experimental outcomes of research	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. Enhance the susceptibility of a host population to a pathogen or toxin.	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. Generate, use, reconstitute, or transfer an eradicated or extinct PPP, or a previously identified PEPP.
Condition 3: Research meets definition	"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."	"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."

While the three conditions must all be met to qualify as Category 1 or 2 Research, investigators should keep in mind the dual use potential of all of their work and responsibly conduct and communicate research accordingly.

In summary:

1. The IBC will work to identify proposals involving agents and/or toxins under the purview of the USA Policy (condition 1). This includes identification of agents as PPP for Category 2 Research.
2. If condition 1 is met for Category 1 and/or Category 2 Research, the IBC will convene a separate, stand-alone meeting as the Institutional Review Entity (IRE). The IRE will assess a proposal for the associated experimental outcomes (condition 2) and definitions (condition 3) in order to identify Category 1 and/or Category 2 Research.
3. Once a protocol is identified as Category 1 and/or Category 2 Research, the IRE will form a DURC/PEPP Subcommittee. This subcommittee will include ad hoc members that provide additional expertise and will work with a Principal Investigator to draft a risk-benefit analysis and risk mitigation plan. If a project is federally funded, it is the funding agency that must ultimately approve the risk mitigation plan.
4. Once a Category 1 and/or Category 2 Research project is approved and begins, the DURC/PEPP Subcommittee will meet at least annually for review, evaluation, assessment, and if needed, clarification or confirmation.

1. Be knowledgeable about and comply with all USA and US Government policies, requirements, and regulations for the oversight of biological agent and toxin research.
2. Investigators proposing to work with (or generating) any replication-competent infectious agent, or proposing to work with any biologically-derived toxin (in IBC oversight) must make an initial assessment of whether the research is reasonably anticipated to be within the scope of Category 1 or Category 2 research. This self-assessment should happen at (1) the proposal stage when seeking funding and (2) during on-going research (continuously throughout the research lifecycle). 
3. Submit an IBC protocol for any research involving infectious agents, recombinant or synthetic nucleic acid molecules, select toxins (at any quantity), and/or human materials using the online IRBNet  system. As part of the normal IBC registration process, all protocols are reviewed for potential Category 1 or Category 2 Research and referred to the IRE as needed.
4. If an Investigator identifies potential Category 1 or Category 2 research at the proposal stage notify the federal funding agency and the USA Biosafety Office and be prepared to develop a risk-benefit assessment and a risk mitigation plan. If research is first identified as potentially within scope of Category 1 or Category 2 during experimentation, halt further work and work with the Institutional Review Entity (DURCCom) to develop the risk-benefit assessments and risk mitigation plan for submission to the federal funding agency for further review and approval to continue.
5. Investigators must ensure that laboratory personnel (i.e., those under the supervision of laboratory leadership, including graduate students, postdoctoral fellows, research technicians, laboratory staff, and visiting scientists) conducting life sciences research falling under the scope of this policy have received education and training on DURC.
6. If research is being proposed as part of a new funding proposal, the federal funding agency (if applicable) will require submission of the risk-benefit assessment and draft risk mitigation plan once the proposal is under consideration for funding. Agencies will give a 30-day deadline, so it is highly recommended that you submit potential Category 1 or Category 2 Research proposals to the IBC as early as possible and not wait until you are notified that the documents are needed.

 

 

 

US Government Policy for Oversight of DURC and PEPP (PDF)

Guidance for 2024 Policy on DURC and PEPP (PDF)

University of Maryland, Baltimore. (2024-2025). Dual Use Research of Concern (DURC) and Pathogens with Enhanced Pandemic Potential (PEPP). Environmental Health and Safety.

https://www.umaryland.edu/ehs/research-registration/institutional-biosafety-committee-ibc/durc/