DURC/PEPP Category 1 research:

1. It involves one or more of the specified biological agents and toxins in the following categories. See the DURC-PEPP Category 1 List for details.
   1. 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.
2. It is reasonably anticipated to result, or does result, in one of the experimental outcomes specified below:
   1. 1. Increase transmissibility of a pathogen within or between host species;
      2. Increase the virulence (e.g. ability to cause disease) of a pathogen or convey virulence to a non-pathogen;
      3. Increase the toxicity of a known toxin or produce a novel toxin;
      4. Increase the stability of a pathogen or toxin in the environment, or increase the ability to disseminate a pathogen or toxin (e.g. environmental stability or aerosolubility);
      5. Alter the host range or tropism of a pathogen or toxin;
      6. Decrease the ability for a human or veterinary pathogen or toxin to be detected using standard diagnostic or analytical methods;
      7. Increase resistance of a pathogen or toxin to clinical and/or veterinary prophylactic or therapeutic interventions (e.g., antimicrobials, antivirals, antitoxins, vaccines);
      8. 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
      9. Enhance the susceptibility of a host population to a pathogen or toxin.
3. 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.

DURC/PEPP Category 2 research:

Category 2 research meets these 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 experimental outcomes or actions specified here:
   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. 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.

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

Dual Use Research of Concern (DURC)

Dual Use Research of Concern (DURC) 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. 

Institutional Contact for Dual Use Research (ICDUR)

The ICDUR is the official designated by the 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.

Pathogen with Enhanced Pandemic Potential (PEPP)

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.

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. Pathogens with pandemic potential are often those with little to no pre-existing immunity in the human population.

Reasonably Anticipated

“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 USG DURC-PEPP Implementation Guide:

• "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.