Dual Use Research of Concern (DURC)/Institutional Review Entity (IRE)

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 directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security.

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

The purpose of this policy is to outline Medical University of South Carolina’s (MUSC) plan for monitoring care, oversight, and the review of research that may fall into the category of Dual Use Research of Concern (DURC), Pathogens with Pandemic Potential (PPP) or Pathogens with Enhanced Pandemic Potential (PEPP).  This policy applies to all research, regardless of funding or source of sponsorship, that involve biological agents and toxins classified as “Category 1” or “Category 2”  in accordance with the United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential (USG DURC-PEPP Policy).  The USG DURC-PEPP Policy supersedes previous DURC policies, and the 2017 Recommended Policy Guidance for Potential Pandemic Pathogen Care and Oversight (P3CO) that covered research on highly transmissible, virulent agents.  The USG DURC-PEPP Policy does not supersede, but complements other existing federal regulations, including the Select Agent Regulations.

Definitions

Dual Use Research is 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) is defined as life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security.

Dual Use Research of Concern Committee (DURC Committee) is defined as the Institutional Review Entity (IRE) at MUSC for research that may meet the criteria of Category 1 or Category 2 in the USG DURC-PEPP Policy.

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.

Pathogen with Enhanced Pandemic Potential (PEPP) is 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.

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.

Categories of Research Subject to This Policy

There are two (2) categories of research, experiments, and risk assessment that fall within the scope of the USG DURC-PEPP Policy.

Category 1 Research 

Category 1 research meets all the following three (3) criteria:

• Involves one or more of the biological agents or toxins within scope of Section 4.1.1 of the USG DURC-PEPP Policy;
• Is reasonably anticipated to result, or does result, in one or more of the experimental outcomes listed in Section 4.1.2 of the USG DURC-PEPP Policy; and
• 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 USG DURC-PEPP Policy.

Category 1 Experiments (Section 4.1.2 of the USG DURC-PEPP Policy) 

Research within the scope of Category 1 are those experimental outcomes with a biological agent or toxin outlined in the Policy (pdf) that are reasonably anticipated to:

• 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 (Section 4.1.3 of the USG DURC-PEPP Policy) 

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, material, or national security.

Category 2 Research

Category 2 research meets all the following three (3) criteria:

• Involves, or is reasonably anticipated to result in, a PPP as specified in Section 4.2.1 of the USG DURC-PEPP Policy;
• 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 USG DURC-PEPP Policy; and
• Based on current understanding, the research institution, federal funding agency, and/or Departmental multidisciplinary review entity 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 USG DURC-PEPP Policy.

Category 2 Experiments

Research within the scope of Category 2 are those experimental outcomes or actions with a pathogen outlined in the USG DURC-PEPP Policy that are reasonably anticipated to:

• 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.

Category 2 Risk Assessment (Section 4.2.3 of the USG DURC-PEPP Policy)

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. See the Implementation Guidance for additional guidance, including illustrative examples.

All MUSC Principal Investigators (PIs) proposing or conducting research involving biological agents and toxins must assess whether their research potentially falls under the USG DURC-PEPP Policy.  Specifically, PIs proposing to work with or generate any replication-competent infectious agent or proposing to work with a toxin of any amount from the Federal Select Agents and Toxins list must make an assessment of whether the research is reasonably anticipated to be within the scope of Category 1 or Category 2 research. If DURC-PEPP research is identified, the PI must work with the MUSC DURC Committee to develop a risk-benefit assessment and risk mitigation plan that must be approved by the funding agency before the work can begin.

USG DURC-PEPP Policy Category 1 Agents

The biological agents and toxins on the USG DURC-PEPP Policy Category 1 list include:

All Select Agents and Toxins controlled by Federal Select Agent Regulations, including those at amounts below the Permissible Toxin Amounts.  For purposes of the DURC-PEPP Policy, there are no exempt quantities for these agents and toxins.  Refer to the Select Agents and Toxins list for any relevant strain exclusions.

All Risk Group 4 pathogens listed in Appendix B-IV of the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). Risk Group 4 agents are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available. Refer to Appendix B-IV of the NIH Guidelines for any relevant strain exclusions.

A subset of Risk Group 3 pathogens listed in Appendix B-III of the NIH Guidelines (see Exceptions). Risk Group 3 agents are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available but are not controlled by the Select Agent Regulations. Refer to Appendix B-III of the NIH Guidelines for any relevant strain exclusions

Other biological agents affecting humans that have not been assigned a Risk Group in the NIH Guidelines, and are recommended to be handled at BSL3 or BSL4 per CDC guidance in the Biosafety in Microbiological and Biomedical Laboratories (BMBL).

Biological agents added during future updates to the USG Implementation Guidance.

DURC/PEPP Review Process

To comply with the USG DURC-PEPP Policy, a standing committee was assigned as the DURC/IRE.  A formal review process for potential USG DURC-PEPP Policy projects has been established, which involves review by both the IBC and DURC/IRE. 

It is the responsibility of the Principal Investigator to identify research involving agents listed in the USG DURC-PEPP Policyand notify the DURC/IRE for review of its DURC-PEPP potential. After notification, a formal review process will start where the IBC will determine whether or not the project falls into USG DURC-PEPP Policy.

If project is determined to fall under the USG DURC-PEPP Policy, the DURC/IRE will work with the PI to draft a risk mitigation plan to be submitted to the applicable U.S. Government funding agency.

To register a potential DURC/PEPP project with the DURC Committee/IRE, please take the following steps:

1. Submit an IBC protocol which will then be routed for review by both the IBC and DURC/IRE committee. Instructions for the IBC submission process are located here.
2. To the IBC protocol, please complete the PI Self Assessment form and upload to DURC/PEEP section of the IBC protocol.
3. Take the “Select Agents” and “Dual Use Research of Concern (DURC) Biosafety/Biosecurity training modules in CITI.
4. Schedule time with the Biosafety Officer, Dr. Chris Voelkel-Johnson (792-3125; johnsocv@musc.edu) to conduct an inspection of the rooms to be used for this project.