See topics forEnvironmental Health & Safety
IRE Overview
The Institutional Review Entity (IRE) is established by the research institution to fulfill oversight responsibilities as outlined in USG DURC-PEPP Policy and the USG Implementation Guidance for identification, review, and oversight of life sciences research that is within Category 1 and Category 2 as defined by that policy.
On May 5, 2025, a new Executive Order (EO) was issued calling for modifications to the 2024 United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential (often referred to as the “USG DURC-PEPP Policy”).
As the institution awaits additional guidance on how the provisions outlined in the May 5, 2025, EO may impact future research operations, researchers should continue to adhere to all applicable rules, regulations, and processes under the purview of UCH IRE, including all expectations set forth by the current USG-DURC-PEPP Policy (outlined in greater detail below).
About the USG DURC-PEPP Policy
At UCH, the USG DURC-PEPP Policy applies to all research, regardless of funding source, which meets the criteria for DURC-PEPP research. Federal sponsors may delay the release of funds if a project identified as DURC-PEPP research does not fulfill all requirements for compliance with the USG DURC-PEPP Policy. This includes research funded or sponsored by federal grants, contracts, cooperative agreements, and other agreements. The United States Government USG DURC-PEPP Policy supersedes previous DURC policies and the 2017 Enhanced Potential Pandemic Pathogens Framework (P3CO). The USG DURC-PEPP Policy does not supersede, but complements, other existing federal regulations, including the Select Agent Regulations.
All UCH Principal Investigators (PIs) proposing or conducting research involving biological agents and toxins must assess whether or not 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 UCH Institutional Review Entity (IRE) (ibc@uchc.edu) to develop a risk-benefit assessment and risk mitigation plan that the funding agency must approve before the work can begin.
Categories of Research
Category 1 Research
Scope: Involves biological agents or toxins from a pre-determined list, which includes over 80 specific agents and toxins (including all select agents and toxins + all RG4 and many/most RG3 agents). These include Bacillus cereus Biovar anthracis, Botulinum neurotoxins, Coxiella burnetii, Ebola virus, Francisella tularensis, SARS-CoV, and others.
Experimental Outcomes: The research is reasonably anticipated to result in, or does result in, one or more of the following nine 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 its ability to disseminate.
- Alter the host range or tropism of a pathogen or toxin.
- Decrease the ability to detect a human or veterinary pathogen or toxin using standard diagnostic or analytical methods.
- Increase resistance of a pathogen or toxin to clinical 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.
- Enhance the susceptibility of a host population to a pathogen or toxin.
Category 2 Research
Scope: Involves a Pathogen with Pandemic Potential (PPP) or a Pathogen with Enhanced Pandemic Potential (PEPP). These include pathogens like H5N1 influenza virus, SARS-CoV-2, and MERS-CoV.
Experimental Outcomes: The research is reasonably anticipated to result in, or does result in, one or more of the following four outcomes:
- Enhance transmissibility of the pathogen in humans.
- Enhance the virulence of the pathogen in humans.
- Enhance the immune evasion of the pathogen in humans by modifying it to disrupt pre-existing immunity via immunization or natural infection.
- Generate, use, reconstitute, or transfer an eradicated or extinct PPP or a previously identified PEPP.
Institutional Oversight
- Establish and maintain internal policies/procedures for DURC and PEPP oversight.
- Maintain records of assessments, RMPs, and compliance activities.
- Assess research with agents that fall under the new DURC policy to determine if research falls under Category 1 or 2.
- Submit required reports to federal agencies.
- Provide education and training to researchers and staff involved in high-risk research.
Researchers Responsibilities
- Conduct initial and ongoing self-assessments of research associated with the agents that fall under the DURC policy.
- Collaborate with the IRE on risk-benefit analyses.
- Draft and implement Risk Mitigation Plans (RMPs) in coordination with the IRE when research is classified as Category 1 or 2.
- Ensure ongoing compliance with approved RMPs for Category 1 or 2 research.
Appendix: Category 1 Agents and Toxins List
HHS Select Agents and Toxins
- Abrin
- Bacillus cereus Biovar anthracis
- Botulinum neurotoxins
- Botulinum neurotoxin producing species of Clostridium
- Conotoxins (Short, paralytic alpha conotoxins containing the following amino acid sequence X1CCX2PACGX3X4X5X6CX7)
- Coxiella burnetii
- Crimean-Congo haemorrhagic fever virus
- Diacetoxyscirpenol
- Eastern Equine Encephalitis virus
- Ebola virus
- Francisella tularensis
- Lassa fever virus
- Lujo virus
- Marburg virus
- Mpox virus
- Reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments (Reconstructed 1918 Influenza virus)
- Ricin
- Rickettsia prowazekii
- SARS-associated coronavirus (SARS-CoV)
- SARS-CoV/SARS-CoV-2 chimeric viruses resulting from any deliberate manipulation of SARS-CoV-2 to incorporate nucleic acids coding for SARS-CoV virulence factors
- Saxitoxin
Overlap Select Agents and Toxins
- Bacillus anthracis
- Bacillus anthracis Pasteur strain
- Brucella abortus
- Brucella melitensis
- Brucella suis
- Burkholderia mallei
- Burkholderia pseudomallei
- Hendra virus
- Nipah virus
- Rift Valley fever virus
- Venezuelan equine encephalitis virus
South American Haemorrhagic Fever viruses
- Chapare
- Guanarito
- Junín
- Machupo
- Sabia
- Staphylococcal enterotoxins (subtypes A,B,C,D,E)
- T-2 toxin
- Tetrodotoxin
Tick-borne encephalitis complex (flavi) viruses
- Far Eastern subtype
- Siberian subtype
- Kyasanur Forest disease virus
- Omsk hemorrhagic fever virus
- Variola major virus (Smallpox virus)
- Variola minor virus (Alastrim)
- Yersinia pestis
USDA Plant Protection And Quarantine (PPQ) Select Agents and Toxins
- Coniothyrium glycines (formerly Phoma glycinicola and Pyrenochaeta glycines)
- Peronosclerospora philippinensis (Peronosclerospora sacchari)
- Ralstonia solanacearum
- Rathayibacter toxicus
- Sclerophthora rayssiae
- Synchytrium endobioticum
- Xanthomonas oryzae
USDA Veterinary Services (VS) Select Agents and Toxins
- African horse sickness virus
- African swine fever virus
- Avian influenza virus
- Classical swine fever virus
- Foot-and-mouth disease virus
- Goat pox virus
- Lumpy skin disease virus
- Mycoplasma capricolum
- Mycoplasma mycoides
- Newcastle disease virus
- Peste des petits ruminants virus
- Rinderpest virus
- Sheep pox virus
- Swine vesicular disease virus
Risk Groups
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
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), Appendix B, Risk Group 4 and subset of Risk Group 3
Risk Group 4 (RG4) – Viral Agents
- Arenaviruses
- Guanarito virus
- Lassa virus
- Junin virus (except the candid #1 vaccine strain listed in Appendix B-II-D Risk Group2 (RG2) – Viruses)
- Machupo virus
- Sabia
- Bunyaviruses (Nairovirus)
- Crimean-Congo hemorrhagic fever virus
- Filoviruses
- Ebola viruses
- Marburg viruses
- Flaviruses – Group B Arboviruses
- Tick-borne encephalitis virus complex including Absetterov, Central European encephalitis, Hanzalova, Hypr, Kumlinge, Kyasanur Forest disease, Omsk hemorrhagic fever, and Russian spring-summer encephalitis viruses
- Herpesviruses (alpha)
- Herpesvirus simiae (Herpes B or Monkey B virus)
- Paramyxoviruses
- Equine Morbillivirus (Hendra virus)
- Hemorrhagic fever viruses as yet undefined
Risk Group 3 (RG3) – Bacterial Agents Including Rickettsia*
- Bartonella
- Brucella including B. abortus, B. canis, B. suis
- Burkholderia (Pseudomonas) mallei, B. pseudomallei
- Coxiella burnetii (except the Phase II, Nine Mile strain listed in Appendix B-II-A, Risk Group 2 (RG2) – Bacterial Agents Including Chlamydia)
- Francisella tularensis (except those strains listed in Appendix B-II-A, Risk Group 2 (RG2) – Bacterial Agents Including Chlamydia)
- Orientia tsutsugamushi (was R. tsutsugamushi)
- Pasteurella multocida type B -“buffalo” and other virulent strains
- Rickettsia akari, R. australis, R. canada, R. conorii, R. prowazekii, R. rickettsii, R. siberica, R. typhi (R. mooseri)
- Yersinia pestis (except those strains listed in Appendix B-II-A, Risk Group 2 (RG2) – Bacterial Agents Including Chlamydia)
Risk Group 3 (RG3) – Viruses and Prions*
- Alphaviruses (Togaviruses) – Group A Arboviruses
- Chikungunya virus (except the vaccine strain 181/25 listed in Appendix B-II-D Risk Group2 (RG2) – Viruses)
- Semliki Forest virus
- Venezuelan equine encephalomyelitis virus (except the vaccine strains TC-83 and V3526, see Appendix-II-D (RG2) – Viruses)
- Other viruses as listed in the reference source (see Section V-C, Footnotes and References of Sections I through IV)
- Arenaviruses
- Flexal
- Lymphocytic choriomeningitis virus (LCM) (neurotropic strains)
- Bunyaviruses
- Hantaviruses including Hantaan virus
- Rift Valley fever virus
- Coronaviruses
- SARS-associated coronavirus (SARS-CoV)
- Middle East respiratory syndrome coronavirus (MERS-CoV)
- Flaviviruses- Group B Arboviruses
- Japanese encephalitis virus (except those strains listed in Appendix B-II-D Risk Group2 (RG2) – Viruses)
- Yellow fever virus
- Other viruses as listed in the reference source (see Section V-C, Footnotes and References of Sections I through IV)
- Orthomyxoviruses
- Influenza viruses 1918-1919 H1N1 (1918 H1N1), human H2N2 (1957-1968), and highly pathogenic avian influenza H5N1 strains within the Goose/Guangdong/96-like H5 lineage (HPAI H5N1).
- Poxviruses
- Monkeypox virus (Clade I & Clade II containing nucleic acids coding for clade I MPVX virus virulence factors)
- Prions
- Transmissible spongiform encephalopathies (TSE) agents (Creutzfeldt-Jacob disease and kuru agents)(see Section V-C, Footnotes and References of Sections I through IV, for containment instruction)
Excluded RG3 Agents
- 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 (sporulating cultures; contaminated soil)
- Histoplasma capsulatum, H. capsulatum var. duboisii