Category 1 Research
Definition
Category 1 research involves biological agents and toxins that pose significant risks due to their inherent properties and potential for misuse. This category requires careful oversight to mitigate risks associated with biosafety and biosecurity.
Category 1 research meets three criteria: (1) it involves one or more of the biological agents and toxins specified in Section 4.1.1 of the USG Policy; (2) it is reasonably anticipated to result, or does result, in one of the experimental outcomes specified in Section 4.1.2 of the policy; and (3) 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 policy.
Key Features
Biological Agents and Toxins:
The research involves specific biological agents or toxins, including:
- All Select Agents and Toxins – refer to the complete List of Select Agents and Toxins.
- All Risk Group 4 pathogens and certain Risk Group 3 pathogens as outlined in the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines).
- Biological agents recommended for Biosafety Level 3 (BSL-3) or BSL-4 handling according to the Biosafety in Microbiological and Biomedical Laboratories (BMBL).
See the full list of Category 1 agents and toxins.
Examples include Botulinum neurotoxins, Chikungunya virus, and Francisella tularensis.
Experimental Outcomes:
Research qualifies as Category 1 if it involves any of the following experimental outcomes with a qualifying agent or toxin:
- 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 research requires IRE assessment, federal agency approval of a Risk Mitigation Plan before initiation, and annual reporting to the FFA.
See the Implementation Guidance for additional guidance on Category 1 research including illustrative examples.
Category 2 Research
Definition
Category 2 research involves any pathogens with pandemic potential (PPP) or enhanced pandemic potential (PEPP) that pose significant risks due to their ability to cause widespread harm, disrupt public health systems, and threaten national security. This category requires heightened oversight to address the unique biosafety and biosecurity challenges associated with these high-risk pathogens.
Category 2 research meets three criteria: (1) it involves, or 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 in Section 4.2.2 of the USG Policy; and (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 as specified in Section 4.2.3.
Note: If research can be classified in both Category 1 and Category 2, it is deemed Category 2 research.
Key Features
The research involves a PPP, or any pathogen that will be modified in a way reasonably anticipated to result in a PPP. This includes work with eradicated or extinct pathogens, such as the 1918 Influenza virus, when they are reconstituted or modified.
Examples include H5N1 influenza virus, SARS-CoV, SARS-CoV-2, and MERS-CoV.
Experimental Outcomes:
Research is classified as Category 2 if it is reasonably anticipated to result in any of the following experimental 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 such as by modifying the pathogen to disrupt the effectiveness of pre-existing immunity via immunization or natural infection; or
- Generate, use, reconstitute, or transfer an eradicated or extinct PPP, or a previously identified PEPP.
Category 2 research requires thorough risk assessment and multiple levels of oversight, including IRE evaluation, federal agency approval of a Risk Mitigation Plan, additional department-level review before initiation, and semiannual progress reports to the sponsor.
See the Implementation Guidance for additional guidance on Category 2 research including illustrative examples.