The UCLA Institutional Review Entity (IRE) supports institutional oversight of high-risk life sciences research that may fall within the scope of the United States Government Policy for Stopping High-Risk Life Sciences Research. The IRE works with Principal Investigators, the Institutional Contact for Dangerous Gain-of-Function Research (ICDGOF), the Institutional Biosafety Committee (IBC), Export Control, and federal funding agencies to assess and manage research that may present DGOF, potential DGOF, or IROC concerns.
The IRE does not replace other applicable compliance requirements or modify federal statutory authorities applicable to relevant departments and agencies, including regulatory authorities managed by the Federal Select Agent Program and export control regulation. Research subject to the USG Policy may also require review under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, BMBL, Select Agent Regulations, export control laws, human subjects’ protections, animal care requirements, data security requirements, sponsor terms, and other applicable federal, state, UCOP, and UCLA policies.
Scope
- All proposed and ongoing UCLA life sciences research receiving or applying for federal support must be evaluated for DGOF, potential DGOF, and IROC concerns.
- Research institutions receiving federal life sciences funding are expected to implement mechanisms to identify non-federally funded potential DGOF and DGOF research and monitor for IROC concerns.
- Research that may meet the DGOF definition or potential DGOF criteria must be escalated to the ICDGOF/IRE before proposal submission.
- Purely computational or in silico research is not prohibited solely because it involves modeling or design of biological agents, unless it involves an entity of concern or otherwise falls within the policy scope.
Definitions
Dangerous gain-of-function (DGOF) research: ‘Dangerous gain-of-function research’ is research with a biological agent that seeks, achieves, or has a substantial risk of achieving one or more of the outcomes listed below and could result in significant negative societal consequences:
- Enhancing the harmful consequences of the biological agent;
- Disrupting beneficial immunological response or the effectiveness of an immunization against the biological agent;
- Conferring to the biological agent resistance to clinically or agriculturally useful prophylactic or therapeutic interventions against that biological agent or facilitating its ability to evade detection methodologies;
- Increasing the stability, transmissibility, or ability to disseminate the biological agent;
- Altering the host range or tropism of the biological agent;
- Enhancing the susceptibility of a human, animal, or plant host population to the biological agent; or
- Generating or reconstituting an eradicated or extinct biological agent.
Potential DGOF research: ‘Potential DGOF’ is research with a biological agent that could potentially result in one or more of the outcomes listed in the DGOF definition above and could result in significant negative societal consequences.
Has/have the potential: ‘Has/have the potential’ 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 but excludes experiments in which experts would anticipate the outcome to be technically possible, but highly unlikely.
Federal Funding Agency (FFA): ‘Federal funding agency’ is a federal department, agency, institute, center, or office that funds or sponsors intramural or extramural research with biological agents at research institutions in the United States or internationally.
International Research of Concern (IROC): Life sciences research involving entities of concern — that is, research conducted in a country of concern, or research conducted outside the United States by an institution of concern or an individual of concern.
Other Risky International Research: Life sciences research that could reasonably pose a threat to public health, public safety, and economic or national security, conducted in a country with inadequate oversight to ensure that the country is compliant with United States oversight standards and policies.
Institutional Contact for Dangerous Gain-of-Function Research (ICDGOF): Institutional Contact for Dangerous Gain-of-Function Research (ICDGOF)’ is the official designated by the research institution to serve as an internal resource for the 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 IRE is the entity established by the research institution to execute the institutional oversight responsibilities described in the USG policy.
Risk Mitigation Plan: ‘Risk mitigation plan’ is a plan that includes experimental modifications to ensure no DGOF research will be conducted and any specific safeguards to ensure such an outcome. These safeguards include but are not limited to: stringent cybersecurity practices, restrictions on physical access to labs and research materials, transfers of technology and intellectual property, disclosure to journal publishers ahead of manuscript submission, and other information sharing management. It is not a plan on how to allow for the performance of DGOF or potential DGOF research.
Mandate
- Education and Training for PIs: All PIs conducting life sciences research should receive education and annual training on the USG Policy for Stopping High-Risk Life Sciences Research. Training should enable PIs to recognize research that may meet the criteria for potential DGOF, DGOF, or IROC; understand their responsibility to disclose relevant research activities and changes; and participate in the institutional review process.
- Risk Identification and Initial Assessment: PIs are responsible for conducting an initial assessment of proposed and ongoing life sciences research to identify whether the research may meet the criteria for potential DGOF, DGOF, or IROC under the USG Policy. Research identified through this assessment or through institutional screening as potentially meeting the Policy criteria will be referred to the IRE for further evaluation and, when applicable, referred for Federal Funding Agency or independent review.
- Risk Assessment and Risk Mitigation: For research identified as potential DGOF, the IRE will work with the PI to characterize the potential risks and anticipated benefits of the research and identify appropriate measures to reduce biosafety, biosecurity, or other relevant risks. The IRE will document its assessment and provide the information required for any additional independent or FFA review. Any required risk mitigation measures, conditions of approval, or other safeguards must be implemented before the applicable research proceeds.
Research determined to meet the definition of DGOF is prohibited from receiving federal support under the Policy and therefore would not proceed.
PI Responsibilities
- Complete annual training on DGOF research in accordance with the USG Policy.
- Continuously evaluate proposed and ongoing life sciences research for DGOF, potential DGOF, and IROC concerns.
- Disclose whether the work involves biological agents or toxins, relevant experimental outcomes, international performance sites, foreign collaborators, and key personnel.
- Prior to proposal submission, certify/attest as required by the federal funding agency that the proposal has been evaluated for DGOF and IROC concerns.
- If research may meet the definition of potential DGOF, work with the IRE to complete an initial risk-benefit analysis before proposal submission and, if required by the funding agency, a full risk-benefit assessment and Risk Mitigation Plan.
- Immediately halt research and notify the ICDGOF, IRE, and federal funding agency within the required timeframe if federally funded research may meet the definition of DGOF or potential DGOF research or if scope of research changes to increase DGOF risk.
Committee Structure and Administration
IRE Membership
The Institutional Review Entity (IRE) is composed of individuals with the scientific expertise and policy knowledge necessary to assess life sciences research conducted at UCLA for potential DGOF concerns.
Membership includes subject matter experts across relevant research disciplines to ensure appropriate scientific breadth, as well as individuals with experience in biosafety, biosecurity, and risk management. The IRE also includes the Institutional Contact for Dangerous Gain of Function research (ICDGOF) and the Biosafety Officer (BSO) as standing members to support coordination across biosafety and compliance functions.
To ensure continued alignment with federal oversight expectations, the IRE will periodically review its membership structure and adjust as needed to maintain appropriate representation based on the evolving scope of research and policy updates.
Committee Administration
Administrative and operational support for the IRE is provided by the Office of Research Policy and Compliance (RPC) under the Office of the Vice Chancellor for Research, Innovation, and Creative Activities.
IRE Meeting Schedule
The IRE convenes full meetings on an as-needed basis to review life science research that has the potential for DGOF. In addition, the IRE meets at least annually to:
- Review ongoing oversight responsibilities;
- Assess the effectiveness of institutional policies and procedures;
- Ensure that the committee remains aligned with federal policy expectations
To streamline the review process and respond efficiently to time-sensitive or routine matters, the IRE may also conduct reviews electronically (e.g., via email).