Unanticipated Dangerous Gain-of-Function (dGOF) Institutional Review Framework

Dangerous Gain-of-Function (dGOF) refers to research on infectious agents or toxins where unanticipated outcomes may increase:

• Pathogenicity
• Transmissibility
• Host range
• Immune evasion
• Resistance to therapeutics or detection
• Environmental stability or dissemination

These outcomes are defined exclusively by Executive Order 14292 §8(a–g).

Importantly, dGOF reporting is triggered by outcomes, not intent. Reporting does not imply wrongdoing or noncompliance—it is a contractual requirement tied to specific awards.

Please see the identifying potential dGOF guidance document for further information. 

This framework applies to:

• Principal Investigators (PIs) with awards containing dGOF reporting clauses
• Research teams working with infectious agents or toxins under those awards
• Awards identified by OSP as containing sponsor-mandated dGOF terms and conditions

Only awards with explicit dGOF requirements are subject to this process.

Same-Day Reporting Is Required

If you observe an unanticipated outcome in your funded research that may plausibly relate to any EO 14292 §8 criterion, you must:

1. Immediately halt the affected research activities

   Only the specific experiment(s) linked to the outcome must stop

   Unrelated work may continue if it does not involve the agent or conditions at issue

2. Notify the IBC the same day
   Email: cu_ibc@cornell.edu

If you are unsure whether an outcome meets the definition, report it anyway. IBC staff will help assess whether sponsor notification is required.

1. Same-Day Sponsor Notification

After you notify the IBC:

• IBC staff coordinate with OSP
• The Authorized Organizational Representative (AOR) sends the required same-day notification to the sponsor

2. Expedited IBC Review

An Expedited IBC Review Panel—consisting of:

• The IBC Chair (or delegate)
• The Biosafety Officer (or delegate)
• Subject Matter Experts, as needed

will review the outcome using a standardized dGOF Review Rubric aligned with EO 14292 §8.

3. Determination and Reporting

• The panel issues a determination: 
  • Meets the definition of dGOF, or
  • Does not meet the definition of dGOF
• The AOR submits the determination to the sponsor within two business days

4. Research Remains Halted

Regardless of the outcome:

• Affected research must remain halted
• Work may resume only after the sponsor provides written authorization

This dGOF framework:

Does not replace existing reviews for: 

• Dual Use Research of Concern (DURC)
• Pathogens with Pandemic Potential (PPP)

• Pathogens with Enhanced Pandemic Potential (PEPP)

  May result in referrals to other oversight bodies when appropriate

  Builds on Cornell’s existing expedited biosafety and incident-review processes

• Rapid response: Same-day reporting and notification
• Proportional halt: Only the activities linked to the outcome must stop
• Expert review: Conducted by experienced biosafety leadership and SMEs
• Sponsor-driven resumption: Only the sponsor can authorize restart
• Transparency: Determinations are reported to the full IBC at the next convened meeting

If you have questions about:

• Whether your award includes a dGOF reporting requirement
• Whether an outcome should be reported
• How the expedited review process works

Please contact:

Institutional Biosafety Committee (IBC)
cu_ibc@cornell.edu
Office of Research Integrity & Assurance
Cornell University

• Guide: Identifying Unanticipated Outcomes
• Example email notifying PIs of specific dGOF terms and conditions
• Executive Order 14292 §8 Criteria
• NIH Notices NOT-OD-25-112 and NOT-OD-25-127

Cornell uses a centralized, expedited institutional review model coordinated by the Institutional Biosafety Committee (IBC), with defined roles for the Office of Research Integrity & Assurance (ORIA) and the Office of Sponsored Programs (OSP).

The framework is designed to:

• Meet sponsor-mandated timelines (same-day and two-business-day deadlines)
• Ensure consistent application of Executive Order 14292 §8
• Limit research disruptions to only affected activities
• Maintain clear separation of compliance, review, and sponsor communication roles

Final institutional authority for this process is delegated to the IBC by the Vice Provost for Research (VPR).

Identification of dGOF Award Terms

• OSP identifies new or amended awards containing dGOF-specific terms and conditions.
• Awards with dGOF clauses are routed to IBC staff for review prior to final processing.
• Award execution may be paused until required notifications and PI acknowledgments are completed.

Staff Coordination

• IBC staff serve as the process coordinator for dGOF compliance.
• OSP retains sole authority for sponsor-facing contractual communications via the Authorized Organizational Representative (AOR).

Once a dGOF term is identified:

• IBC staff notify the PI that their award includes a mandatory dGOF reporting obligation.
• PIs receive: 
  • A summary of reporting requirements
  • A potential dGOF identification Guide tied directly to EO 14292 §8
  • Instructions for same-day reporting and research halts
• The PI must acknowledge understanding of these obligations in writing.

IBC staff notify OSP when acknowledgment is complete so the condition can be documented in institutional systems.

Initial Notification

• PIs notify cu_ibc@cornell.edu the same day an unanticipated outcome is observed.
• IBC staff log the event and initiate the expedited workflow.

Immediate Staff Actions

IBC staff, in coordination with the IBC Chair and Biosafety Officer (BSO):

• Confirm receipt and timing of the report
• Verify that affected research activities have been halted
• Ensure containment and biosafety controls remain in place
• Begin assembling documentation for sponsor notification and review

• IBC staff prepare a notification package summarizing: 
  • The reported unanticipated outcome
  • Confirmation of halted activities
  • Initiation of expedited institutional review
• The package is transmitted to the AOR in OSP.
• The AOR sends the required same-day notification to the sponsor.

This division of responsibility ensures:

• Accurate scientific context from biosafety staff
• Contractual compliance through authorized institutional channels

Panel Composition

The Expedited IBC Review Panel consists of:

• IBC Chair (or delegate)
• Biosafety Officer (or delegate)
• Subject Matter Experts, as needed

This is the review mechanism for dGOF-related unanticipated outcomes.

Review Scope

The panel evaluates whether the reported outcome meets or does not meet the definition of dGOF based solely on EO 14292 §8(a–g) and applicable sponsor terms.

The review:

• Is not a convened IBC meeting
• Does not produce formal IBC minutes
• Results in a documented Expedited Review Record

Staff Responsibilities

IBC staff are responsible for maintaining the official review record, including:

• Information reviewed
• EO §8 criteria analysis
• Panel rationale
• Names and roles of reviewers
• Date and time of determination

Determination Standard

The panel issues a determination based on discussion of the dGOF review rubric:

• Meets the definition of dGOF, or
• Does not meet the definition of dGOF

• IBC staff prepare the determination summary and supporting materials.
• The AOR in OSP submits the determination to the sponsor within two business days of the panel’s decision.
• This submission fulfills sponsor and federal reporting requirements.

Regardless of the determination:

• Affected research activities remain halted
• Work may resume only after the sponsor issues explicit written authorization
• IBC staff communicate sponsor instructions to the PI and document compliance

For institutional transparency and oversight:

• Expedited dGOF determinations are reported to the full IBC at the next convened meeting.
• The committee acknowledges the review and determination.
• No revote is required unless additional review is requested.
• This report out is not captured in the IBC meeting minutes as this requirement is not mandated by the NIH guidelines for r/sNA for minute reporting.

This ensures accountability while preserving the expedited nature of the process.

IBC staff maintain all records associated with dGOF reviews, including:

• PI notifications and acknowledgments
• Expedited review records and rubrics
• Sponsor notifications and responses
• Determination memo
• Documentation of reporting to the full IBC

Records are retained in accordance with institutional policy and sponsor requirements.