Food and Drug Administration (FDA) Guidance on Safety Reporting

​In December 2025, FDA released two final guidance documents focused on safety reporting in clinical research, replacing earlier FDA guidance issued in 2009 and 2012.

• Investigator Responsibilities Safety Reporting for Investigational Drugs and Devices and

• Sponsor Responsibilities – Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies.

 Key Takeaways

• Sponsors should limit their safety reports to both the FDA and investigators to the list below of reportable information. This limitation allows for focus on critical issues which may need prompt action to protect human subjects.

• Investigators are responsible for reviewing safety reports and for promptly (within 5 business days1) reporting unanticipated problems to the institutional review board (IRB).

Reportable Information

Under FDA regulations, the following safety reports must be treated as unanticipated problems involving risks to subjects or others and therefore require IRB review. Other events not listed may be included in periodic reports such as the annual IND report. 

• Serious and unexpected suspected adverse reaction2

• ​Findings from other clinical studies suggesting significant risk in humans exposed to the drug2

• ​Animal or in vitro findings suggesting human risk2

• ​Increased rate of occurrence of serious suspected adverse reactions2

• ​ All serious adverse events in IND-exempt bioavailability / bioequivalence studies3

• ​All unanticipated adverse device effects4

 Resources

1 HRP-103 Investigator Manual

2 21 CFR 312.32(c)(1)

3 21 CFR 320.31(d)(3)

4 21 CFR 812.150(a)(1)

Reporting a Problem

Protocol Event Table

HRP-001 SOP – Definitions