USFDA Updates on Safety Reporting Requirements for INDs and BA/BE Studies
The US Food and Drug Administration (FDA) revised its Small Entity Compliance Guide: Safety Reporting Requirements for INDs and BA/BE Studies in October 2026. The guidance helps small businesses understand safety reporting requirements for investigational drugs and biological products under Investigational New Drug (IND) applications and bioavailability (BA) and bioequivalence (BE) studies exempt from IND requirements. The revision updates the history of related guidance documents, replaces outdated references and makes minor editorial changes.
Background and Key Definitions
The Small Entity Compliance Guide was developed to clarify these requirements by answering frequently asked questions from sponsors and investigators.
Investigational New Drug (IND): An application under which a drug or biological product is investigated in humans.
Bioavailability (BA): The availability of a drug substance to the body, evaluated through a BA study.
Bioequivalence (BE): The evaluation of whether drug products meet applicable bioequivalence criteria.
Sponsor-investigator: An individual who both initiates and conducts an investigation and has responsibilities applicable to both a sponsor and an investigator.
Safety Reporting Requirements for Small Entities
The FDA confirms that small entities must comply with the applicable safety reporting requirements for IND studies under 21 CFR 312.32 and 312.64(b), and for BA/BE studies under 21 CFR 320.31(d)(3).
Sponsor-investigators conducting investigator-initiated studies must also comply with the applicable IND safety reporting requirements. These responsibilities apply even when an individual conducts the study rather than a larger commercial organisation.
Evaluation of Available Safety Information
Sponsors and sponsor-investigators may not have access to all safety data maintained by other organisations. However, they must evaluate the safety information available to them to determine whether it meets the applicable reporting criteria.
The FDA recommends reviewing scientific literature and conducting literature searches to identify new safety information about the investigational drug. It also recommends that organisations providing or receiving a drug share safety information with one another to help protect clinical trial participants.
Aggregate Safety Analysis and Expedited Reporting
Sponsors should establish a predefined safety monitoring plan describing the processes for reviewing, evaluating and managing safety information.
For aggregate safety reporting, sponsors should analyse specific events within individual studies and across studies, including studies conducted under different INDs for the same drug. These analyses help determine whether events occur more frequently in the drug treatment group than in the control group and meet the applicable criteria for expedited reporting.
The analyses should be based on the safety data available to the sponsor.
IND Annual Reports and IRB Reporting
The FDA clarifies that the revised safety reporting requirements did not change the existing requirements for IND annual reports under 21 CFR 312.33. The final rule also did not change investigators' reporting requirements to Institutional Review Boards (IRBs).
Sponsors and investigators should therefore continue to follow the applicable requirements for these reporting activities.
Current Guidance and Regulatory Contacts
For current recommendations on sponsor responsibilities, the FDA directs stakeholders to its December 2025 guidance, Sponsor Responsibilities — Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies.
For investigator responsibilities concerning adverse event reporting to sponsors and IRBs, stakeholders should refer to the December 2025 guidance, Investigator Responsibilities — Safety Reporting for Investigational Drugs and Devices.
Questions about IND safety reporting should be directed to the responsible review division within the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). Questions concerning BA/BE safety reporting can be directed to OGD-PremarketSafetyReports@fda.hhs.gov.
Comments