The FDA’s Updated IRB Bioresearch Monitoring (BIMO) Inspection Manual

On April 4, 2025, the FDA released an update to the Bioresearch Monitoring (BIMO) Inspection Manual 7348.809, which outlines the FDA’s approach to inspecting Institutional Review Boards (IRBs). This updated manual is a comprehensive reorganization of the document and includes: formal addition of Remote Regulatory Assessments (RRAs), new information on IRB and study selection criteria, assent considerations, and details regarding electronic records.

Remote Regulatory Assessments

The 2025 BIMO update now specifically references RRAs, a practice adopted during the COVID-19 pandemic. The revised manual for IRBs states that RRAs may be requested in lieu of on-site inspections. In June 2025, the FDA also finalized the Guidance for Industry: Conducting Remote Regulatory Assessments: Questions and Answers; the initial draft guidance was issued in 2022 and revised in 2024.

Inspection Criteria

The updated manual previously indicated that IRBs would be selected for inspection based on multiple criteria. These standards included whether they had never been inspected, had not been inspected in the last five years, received warning letters, a previous Official Action Indicated (OAI) inspection finding, and involvement in first-in-human studies. The updated manual no longer includes these criteria, suggesting a shift in the FDA’s selection approach. Recent offline communications with the FDA indicate that study volume and risk-based factors may now influence selection of IRBs for FDA inspections.

The revised manual also includes a change in the approach to selecting studies during inspections. The 2018 version stated that “generally no more than three” studies should be identified for review during inspections. This statement is now deleted, which suggests a larger number of studies may be requested. This is consistent with recent personal experience. In historical inspections, the FDA had only requested three to five IRB studies for review. In recent inspections, the FDA inspector requested more than a dozen IRB studies.

The FDA also updated the list of criteria for which studies should be pulled during inspections. The study types removed from the previous version are:

• Studies where privacy/confidentiality protections may be of concern (e.g. HIV studies, etc.).
• Comparison studies of one or more marketed products with an investigational product. This falls under the existing category of studies for which an Investigational New Drug (IND) or Investigational Device Exemption (IDE) would not be required. Thus, it seems to be a removal of a redundant criterion.

Study types added to the list include:

• Sponsor-investigator initiated clinical trials.
• Studies involving an exception from informed consent under 21 CFR 50.24 were previously under “studies involving vulnerable populations,” but that point is now a separate bullet.

Assent

The 2018 and 2025 versions of the BIMO Inspection Manual both list the basic requirements that IRBs must determine whether adequate provisions are made to obtain the assent of children in studies involving pediatric participants. However, the 2025 edition puts greater emphasis on the IRB’s documentation of assent and parental consent determinations. This does not represent a change in the FDA’s requirements; however, it underscores the expectation that inspectors should identify and obtain this documentation.

Electronic Records

The previous version of the manual noted that electronic records were “more commonly being used by IRBs” and referenced the “Guidance for Industry – Part 11, Electronic Records; Electronic Signature.” The revised manual continues to reference Part 11. It also explicitly states the FDA must be granted access to electronic records and information systems used to hold, analyze, process, or transfer information. The new version also highlights expectations for disaster recovery, system failures, checks on whether any system upgrades or changes resulted in data loss, and the IRB’s corrective actions and reporting obligations to the institutional official and/or the FDA.

Additional New Information

Two new items which were not in the 2018 version of the IRB BIMO Inspection Manual are listed below. They are notable, not only because they represent a change in regulatory interpretation, but because of their unusual new emphasis.

• Institutional Approval of Research Not Approved by the IRB: The manual reinforces that per 21 CFR 56.112 institutions may not approve research that has been disapproved by the IRB. However, institutions are allowed to disapprove of research that is approved by the IRB. Based on review of recent FDA warning letters of IRBs, there do not seem to be any findings of institutions approving research that had been disapproved by the IRB. Thus, it is curious to see this highlighted in the updated manual.

• IRB Review and Emergency Use of Investigational Products: IRB review may be temporarily waived for investigational product use in emergency situations under 21 CFR 50.24. Physicians must report emergency use to the IRB, and any subsequent use requires IRB review. The updated manual prompts IRBs to identify any instances where an investigational product initially used under emergency provisions was subsequently used without IRB approval. This does not represent a shift in regulatory perspective; however, it is notable because the prior version did not prompt inspectors to check this at all. A possible indication for this addition to the revised manual is an FDA warning letter issued in 2024. This warning letter was issued to an investigator who initially reported emergency use of a study drug to the IRB but failed to submit information regarding subsequent uses, which involved administration of nearly 50 additional doses.

Conclusion

The FDA’s revised manual update is primarily a reorganization of previous information. While certain content has been clarified, such as criteria for inspections, remote regulatory assessments, and documentation requirements, the changes focus on restructuring the manual for improved clarity and ease of use, rather than introducing substantive changes to the FDA’s criteria in inspecting IRBs. Nonetheless, the changes highlighted in the revised manual offer valuable insight into the FDA’s current approach.

If you have questions about the FDA’s updated manual or want to better understand how these changes may impact your organization, reach out to WCG’s IRB today. We are here to support your regulatory inquiries and ethical review needs. Let’s connect to explore how we can help.