Comment from NMDP

The NMDP IRB Office is submitting these comments to Docket # FDA-2023-D-5016, Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices Guidance for Industry. NMDP is a leader in cell therapy, helping find cures and save lives for patients with blood cancers and disorders. The NMDP IRB serves as the IRB of record for CIBMTR (Center for International Blood and Marrow Transplant Research), a research collaboration between NMDP and the Medical College of Wisconsin which invests more than $77 million annually in research and facilitates approximately 200 ongoing studies and clinical trials annually in cooperation with more than 360 global transplant centers. The NMDP IRB Office requests FDA consider clarifying the following items to ensure compliance with the regulations and consistency in terminology: 1.Are important deviations to be considered serious noncompliance? 2.Are IRBs are expected to revise their definition of “serious noncompliance” in their written procedures to encompass the definition of “important deviations?” 3.Will 21 CFR 56.108(b) apply to important deviations? According to 21 CFR 56.108(b), the IRB must follow written procedures to ensure prompt reporting of any instance of serious or continuing noncompliance to the IRB, appropriate institutional officials, and the Food and Drug Administration (FDA). The FDA does not define “serious noncompliance.” The definition of “important deviations” aligns with what most IRBs, including our own, would consider serious noncompliance. The guidance on reporting important deviations to the IRB includes the phrase “where possible,” whereas 21 CFR 56.108(b) mandates prompt reporting of serious noncompliance. This raises several questions on whether the FDA consider important deviations to be serious noncompliance, whether IRBs will be expected to revise their definition of “serious noncompliance” in their written procedures to encompass the definition of “important deviations, and whether 21 CFR 56.108(b) applies to important deviations. Clarification on these points within the guidance document would help ensure compliance with FDA regulations and consistency in terminology.