03/10/2025
Photo by Alexandar Todov on Unsplash
On September 27, 2024, the US Food and Drug Administration (FDA) issued a warning letter to an Institutional Review Board (IRB) as a result of a (BIMO) inspection from July of 2023. BIMO inspections evaluate compliance with of FDA regulatory requirements, in this case, title 21 CFR Parts 50, protection of human subject, and 56, Intuitional Review Boards.
The following are the listed observations;
§ 56.109(f) - The IRB failed to conduct continuing review of research at intervals of not less than once per year.
During the conduct of two separate protocols the IRB failed to convene for continuing review of both protocols within the required 1 year minimum.
Protocol A was approved by the IRB on August 8th, 2019, the continuing review meeting was not until August 19th, 2020 (12 days late), then again on October 22nd, 2021 (78 days late). The latter meeting was of particular concern due to the study enrolling 2 new participants and the occurrence of site protocol deviations between August and September of 2021.
Protocol B was approved January 15th, 2021, however, IRB did not have a continuing review meeting until March 14th, 2022 (59 days late), and then again on April 2023 (46 days late).
The primary purpose of the continuing review meetings of IRBs is to ensure the protection of trial participant’s rights, safety, and welfare. By reviewing all relevant trial documents on a minimum annual basis, including newly enrolled participants and any noncompliance from the site, the IRB can evaluate if any of the patients are at risk and can suspend or terminate the trial if necessary. By neglecting these duties, any issues that may arise, such as the case of Protocol A, would not be dealt with in a timely manner and puts the trial participants at risk.
§ 56.115(a)(6) and 56.108(b)(3) - The IRB failed to prepare, maintain, and follow required written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the FDA.
This observation has two critical parts;
The IRB’s written procedures did not specify procedures on reporting suspensions and terminations of trials to the FDA as required per regulations.
On 8 separate instances the IRB closed (suspended or terminated) a trial and did not send any report to the FDA.
IRBs have the ability to suspend or terminate any trial that is either being conducted in a way that violates the IRB’s requirements or has been associated with serious harm to a trial participant as per § 56.113. While this CFR does not specify the exact amount of time these suspensions or terminations need to be reported, it is expected that they are to be reported promptly to the FDA and that the IRB would have written procedures that govern the acceptable timeframe.
In their response, the IRB provided multiple corrective actions such as updating their standard operating procedures (SOP) to have set reminders for continuing review deadlines and educating their administrative staff on IRB suspensions and terminations annually. However, their response did not include any preventive actions that would ensure the issues do not reoccur in the future, a common pitfall in warning letter responses. Due to the lack of detail, the FDA could not complete an informed evaluation of the IRB’s written response and have asked for these details to be provided within 15 business days from the receipt of the letter.
The entire warning letter with further information can be found on the FDA website. While it is important for IRBs to follow their SOPs to ensure consistency throughout their operation, the SOPs must also be compliant to all relevant CFRs and other applicable regulatory requirements. Failure to meet these standards will ultimately result in an increased risk to all of the trial participant’s rights, safety, and welfare.
-The Clinical Pathways Team
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