Ongoing Effort to Harmonize Human Subject Research Regulations
The U.S. Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP), both part of the Department of Health and Human Services (HHS), issued final joint guidance on maintaining meeting minutes for Institutional Review Boards (IRBs). FDA Guidance for Institutions and IRBs: Minutes of Institutional Review Board (IRB) Meetings (Sept. 2017) (IRB Meeting Minutes Guidance). IRBs are generally responsible for approval and oversight of human subject research, and are subject to HHS and FDA regulations at 45 CFR part 46 and 21 CFR parts 50 and 56, respectively, when reviewing research covered by the regulations. HHS regulations apply to all research involving human subjects conducted or supported by HHS or conducted by an institution that provides assurance of responsibility under 45 CFR 46. FDA’s regulations cover clinical investigations regulated by FDA under various sections of the Federal Food, Drug, and Cosmetic Act, as well as those that support marketing applications for medical products (including human drugs, medical devices, and biological products).
Although FDA’s regulations closely mirror HHS’ regulations (commonly referred to as “the Common Rule”), there are a number of differences between the two sets of regulations, e.g., the ability to waive elements of informed consent. The 21st Century Cures Act, passed in December 2016, directed HHS to harmonize “to the extent practicable and consistent with other statutory provisions” the differences between the Common Rule at 45 CFR 46 and FDA’s regulations at 21 CFR 50, 56, 312, and 812. The statute requires that the harmonization process be completed by December 13, 2019 (three years from the date of enactment). However, the statute merely codified the ongoing effort by the agencies to harmonize the regulatory requirements for human subject research. The agencies had already released a number of joint guidance documents, including guidance on the use of electronic informed consent in HHS- and FDA-regulated human subject research.
The IRB Meeting Minutes Guidance finalizes draft guidance released by FDA and OHRP in November 2015. Both HHS and FDA require IRBs to document IRB activities, including:
- Attendance at meetings;
- Actions taken by the IRB;
- Votes on actions taken (including the number of members voting for, against, by the IRB
- and abstaining);
- The basis for requiring changes in or disapproving research; and
- Discussion of controverted issues and their resolution.
The guidance notes that IRBs have been cited for noncompliance with these requirements in OHRP Determination Letters and FDA Warning Letters and seeks to clarify best practices for maintaining minutes. Examples of noncompliance cited in the guidance include missing minutes, a lack of sufficient detail in minutes or incomplete minutes regarding voting actions, multiple sets of minutes for the same meeting, and failure to include a summary of discussion of controverted issues. The guidance also recognizes that IRBs have flexibility in preparing minutes, consistent with their institution’s written policies and procedures.
One significant clarification from the draft guidance is that IRBs may document additional findings and determinations to fulfill regulatory requirements other than those found at 45 CFR 46.115(a)(2) and 21 CFR 56.115(a)(2) elsewhere in IRB records to avoid redundancy. These regulatory determinations include, for example, those relating to: approval of research; informed consent; emergency research; special considerations for studies involving children, pregnant women, human fetuses, neonates, and prisoners; significant risk determinations for FDA-regulated medical device studies; expedited review, and unanticipated problems, serious or continuing noncompliance, suspension, or termination of IRB approval. The guidance specifies other places where this information may be recorded, such as an IRB reviewer form/checklist, database entries, or other physical or electronic records.
In addition, the IRB Meeting Minutes Guidance clarifies that the references in the guidance do not incorporate changes made by the final rule revising the Common Rule, which does not go into effect until January 19, 2018. Overall, the issuance of the joint guidance is consistent with the overarching goals in the Cures Act to reduce administrative burden and duplication, and continues the agencies’ work of harmonizing the two sets of regulations before 2020.