To comply with the 21st Century Cures Act,1 the Food and Drug Administration (FDA or USFDA) has released two Notices of Proposed Rulemaking (NPRMs). NPRMs are the initial public notice of a proposed change to federal regulations. These two NPRMs are intended to harmonize the FDA institutional review board (IRB) and informed consent regulations with the Federal Policy for the Protection of Human Subjects (the “Common Rule”) to the extent possible.
The Common Rule was revised in 2018, and the FDA’s two recent NPRMs will harmonize the FDA regulations with the majority of those 2018 revisions. The Common Rule has been adopted by 20 federal agencies and applies to research that is conducted or supported by those agencies. One NPRM describes a potential requirement for multi-site research that is under FDA oversight to use a single IRB for the review of all study sites.2 The second NPRM describes changes to FDA regulations to harmonize with the Common Rule regarding informed consent requirements, among other things.3
This paper will discuss the new single IRB NPRM.
The FDA NPRM on “cooperative research” focuses on harmonization with the Common Rule requirement that “[any] institution located in the United States that is engaged in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States.”2 The FDA proposed language is virtually identical. “Cooperative research” is research involving more than one institution or site.
Although the essential requirement for single IRB use is virtually identical, FDA has proposed differences in the exceptions to the rule. The Common Rule provides two exceptions:
While the FDA has proposed acceptance of the first exception, it has not proposed adoption of the second exception from the Common Rule because the FDA does not support or conduct the research that it oversees through regulations 21 CFR 50 and 56. Therefore, FDA has declined to include this exception in the NPRM.
However, FDA is proposing three additional exceptions that were not included in the Common Rule. The first unique exception is:
The other two unique exceptions are for clinical investigations with drugs and biologics that do not require an IND and for clinical investigations of medical devices that do not require an IDE:
Potential Impact of the Unique Exceptions
This first unique exception is unlikely to apply very often. No definition is provided for a “highly specialized FDA-regulated medical product” or “unique, localized expertise.” In addition, individual or entity who makes this decision is not identified. Also, studies that are this unique would likely be single site studies in the first place.
The second and third unique exceptions, for IND and IDE exempt clinical investigations, may be used occasionally. These types of studies are often small in size and often do not have commercial sponsorship. Also, a single IRB could be utilized, even if not required under the new regulation.
These three unique exemptions have the potential to create regulatory conflicts for research that is both FDA-regulated and federally-funded; and thus, it would be subject to the Common Rule. For instance, if an NIH funded study qualified for one of the three unique exceptions in the FDA regulation, there would be conflicting regulatory requirements with the Common Rule.
Because the Common Rule does not include these provisions, the Common Rule would still require single IRB review unless the NIH took action under 45 CFR 46.114(b)(2)(ii) to determine that “[research] for which any Federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context.”4
While these regulatory conflicts would create some additional regulatory burden, it will not be unmanageable for the regulated community.
IRBs, institutions, and investigators involved in the review and conduct of federally-funded research have already adopted the single IRB requirement as it was implemented in 2018 in the Common Rule. On the other hand, those institutions and investigators who only conduct FDA regulated research will need to review their policies and ensure they are prepared for compliance with this requirement, particularly at institutions with local IRBs.
Commercial sponsors and CROs should be prepared to address this new requirement if and when it is implemented, although the change should lead to less administrative burden on sponsors and CROs as only one IRB will review each study. That said, the timeline for adoption of these proposed changes to the FDA regulations is unclear; it could take several months or even several years. However, forward thinking sponsors, institutions and investigators may want to start updating their policies now.
- 21st Century Cures Act, Section 1002, Public Law 114-255. https://www.govinfo.gov/app/details/PLAW-114publ255
- Notice of Proposed Rulemaking: Institutional Review Boards; Cooperative Research (87 FR 58752) https://www.federalregister.gov/documents/2022/09/28/2022-21089/institutional-review-boards-cooperative-research
- Notice of Proposed Rulemaking: Protection of Human Subjects and Institutional Review Boards (87 FR 58733) https://www.federalregister.gov/documents/2022/11/14/2022-24689/protection-of-human-subjects-and-institutional-review-boards-and-institutional-review-boards
- Code of Federal regulations Title 45 46.114 https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-A/section-46.114
Note: While the term “research participant” or “research volunteer” is generally preferred, US federal regulations use “research subject.” This paper uses the regulatory terminology, since the focus is on federally proposed regulations.
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