21 CFR Part 56 (Institutional Review Boards)

21 CFR Part 56 (Institutional Review Boards) is the U.S. Food and Drug Administration’s own regulation governing IRB review of clinical investigations that fall under FDA’s product-jurisdiction authority. It runs parallel to, but is legally distinct from, the Department of Health and Human Services’ Common Rule at 45 CFR 46. Where the Common Rule’s applicability turns on whether a study is federally funded or federally conducted, Part 56’s applicability turns on whether the study is regulated by FDA — a different, independent trigger that has nothing to do with a study’s funding source.

What Triggers Part 56

Under 21 CFR 56.103, IRB review and approval is required before initiation, and continuing IRB review is required for the duration, of any clinical investigation that must be submitted to FDA under one of three parallel regulatory tracks: an Investigational New Drug application (IND, 21 CFR Part 312) for a drug or biologic study, an Investigational Device Exemption (IDE, 21 CFR Part 812) for most significant-risk device studies, or a study otherwise submitted to FDA in support of a research or marketing permit application (21 CFR Part 813, medical devices). FDA may decline to rely on data from an investigation that was not reviewed and approved, both initially and on a continuing basis, by an IRB meeting Part 56’s requirements. Because this trigger is about product jurisdiction rather than funding, Part 56 applies regardless of whether the study receives any federal grant support — a privately funded, industry-sponsored IND trial at a single site is just as subject to Part 56 as a federally funded one.

Structure of the Regulation

Part 56 is organized into five subparts:

• Subpart A — General Provisions (§§56.101–105): scope, definitions, the circumstances requiring IRB review (§56.103), and the (narrow) exemptions.
• Subpart B — Organization and Personnel (§§56.106–107): IRB registration with FDA and membership composition — requirements that closely parallel, but are separately codified from, the Common Rule’s §46.107.
• Subpart C — IRB Functions and Operations (§§56.108–114): written procedures, review criteria, expedited review (§56.110), and continuing review (§56.109). §56.108(b) specifically requires IRB written procedures for prompt reporting of unanticipated problems involving risk to subjects or others to the IRB, institutional officials, and FDA — a broader reporting category than a SUSAR under ICH E2A, since it can include non-serious findings that still carry safety implications.
• Subpart D — Records and Reports (§56.115): IRB recordkeeping requirements, including retention of protocols, approved consent documents, membership rosters, and meeting minutes, generally for at least 3 years after study completion.
• Subpart E — Administrative Actions for Noncompliance (§§56.120–124): FDA’s authority to disqualify an IRB that repeatedly or materially fails to comply, up to and including refusing to consider data reviewed by that IRB.

Part 56 vs. the Common Rule: Two Separate Tracks

Part 56 and the Common Rule are not the same regulation wearing two names — they are independently codified, administered by different federal bodies (FDA for Part 56; the HHS Office for Human Research Protections, OHRP, for the Common Rule), and can each apply on their own or together:

• Common Rule only: a federally funded study with no FDA product jurisdiction (for example, an NSF-funded behavioral survey).
• Part 56 only: a privately or industry-funded IND or IDE study with no federal grant support.
• Both at once: a federally funded IND or IDE study — for instance, an NIH-funded drug trial — must independently satisfy both tracks’ IRB-review and informed-consent requirements. In practice a single IRB submission and a single approval letter usually cover both, but the IRB’s written procedures and documentation need to address each regulation’s criteria, since the two remain separately codified and FDA and OHRP can each audit their own track’s compliance independently (including through FDA’s own Bioresearch Monitoring, BIMO, inspection program).

The same dual-track structure applies to informed consent: FDA’s parallel consent regulation is 21 CFR Part 50 (Protection of Human Subjects), whose basic-elements list at §50.25 runs closely parallel to — but is separately codified from — the Common Rule’s §46.116. A study that is both federally funded and FDA-regulated must satisfy both Part 50 and 45 CFR 46.116’s consent requirements, just as its IRB review must satisfy both Part 56 and the Common Rule.

Why This Distinction Matters in Practice

Research administrators and IRB staff need to identify which track (or both) applies to a given protocol early, because it determines which regulator’s requirements govern registration, membership documentation, reporting timelines, and recordkeeping — and because FDA and OHRP can each independently audit their own track’s compliance on the very same study. Institutions typically operationalize this through their Federalwide Assurance (FWA) and IRB standard operating procedures, which are written to satisfy both regulations simultaneously rather than running two separate review processes for a dual-track study.

References

• 21 CFR Part 56 (Institutional Review Boards) — full text: law.cornell.edu/cfr/text/21/part-56
• 21 CFR 56.103 (circumstances requiring IRB review)
• 21 CFR Part 50 (Protection of Human Subjects) — FDA’s parallel informed-consent regulation
• Common Rule, 45 CFR 46 (2018 revision)