Direct comparison
45 CFR 46 vs. 21 CFR 50 Compared
How the HHS Common Rule (45 CFR 46) differs from FDA's 21 CFR 50, when a trial must satisfy both, and where their consent/exemption rules diverge.
Side-by-side comparison
| Dimension | 45 CFR 46 (Common Rule) | 21 CFR 50 (FDA) |
|---|---|---|
| Issuing authority | HHS; Subpart A adopted by ~20 federal agencies as the "Common Rule" | FDA, independently codified |
| What triggers applicability | Research conducted or funded by a federal department/agency that has adopted the Common Rule, meeting the §46.102(l) definition of human-subjects research | A clinical investigation FDA regulates under the FD&C Act or PHS Act — supporting an IND, IDE, or other FDA marketing application (21 CFR 50.1) |
| Does federal funding matter? | Yes — funding or a covered federal agency is the trigger | No — applies purely from FDA product jurisdiction, even for a 100% privately funded trial |
| General exemption categories | Eight categories at §46.104 (2018-revised): e.g. certain educational-test/survey/interview research, benign behavioral interventions, some secondary-data research | No equivalent general exemption list; only narrow, specific exceptions written into FDA’s own regulations |
| Basic informed-consent elements | §46.116 | 21 CFR 50.25 — closely parallel in substance, independently codified |
| Emergency research without consent | §46.101(i) — HHS Secretary waiver authority; not for pregnant women, fetuses, neonates, or prisoners | 21 CFR 50.24 (EFIC) — requires community consultation, public disclosure before the study begins, and an independent data monitoring committee |
| IRB review regulation | 45 CFR 46 (institutional IRB, OHRP-registered) | 21 CFR Part 56 — separate but closely parallel FDA IRB regulation |
| Continuing review exceptions | §46.109(f) removes continuing review for several 2018-added categories | 21 CFR 56.109(f) has no equivalent carve-outs — generally requires annual continuing review |
| Short-form consent (non-English speakers) | §46.117(b)(2) | 21 CFR 50.27(b)(2) — essentially identical mechanics |
| Can both apply to one study? | Yes | Yes — e.g. an NIH-funded IND drug trial must satisfy both independently, in full |
Common questions
FAQ
Can a clinical trial be subject to both 45 CFR 46 and 21 CFR 50 at the same time?+
Yes. Federal funding and FDA product jurisdiction are independent triggers. An NIH-funded trial of an investigational drug must satisfy both the Common Rule and 21 CFR Parts 50/56 in full — there is no substitution or partial credit for meeting only one.
Does 21 CFR 50 have exemption categories like the Common Rule's §46.104?+
No. FDA's human-subjects protection regulations do not include a general exemption list comparable to the Common Rule's eight §46.104 categories. FDA recognizes only narrow, specific exceptions — for example, the emergency-research exception at 21 CFR 50.24 — not a broad minimal-risk exemption framework.
If a study is exempt under 45 CFR 46.104, is it also exempt from 21 CFR 50?+
Not automatically. A §46.104 exemption is a determination under the Common Rule only. If the same study also involves an FDA-regulated product, it must independently satisfy 21 CFR 50 and Part 56 requirements regardless of its Common Rule exemption status.
Which regulation applies to a privately funded drug trial with no federal money involved?+
21 CFR 50 (and Part 56 for IRB review) applies on its own, triggered purely by FDA jurisdiction over the investigational drug. The Common Rule does not apply unless the research is also federally funded or conducted by a covered federal agency.
