Protection of Human Subjects (Informed Consent)
The US regulation setting the requirements for informed consent of human subjects in FDA-regulated clinical investigations, including the elements of consent, its documentation, and additional safeguards for vulnerable populations such as children (Subpart D).
What this does not cover
stated in the document's own scope- Covers informed consent and subject protection, not the committee that reviews the study — Institutional Review Boards are governed by 21 CFR Part 56.
- Sets human-subject protections, not the conduct or content of the trial itself, which for drugs sits in 21 CFR Part 312 and for devices in Part 812.
- Applies to FDA-regulated investigations; federally conducted or funded research not involving an FDA product may instead fall under the HHS Common Rule at 45 CFR 46.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
21 CFR Part 50 is the US regulation on the protection of human subjects in FDA-regulated clinical investigations, centred on informed consent. It requires that, with narrow exceptions, no investigator may involve a person as a subject without the legally effective informed consent of the subject or their representative, obtained under circumstances that allow free choice and minimise coercion. It specifies the basic and additional elements that a consent must contain, how consent is documented, and the exceptions — including certain emergency-research and life-threatening situations. Subpart D adds safeguards for children enrolled in clinical investigations.
Scope & applicability
All FDA-regulated clinical investigations involving human subjects. Works in tandem with 21 CFR Part 56 (IRBs) and Part 312 (IND).
Legal basis & how it acquires force
Part 50 is a binding regulation in Title 21 CFR, issued under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act, which authorise FDA to protect the rights and safety of human subjects in investigations of FDA-regulated products. It operates together with the IND, IDE, and IRB regulations: a clinical investigation subject to FDA oversight must satisfy Part 50’s consent requirements as a condition of lawful conduct. Its provisions are closely coordinated with the Department of Health and Human Services human-subject protections (the “Common Rule”, 45 CFR 46).
Document structure
| Part | Covers |
|---|---|
| Subpart A | General provisions — scope, definitions, and applicability to FDA-regulated clinical investigations |
| Subpart B — §50.20, §50.25 | General requirements for informed consent and the basic and additional elements a consent must contain |
| Subpart B — §50.23, §50.24 | Exceptions from the consent requirement, including emergency use and planned emergency research |
| Subpart B — §50.27 | Documentation of informed consent, including the written consent form and its signing |
| Subpart D | Additional safeguards for children in clinical investigations, including risk categories and assent/permission requirements |
Key requirements
- Obtain legally effective informed consent before any trial-specific procedure
- Include all required elements, including the concise key-information summary
- Document consent with a signed and dated form using the IRB-approved version
- Apply additional protections for children and other vulnerable subjects
Implementation tips
- Version-control consent forms and reconcile the signed version against the IRB-approved version at monitoring visits
- Front-load the "key information" section so subjects grasp the essentials before the full form
Revision notes
Harmonised with the revised Common Rule ("key information" summary) following the 2017-2018 updates.
International alignment
Part 50 gives US regulatory effect to the informed-consent principles of the Declaration of Helsinki and the ICH E6 Good Clinical Practice guideline, and it is coordinated with the HHS Common Rule (45 CFR 46) so that studies subject to both frameworks can meet a consistent standard. Subpart D’s child-safeguard categories mirror the corresponding Common Rule provisions, supporting harmonised protection of paediatric subjects across the federal agencies.
21 CFR Part 50: frequently asked questions
Quick answers to common questions about 21 CFR Part 50.
What does 21 CFR Part 50 require?
That subjects in FDA-regulated clinical investigations give legally effective informed consent before participating, obtained freely and containing the elements set out in §50.25, with documented consent under §50.27 — subject to narrow exceptions such as certain emergency situations.
How does Part 50 relate to the Common Rule?
Part 50 is the FDA human-subject protection framework; the HHS Common Rule (45 CFR 46) is the counterpart for federally conducted or funded research. They are coordinated so studies subject to both can meet one consistent consent standard.
What is Subpart D of Part 50?
Subpart D adds safeguards for children in clinical investigations, classifying research by risk and benefit and setting requirements for the child’s assent and the permission of parents or guardians.