Part 50 is the FDA’s rule on protection of human subjects. It says who must give consent, what the consent must contain, how it is documented and the narrow situations where consent can be handled differently. This guide walks the sections a trial team actually uses.
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Research statement, purpose, duration, procedures
50.25(a)(1)
Risks and discomforts
50.25(a)(2)
Benefits and alternatives
50.25(a)(3)-(4)
Confidentiality and FDA access to records
50.25(a)(5)
Injury compensation, contacts, voluntariness
50.25(a)(6)-(8)
Registry statement where applicable
50.25(c)
What to know
Scope
Part 50 applies to clinical investigations regulated by FDA, such as studies of drugs, biologics and devices under an IND or IDE, and others that support applications to FDA. Research funded by US federal agencies that follow the Common Rule has a parallel set of rules at 45 CFR 46. Many studies must comply with both, and the two lists of consent elements overlap but are not identical.
FDA proposed rules in September 2022 to harmonize Parts 50 and 56 with the 2018 Common Rule, including a "key information" section at the start of the consent form and further elements on biospecimens. As of the last check for this page, we did not find a final rule, so confirm the current status. IRBs often ask for a key information section regardless.
Subpart B, 50.20
Section 50.20 sets the ground rules. Consent must be obtained from the subject or the legally authorized representative before the person is involved in the study, unless an exception applies. The investigator must give the possible subject enough opportunity to consider whether to participate and minimize the possibility of coercion or undue influence. The information must be in language the subject or representative can understand. And consent may not include exculpatory language, in which the subject appears to waive legal rights or release the investigator, sponsor, institution or agents from liability for negligence.
In practice this is where readability, timing and process come in. A consent form written at a level the participant cannot follow, or a signature collected at the moment of the first procedure, can be a problem even if every element in 50.25 is present. See the informed consent readability checker.
50.25
A summary of 21 CFR 50.25 as generally described. Use the eCFR text for the exact wording.
| Reference | Element | In plain terms |
|---|---|---|
| 50.25(a)(1) | Research statement | That the study involves research, its purposes, expected duration, procedures, and which procedures are experimental |
| 50.25(a)(2) | Risks | Reasonably foreseeable risks or discomforts |
| 50.25(a)(3) | Benefits | Benefits to the subject or others that may reasonably be expected |
| 50.25(a)(4) | Alternatives | Appropriate alternative procedures or treatments that might benefit the subject |
| 50.25(a)(5) | Confidentiality | How records are kept confidential, with a note that FDA may inspect them |
| 50.25(a)(6) | Injury | For more than minimal risk, whether compensation and medical treatment are available if injury occurs |
| 50.25(a)(7) | Contacts | Who to contact about the research, about rights and about research-related injury |
| 50.25(a)(8) | Voluntary | Participation is voluntary; refusal or discontinuing involves no penalty or loss of benefits |
| 50.25(b) | Additional, when appropriate | Unforeseeable risks (including to an embryo or fetus), termination by the investigator, additional costs, consequences of withdrawal, significant new findings, approximate number of subjects |
| 50.25(c) | Registry statement | For applicable clinical trials, a statement that a description will be available on ClinicalTrials.gov (check the exact required wording) |
The 2022 proposal would add further elements. If your IRB template already includes them, that is consistent with where the rule is heading.
50.27
Under 50.27, informed consent is documented by a written form approved by the IRB and signed and dated by the subject or the legally authorized representative at the time of consent. A copy must be given to the person signing.
The rule also allows a short form stating that the elements of consent have been presented orally. In that case there must be a witness to the oral presentation, the IRB must approve a written summary of what is said, the subject or representative signs the short form, the witness signs both the short form and a copy of the summary, and the person obtaining consent signs the summary. A copy of the summary and the short form goes to the subject. See impartial witness eConsent for how this is handled electronically.
Electronic signatures on consent have their own rule set, 21 CFR Part 11, which covers audit trails, signature manifestations and the link between signature and record. FDA also publishes guidance on electronic informed consent. Part 11 is about the system and records; Part 50 is about the consent process. See the Part 11 compliance checklist.
Consent may be given by a legally authorized representative where the subject cannot consent, as defined by applicable law. Subpart D (50.50 to 50.56) adds protections for children, with categories of permitted research by level of risk and prospect of direct benefit, parental permission and assent requirements. See legally authorized representative consent and the pediatric assent template.
Exceptions
These are narrow. They exist for specific circumstances, not convenience, and each carries documentation duties.
| Section | Applies to | Headline conditions (summary) |
|---|---|---|
| 50.22 | Minimal-risk clinical investigations | IRB may waive or alter consent if criteria are met, such as the study involving no more than minimal risk and not being practicable without the waiver, with safeguards (final rule effective January 2024) |
| 50.23 | Life-threatening use of a test article outside research | Written certification by the investigator and an independent physician that the person has a life-threatening condition, consent cannot be obtained and there is no time and no accepted alternative; reporting to the IRB follows. Separate provisions deal with military operations and waivers |
| 50.24 | Planned emergency research | Strict IRB findings and safeguards, such as a life-threatening condition with unproven treatments, consent not feasible, prospect of direct benefit, community consultation, public disclosure and an independent data monitoring committee |
Do not rely on this summary to use an exception. Each has specific findings, documentation and notification duties. The IRB and regulatory affairs decide.
Capture and Part 50
Capture’s eConsent module supports the documentation side of consent: the participant reads the IRB-approved text, signs on screen after an email one-time-passcode check and acknowledges a legal-binding statement. An authorized staff member countersigns with password re-authentication. The signed document is hashed to its exact content and exports as a PDF with timestamps and the audit trail. Capture does not decide what your consent must say, and it does not replace the consent conversation.
Meaning of signature
I have reviewed this adverse event and confirm the assessment of seriousness, severity and causality.
Signer
Dr. A. Ozola, PI
Password
••••••••••
Pick a template from the library, send yourself the link and see the signed PDF and audit trail in the free sandbox.
Practical check
Tick them off against the regulation, not a memory of it.
Include those that apply to your design.
Included if the trial is an applicable clinical trial.
Check liability wording against 50.20.
Test readability; offer time to consider.
Long form, short form or electronic, and who obtains and countersigns.
Signed copy provided in the version signed.
LAR and assent processes defined where relevant.
How new information (50.25(b)(5)) will be communicated and documented.
It is FDA’s regulation on protection of human subjects in clinical investigations it regulates. Subpart B covers informed consent, Subpart D covers additional protections for children. IRB rules are in the companion Part 56.
The basic elements in 50.25(a) are a research statement, risks, benefits, alternatives, confidentiality (including FDA inspection), injury compensation for more than minimal risk, contacts and the voluntary nature of participation. 50.25(b) lists additional elements to include when appropriate, and 50.25(c) adds a registry statement for applicable clinical trials.
Under 50.27, with a written form approved by the IRB, signed and dated by the subject or representative, with a copy given to them. A short form plus witness and written summary is a permitted alternative.
Only in narrow circumstances: 50.22 for minimal-risk investigations (IRB waiver or alteration), 50.23 for certain life-threatening emergency uses of a test article and 50.24 for planned emergency research. Each has conditions and documentation duties.
Part 50 does not require paper, but consent must meet the same content and documentation requirements. Electronic signatures and records also have to meet Part 11, and FDA has issued guidance on electronic informed consent. Your IRB approves the process.
FDA proposed to harmonize Part 50 with the 2018 Common Rule in September 2022. We did not find a final rule at the last check, so confirm the status in the Federal Register.
Yes. Both require informed consent, and their elements overlap, but the lists are not identical (for example FDA’s inspection statement and registry statement, and the Common Rule’s key information requirement). A study subject to both must satisfy both.
No tool does that on its own. Capture records signed electronic consent with an audit trail and Part 11-aligned controls. The content must be approved by your IRB and meet Part 50 and any other rule that applies.
Keep exploring
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Impartial witness eConsent
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Informed consent readability checker
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21 CFR Part 11 compliance checklist
Electronic records and signatures.
IRB submission checklist
Prepare the package.
Pediatric assent template
Assent for children.
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