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21 CFR Part 312

Investigational New Drug Application (IND)

The US regulation governing the investigational use of drugs and biologics in human clinical trials. Part 312 establishes when an IND is required, its content and format, sponsor and investigator responsibilities, IND safety reporting, and recordkeeping — the operational backbone of US clinical research.

LAST REVISED
January 2023
PRODUCT AREAS
Clinical
SCOPE & APPLICABILITY

Sponsors and investigators conducting clinical investigations of drugs and biologics under a US IND, including commercial and investigator-initiated studies.

KEY REQUIREMENTS
  • 01Submit an IND before administering an investigational drug to human subjects (unless exempt)
  • 02Report serious, unexpected suspected adverse reactions within 15 calendar days (7 for fatal/life-threatening)
  • 03Maintain drug accountability and case-history records for each subject
  • 04Sponsors must select qualified investigators and monitor the investigation
IMPLEMENTATION TIPS
Align SUSAR assessment logic with §312.32 causality and expectedness definitions to avoid over/under-reporting
Keep the investigator site file and drug accountability logs inspection-ready throughout the trial
REVISION NOTES

The §312.32 safety-reporting requirements were substantially revised by the 2010 final rule harmonising expedited reporting with ICH E2A concepts.

21 CFR Part 312: frequently asked questions

Quick answers to common questions about 21 CFR Part 312.

What is 21 CFR Part 312?

21 CFR Part 312 — Investigational New Drug Application (IND) — is a regulation issued by the Food and Drug Administration (United States). The US regulation governing the investigational use of drugs and biologics in human clinical trials. Part 312 establishes when an IND is required, its content and format, sponsor and investigator responsibilities, IND safety reporting, and recordkeeping — the operational backbone of US clinical research.

Who does 21 CFR Part 312 apply to?

Sponsors and investigators conducting clinical investigations of drugs and biologics under a US IND, including commercial and investigator-initiated studies.

What are the key requirements of 21 CFR Part 312?

FDA 21 CFR Part 312 requires, among other things: Submit an IND before administering an investigational drug to human subjects (unless exempt); Report serious, unexpected suspected adverse reactions within 15 calendar days (7 for fatal/life-threatening); Maintain drug accountability and case-history records for each subject; Sponsors must select qualified investigators and monitor the investigation.

When was 21 CFR Part 312 last updated?

The current version of 21 CFR Part 312 dates from January 2023. The §312.32 safety-reporting requirements were substantially revised by the 2010 final rule harmonising expedited reporting with ICH E2A concepts.

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