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.
What this does not cover
stated in the document's own scope- Governs investigational drugs and biologics; investigational medical devices follow the separate Investigational Device Exemption at 21 CFR Part 812.
- Covers the conduct and oversight of clinical investigations, not informed consent or IRB review, which are set out in 21 CFR Parts 50 and 56 respectively.
- Applies to the investigational stage; post-marketing adverse-experience reporting for approved drugs is the subject of 21 CFR §314.80.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
21 CFR Part 312 is the US regulation governing the investigational use of drugs and biologics in human beings — the Investigational New Drug (IND) framework. It sets when an IND is required before a drug may be shipped and administered in a clinical investigation, what the IND application must contain and how it is formatted, and the phases of clinical investigation. It defines the responsibilities of sponsors and investigators, the IND safety-reporting duties for serious and unexpected adverse events, recordkeeping and retention, and the mechanisms for FDA to place a study on clinical hold. It also provides expanded-access and treatment-IND routes.
Scope & applicability
Sponsors and investigators conducting clinical investigations of drugs and biologics under a US IND, including commercial and investigator-initiated studies.
Legal basis & how it acquires force
Part 312 is a binding regulation in Title 21 CFR, issued under the Federal Food, Drug, and Cosmetic Act — principally §505(i), which authorises FDA to exempt investigational drugs from the premarket-approval requirement subject to conditions — and, for biologics, under §351 of the Public Health Service Act. The IND is the legal mechanism by which an unapproved drug may lawfully be shipped across state lines and given to humans for investigation. Compliance is a condition of that exemption, and its safety-reporting provisions live at §312.32.
Document structure
| Part | Covers |
|---|---|
| Subpart A | General provisions — scope, definitions, and the labelling of investigational drugs |
| Subpart B | IND content and format (§312.23), phases of investigation, protocols, and the clinical-hold provisions |
| Subpart C | Administrative actions, including clinical holds, inactive status, and termination |
| Subpart D | Responsibilities of sponsors and investigators, including safety reporting (§312.32) and monitoring |
| Subparts E–F | Drugs intended to treat life-threatening and severely debilitating illnesses; miscellaneous provisions, import and export |
| Expanded access / charging | Expanded access to investigational drugs for treatment use and the conditions for charging for them |
Key requirements
- 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
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.
Where this control fails
live FDA enforcementLive FDA recalls SPEQ maps to this standard’s topics — a SPEQ interpretation, not an FDA classification.
International alignment
Part 312 is the US implementation of the Good Clinical Practice principles harmonised in ICH E6, and its safety-reporting provisions at §312.32 give US effect to the serious-and-unexpected reporting standard set in ICH E2A. It parallels the EU Clinical Trials Regulation (536/2014), which performs the equivalent authorisation and oversight role in Europe. Nonclinical safety studies supporting an IND are conducted under the Good Laboratory Practice regulation at 21 CFR Part 58.
21 CFR Part 312: frequently asked questions
Quick answers to common questions about 21 CFR Part 312.
What is the statutory basis for the IND regulation?
Section 505(i) of the Federal Food, Drug, and Cosmetic Act (and §351 of the Public Health Service Act for biologics), which lets FDA exempt an investigational drug from premarket approval so it can be studied in humans under defined conditions.
Where are IND safety-reporting requirements found?
At 21 CFR §312.32. It requires sponsors to report serious and unexpected suspected adverse reactions to FDA and investigators within defined timeframes, giving US effect to the ICH E2A reporting standard.
Does Part 312 cover informed consent and IRBs?
No. Those are set out separately — informed consent in 21 CFR Part 50 and Institutional Review Boards in 21 CFR Part 56. Part 312 governs the IND itself and the conduct of the investigation.
This standard in practice
Recall domain is a SPEQ mapping of this standard’s topics, not an FDA classification.