Part 312 is the section of the US Code of Federal Regulations that governs investigational new drug applications and the duties of sponsors and investigators. This is a map of the regulation, not a filing how-to. Not legal advice.
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| Sections | Topic | |
|---|---|---|
| Subpart A | 312.1-312.10 | General provisions: scope, definitions, waivers |
| Subpart B | 312.20-312.38 | The IND: content, amendments, safety reports, annual reports |
| Subpart C | 312.40-312.48 | Administrative actions: clinical holds, inactive status, meetings |
| Subpart D | 312.50-312.70 | Sponsor and investigator responsibilities |
| Subpart E | 312.80-312.88 | Life-threatening and severely debilitating illnesses |
| Subpart F, G | 312.110-312.160 | Miscellaneous, and laboratory research animals or in vitro |
| Subpart I | 312.300 onward | Expanded access to investigational drugs |
Part 312 in one page
Overview
Part 312 is titled Investigational New Drug Application. It implements FDA authority over clinical investigations of drugs and biological products that have not been approved. In broad terms, if you plan a clinical investigation of such a product in the US and it is not exempt, you need an IND in effect before you ship the drug and begin. The scope and exemptions are set out in the early sections, so read them before assuming your study needs or does not need an IND.
The rule applies to two key actors. The sponsor takes responsibility for and initiates the investigation. The investigator conducts it. Many academic studies have one person in both roles, a sponsor-investigator, which combines both sets of duties. Our guide to becoming a sponsor-investigator explains what that means in practice.
Part 312 does not stand alone. Informed consent (Part 50), IRB review (Part 56), financial disclosure (Part 54) and electronic records (Part 11) sit alongside it. See our 21 CFR Part 11 checklist for the electronic records side.
The structure
| Subpart | Sections | What it does |
|---|---|---|
| A: General provisions | 312.1-312.10 | Scope, definitions, FDA review principles, and the route to request a waiver of a requirement. |
| B: Investigational New Drug Application | 312.20-312.38 | When an IND is required, phases, general principles, content, protocol and information amendments, IND safety reports (312.32), annual reports (312.33) and withdrawal. |
| C: Administrative actions | 312.40-312.48 | When an IND goes into effect, clinical holds, termination, inactive status, and meetings and dispute resolution with FDA. |
| D: Responsibilities of sponsors and investigators | 312.50-312.70 | Sponsor duties (selecting investigators, monitoring, informing investigators, review of ongoing investigations, records) and investigator duties (conduct, drug control, reports, records, disqualification). |
| E: Life-threatening and severely debilitating illnesses | 312.80-312.88 | Early consultation and treatment protocols for serious conditions. |
| F: Miscellaneous | 312.110-312.145 | Import and export, foreign clinical studies not under an IND, availability of information and guidance. |
| G: Laboratory research animals and in vitro | 312.160 | Labelling and requirements for drugs used only for laboratory research. |
| I: Expanded access | 312.300 onward | Individual patient, intermediate-size and treatment IND routes outside a standard trial. |
Subpart H is reserved. Section ranges per the current Code of Federal Regulations; check the eCFR for the latest text.
Build your forms, edit checks and safety reporting in the free sandbox, then export the audit trail and blank eCRF before your first participant.
Subpart D
Subpart D is the part most trial teams live in day to day. It gives each role a defined list of duties, and these map closely onto the work of your data system.
The sponsor is responsible for selecting qualified investigators, providing them the information they need, ensuring proper monitoring and ensuring the investigation is conducted in accordance with the general investigational plan and protocols in the IND. It also reviews ongoing safety and effectiveness information, may transfer obligations to a contract research organisation in writing, keeps records of drug shipment and disposition, and allows FDA inspection of records. Selecting investigators includes obtaining a signed investigator statement, commonly Form FDA 1572, so check the current section for requirements.
The investigator ensures the study is conducted according to the signed statement, the protocol and applicable regulations, protects the rights, safety and welfare of subjects, and controls the investigational drug. Informed consent and IRB review are required. The investigator keeps adequate and accurate case histories, reports adverse events to the sponsor, provides progress, safety and final reports, and keeps records for the required period. FDA may inspect records and can disqualify an investigator who repeatedly or deliberately violates the rules.
Sound case histories are the data capture function: complete eCRFs, a field-level audit trail and signed-off forms. Monitoring is supported by source data verification and queries. Drug accountability depends on your process. See our risk-based monitoring and SDV software page and audit trail export for inspectors.
Safety reporting
Section 312.32 requires the sponsor to review all information relevant to the safety of the drug and to notify FDA and all participating investigators of potential serious risks. The expedited reports are called IND safety reports. Two timelines are the ones people remember. A serious and unexpected suspected adverse reaction must be reported to FDA within 15 calendar days. An unexpected fatal or life-threatening suspected adverse reaction must be reported as soon as possible and no later than 7 calendar days, and the initial notice can be by telephone or fax if followed up in writing. Sources describing the rule disagree slightly on whether the clock runs from the sponsor's initial receipt of the information or from its determination that the event qualifies, and on follow-up report timing, so read the current text of 312.32 for the precise wording.
Beyond individual cases, 312.32 also covers findings from other studies, animal or in vitro testing that suggest a significant risk, and clinically important increases in the rate of a serious suspected adverse reaction. The sponsor must evaluate whether an event is a suspected adverse reaction, serious and unexpected, and the investigator must report serious adverse events to the sponsor promptly. Our SAE reporting timelines guide, SAE deadline calculator and SUSAR reporting software pages go deeper on the mechanics.
The annual report under 312.33 is a different obligation: a brief progress report due within 60 days of the anniversary date that the IND went into effect, summarising study status, subjects and adverse events.
SAE timeline
SAE reported
Day 0 · 09:12
Safety alert acknowledged
Medical monitor · 09:40
Site staff attestation
Study coordinator · 11:05
AE sign-off (PI / Sub-I)
Awaiting signature
Records
A practical list drawn from the duties above. It is not a substitute for reading the sections.
Keep a dated record of each version and what changed.
Keep signed statements and a log of who may do what.
Complete eCRFs with a field-level audit trail showing who changed what, when and why.
Records of shipment, receipt, dispensing and return or destruction.
Each serious event assessed and reported on time, with the date the information was received.
Retain Part 312 records for the period required, commonly two years after approval or discontinuation and FDA notification, or longer by contract. See data archiving and retention.
In Capture
Capture is the data capture and safety reporting side of an IND study. It provides 21 CFR Part 11-aligned controls: a field-level audit trail, electronic signatures with re-authentication on countersignature, role-based access, and a draft to approved form lifecycle. Edit checks raise auto-queries, source data verification can be set per field, and safety reporting and monitoring workflows sit in the same system. Compliance is a shared responsibility with your own validated use.
Weight changed 68.0 to 68.5 kg
Site coordinator · Reason: Transcription error
Query Q-0014 answered on Weight
Site coordinator · Reason: Source checked
Vital signs form locked
Data manager · Reason: Visit cleaned
It is the section of the US Code of Federal Regulations titled Investigational New Drug Application. It sets out when an IND is needed, what it contains, how FDA can act on it and what sponsors and investigators must do.
The application guide explains how to prepare and file an IND. This page maps the regulation itself: the subparts, the duties of sponsors and investigators, safety reporting and records.
Serious and unexpected suspected adverse reactions are generally reported within 15 calendar days, and unexpected fatal or life-threatening ones within 7 calendar days. Check the current text for how the clock is measured and follow-up reporting.
Under 312.33 the sponsor submits an annual progress report within 60 days of the anniversary date that the IND went into effect.
Sponsors and investigators must retain records for two years after a marketing application is approved, or if none is approved, two years after the investigation is discontinued and FDA is notified. Contracts or other rules may require longer.
A person who both initiates and conducts an investigation, so takes on both sponsor and investigator duties under Part 312.
Part 312 places duties on people and organisations, not software. Capture provides 21 CFR Part 11-aligned controls, audit trail, safety forms and monitoring workflows that support those duties.
No. It is orientation. Read the current regulation on the eCFR and consult regulatory professionals.
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