Investigational New Drug (IND)

An Investigational New Drug (IND) is both a regulatory status and the FDA application that establishes it: under 21 CFR Part 312, a sponsor must hold an active IND before shipping an unapproved drug or biologic across state lines for use in a human clinical investigation, or before using an already-approved drug in a way that falls outside its approved labeling and meets the triggering criteria in 21 CFR 312.2(b). “IND” is used interchangeably for the legal status of the drug (an “investigational new drug”), the submission itself (the IND application), and the FDA-assigned tracking number a study operates under.

What triggers the IND requirement

Under 21 CFR 312.2(b), a clinical investigation of a drug that is already lawfully marketed in the United States is exempt from IND requirements if it meets all of the listed conditions — broadly: the study is not intended to support a new indication or a significant change in labeling/advertising, does not involve a route, dose, patient population, or other factor that significantly increases the risk associated with the drug’s approved use, is conducted in compliance with IRB review and informed consent requirements (21 CFR Parts 56 and 50), and is not intended to promote the drug for a use for which it is not approved. If a study fails any of those conditions — most commonly because it targets a new indication, a materially different dose or route, or a higher-risk population — an IND is required even though the drug itself is already FDA-approved for some other use. Any study of a drug or biologic with no approved marketing status at all requires an IND as a matter of course, regardless of these criteria.

Who sponsors an IND

21 CFR 312.3 defines “sponsor” as the person or entity that takes responsibility for and initiates a clinical investigation — this can be a pharmaceutical company, a federal agency, an academic institution, or an individual. When an individual both initiates and personally conducts the investigation, that person is a sponsor-investigator and holds both the sponsor’s and the investigator’s regulatory obligations under Part 312 in full — there is no reduced or merged obligation for holding both roles simultaneously. See CASRAI’s Investigator-Initiated Study (IIS) entry for how this plays out operationally at a research institution. FDA distinguishes several IND categories in practice, most commonly: a commercial IND filed by a company intending to eventually market the drug; a research (non-commercial) or Investigator IND, filed by a physician-scientist who both initiates and conducts an investigation of an unapproved drug, or of an approved drug for a new indication or patient population; and emergency use and treatment IND mechanisms that allow expanded access to an investigational drug outside a formal trial under defined circumstances.

What the IND application must contain

21 CFR 312.23 sets out the required content and format. In summary order, a complete IND includes: a cover sheet (Form FDA-1571); a table of contents; introductory statement and general investigational plan; the Investigator’s Brochure; the protocol(s) for the planned study or studies; chemistry, manufacturing, and controls (CMC) information sufficient to assess the identity, quality, purity, and stability of the investigational drug; pharmacology and toxicology data from animal or in vitro studies supporting the sponsor’s conclusion that it is reasonably safe to proceed to human testing; any prior human experience with the drug; and, where applicable, additional information such as radioactive drug data. The sponsor’s own Form FDA-1571 cover sheet is distinct from the investigator-facing FDA Form 1572 (Statement of Investigator), which the sponsor collects from each participating investigator once the IND is active, before that investigator may begin enrolling subjects.

The 30-day review clock and clinical hold

Once a sponsor submits an IND, FDA assigns an IND number and the sponsor must wait 30 calendar days from the date FDA receives the application before initiating any clinical trial under it, unless FDA notifies the sponsor sooner that the studies may begin. During this window FDA reviews the submission for subject safety. If FDA identifies a deficiency serious enough to warrant delaying or suspending a trial, it can place the IND on clinical hold; FDA must provide a written explanation of the basis for the hold within 30 days of imposing it, and once the sponsor submits a complete response, FDA generally has 30 calendar days to determine whether the response resolves the hold. A sponsor may proceed with the trial once the 30-day initial review period passes without a clinical hold being imposed, or once FDA lifts a hold that was imposed.

Ongoing sponsor obligations under an active IND

Holding an active IND is not a one-time filing — Part 312 Subpart D imposes continuing obligations for as long as the IND remains open, including: selecting qualified investigators and monitors and obtaining each investigator’s Form 1572 before they participate (312.53); maintaining records of investigational drug shipment and disposition (312.57); reviewing the ongoing safety of the investigation and reporting safety information to FDA and investigators (312.32, 312.56); submitting annual reports summarizing the IND’s status; and updating the protocol, Investigator’s Brochure, and CMC sections as the development program progresses. See CASRAI’s guide on pharmacovigilance in clinical research for how adverse-event reporting obligations flow from an active IND.

IND vs. related mechanisms

An IND is the drug/biologic-specific mechanism under 21 CFR Part 312. The parallel mechanism for medical devices is the Investigational Device Exemption (IDE) under 21 CFR Part 812, which is further split into significant-risk and nonsignificant-risk device studies with different approval pathways. A related but separate designation, Humanitarian Use Device (HUD) status, applies only to devices, not drugs. Before formally submitting an IND, many sponsors request a Pre-IND meeting with FDA to get early feedback on the proposed development plan; this meeting is optional and does not itself create or require an IND. See also CASRAI’s guide to clinical trial phases for how the IND relates to the Phase 1–3 structure it authorizes, and the Orphan Drug Designation guide for a related but distinct FDA designation that a sponsor can pursue in parallel with an IND for rare-disease indications.