The FDA IND application, explained for academic investigators

Many academic studies use drugs that are already on the market, so the first question is whether the study is exempt. Under 21 CFR 312.2(b)(1), a clinical investigation of a lawfully marketed drug is exempt only if all of the following apply: it is not intended to be reported to FDA as a well-controlled study supporting a new indication or another significant labeling change; for a prescription drug, it is not intended to support a significant change in advertising; it does not involve a route of administration, dose, patient population or other factor that significantly increases the risk or decreases the acceptability of the risk; it follows the IRB and informed consent rules in 21 CFR parts 56 and 50; and it complies with the promotion and charging rules in 312.7.

The third condition is where most academic studies get caught. A higher dose than labeled, a new route, children when the label covers adults, or a population with organ impairment can each change the risk picture. FDA explains how it applies the test in its guidance Investigational New Drug Applications (INDs): Determining Whether Human Research Studies Can Be Conducted Without an IND (September 2013). If you are unsure, ask the relevant FDA review division; your IRB will usually want the reasoning documented either way. Note that FDA will not accept an IND for a study that is exempt.

Form FDA 1571 is the IND application itself and the cover sheet for every later submission: amendments, safety reports and annual reports. It is where you commit to follow Part 312, to wait until the IND is in effect, and to have an IRB review the study. Form FDA 1572 is the statement of investigator. As a sponsor-investigator you sign it as the investigator; FDA accepts the 1572 and its attachments, such as your CV, to cover the investigator information the 1571 asks for. Add a new 1572 when you add an investigator at another site.

Form FDA 3674 certifies that the ClinicalTrials.gov registration and results requirements in 42 U.S.C. 282(j) have been met where they apply, with NCT numbers where available. Register early: our ClinicalTrials.gov registration guide covers who must register and when. FDA's sponsor-investigator page describes paper submission in triplicate; noncommercial INDs are not required to use eCTD, and CDER also accepts non-eCTD research IND submissions electronically through its NextGen portal. Check the current route with your review division before you send anything.

Holding the IND means you carry both sets of duties in Part 312: the sponsor's (subpart D, from 312.50) and the investigator's (from 312.60). The ones that catch academic teams out are timed reports. Under 21 CFR 312.32, you must report to FDA and all participating investigators, within 15 calendar days, any suspected adverse reaction that is both serious and unexpected, along with certain findings from other studies or animal data. Unexpected fatal or life-threatening suspected adverse reactions must reach FDA within 7 calendar days of your first receipt of the information. Follow-up information goes in as a follow-up IND safety report. In December 2025 FDA published final guidance on investigator responsibilities for safety reporting, alongside updated guidance for sponsors; read both, because you are both.

Annual reports under 21 CFR 312.33 are due within 60 days of the anniversary of the date the IND went into effect. They summarise each study's status and enrolment, adverse events, IND safety reports, deaths and dropouts, and the plan for the coming year. Protocol changes go in as protocol amendments, and a new protocol needs both an amendment to FDA and IRB approval before it starts. You also need monitoring proportionate to the study, records retained for the period Part 312 sets, and readiness for an FDA inspection. The FDA inspection checklist for clinical trial data shows what inspectors ask to see.