IND Annual Report

The IND Annual Report is the yearly progress summary that a sponsor holding an active Investigational New Drug (IND) application must submit to FDA under 21 CFR 312.33. It is due within 60 days of the anniversary date the IND went into effect, and the obligation repeats every year the IND stays open — regardless of whether any study under it is actively enrolling. It is a distinct requirement from the event-triggered IND Safety Report and from the ICH-harmonized Development Safety Update Report (DSUR), though the three are closely related and often discussed together.

When it is due

The 60-day clock runs from the IND’s anniversary date — the date the IND went into effect, which is typically 30 days after FDA received the original application (absent a clinical hold). This anniversary date does not change based on protocol amendments, safety reports, or other IND correspondence filed during the year; sponsors are expected to track it independently and submit on schedule even in years with little study activity.

What the annual report must contain

21 CFR 312.33 specifies the required content in detail. A complete annual report includes:

• Individual study information — a brief summary of the status of each study in progress and each study completed during the year: title, purpose, patient population, and whether it is complete, along with subject counts (planned, entered to date, tabulated by age, sex, and race, completed as planned, and dropped out for any reason).
• Safety information — a summary of all IND Safety Reports submitted during the year, a list of subjects who died during the investigation with cause of death for each, and a list of subjects who dropped out in association with any adverse experience, whether or not thought to be drug-related.
• Drug action information — a brief description of anything learned that is pertinent to understanding the drug’s actions, including dose-response, controlled-trial, and bioavailability findings.
• Preclinical studies — a list of preclinical (including animal) studies completed or in progress during the year and a summary of major findings.
• Manufacturing changes — a summary of any significant manufacturing or microbiological changes made during the year.
• Investigator’s Brochure updates — if the Investigator’s Brochure was revised, a description of the revision and a copy of the new version.
• Phase 1 protocol modifications — a description of any significant Phase 1 protocol changes made during the year that were not already reported via a protocol amendment.
• Investigational plan and foreign marketing — an updated general investigational plan for the coming year (replacing the one submitted the prior year), plus a brief summary of significant foreign marketing developments for the drug during the year.

IND Annual Report vs. IND Safety Report vs. DSUR

• vs. IND Safety Report: the IND Safety Report is an expedited, event-triggered notification of a single suspected unexpected serious adverse reaction (SUSAR), filed within 7 or 15 calendar days under 21 CFR 312.32. The annual report is a scheduled, once-a-year rollup that aggregates and summarizes those individual reports alongside enrollment, manufacturing, and preclinical information — it does not substitute for filing the expedited reports themselves.
• vs. DSUR: the DSUR is the ICH E2F-standardized annual aggregate safety report, anchored to the product’s own Development International Birth Date/data-lock point rather than the IND’s anniversary date, and due within 60 days of that data-lock point. Current FDA guidance permits a properly prepared DSUR to satisfy the 312.33 annual report requirement in place of a separately formatted US progress report, which is why many multinational sponsors submit one DSUR to cover both obligations. A December 2022 Federal Register proposed rule would go further and formally replace the 312.33 format with the DSUR for most INDs, but that rule had not been finalized as of this writing — sponsors should confirm current status before assuming the formats have merged.

For the broader adverse-event reporting framework this sits alongside — AE/SAE/SUSAR definitions, investigator-to-sponsor reporting, and expedited IND Safety Reports — see CASRAI’s guide to Pharmacovigilance in Clinical Research: AE, SAE, and SUSAR Reporting.