5 SUSAR reporting mistakes early-stage biotechs make — and how to avoid them

The FDA inspector reviewing an IND for a Phase 2 oncology drug asks to see the SUSAR tracking log. The sponsor produces a spreadsheet. Three cases from the previous year are marked as "non-reportable" with the notation "causality assessed as unlikely." The inspector immediately identifies the problem: causality assessment of "unlikely" does not exclude SUSAR status — and all three events should have been reported. The inspection ends with a major GCP finding.

Mistake 1: Treating "unlikely" causality as non-reportable

Under ICH E2A and 21 CFR 312.32(a), a SUSAR requires that there is "a reasonable possibility" that the drug caused the event — not that causality is probable or confirmed. "Reasonable possibility" is a low threshold. FDA and EMA guidance makes clear that unless causality can be definitively excluded (which is rarely possible), the event should be assessed as suspected.

Investigators frequently assess events as "unrelated" or "unlikely related." This is the investigator's opinion — but sponsors must apply the reasonable possibility threshold independently. If the sponsor cannot definitively rule out drug causality based on the available data, the event must be treated as suspected.

Mistake 2: Starting the reporting clock from the event date

The 7-day and 15-day reporting timelines under 21 CFR 312.32 and GVP Module VI run from Day 0 — the date the sponsor receives the information and determines it qualifies for reporting. Not the date the adverse event occurred in the patient. Not the date the investigator observed it. Not the date the investigator's report was written.

A sponsor that records "event date" as their Day 0 will consistently file late for events that were reported to the sponsor days or weeks after occurrence. The date stamp on the sponsor's initial receipt of the SAE report — email, fax, safety portal submission — is Day 0.

Mistake 3: Not reporting to all relevant regulatory authorities

A SUSAR from an EU clinical trial must be reported to all EU Member States in which the trial is running, via EudraVigilance EVCTM under EU CTR 536/2014. A SUSAR from a US IND trial must go to FDA. If the same trial runs in both jurisdictions, both reports are required — within their respective timelines, in the required formats (E2B(R3) for EU; MedWatch 3500A for FDA).

Small sponsors with multi-country trials frequently report to the country where the event occurred but miss reporting obligations to other regulatory authorities with jurisdiction over the trial.

Mistake 4: Not notifying investigators of SUSARs from other sites

ICH E6(R3) and FDA regulations require sponsors to notify all participating investigators of SUSARs — including SUSARs that occurred at other sites or in other trials with the same investigational product. The rationale: an investigator who is unaware of a serious unexpected event at another site may miss the same event in their own patients.

Many sponsors send SUSAR notifications only to the site where the event occurred. This is non-compliant. All active sites on the IND must receive SUSAR notifications for all qualifying events, regardless of where they occurred.

Mistake 5: Missing follow-up reports when new information arrives

A SUSAR report is not closed when the initial 7-day or 15-day report is filed. If significant follow-up information becomes available — the patient's outcome changes, new clinical information supports or changes the causality assessment, or additional laboratory results clarify the event — a follow-up SUSAR report is required within 15 calendar days of receipt of the new information.

Sponsors that file initial reports and consider the case closed when the patient recovers miss the follow-up reporting obligation. Inspectors review initial reports against follow-up records and identify cases where outcomes changed without a follow-up submission.

Nimble PV manages SUSAR tracking, assessment, and reporting for Phase 1-3 sponsors. Talk to Vera at nimblepv.com.