Usage Examples
- The fatal case went to FDA on day five, inside the 7-calendar-day clock for a SUSAR.
- It is serious and drug-related, but the current brochure already lists it at that severity, so it is not a SUSAR.
- Three SUSARs of the same hepatic injury in six weeks forced a brochure update and a protocol amendment.
What is SUSAR (Suspected Unexpected Serious Adverse Reaction)?
SUSAR is a serious adverse reaction observed in a clinical trial that is both suspected to be caused by the investigational drug and not already described in the current investigator brochure, triggering expedited regulatory reporting.
SUSAR reporting exists because during an ongoing trial nobody yet knows the drug's full risk profile. Regulators and treating investigators need the events that contradict the current risk picture within days, not in an annual summary. A SUSAR isolates exactly those events: serious, plausibly caused by the investigational product, and absent from the risk information already circulating to sites.
A SUSAR covers only trial events that clear three filters at once: serious under FDA's criteria, suspected of a causal link to the investigational product, and unexpected against the current investigator brochure. Serious events the brochure already describes are out of scope. Unexpected but non-serious events are out of scope. Safety reporting for an approved marketed product is not made under the IND safety reporting rule at all.
A SUSAR moves through three hands in practice. The site reports the serious adverse event to the sponsor immediately, with its causality assessment. Sponsor pharmacovigilance runs the expectedness check against the brochure version current that day and codes the case. Regulatory then files the IND safety report inside the 7 or 15 calendar day clock and pushes the same information out to every participating investigator.
Not to be confused with
- Serious Adverse Event (SAE)
- an SAE only has to meet the seriousness criteria. A SUSAR is the narrower subset of SAEs that is also suspected to be drug-caused and not already described in the investigator brochure. Most SAEs in a trial never become SUSARs.
- Adverse Event
- an adverse event is any untoward medical occurrence, drug-related or not. A SUSAR requires a reasonable possibility that the drug caused the event, so causality is the dividing line between the two.
- DSUR
- the DSUR is the annual aggregate safety report covering the whole development programme. A SUSAR is a single-case expedited report on a 7 or 15 calendar day clock. An aggregate report never satisfies the expedited clock.
- Investigator Brochure
- the investigator brochure is the reference document that decides expectedness, not a report. An event is unexpected only relative to whichever brochure version is current at the moment of assessment.
The obligations split between the site and the sponsor, and the split is where most timeline failures happen.
What you must do
- 1Report every serious adverse event to the sponsor immediately, whether or not it is considered drug related, including an assessment of whether there is a reasonable possibility that the drug caused the event (investigator)21 CFR 312.64(b)
- 2Test the event against the FDA seriousness criteria first: death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant incapacity, or a congenital anomaly (sponsor PV)21 CFR 312.32(a)
- 3Judge expectedness against the current investigator brochure by specificity and severity, not by the event term alone (sponsor PV)21 CFR 312.32(a)
- 4Notify FDA of a serious and unexpected suspected adverse reaction no later than 15 calendar days after the sponsor determines that the information qualifies for reporting (sponsor RA)21 CFR 312.32(c)(1)
- 5Notify FDA of an unexpected fatal or life-threatening suspected adverse reaction as soon as possible and no later than 7 calendar days after the sponsor's initial receipt of the information (sponsor RA)21 CFR 312.32(c)(2)
Common mistakes
Starting the clock at database entry instead of at awareness
The 7-day clock runs from the sponsor's initial receipt of the information and the 15-day clock from the determination that the information qualifies for reporting, not from the date the case is keyed into the safety database. A site or vendor that sits on a fatal case for four days has already spent more than half the window before pharmacovigilance sees it, and the reconstructed timeline is the first thing an inspector pulls.
Assessing expectedness against the wrong brochure version, or against the event term only
Expectedness turns on specificity and severity, not on whether a similar term appears somewhere in the brochure. A team that matches "hepatic injury" in a superseded brochure and stops there systematically under-reports severe cases that the brochure describes only as mild, and every one of those becomes a late report once the assessment is redone.
Treating the site's "not related" call as the end of the matter
21 CFR 312.64(b) puts the immediate report and the causality assessment on the investigator, but 21 CFR 312.32 puts the duty to notify FDA on the sponsor. A sponsor that files nothing because the site called the event unrelated still owns the reporting failure, and the exposure is the whole IND, not the single case.
When This Matters
- The fatal case went to FDA on day five, inside the 7-calendar-day clock for a SUSAR.
- It is serious and drug-related, but the current brochure already lists it at that severity, so it is not a SUSAR.
- Three SUSARs of the same hepatic injury in six weeks forced a brochure update and a protocol amendment.
Frequently Asked Questions
A SUSAR must be serious, suspected to be caused by the investigational drug, and unexpected against the current investigator brochure. FDA defines serious as death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant incapacity, or a congenital anomaly. Miss any one criterion and the event is not expedited-reportable as a SUSAR.
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