FDA Requirements
Mandatory Safety Report Requirements
- IND application sponsors are required to notify FDA (and all participating investigators) in a written safety report of:
- Any adverse event (AE) associated with the use of the drug that is both serious and unexpected
- Any findings from other studies or animal testing that suggest a significant risk for human subjects, including reports of mutagenicity, teratogenicity, and carcinogenicity
- Initial report: Any suspected adverse reaction that is both serious and unexpected must be reported to FDA within 15 calendar days of the Sponsor-Investigator's initial receipt of the information, otherwise referred to as a Suspected Unexpected Serious Adverse Reaction (SUSAR). Unexpected fatal or life-threatening SUSARs must be reported to FDA as soon as possible but no later than 7 calendar days following the sponsor's initial receipt of the information.
- Serious Adverse Drug Event - Any adverse drug event occurring at any dose that results in any of the following outcomes:
- Death
- A life-threatening adverse drug event
- Inpatient hospitalization or prolongation of existing hospitalization
- A persistent or significant disability/incapacity
- Or a congenital anomaly or birth defect
- Unexpected Adverse Drug Event - Any event that is not listed in the current investigator brochure (IB) or in which the specificity or severity of which is not consistent with the IB or package insert;
- Or, if an IB is not required or available, the specificity or severity of which is not consistent with the risk information described in the general investigational plan or elsewhere in the application.
- Note: “expected” does not include events anticipated based on pharmacological properties (not theoretical expectedness)
- Serious Adverse Drug Event - Any adverse drug event occurring at any dose that results in any of the following outcomes:
- Follow-up report: Any relevant additional information related to a previously submitted IND safety report must be submitted without delay, no later than 15 calendar days after the Sponsor-Investigator receives the information.
Submitting IND Safety Reports
All IND safety reports must be submitted:
- On a Form 3500A (if from clinical trials). See Instructions for completing Form 3500A
- Accompanied by FDA Form 1571 - Investigational New Drug Application (IND).
- Optional UCSF template: IND Safety Report Cover Letter
- The type of report (initial or follow-up) should be checked in the respective boxes on Forms 3500A and 1571.
The submission must be identified as:
- “IND safety report” for 15-day reports, or
- “7-day IND safety report” for unexpected fatal or life-threatening suspected adverse reaction reports, or
- “Follow-up IND safety report” for follow-up information.
It is recommended that Sponsor-Investigators of IND applications submit Protocol and Information Amendments through the method used for submitting the initial IND. This will typically be electronically through the CDER NextGen Porta external site (opens in a new window) l or the FDA Electronic Submissions Gateway (ESG) external site (opens in a new window) , or as a hard-copy submission directly to the FDA.
Other means of rapid communication to the respective review division’s Regulatory Project Manager (e.g., telephone, facsimile transmission, email) may also be used.
FDA Guidance Documents
- Terms such as Adverse Event, Suspected Adverse Reaction, Adverse Reaction, Unexpected, Serious and Life-threatening are defined on this FDA page
- Investigator Responsibilities – Safety Reporting for Investigational Drugs and Devices
- Final Rule: Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans
- Sponsor Responsibilities—Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies Guidance for Industry