IND application sponsors are required to notify FDA in a written safety report of:
any adverse experience associated with the use of the drug that is both serious and unexpected or
any findings from tests in laboratory animals that suggest a significant risk for human subjects including reports of mutagenicity, teratogenicity, and carcinogenicity.
Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Suspected adverse reaction means any adverse event for which there is a reasonable possibility that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable possibility’ means there is evidence to suggest a causal relationship between the drug and the adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality than an adverse reaction.
Adverse reaction means any adverse event caused by a drug. Adverse reactions are a subset of all suspected adverse reactions where there is reason to conclude that the drug caused the event.
Unexpected adverse event or suspected adverse reaction refers to an event or reaction that is not listed in the investigator’s brochure or is not listed at the specificity or severity that has been observed; or, if an investigator’s brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the current IND application.
Serious adverse event or suspected adverse reaction refers to an event or reaction that, in the view of either the investigator or sponsor, results in any of the following outcomes:
a life-threatening adverse event,
in-patient hospitalization or prolongation of existing hospitalization,
a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or
a congenital anomaly or birth defect.
Life-threatening adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a more severe form, might have caused death.
Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or research subject and may require medical or surgical intervention to prevent one of the outcomes listed as serious.
Mandatory Safety Reporting
- Initial reporting: IND application sponsor must report any suspected adverse reaction or adverse reaction to study treatment that is both serious and unexpected.
Unexpected serious suspected adverse reactions and observations from animal studies suggesting significant risk to human subjects must be reported to FDA as soon as possible but no later than within 15 calendar days following the sponsor’s initial receipt of the information.
Unexpected fatal or life-threatening suspected adverse reactions represent especially important safety information and 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.
- Follow-up reporting: Any relevant additional information obtained by the sponsor that pertains to a previously submitted IND safety report must be submitted as a Follow-up IND Safety Report. Such report should be submitted without delay, as soon as the information is available but no later than 15 calendar days after the sponsor receives the information.
All IND safety reports must be submitted on Form 3500A (PDF - 1MB) (if from clinical trials) or in a narrative format (if from animal or epidemiological studies) and be accompanied by Form 1571 (PDF - 830KB). The type of report (initial or follow-up) should be checked in the respective boxes on Forms 3500A and 1571. See Instructions for completing Form 3500A.
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.
The report must be submitted to an appropriate Review division that has the responsibility to review the IND application under which the safety report is submitted. FDA recommends that sponsors submit safety reports electronically. Other means of rapid communication to the respective review division’s Regulatory Project Manager (e.g., telephone, facsimile transmission, email) may also be used.
For detailed explanation of the above definitions, requirements, and procedures related to IND application safety reports and the responsibilities of IND applications sponsors with regard to such reporting, refer to Guidance for Industry and Investigators: Safety Reporting Requirements for INDs and BA/BE Studies (PDF - 227KB)
For additional information on safety reporting refer to the 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.