Clinical Trials Expedited Reporting to FDA

Adverse drug reaction reporting / safety reporting from clinical trials is a key component for drug regulatory authorities to take decision as whether to approve or deny market authorisation of the investigational medication and it is used to establish a drug’s safety profile in humans.

Expedited reporting refers to an individual case safety report (ICSR) which involve a serious and unexpected event that is considered to be related to the use of investigational drug.

The purpose of expedited reporting is to make regulators, investigators and others involved in trials aware of new, important information on serious adverse reactions. There for expedited reports generally involve events which are previously not observed/not documents.

IND Safety Reporting:

The sponsor must report to FDA and all participating investigators in an IND safety report of potential serious risk from clinical trials or any other sources as soon as possible. In each IND safety report, the sponsor must identify all IND safety reports previously submitted to FDA concerning a similar suspected adverse reaction, and must analyze the significance of the suspected adverse reaction in light of previous, similar reports or any other relevant information.

1. Serious and unexpected suspected adverse reactions (SUSAR) such as;
   • a. A single occurrence of an event that is uncommon and known to be strongly associated with the drug exposure
   • b. One or more occurrences of an event that is not commonly associated with drug exposure but is otherwise uncommon in the population exposed to the drug
   • c. An aggregate analysis of specific events observed in a clinical trials that indicated those events occur more frequently in the drug treatment group than in concurrent or historical control group.

1. The sponsor must promptly review all information relevant to the safety of investigational drug from foreign or domestic sources, including information from any clinical, pre-clinical, epidemiological, investigational, invitro studies, literature as well as reports from foreign regulatory authorities and reports of foreign commercial marketing experiences for drugs that are not marketed in US.
2. The sponsor must report any clinical importance increase in the rate of a serious suspected adverse reaction that listed in Investigator broucher.
3. Study endpoints (e.g., mortality or major morbidity) must be reported to FDA by the sponsor as described in the protocol. However, if a serious and unexpected adverse event occurs for which there is evidence suggesting a causal relationship between the drug and the event (e.g., death from anaphylaxis), the event must be reported as a serious and unexpected suspected adverse reaction even if it is a component of the study endpoint (e.g., all-cause mortality).

IND Expedited Reports Submission timelines:

• Fatal or LIfe-threatening SUSAR: The sponsor must notify FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than 7 calendar days after the sponsor’s initial receipt of the information.
• Reports of Other SUSAR and serious ADRs: The sponsor must report such suspected adverse reaction in an IND safety report as soon as possible, but in no case later than 15 calendar days.
• Relevant follow-up information to an IND safety report must be submitted as soon as the information is available and must be identified as such, i.e., “Followup IND Safety Report.”
• IND exempt Bioequivalence/bioavilability studies – Must report all serious Adverse events with in 15 calendar days.
• If FDA requests any additional data or information: Submit to FDA as soon as possible but no later that 15 calendar date after receiving the request.

References:

• FDA – 21CFR312.32 – Investigational New Drug Application (IND)
• ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
• IND Application Reporting: Safety Reports