Under which condition must the sponsor submit an IND Safety Report to the FDA?

The requirement for submitting an IND Safety Report to the FDA hinges on the presence of a "reasonable possibility" that the drug in question caused an adverse event. This principle is grounded in the need for vigilance in drug safety, allowing for prompt reporting of potential drug-related risks to ensure patient safety and ongoing evaluation of the drug's safety profile.

When there is a reasonable possibility that the drug caused an adverse event, it triggers the obligation to report, as such occurrences warrant further investigation and monitoring by regulatory authorities. This is essential for maintaining transparency and accountability in clinical research and can lead to actions such as additional studies or modifications in treatment protocols.

In contrast, while serious, unexpected events and those that may recur are significant, they do not automatically necessitate an IND Safety Report unless there is reasonable causality linked to the drug. Similarly, an event listed in the Investigator's Brochure, even if life-threatening, may not require reporting if it has been previously documented and understood within the context of the drug's safety profile. Thus, "reasonable possibility" is the key criterion for initiating an IND Safety Report submission.