The classification of adverse events as expected or unexpected determines the urgency and nature of regulatory reporting requirements and influences how events are characterized in safety communications. An expected adverse event is one whose nature, severity, specificity, and outcome are consistent with the information contained in the relevant reference document, typically the Investigator's Brochure for investigational products or the approved product labeling for marketed products. An unexpected adverse event deviates from this reference in a clinically meaningful way.

The reference safety information represents the current understanding of a product's safety profile and serves as the benchmark for expectedness determinations. For investigational products, the Investigator's Brochure should include all known adverse reactions based on preclinical studies and prior clinical experience. This information must be kept current; new findings that change the expected safety profile require IB updates. When the reference document is ambiguous or when an event occurs with substantially different severity, specificity, or frequency than documented, the event should generally be treated as unexpected.

The expectedness classification specifically applies to adverse reactions, not to all adverse events. An event that is not suspected to be related to the investigational product does not require expectedness assessment because it is not an adverse reaction. However, for serious adverse events suspected to be related to the investigational product, the expectedness determination is critical: unexpected serious adverse reactions qualify as SUSARs and trigger expedited reporting requirements. Proper training on expectedness assessment is therefore essential for all personnel involved in safety evaluation and reporting.