An important identified risk, important potential risk or missing information.

It is noted that the ICH definition of safety concern is: an important identified risk, important potential risk or important missing information, i.e. includes the qualifier “important” in relation to missing information (see GVP Annex IV, ICH-E2C(R2) Guideline). The ICH-E2E Guideline (see GVP Annex IV) uses the terms safety issue and safety concern interchangeably with the same definition for safety concern as defined in the ICH-E2C(R2) Guideline.

See also Important identified risk and Important potential risk, Missing information