• In the pre-approval clinical experience with a new investigational product or its new usages (particularly as the therapeutic dose(s) may not be established): unfavourable and unintended responses, such as a sign (e.g., laboratory results), symptom or disease related to any dose of a medicinal product where a causal relationship between a medicinal product and an adverse event is a reasonable possibility. The level of certainty about the relatedness of the adverse drug reaction to an investigational product will vary. If the ADR is suspected to be medicinal product- related with a high level of certainty, it should be included in the reference safety information (RSI) and/or the Investigator’s Brochure (IB).
• For marketed medicinal products: a response to a drug that is noxious and unintended and that occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of diseases or for modification of physiological function.
(See ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.)