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 productrelated 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. ICH E6(R3)

A response to a medicinal product which is noxious and unintended [DIR 2001/83/EC Art 1(11)]. GVP Annex I - Definitions (Rev 5)