**12. Appendix 1**

ICH Guideline on E2D post-approval drug safety defined an adverse drug reaction (ADR) and a serious adverse drug reactions (SADR) as follows:

An adverse drug reaction, as established by regional regulations, guidance and practices, is concern noxious and unintended responses to a medicinal product. The phrase "responses to a medicinal product" means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility (refer to the ICH E2A guideline). A reaction, in contrast to an event, is characterized by the fact that a causal relationship between the drug and the occurrence is suspected. For regulatory reporting purposes, if an event is spontaneously reported, even if the relationship is unknown or unstated, it meets the definition of an adverse drug reaction".

Serious adverse event /ADR. In accordance with ICH E2A guideline, a serious adverse event or reaction is any untoward medical occurrence that at any dose:


Medical and scientific judgment should be exercised in deciding whether other situations should be considered serious, such as important medical events that might not be immediately life-threatening or result in death or hospitalization but might jeopardize the patient or might require intervention to prevent one of the other outcomes listed in the definition above. Examples of such events are intensive treatment in a emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or development of drug dependency or drug abuse.
