2. Adverse Event (AE) versus Adverse Reaction (adverse drug reaction ADR) – the distinction

A response to a medicinal product which is noxious and unintended [DIR 2001/83/EC Art 1(11)]1.

Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility (see GVP Annex IV, ICH-E2A Guideline).

An adverse reaction, in contrast to an adverse event, is characterised by the fact that a causal relationship between a medicinal product and an occurrence is suspected.

For regulatory reporting purposes, if an event is spontaneously reported by a healthcare professional or consumer as primary source, even if the relationship is unknown or unstated, it meets the definition of an adverse reaction (see GVP Annex IV, ICH-E2D) and is therefore considered a suspected adverse reaction, since it conveys the suspicions of the primary sources, unless the primary source specifically state that they believe the event to be unrelated or that a causal relationship can be excluded.

Adverse reactions may arise from:

• Use of the product within the terms of the marketing authorisation or from occupational exposure [DIR 2001/83/EC Art 101(1)].


• Use outside the marketing authorisation which includes
• off- label use, (use for indications that are not approved)
• overdose,
• misuse,
• abuse
• medication errors. [An unintended failure in the drug treatment process that leads to, or has the potential to lead to, harm to the patient (see EMA-PRAC Good Practice Guide on Recording, Coding, Reporting and Assessment of Medication Errors, October 2015).

• Interactions with other medicines (drug-drug-interactions).

• Product technical or quality issues, such as a missing tablet or damaged product.

• Using falsified medicines [Any medicinal product with a false representation of (a) its identity, including its packaging and labelling, its name or its composition as regards any of the ingredients including excipients and the strength of those ingredients; (b) its source, including its manufacturer, its country of manufacturing, its country of origin or its marketing authorisation holder; or (c) its history, including the records and documents relating to the distribution channels used [DIR 2001/83/EC Art 1(33)]].