V.A.1. Terminology

The definitions from GVP Annex I apply also for the purpose of this GVP Module. However, the RMP should focus on those risks that are relevant for the risk management activities for the authorised medicinal product.

From the identified risks of the medicinal product, the RMP should address only the risks that are undesirable clinical outcomes and for which there is sufficient scientific evidence that they are caused by the medicinal product. Reports of adverse reactions may be derived from multiple sources such as non-clinical findings confirmed by clinical data, clinical trials, epidemiological studies, and spontaneous data sources, including published literature. They may be linked to situations such as off label use, medication errors or drug interactions. Not all reported adverse reactions are necessarily considered a relevant risk of the product in a given therapeutic context.

From the potential risks of the medicinal product, the RMP should address only the risks that are undesirable clinical outcomes and for which there is scientific evidence to suspect the possibility of a causal relationship with the medicinal product, but where there is currently insufficient evidence to conclude that this association is causal.

The RMP should focus on the important identified risks that are likely to have an impact on the riskbenefit balance of the product. An important identified risk to be included in the RMP would usually warrant:

• Further evaluation as part of the pharmacovigilance plan (e.g. to investigate frequency, severity, seriousness and outcome of this risk under normal conditions of use, which populations are particularly at risk);
• Risk minimisation activities: product information advising on specific clinical actions to be taken to minimise the risk (see V.B.8.), or additional risk minimisation activities.

The important potential risks to be included in the RMP are those important potential risks that, when further characterised and if confirmed, would have an impact on the risk-benefit balance of the medicinal product. Where there is a scientific rationale that an adverse clinical outcome might be associated with off-label use, use in populations not studied, or resulting from the long-term use of the product, the adverse reaction should be considered a potential risk, and if deemed important, should be included in the list of safety concerns as an important potential risk. Important potential risks included in the RMP would usually require further evaluation as part of the pharmacovigilance plan.

Missing information relevant to the risk management planning refers to gaps in knowledge about the safety of a medicinal product for certain anticipated utilisation (e.g. long-term use) or for use in particular patient populations, for which there is insufficient knowledge to determine whether the safety profile differs from that characterised so far. The absence of data itself (e.g. exclusion of a population from clinical studies) does not automatically constitute a safety concern. Instead, the risk management planning should focus on situations that might differ from the known safety profile. A scientific rationale is needed for the inclusion of that population as missing information in the RMP.