A safety signal is information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. Signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. The European Medicines Agency manages safety signals together with the European Economic Area (EEA) Member States and marketing-authorisation holders (MAHs).
The presence of a safety signal does not mean that a medicine has caused the reported adverse event. The adverse event could be a symptom of another illness or caused by another medicine taken by the patient. The evaluation of safety signals is required to establish whether or not there is a causal relationship between the medicine and the reported adverse event.
The evaluation of safety signals is part of routine pharmacovigilance and is essential to ensuring that regulatory authorities have the most up-to-date information on a medicine’s benefits and risks.
The assessment of safety signals by the PRAC is a deliverable of the 2010 pharmacovigilance legislation.
Designated medical events (updated)
EMA has developed a list of designated medical events containing medical conditions that are inherently serious and often medicine-related:
It does not address product specific issues or medical conditions with high prevalence in the general population.
The list contains Medical Dictionary for Regulatory Activities (MedDRA) terms and serves as a safety net in signal detection. EMA and Member States use it to focus on reports of suspected adverse reactions that deserve special attention, irrespective of statistical criteria used to prioritise safety reviews.
The designated medical event list is one of the tools the European medicines regulatory network uses and is not intended as a comprehensive list of terms for signal detection activities.
EMA has published the list to ensure its approach is transparent. It is subject to review in light of further experience with its use.
Recommendations from the Pharmacovigilance Risk Assessment Committee
The Agency's Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for the analysis, prioritsation and assessment of validated signals, resulting in a PRAC recommendation. These recommendations can cover any medicine with a valid marketing authorisation in the EU, including nationally and centrally authorised medicines.
In cases where a causal relationship is confirmed or considered likely, the MAHs concerned may be asked to provide further information. Regulatory action may also be necessary; this usually takes the form of an update of the summary of product characteristics (SmPC) and the package leaflet.
- PRAC recommendations to supply additional information are actionable directly by the MAHs concerned.
- PRAC recommendations for regulatory action concerning centrally authorised medicines are submitted to the Committee for Medicinal Products for Human Use (CHMP) for endorsement.
- PRAC recommendations for regulatory action concerning nationally authorised medicines are submitted to the Coordination Group for Decentralised and Mutual Recognition Procedures - Human (CMDh).
After this, MAHs are expected to take action according to the recommendations.
The Agency publishes PRAC recommendations every month under PRAC recommendations on safety signals. Marketing-authorisation holders should monitor the information on this page regularly to keep informed about the PRAC recommendations concerning their products.
As of January 2015, the Agency publishes translations of recommendations for the updating of product information into all official EU languages plus Norwegian and Icelandic. These translations are quality reviewed by the national regulatory authorities. Marketing-authorisation holders can use these translations to update their product information. The Agency expects this initiative to accelerate the updating of product information and ensure consistency across different countries, thereby helping to ensure that clear information is provided to patients about their medicines.
For more information on how signals are managed and the responsibilities of MAHs, see:
- Guideline on good pharmacovigilance practices: Module IX - Signal management
- Questions and answers on signal management
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