IX.C.2. Emerging safety issues

When the marketing authorisation holder in the EU becomes aware of an emerging safety issue from any source (see IX.A.1.1.), they should notify it in writing to the competent authority(ies) of Member State(s) where the medicinal product is authorised (11) and to the Agency to the mailbox “P-PVemerging-safety-issue@ema.europa.eu”. This should be done as soon as possible and no later than 3 working days after establishing that a validated signal or a safety issue from any source meets the definition of an emerging safety issue.

This is in addition to the ICSR submission requirements detailed in GVP Module VI, when the emerging safety issue refers to a single case of suspected adverse reactions.

When notifying an emerging safety issue, the marketing authorisation holder should describe the safety issue, the source(s) of information, any planned or taken actions with timelines, and should provide any relevant documentation available at the time of initial notification. Any further information relevant to the issue should be provided to the Agency and relevant national competent authorities as soon as it becomes available.

Upon being notified of an emerging safety issue, the national competent authorities and/or the Agency as appropriate should promptly assess the urgency and potential impact of the issue and agree on appropriate next steps and the potential regulatory procedure to address the matter raised. This may involve the consultation of the Incident Review Network, if warranted (see European Union Regulatory Incident Management Plan for Medicines for Human Use (12)).

For signals notified as emerging safety issues, a standalone signal notification (see IX.C.4.3.) is not required, unless the national competent authorities and/or the Agency consider it appropriate to handle the issue within the EU signal management process, in which case the marketing authorisation holder may be requested to complete and provide a standalone signal notification form.

The marketing authorisation holder should collaborate with the Agency and national competent authorities in the assessment of the emerging safety issue [DIR Art 23(4) and REG Art 16(3a)].

In order to ensure its effectiveness, the system should not be saturated by the transmission of less urgent information. Marketing authorisation holders should only communicate as emerging safety issues those safety concerns which meet the definition provided in IX.A.1.1., i.e. whose urgency and seriousness cannot permit any delay in handling.

Should the marketing authorisation holder decide as a result of the emerging safety issue to take any of the following actions: temporary or permanent cessation or suspension of marketing of a medicinal product, withdrawal of a medicinal product from the market, request for the withdrawal of a marketing authorisation or non-application for the renewal of a marketing authorisation, the notification of such action should be done in parallel to the Agency (withdrawnproducts@ema.europa.eu) and/or competent authority(ies) of the Member State(s) concerned in accordance with the requirements set out in Articles 13(4) and 14b of Regulation (EC) No 726/2004 and Articles 23a and 123(2) of Directive 2001/83/EC.

New safety information related to quality defects or suspected falsified medicinal products which might influence the evaluation of the benefits and risks of the medicinal product and which may give rise to an abnormal restriction in supply should not be notified as an emerging safety issue. These should be notified to the Agency (qdefect@ema.europa.eu) and/or to relevant competent authority(ies) of Member State(s) according to national requirements in accordance with Article 16(2) of Regulation (EC) No 726/2004 and Article 23(2) of Directive 2001/83/EC. More detailed guidance on notifications of product withdrawals and quality defects is available on the Agency’s website.