XV.C.1. Coordination of safety announcements in the EU

In the EU, patients and healthcare professionals increasingly look at competent authorities as providers of important information on medicines. For safety communication to be effective, adequate coordination and cooperation is required within the EU regulatory network3 . A good level of coordination of safety communication is of particular importance so that healthcare professionals and patients receive consistent information on regulatory decisions in the EU.

When issuing safety announcements, competent authorities may make use of the different tools and channels described in XV.B.5.. Prior to the publication of a safety announcement, the Member States, the Agency or the European Commission shall inform each other not less than 24 hours in advance, unless urgent public announcements are required for the protection of public health [DIR Art 106a(2)].

For active substances contained in medicinal products authorised in more than one Member State, the Agency shall be responsible for the coordination between national competent authorities of safety announcements and shall provide timetables for the information being made public [DIR Art 106a(3)].

For practical reasons, not all safety information made public by a Member State or the Agency will be subject to systematic coordination. Only safety announcements that relate to the following and that pertain to active substances contained in medicinal products authorised in more than one Member State require coordination within the EU regulatory network:

• the suspension, withdrawal or revocation of a marketing authorisation due to changes to its riskbenefit balance;
• the start or finalisation of an EU referral procedure for safety reasons;
• restriction of indication or treatment population or the addition of a new contraindication;
• dissemination of a DHPC (see XV.C.2.1.);
• other emerging safety concerns judged by a national competent authority or the Agency to be likely to give rise to public or media interest in more than one Member State (e.g. a publication of important safety findings in a (scientific) journal, safety-related regulatory action taken in a Member State or in a country outside the EU).

XV.C.1.1. Process for exchange and coordination of safety announcements

A competent authority of a Member State or the Agency shall inform the EU regulatory network prior to the publication of a safety announcement that pertains to active substances contained in medicinal products authorised in more than one Member State and that refer to any of the situations identified in XV.C.1.. It shall include a timetable for the information being made public [DIR Art 106a(3)]. Whenever possible the safety announcement shall be sent to the network under embargo not less than 24 hours prior to the publication [DIR Art 106a(2)], in order to allow the members of the EU regulatory network to prepare or plan their own communication, if necessary. Under the coordination of the Agency, the Member States shall make all reasonable efforts to agree on a common message in relation to the safety of the medicinal product concerned and the timetables for the distribution [DIR Art 106a(3)].

The Agency, together with the relevant Member States, should decide for each case, on the basis of the public health relevance and urgency of the safety concern, the population and number of Members States affected and the potential for media attention, whether further communication action in addition to the dissemination of the safety announcement is needed, such as:

• the preparation of lines-to-take (see XV.B.5.7.) for dissemination to the EU regulatory network. The lines-to-take document should help the EU regulatory network to respond to any request for information which may follow the publication of the safety announcement;
• the preparation of an Agency safety announcement in addition to that of the Member State, which should also be disseminated under embargo to the EU regulatory network together with a timetable for its publication.

The Agency should prepare lines-to-take documents and any Agency safety announcement together with the Member States who originated the process and the PRAC Lead Member State or the PRAC Rapporteur, as appropriate. The PRAC, as well as the CHMP or CMDh, should also be consulted as necessary.

Coordination of safety announcements should be done in cooperation with the concerned marketing authorisation holder(s). Whenever possible, the Agency and the competent authorities in the Member States should provide any safety announcement prior to its publication to the concerned marketing authorisation holder(s), together with the timetable for the information being made public. Any information of a personal or commercially confidential nature shall be deleted unless its public disclosure is necessary for the protection of public health [DIR Art 106a(4)].

The exchange and coordination of safety announcements within the EU regulatory network should make use of the EU Early Notification System (ENS). The ENS includes the Heads of Medicines Agencies (HMA), the members of the PRAC, CHMP, PDCO, CMDh, the operational contact points for safety announcements at the competent authority in the Member States, the European Commission and the Agency. Operational contact points should ensure that any information exchanged via the system reaches in a timely manner the relevant staff within each competent authority, including relevant staff working within the communications departments.

Safety announcements from the EU regulatory network should be shared with international partners, subject to embargo and any specific confidentiality arrangements in place.

As a complement to the coordination of safety announcements within the EU regulatory network, competent authorities in Member States and the Agency should interact with concerned stakeholders in the EU (mainly patients’ and healthcare professionals’ organisations), who can play a key role in reviewing and disseminating information to the end users (patients and healthcare professionals). It is recommended that national competent authorities and the Agency keep up-to-date contact details of relevant patients’ and healthcare professionals’ organisations.

XV.C.1.2. Exchange of safety information produced by third parties

There are situations where new safety information is to be published or has been published by a party other than a competent authority of a Member State or the Agency (e.g. scientific journals, learned societies). Competent authorities should bring to the attention of the EU regulatory network any such safety information that they become aware of, together with the timing of the publication if known. Where necessary and after evaluation of the information, the Agency should prepare and disseminate a lines-to-take document or an Agency safety announcement to address the information from the third party (see XV.C.1.1.).

In the context of collaboration with authorities outside the EU, competent authorities may become aware of safety announcements to be published by authorities outside the EU. In these cases the Agency should, as necessary, prepare and disseminate lines-to-take or safety announcements within the EU regulatory network. In all cases, the terms of relevant confidentiality agreements with non-EU regulatory authorities and the embargoes on the information received should be respected.

XV.C.1.3. Requirements for the marketing authorisation holder in the EU

As soon as a marketing authorisation holder in the EU intends to make a public announcement relating to information on pharmacovigilance concerns in relation to the use of a medicinal product, and in any event at the same time or before the public announcement is made, the marketing authorisation holder shall be required to inform the competent authorities in the Member States, the Agency and the European Commission [DIR Art 106a]. This should apply to announcements intended for the EU as well as outside the EU (when they concern medicinal products authorised in the EU or those for which an opinion under REG Article 58 has been given). Informing the competent authorities at the same time as the public (i.e. without advance notice to the competent authorities) should only occur exceptionally and under justified grounds. Whenever possible, the information should be provided under embargo at least 24 hours prior to its publication.

The marketing authorisation holder shall ensure that information to the public is presented objectively and is not misleading [DIR Art 106a].

Whenever a marketing authorisation holder becomes aware that a third party (see XV.C.1.2.) intends to issue communications that could potentially impact the risk-benefit balance of a medicinal product authorised in the EU, the marketing authorisation holder should inform the relevant competent authorities in Member States and the Agency and make every effort to share the content of the communications with the relevant competent authorities.

XV.C.1.4. Consideration for third parties

Third parties (e.g. editors of scientific journals, learned societies, patients’ organisations) are encouraged to inform the Agency and the competent authorities in the Member States of any relevant new information on the safety of medicines authorised in the EU and, if publication is planned, to share the information ahead of publication.

XV.C.1.5. Languages and translations

Consistent messages should reach the public across the EU in a timely manner and in the official languages of the Member States as specified by the Member States where the medicinal product is placed on the market.

For the purpose of coordination, the Agency shall use English to inform the EU regulatory network of any safety announcement. When informing the Agency, the competent authorities in the Member States are encouraged to provide English translations of their safety announcements for the purpose of initiating the coordination process within the network. In the absence of a full text translation, an English summary should be provided.