New legal EudraVigilance obligations as of 22 November 2017

As of 22 November 2017 new obligations in respect of signal management and reporting of suspected adverse reactions (ADRs) will apply to both marketing authorisation holders and national competent authorities. With the new EudraVigilance system fulfilling the functional requirements the legal transition period will end in November.

Although the pharmacovigilance legislation has already entered into force in July 2012, the transition period for EudraVigilance is still applicable. Certain legal obligations may only come into effect after adjustment of the EudraVigilance system. Based on an independent audit, the Pharmacovigilance Risk Assessment Committee (PRAC) and the EMA Management Board have confirmed that the new EudraVigilance system complies with the functional requirements that were agreed for this purpose.

Signal management

Marketing authorisation holders shall monitor the data available in EudraVigilance to the extent that they have access to the database to determine whether there are new risks or whether risks have changed for their medicinal product(s) and active substances for which they hold a marketing authorisation (see also under Art 57 database). Validated signals should be reported to the competent authorities. Detailed instructions for the steps in this signal management process will be provided in the revised version of Guideline on good pharmacovigilance practices (GVP) Module IX – Signal Management that will be published by the EMA later this year.

ADR reports

The main changes to electronic reporting requirements for marketing authorisation holders  are:

  • All reports of suspected adverse drug reactions requiring submission according to Regulation (EC) No 726/2004 and/or Directive 2001/83/EC should be sent to EudraVigilance directly. This obligation was already in place in The Netherlands, but will now apply in all EU Member States. Reports from marketing authorisation holders will be automatically re-routed to the Member State where the reaction occurred.  Dutch reports will be forwarded to Lareb.
  • Marketing authorisation holders will no longer receive ADR reports directly from EU national competent authorities, but will be provided access to these reports via EudraVigilance. The Netherlands Pharmacovigilance Centre Lareb maintains the Dutch spontaneous reporting system on behalf of the Medicines Evaluation Board (MEB). Marketing authorisation holders will no longer receive regulatory reports from  Lareb directly, but will use the download functionality in EudraVigilance to retrieve them.
  • Non-serious ADR reports from the European Economic area should be submitted to EudraVigilance within 90 days. Marketing authorisation holders will have standard access in EudraVigilance to both serious as well as non-serious reports, including the Lareb reports.
  • From 22 November 2017 onwards, the revised Guideline on good pharmacovigilance practices Module VI - Management and reporting of adverse reactions to medicinal products should be adhered to. This  document is expected to be published on the EMA website this summer.

ICH E2B(R3) format

From 22 November 2017 onwards, the new ICH E2B(R3) format can be used for  the electronic exchange of ADRs. This will improve the data quality and the new format will eventually replace the current ICH E2B (R2) format.  Downloads of ADR reports from the  EudraVigilance database follow the new format and also the Lareb database is adapted to ICH E2B (R3). This has significant consequences for the content of the ADRs. For example, in E2B(R3), seriousness is reported at event level rather than at case level in E2B(R2).

Art 57 database

In order to comply with their pharmacovigilance obligations, it is important that marketing authorisation holders have the right access to EudraVigilance. This access is granted on the basis of the product data supplied by the EMA in accordance with Article 57 (2) of Regulation (EU) No. 726/2004. It is therefore essential that marketing authorisation holders ensure that data in the Art 57 database is always complete and up to date.

More information and training

With the end of the legal transitional period for EudraVigilance approaching, all stakeholders (marketing authorisation holders, EMA, national competent authorities and pharmacovigilance centers) must prepare for their new obligations. The necessary changes not only require adjustments to IT systems, but also to business processes. To support these changes, the EMA website offers useful information and training opportunities. The website is regularly updated, for example, if new guidelines or training opportunities are available.