The EMA has recently opened a public consultation on the draft Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 (Clinical Trials Regulation – CTR) or the clinical trial protocol.

Article 52 of the CTR introduces a requirement for the sponsor to notify the member states concerned (MSC) of all serious breaches of the CTR or of the clinical trial protocol (the version applicable at the time of the breach). The CTR defines a serious breach as a “breach likely to affect to a significant degree the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial”. The sponsor must notify the breach through the EU portal established by the CTR (Article 80) without undue delay and within seven days of becoming aware of the breach.

Directive 2001/20/EC, which currently sets out the general regulatory framework for clinical trials in the EU, does not contain an explicit obligation for sponsors to notify breaches of the clinical trial rules or protocol. However, several EU member states have introduced similar obligations by means of national law or guidance. For example, UK law requires the sponsor of a clinical trial to notify the licensing authority in writing of any serious breach of good clinical practice or the trial protocol within 7 days of becoming aware of the breach. Under French law, clinical trial sponsors and investigators must take urgent and appropriate safety measures when a “new fact” related to a trial or trial product may affect the safety of the trial subjects.

By means of its Article 52, the CTR establishes a harmonised notification obligation at EU level that will apply with respect to all clinical trials conducted in the EU. Although this may result in more stringent notification requirements in some EU member states, overall it will reduce regulatory uncertainty for clinical trial sponsors.

The scope of the draft EMA Guideline is triple and includes:

  • Outlining the practical arrangements for the notification of serious breaches;
  • Providing advice on what should and what should not be classified as a serious breach as well as what must be reported;
  • Outlining possible actions that may be taken by the EU/EEA MSC in response to notifications of serious breaches.

In particular, the Guideline elaborates in practical terms on the requirement to notify serious breaches, in terms of who should notify (sponsor, authorised representative, CRO), when and how the notification should be made, the responsibilities of the parties involved in the notification and what needs to be reported. The Guideline especially provides practical insights on what constitutes a serious breach by listing some examples (Appendix I) and on relevant points to consider for the assessment of a breach (Appendix II).