4. Clarification on reporting requirements: Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol

• Serious breaches which occurred outside the EU/EEA while the application for a clinical trial authorisation (CTA) is submitted but not yet authorised in the EU/EEA territory and the serious breach has an impact on the safety and/or the rights of a trial participant or reliability and robustness of data filed in an application dossier, the sponsor should address the concerns during the evaluation of the CTA. If this is not feasible or not satisfactory, this might lead to the withdrawal of the application via CTIS. If for example the serious breach resulted from flaws in the design of the clinical trial, the CTA may need to be withdrawn

• Serious breaches of an EU/EEA authorised clinical trial occurring exclusively outside the EU/EEA that are likely to affect the safety and/or the rights of a trial participant or the reliability and robustness of the data generated in a clinical trial already authorised or being conducted in the EU/EEA territory, should be notified to the MSC via the CTIS under the reporting requirement of Article 52.

• When a sponsor notifies a serious breach, they should also consider if there are any other relevant notifications that need to be undertaken to comply with the Regulation (EU) No 536/2014, for example, requirements under Article 53 for unexpected events, or under Article 54 for urgent safety measures, or substantial modifications following a temporary halt or the decision to early terminate the trial under Article 37 and Article 38, respectively.

All relevant fields in CTIS, as presented in Appendix IIIa of this document must be completed. Unless the information reported in the CTIS fields is deemed exhaustive, the sponsor is encouraged to upload a report (using the “Add document” bottom) which should include all the details needed for AMSs/MSCs to assess the reported serious breach. To this purpose, the Appendix III b lists the topics which are expected to be covered. Sponsors should update the serious breach details in the CTIS fields and/or with a follow-up report if new information becomes available.

The sponsor should follow the below diagram and indicate which is the Member State most affected by the serious breach reported in the title of the notification and should report more details in Appendix III b.

© European Medicines Agency, 2021