Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol

European Union (EU) pharmaceutical legislation known as the Clinical Trials Regulation entered into application on 31 January 2022. It aims to ensure the EU offers an attractive and favourable environment for carrying out clinical research on a large scale, with high standards of public transparency and safety for clinical trial participants. 

On 31 January 2022, the Regulation repealed the Clinical Trials Directive (EC) No. 2001/20/EC and national implementing legislation in the EU Member States, which regulated clinical trials in the EU until the Regulation's entry into application.

A transition period applies to clinical trial submission under the Regulation.

Table of Contents



1. Legal requirement

2. Scope

3. How to report a serious breach

4. Clarification on reporting requirements

5. Reporting serious breaches – Points to consider

6. Responsibilities of parties involved in the notification of a serious breach

7. General considerations for serious breaches

8. Possible actions taken by the EU/EEA Member States concerned (MSC)

9. References

Appendix I – Examples of serious breaches

Appendix II – Points to consider for sponsors in relation to the assessment of a breach

Appendix III a – Template form for reporting serious breaches

Appendix III b – Information to be submitted with a notification of a serious breach


Source: Medicines & Healthcare products Regulatory Agency, the UK.

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