Reference:EU EMA/698382/2021 - Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol 2021 4

Document information
Reference	EU EMA/698382/2021 - Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol 2021
Validity area	EU
Scope(s)	G
Document name	EMA/698382/2021 - Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol
Version / Revision	2021
Status	Current
Document type	Official guideline
Language(s)	EN
Description	EMA/698382/2021 Quality and Safety of Medicines Department Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol
Official source	Official link
Restricted access	No
Submitted by	Florian Adragna
Contributors

Reference Details
Module	Module 4 — Unit 4.1.4
Scope	G
Document part	4
Language	EN
Original entry by	Florian Adragna
Contributors
Tags	Serious breach, Reporting timeline, CTIS, Safety

Content

4. Clarification on reporting requirements • 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 If for example the serious breach resulted from flaws in the design of the clinical trial, the CTA may need to be withdrawn.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.