6. Responsibilities of parties involved in the notification of a serious breach: Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol

6.1. Sponsor

There should be a formal process in place to cover the legislative requirements of serious breach notifications. The following key points are to be considered:

• suspected serious breaches should be promptly reported to the sponsor by investigators and by service providers in order for the sponsor to perform further investigation and assess if the breach qualifies as serious breach;
• the management of the serious breaches should be included in the quality system of the sponsor, as a specific standard operating procedure and/or written in the protocol;
• after receipt, an assessment of the breach should be performed in order to establish whether it is “serious” (i.e. assessment of deviations/violations, isolated/systematic incident(s), trial participant(s) harmed or put at risk, data credibility etc.);
• an investigation of the serious breach, including a root cause analysis (this can be ongoing at time of reporting) should be performed;
• corrective and preventive actions should be identified (this can be ongoing at the time of reporting);
• reporting of the serious breach through the CTIS should be done within 7 calendar days of the sponsor becoming aware of a serious breach; lack of an adequate system in place and/or failure to report serious breaches may result in findings during GCP inspections (the grading will depend on the impact of the issue).

6.2. Delegated party

The delegated party performs the tasks set out in paragraph 6.1, as transferred by the sponsor as per written contract.

In addition, the delegated party keeps the sponsor informed about the management of all the breaches related to the clinical trials of that sponsor.

6.3. Service providers

Service providers (including service providers delegated by the principal investigator/institution):

• should have a written process in place to identify the occurrence of a (suspected) serious breach;
• should promptly communicate to the sponsor or delegated party a (suspected) serious breach, according to the contractual agreements stipulated and through the contacts (e-mail address or telephone number) provided by the sponsor or delegated party.

6.4. Principal Investigator

The principal investigator should have a process in place to ensure that:

• the site staff or service providers delegated by the principal investigator/institution are able to identify the occurrence of a (suspected) serious breach;
• a (suspected) serious breach is promptly reported to the sponsor or delegated party, through the contacts (e-mail address or telephone number) provided by the sponsor or delegated party;

This may be a formal standard operating procedure or a study-specific guidance.

© European Medicines Agency, 2021