What is a serious breach under the EU Clinical Trials Regulation?

Short answer

A serious breach is a breach of the Regulation or of the protocol that is likely to affect, to a significant degree, participants' safety and rights or the reliability and robustness of the trial data. The sponsor must notify the Member States concerned through CTIS without undue delay and within 7 days of becoming aware of it.

Why

Article 52 of Regulation (EU) No 536/2014 sets the duty, and EMA's guideline on notifying serious breaches explains how to apply it. Most deviations are not serious breaches. The word that matters is significant.

Dosing a participant with the wrong strength that caused harm, systematic enrollment of ineligible participants, or fraud at a site would usually qualify. A single missed questionnaire would not. Only serious breaches must be notified, not suspected ones, but the guideline says that when the sponsor has reasonable grounds to believe one occurred it should notify within 7 days and investigate in parallel.

Assessment time does not extend the clock. Sponsors must ensure, by contract, that sites and service providers report possible serious breaches to them immediately. The sponsor may delegate notification to a CRO, but stays responsible.

The US has no direct equivalent term. FDA expects sponsors to secure compliance or end an investigator's participation under 21 CFR 312.56.

A strong answer covers

Article 52 definition: significant effect on safety, rights or data reliability
7 days from sponsor awareness, through CTIS
Investigate in parallel, do not wait for full detail
Contracts that make sites and vendors report immediately
Not every deviation is a serious breach

Common mistakes

Reporting every protocol deviation as a serious breach.
Waiting for the root cause analysis to finish before notifying.
Assuming delegation to a CRO moves the legal responsibility.

The interviewer might ask next

Which kinds of data integrity problem would you treat as a likely serious breach?