The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has issued guidance on when and how to report serious breaches of Good Clinical Practice (GCP) or trial protocols in clinical studies.

The guidance comes in response to new legal requirements in the Medicines for Human Use (Clinical Trials) Amendment Regulations 2006, which entered into force last August. These amendments to the Medicines for Human Use (Clinical Trials) Regulations 2004, which incorporated the European Union’s Clinical Trials Directive (2001/20/EC) into UK law, were concerned mainly with implementing the EU’s Good Clinical Practice Directive (2005/28/EC).

Regulation 29A of the amendments says clinical trial sponsors must inform the licensing authority in writing about any serious breach of “the conditions and principles of GCP” in a study or of the trial protocol. “Serious breach” in this context means “likely to affect to a significant degree: (a) the safety or physical or mental integrity of the trial subjects; or (b) the scientific value of the trial. Sponsors should notify the licensing authority within seven days of becoming aware of the breach.

The MHRA’s guidance outlines the practical arrangements for notification, as well as any actions that may be taken by the agency in response (e.g., requesting additional from the sponsor, suspending/terminating the clinical trial authorisation), and provides further clarification on what could qualify as a “serious breach” in this context.

Deviations from GCP and protocols are a regular occurrence in clinical studies, the MHRA notes. The majority are technical lapses that do not result in any harm to trial subjects or significantly dilute the scientific value of the results. They should be documented and included in the clinical trial report but not every deviation has to be reported to the agency as a serious breach.

A breach of GCP or the trial protocol that led to a serious adverse event or suspected unexpected serious adverse reaction might fall into the “serious” category, for example. So might confirmed instances of clinical trial fraud, where the fraud was likely to have a significant impact on the integrity of trial subjects or the scientific value of the data. However, failure to honour a visit date would constitute a minor protocol deviation not subject to the notification criteria, the MHRA said.

The new guidance is available on the UK agency’s website at