GCP & Serious Breach Reporting

GCP and serious breach

The Clinical Trials Regulations require all clinical trials of investigational medicinal products (CTIMPs) to be run to the conditions and principles of Good Clinical Practice (GCP). These regulations define GCP as:

“.... a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.”

Compliance with GCP provides assurance that the rights, safety and well-being of subjects are protected and that the results of CTIMPs (and other clinical research) are credible.

For CTIMPs, the core conditions and principles of GCP were specified in the European Commission GCP Directive (2005/28/EC) (PDF, 68 KB). This Directive was transposed into UK law by means of The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (PDF, 71 KB) (which amended the Medicines for Human Use (Clinical Trials) Regulations 2004). A summary document can be accessed here (pdf, 84.35 KB) outlining the conditions and principles which must be applied when conducting CTIMPs in the UK.

It is recognised however, that there is some flexibility in the interpretation of GCP and where appropriate, a risk adapted approach should be considered. See the Risk-adapted Approaches to the Management of Clinical Trials of Investigational Medicinal Products (PDF, 247 KB) for more information.

For trials run by commercial sponsors where data are intended to be submitted to regulatory authorities, the ICH GCP E6 (R2) Guideline is the internationally recognised GCP standard and should be adhered to (in addition to the Clinical Trials Regulations and the European Commission Detailed Guidance Documents). 

The MHRA Inspectorate has published the Good Clinical Practice Guide giving information and practical examples relating to the implementation of the Clinical Trials Regulations.

For non-CTIMP research, the UK Policy Framework for Health and Social Care Research, requires all research to be run to the principles of GCP.

Participating Sites Responsibilities:

For a multi-site trial, the person with overall responsibility for the trial at each site is defined as the Principal Investigator. Guidelines for GCP, from the perspective of the Principal Investigator, are detailed in Section 4 of ICH GCP E6 (R2).

The sponsor should ensure that each site is aware of all regulations and quality standards that apply to CTIMPs by:

    1. Specifying the standards that must be adhered to in any site agreements
    2. Ensuring that site staff have received GCP and Clinical Trials Regulation training commensurate to their role.

Serious Breach of GCP/Protocol:

The Clinical Trials Regulations require the reporting of serious breaches of GCP or the protocol (regulation 29A of S12004-1031 as amended). Guidance on the definition and reporting requirements can be found on the MHRA web pages: Serious Breach and Good Clinical Practice Reporting.  In the UK, serious breaches should also be reported to the relevant ethics committee at the same time as the report to the MHRA, in accordance with Research Ethics Committee Standard Operating Procedures.

Sponsors of CTIMPs should ensure the requirement to report serious breaches to the MHRA and the ethics committee is incorporated into their standard operating procedures to ensure all relevant staff are aware of this legal requirement. This should include detail of how site staff are made aware of requirements (via training or protocol procedures). Host organisations and other parties working with the trial sponsor may also need to consider their own mechanisms for reporting serious breaches (including arrangements for reporting serious breaches directly to the MHRA if the sponsor is in breach).

For non-CTIMP research, serious breaches of GCP or the protocol should be reported to the relevant ethics committee in accordance with the Research Ethics Committee Standard Operating Procedures.

Further reading: