MHRA GCP Symposium: Key Takeaways on ICH E6 (R3)

Although I did not attend in person, I participated in this year’s MHRA Good Clinical Practice (GCP) Symposium on February 11, looking forward to their updates—particularly their insights on the ICH E6 (R3) Good Clinical Practice (GCP) guideline. E6 (R3) will be incorporated into UK law alongside updates to the UK Medicines for Human Use (Clinical Trials) Regulations 2004 later this year, with implementation planned for Spring 2026.

The sessions I attended highlighted key changes in ICH E6 (R3) that are already being discussed across the industry, including risk-based approaches, data governance, and investigator/sponsor responsibilities. Here are the main takeaways on how these updates will affect clinical trials in the UK:

1. Emphasis on Risk Proportionality

A substantial shift in ICH E6 (R3) is the encouragement of a risk-proportionate approach to clinical trials. The MHRA states: “A trial should be initiated and continued only if the anticipated benefits justify the known and anticipated risks.” This means trial processes should align with the level of risk assessed, ensuring that resources are optimized without compromising safety or quality. The UK’s updated legislation will reflect this by mandating adherence to GCP principles while allowing for context-specific adaptations.

2. Reinforced Focus on Data Governance and Integrity

The updated E6 (R3) guideline introduces a new section on data governance, outlining responsibilities for investigators and sponsors. The MHRA highlighted key regulatory impacts:

·         Data lifecycle management: Ensuring traceability, accuracy, and security from data capture to retention and destruction.

·         Blinding safeguards: Maintaining trial integrity by clearly defining roles and procedures for handling unblinded data.

·         Increased use of computerized systems: Ensuring systems are “fit for purpose” with appropriate validation, user management, and security measures.

These updates will also align with guidance in ICH E8 (R1), ICH E9, and GXP Data Integrity Guidance, reinforcing the importance of data integrity in clinical trials.

3. Expanded Investigator and Sponsor Responsibilities

Sponsors and investigators now have clearer roles in ensuring GCP compliance. Investigator responsibilities emphasize proportionate training and delegation—routine tasks will require less supporting documentation, while new trial-specific processes will require formal, fully documented training and oversight.

With a greater emphasis on participant understanding of the informed consent process—especially with new approaches in clinical trials like e-consent—the MHRA will ensure that procedures such as remote consenting and re-consent receive proportionate scrutiny.

In E6 (R3) sponsors also have expanded responsibilities. They must ensure greater oversight of service providers by assessing, documenting, and maintaining ongoing GCP compliance across all trial activities.

The MHRA stated that Sponsors must also design clinical trials with “Critical to Quality” factors in mind—those that impact participant safety or data integrity.

4. Updates to Essential Records and TMF Requirements

The MHRA is placing greater emphasis on the management and integrity of essential records in the Trial Master File (TMF).

The use of electronic TMS (eTMF systems) is encouraged, as they streamline processes. The UK’s revised regulations will provide clearer guidance on access control, version management, and audit trails. Tying into the MHRA’s emphasis on risk proportionality, a risk-based approach will allow flexibility in TMF documentation, reducing unnecessary duplication while maintaining compliance.

Additionally, the MHRA will align retention requirements with EMA guidance—TMF and medical records must be retained and retrievable for 25 years after the end of a clinical trial.

Sponsor responsibilities regarding the validation of computerized systems will also be clarified.  Any system used to store or manage TMF records must be assessed for fitness for purpose, ensuring compliance with GCP. This means both electronic and non-trial-specific systems must meet regulatory standards.

Final Thoughts

It was refreshing to hear how the MHRA’s planned revisions to UK regulations reinforce the importance of flexibility and risk-based approaches to clinical trials. By embracing these changes as early as possible, clinical trial stakeholders can ensure a smooth transition into the next era of Good Clinical Practice.