Hot Off the Press: E6 R3 is Here

ICH has just announced that the much-anticipated E6(R3) Good Clinical Practice (GCP) guideline has been adopted by the ICH Regulatory Members of the ICH Assembly as an ICH Harmonised Guideline. The next and final stage is regulatory implementation, which is carried out in accordance with national/regional procedures. This revision highlights a “fit for purpose”, more proportionate risk-based approach to quality management in clinical trials, and aims to enhance participant safety and data governance, for data integrity and more reliable results.

This guidance encourages the exploration of technology, with principles intended to support efficient and innovative approaches to trial design and conduct such as digital health technologies. It dictates technology be adapted to fit trial design, lending to the concept of Quality by Design. E6 R3 mandates this concept be implemented to identify the factors critical to trial quality, and the risks that threaten the integrity of those factors. Badly designed clinical trials waste resources and have the potential to put at risk the safety of the participants.

E6(R3) has also been restructured for clarity. Annexes and appendices will enable easier and faster updates in the future. Of note is Appendix C: Essential Records for the Conduct of a Clinical Trial. The statement “If these trial records are produced, they are considered essential and should be retained” thankfully means the 2nd table and concept of “potential” essential records has been removed from the final guidance.  Appendix C emphasizes that essential records should be maintained in the TMF or Investigator Site File (ISF) and highlights the importance of correct identification, version control, and accessibility of records to demonstrate compliance with GCP and regulatory requirements.

Incorporating these updates into TMF management will require sponsors and investigators to:

• Implement RBQM strategies: Ensure that TMF processes focus on critical data and processes that impact patient safety and data integrity.
• Enhance data governance: Adopt advanced data management style practices to maintain the accuracy, completeness, and traceability of TMF documents.
• Adapt their monitoring practices: Integrate remote and centralized monitoring approaches into TMF oversight to align with the guideline's recommendations.
• Support service provider oversight: Establish clear procedures for managing and documenting interactions with service providers within the TMF.

Also look out for new and revised glossary terms such as “service provider” as opposed to CRO and “essential records” as opposed to essential documents. Essential records are clearly defined as “the documents and data,” including relevant metadata.

In practical terms, by aligning TMF management practices with the principles outlined in ICH E6(R3), organizations can enhance the quality and compliance of their clinical trials, ultimately contributing to more reliable and efficient research outcomes.