01/15/2025

On January 6, 2025, the International Council of Harmonisation’s ICH E6(R3) for Good Clinical Practices (GCP) reached step four of the formal ICH procedure. This means that the ICH E6(R3) draft guidelines, since its release in May of 2023, were submitted to and approved by the ICH Regulatory Members of the ICH Assembly for adoption as an ICH Harmonised Guideline replacing E6(R2). E6(R3) reflects the advances and innovations in clinical trial related technologies and methodologies for trial design, planning, and conduct since the preceding guidelines were implemented in 2016. ICH E8(R1), General Considerations for Clinical Studies, and its Quality by Design foundation is interwoven in the updated guideline.

The ICH E6(R3) contains the ICH’s current stance on what is considered the standards of ethics, science, and quality in clinical trials that involve human participants. Starting with the 11 principles of ICH GCP all of which have origins tracing back to the Declaration of Helsinki. In Annex 1 of the draft, these principles have been expanded upon and redesigned to be more flexible to unique study characteristics. Section III (Annex 1 of the Final) breaks down all of the roles and responsibilities of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC), Sponsor, and Investigator all of which have been reorganized and expanded upon. Section III also has the new addition of Data Governance for the Sponsor and Investigator which covers Data Life Cycle Elements as well as Computerized Systems which are now present in every clinical trial. The appendices detail what is to be expected in the Investigator’s Brochures, Clinical Trial Protocols and Protocol Amendments, and Essential Records for the Conduct of a Clinical Trial.

Innovations such as the use of decentralized and pragmatic elements within trials are address within the guideline as well as the use of real-world data which has helped to streamline clinical research procedures. The terminology used within the guideline has also changed with the addition of new terms and updates to the definitions of existing terms all of which is found at the end of the guideline in the glossary. For example, you will notice that the term “subjects” has been replaced throughout the guideline with “trial participant”. Within the glossary, terms such as “Assent” and “Suspected Unexpected Serious Adverse Reaction (SUSAR)” have also been added.

For further information on the changes, please see our previous blog entries on Annexes 1 and 2 of the draft guidelines:

Step 5 is the final step in the formal ICH procedure for E6(R3) which is regulatory implementation. This will vary between ICH regions and countries as each has their own unique process for the implementation of new rules and regulations however the results will be the same, international harmonisation of GCP standards (For more information on the formal ICH procedure visit the ICH website). The U.S. Food and Drug Administration (FDA) and Health Canada will be conducting a joint virtual ICH public meeting where the new guideline will be discussed prior to the biannual ICH Assembly meeting May 13-14, 2025 to provide information to shareholders and solicit their input. For those interested in attending this virtual webinar the link is on the FDA website. Other medical agencies around the world have also been awaiting these changes such as the Medicines and Healthcare products Regulatory Agency MHRA and the European Medical Association (EMA) and we will expect to see updates regarding the adoption and implementation of the guideline the near future.

The final version of the ICH E6(R3) guideline can be found here, and for supplementary information please see the ICH website. Clinical Pathways is dedicated to keeping our clients up to date on updates to clinical trial rules and regulations including the changes within this guideline. We are currently reworking our ICH E6(R2) GCP eTraining course to reflect the changes in R3, keep an eye out for the updated version. For a list of all our other training and consulting services or to sign up for our blog and newsletter to stay informed about such changes, please visit our website at the following link: https://www.clinicalpathwaysresearch.com.

The Clinical Pathways Team

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