On January 6, 2025, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) issued its final version of the “Guideline for Good Clinical Practice E6(R3)” to update its 2016 E6(R2) GCP guideline.
On January 27, 2025, the European Medicines Agency (EMA) announced an effective date of July 23, 2025 for E6(R3) – Principles and Annex 1. E6(R3) is still pending adoption by other ICH member nations and regions.
Key Changes in E6(R3)
E6(R3) restructures the previous guideline with one section on general principles, Annex 1 on interventional trials, and Annex 2 on non-traditional interventional trials; however, Annex 2 was not released as part of the final version. Several other notable changes in E6(R3) include:
- Recognition of the increasing use of decentralized clinical trial designs
- Greater emphasis on Quality Management Systems (QMSs) to ensure trial quality
- Introduction of a “fit for purpose” approach to quality-by-design
- Increased focus on study participants, considering their perspective in trial design and conduct
- More detailed guidance on obtaining informed consent, including the use of technologies to inform participants and obtain consent
- Expanded guidance on the use of electronic systems, including digital health technologies (DHTs) and electronic sources (eSources)
- Recognition of the varied roles of contract research organizations
- Adoption of a “media neutral” approach to applying GCP principles
A Future-Proof Approach to GCP
ICH E6(R3) acknowledges that E6(R2) has become increasingly outdated. The new guideline introduces a more flexible and adaptive approach to GCP, aiming to be as future-proof as possible.
FDA’s Response to the E6(R3) Draft
Following the release of the E6(R3) draft in May 2023, the FDA issued its guidance document to accompany the guideline. The draft guidance aligns with the FDA’s steps to modernize clinical trials. However, similar to E6(R2), the guidance includes a disclaimer stating that ICH E6(R3) will only “represent the current thinking” of the FDA and will not be “binding on the FDA or the public.” Currently, the final version of E6(R3) is pending adoption by the FDA.
CITI Program’s Response to E6(R3)
CITI Program is reviewing the final version of E6(R3) and will update its GCP and other content accordingly. More information about future updates will be shared at a later date.
Additional Resources
