02/03/2026
On September 8th, 2025, the US Food and Drug Administration (FDA) released their final guidance for industry on the ICH E6(R3) Good Clinical Practice (GCP). ICH E6(R3) Principles and Annex 1 were finalized on January 6th, 2025, officially taking over the preceding 2016 ICH E6(R2). Annex 2 is expected to be finalized in early 2026. We have paid close attention to this long-awaited update to GCP from the initial draft in 2021 to the final adoption in 2025, for more information and details about the R3 have a look at our previous entries:
The FDA’s release of the Principles and Annex 1 of the new GCP guidelines closely follows that of the European Medicines Agency’s (EMA) which adopted E6(R3) two months prior in July 2025, as well as Switzerland’s Swissmedic in August 2025. The Medicines & Healthcare products Regulatory Agency (MHRA) also released UK-specific annotations to ICH E6(R3) on January 12, 2026, a slight adaptation to align with UK legislation, and Health Canada has announced their intentions to implement the guidelines in April of 2026. As there are no fundamental differences between the FDA’s, EMA’s, MHRA’s, Swissmedic’s and ICH’s guidance for E6(R3), these new global standards will facilitate clinical trials and reduce the need for repeated studies in different regions.
ICH E6(R3) reflects the scientific and technological evolution of the clinical trial ecosystem by encouraging innovation in trial design and conduct while retaining data accuracy and reliability through Quality by Design methods. This flexible approach to clinical trials is considered media neutral, allowing for existing and future technologies to be implemented into clinical trials without hindrance. Implementation of these new technologies allows researchers to adapt a trial design to fit the unique participant characteristics such as specific disease detection, progression, or treatment. The flexibility, however, cannot come at the cost of participant rights, safety, and wellbeing or data reliability. The guidance encourages the implementation of Quality by Design when developing a trial which entails identifying Critical to Quality factors (CTQ) which are factors closely linked to participant safety or data reliability. CTQs could include but are not limited to:
investigational product (IP) management which can have a direct impact on participant safety
uploading case report form information into an electronic data capture system which would impact data reliability if done poorly.
ICH E6(R3) also includes different terms and definitions used throughout the guidance than R2. For instance, the use of “patient” when referring to an individual who agrees to partake in a study has been changed to “participant” to reflect that they are actively volunteering to assist in the study whereas “patient” assumes passivity. The guidance’s glossary has also been expanded, now including terms such as:
Assent: Affirmative agreement of a minor to participate in clinical trial. The absence of expression of agreement or disagreement should not be interpreted as assent.
Suspected Unexpected Serious Adverse Reaction (SUSAR): an adverse reaction that meets three criteria: suspected, unexpected, and serious.
Suspected: There is a reasonable possibility that the drug caused the adverse drug reaction.
Unexpected: An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator’s Brochure or alternative documents according to applicable regulatory requirements; see RSI).
Serious: See above for SAE.
The full guidance can be found on the FDA’s website, and those who would like to comment may do so here. There are many changes that came with ICH E6(R3) including updates to the core principles as well as the individual responsibilities of investigators, sponsors, and institutional review boards. Finding and understanding each of these changes can be difficult and trying to remember all of the information at once can be overwhelming. This is where Clinical Pathways can help, we offer a wide variety of clinical trial related consultation and training, including training on all the major changes from R2 to R3. For a full list of services, have a look at our Course Catalog and Services or contact us directly to see if we could help you or your company. While you’re there, sign up for our free blog and newsletter to stay up to date on clinical trial related news such as this and more.
-The Clinical Pathways Team
Enjoy this blog? Please like, comment, and share with your contacts.