Key Changes and Implications for Interventional Clinical Trials

SVP Global Regulatory and Quality
On January 6, 2025, the International Council for Harmonisation (ICH) officially released (adopted) the final version of its Good Clinical Practice (GCP) Guideline E6(R3) (available here: ICH E6(R3) Final Guideline). This updated version reflects the latest standards for the ethical, scientific, and quality conduct of clinical trials involving human participants.
The primary goal of E6(R3) is to protect the rights, safety, and well-being of trial participants, ensuring that clinical trials are conducted ethically and scientifically. The Guideline emphasizes the importance of adhering to principles rooted in the Declaration of Helsinki, while ensuring that clinical trial results are reliable and trustworthy. It applies specifically to interventional clinical trials involving drugs, medicines, medical products, vaccines, and biological products intended for submission to regulatory authorities.
Key Changes in ICH E6(R3)
E6(R3) introduces a significant restructuring compared to previous versions. The main body of the guideline now focuses on general principles, while Annex I outlines the interpretation and implementation of these principles. The revision also retains sections (now in the form of appendices) that provide recommendations for key documents such as the investigator brochure, clinical trial protocol, and protocol amendments. Additionally, a revised glossary is included. A second annex (Annex 2) is under public consultation from November 2024 to March 2025.
Substantial Revisions and New Principles
Among the most notable substantial changes in E6(R3) content are the introduction of two new principles:
- Risk Proportionality: This principle emphasizes that risk management strategies should be tailored to the level of risk posed by the trial, ensuring appropriate oversight and control.
- Roles and Responsibilities: This principle clarifies and expands on the expectations for the various roles in a clinical trial, ensuring accountability and clarity in the responsibilities of all parties involved.
In addition to these new principles, several existing principles have been revised, including those on Ethics, Informed Consent, IRB/IEC Review, Science, and Qualified Individuals. These updates reflect the evolving landscape of clinical trial conduct and regulatory requirements, ensuring that GCP standards remain relevant and effective.
Resources and Training
To help stakeholders understand the new E6(R3) guidelines, the ICH E6(R3) Expert Working Group (EWG) has developed a “Step 4 Introductory Training Presentation,” which provides a high-level overview of the guideline, its development process, and a summary of the key changes. This presentation is available here: E6(R3) Step 4 Presentation.
Additionally, the U.S. Food and Drug Administration (FDA), a founding regulatory member of ICH, plays a crucial role in the development of ICH guidelines, which FDA then adopts and issues as guidance to industry. Following the release of the E6(R3) draft in May 2023 (which we wrote about here), the FDA published a draft guidance titled “E6(R3) Guideline for Good Clinical Practice,” available here: FDA Draft Guidance. While the draft follows the ICH format, the FDA has indicated that the final version will be reformatted to align with its good guidance practices regulations (21 CFR 10.115) before being published.
Conclusion
The adoption of ICH E6(R3) marks a significant step forward in the evolution of clinical trial standards. By incorporating new principles, revising existing ones, and aligning practices with modern trial challenges, this updated guideline promises to improve the quality, safety, and reliability of clinical trials worldwide. As clinical trial professionals, it’s essential to understand changes and integrate them into our daily practices to ensure compliance and uphold the highest ethical standards in trial conduct.
At Beaufort, we share the same vision set forth by the ICH E6(R3) EWG. Their intent to facilitate innovations in clinical trial design and conduct while ensuring participant safety and reliable results is at the heart of what we do.
If you’re looking for a partner that aligns with these principles, come work with us. We are committed to advancing clinical trials with integrity, quality, and an unwavering focus on participant well-being.