EMA publishes Consolidated ICH E6(R3) Guideline

The European Medicines Agency (EMA) published a consolidated version of the ICH E6(R3) Guideline. The ICH E6(R3) guideline builds on key concepts outlined in ICH E8(R1) Revision of General Considerations for Clinical Studies. This includes fostering a quality culture and proactively designing quality into clinical trials and drug development planning, identifying factors critical to trial quality, and engaging interested parties, as appropriate, using a proportionate risk-based approach.

ICH E6(R3) Step 4 document consolidated with E6(R3) Annex 2 Step 4 document

To provide clarity and better readability ICH E6(R3) has a new structure and is composed of:

• An overarching principles and objectives document;
• Annex 1 (interventional clinical trials);
• Annex 2 (additional considerations for non-traditional interventional clinical trials).

The principles are intended to support efficient approaches to trial design and conduct. They are interdependent and should be considered in their totality to assure ethical trial conduct and reliable results.

Annex 1, including its Appendices, is intended to provide information on how the principles can be appropriately applied to clinical trials. This Annex has been developed alongside the principles and objectives document to ensure consistency and to offer stakeholders a comprehensive package that can serve as a replacement for ICH E6(R2).

Annex 2 covers designs such as pragmatic clinical trials and decentralized clinical trials, as well as those trials that incorporate real world data (RWD). The goal of Annex 2 is to offer GCP considerations for clinical trials with various design elements and data sources, ensuring that they are fit for their intended purpose. Annex 2 reached Step 4 following ICH adoption on 3 June 2026 and CHMP adoption on 25 June 2026 and will come into effect on 15 January 2027. This Annex should be read in conjunction with the Principles and Annex 1.

More information is available at the EMA website ICH E6 Good clinical practice - Scientific guideline.