Finalised on 6 January 2025, the revision goes legally effective on 23 July 2025!
ICH E6 (R3) applies specifically for investigational product (IP) trials (medicines and biologicals) intended for regulatory submission. The guideline now clarifies that the principles of GCP may apply to other IP trials, rather than the full guidelines.
What’s New in E6(R3)?
Updated Structure
- Introduction
- Principles
- Annex 1
-
Institutional review board/independent ethics committee (IRB/IEC)
-
Investigator
-
Sponsor
-
Data governance – Investigator and sponsor
-
- Glossary
- Appendices
-
Investigator’s Brochure
-
Clinical trial protocol and protocol amendment
-
Essential records for conducting a clinical trial
-
Summary of key changes
- Emphasis on quality by design
The introduction of the “Quality by Design” concept aims to proactively incorporate quality into a trial by identifying critical-to-quality factors to prevent errors that could significantly impact patient safety and data reliability. -
Introduction of risk-proportionality and fitness-for-purpose
Αims to improve trial efficiency and extend the applicability of GCP to a broader range of trials with focus on data integrity, i.e., data does not have to be error-free if it supports conclusions equivalent to those drawn from error-free data. -
Data governance & integrity
Strengthened controls for digital records, eConsent, traceability, and cybersecurity. Overall, data governance requirements are increased including a new sponsor section covering data and records (Section 3.6) and a new stand-alone section for Data Governance (Section 4). -
Expanded focus on ethics
More inclusive language (“trial participant” instead of “subject”) and enhanced informed consent guidance. In addition, there are references to public involvement and participant diversity, including the requirement for sponsors to clearly describe the rationale for exclusion of participants. -
Targeted allocation of responsibilities
The roles and responsibilities for sponsors, CROs, investigators, and oversight bodies have been updated to promote accountability and transparency. -
Acknowledgment of innovative trial designs and new technologies
Novel trial designs and technologies, such as trials with decentralised elements are endorsed as the use of remote monitoring/consent/audit, eSource, real-world data & digital tools, home nurses are formally acknowledged. -
Management of trial activities
There is expanded guidance on how to support critical activities, such as randomisation, blinding/masking and participant retention. -
Safety reporting updates
Removal of the requirement for all SUSARs to be expedited to investigators and IRBs/IECs and introduction of alternative arrangements for safety reporting to regulatory authorities.
There are no explicit references to non-therapeutic trials in R3.
