ICH GCP E6 (R3): Transformative updates make Good Clinical Practice better (2025)

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New guidelines for Good Clinical Practice Why update ICH Good Clinical Practice? What has changed in GCP E6 (R3)? Next steps

New guidelines for Good Clinical Practice

The long awaited and much anticipated final version of ICH Good Clinical Practice (GCP) E6 (R3) is here. After draft, finalisation and publication, we have reached the adoption step (step 4) as of 6 January 2025. We anticipate implementation (step 5) will begin in the US and Europe in the coming months, with other countries following throughout 2025.

Changes to ICH GCP E6 are far-reaching and affect terminology and definitions, processes, systems, data supervision, consent, participant protection, risk-based approaches and use of technology. With rolling global implementation forthcoming and a wide range of impacts to stakeholders across the clinical research continuum, it’s important to understand the scope and next steps to move forward efficiently.

Why update ICH Good Clinical Practice?

The updates to ICH GCP E6 (R3) are the biggest overhaul to the GCP guidelines since their inception more than 27 years ago. In 2016, the R2 version touched upon risk-based approaches and addressed some technology advancements to keep up with modern clinical practice, but the R3 revision is more transformative.

As long ago as 2017, anICH Reflection Paper noted that E6 (R2) did not “sufficiently recognize variations in the level of risk for participants in different types of trials and allow corresponding flexibility in managing the risks”. The E6 (R2) guideline was also more limited in scope, which has been remedied in the E6 (R3) updates with a more holistic approach to the planning and conduct of clinical trials.

What has changed in GCP E6 (R3)?

A lot has changed from GCP E6 (R2) to (R3), from basic structure to detailed content. The guidance has undergone substantial structural changes and is now organised as described in Figure 1 below.

Figure 1: Revised structure of ICH GCP E6 (R3)

More significant, though, are the changes to the content; the wording, terminology and positioning within the guidelines as shown below.

1. Risk-based quality management, from trial

Encouragement of holistic and broad approach to risk management, from trial design phase through to data analysis and reporting
Emphasis on risk control being proportionate to impact on participants’ rights, safety and well-being, and reliability of trial results
Focus on Critical to Quality factors (CTQs) to enhance trial efficiency and effectiveness

2. Expanded role of technology

More robust requirements for data integrity and cybersecurity within a data governance framework
Emphasis on importance of protecting participant data against unauthorised access or breaches throughout the trial process
Raised profile of decentralised clinical trials (DCTs) and hybrid trial models, including detail on remote monitoring and digital health technologies, such as wearable devices

3. Investigator responsibilities and qualifications

More detail on delegation of responsibilities, including use of
service providers (with the requirement for the
Investigator/institution to document agreements made) and other
qualified healthcare professionals
Promotion of transparency of results with participants and on
respecting their preferences
Increased emphasis on investigator responsibility to oversee data
integrity and a focus onto the quality of the electronic systems
that investigators are using

4. Participant protection

Modernisation of informed consent practices, including the role of digital technologies such as electronic consent (eConsent) and remote consent
Changes to ICF content, including addition of risk to participant's partner, data handling process, explanation of public registries and participant's option to receive trial results and details of their actual treatment
Additional safeguards related to vulnerable participants

5. Collaboration and data-sharing

More participant-centric, with sponsors being encouraged to actively seek feedback from participants and incorporate their perspectives into trial design.
Wider stakeholder engagement, including with healthcare providers, regulators and patient advocacy groups
Best practices for data handling, storage and transmission, including use of encryption, secure data storage solutions and cybersecurity assessments

Next steps

Stakeholders must now undertake a comprehensive analysis and comparison between E6 (R2) and (R3), to assess and implement changes that are needed to update procedures, systems and working practices, as needed. The scope of E6 (R3) is broad, with potential impacts on investigators, institutions, sponsors and service providers.

ICON’sRegulatory Affairs team has been evaluating the potential impacts of the ICH GCP E6 updates since the draft stage. With the updated final guidance, our cross-functional initiative is working to ensure effective and timely implementation across the organisation. As part of this initiative, we have been conducting an extensive risk and impact assessment to organise and prioritise the multidisciplinary implementation efforts. Our commitment to staying at the forefront of ICH GCP E6 (R3) implementation ensures we are ready and able to assist our partners in their implementation journeys.

Connect with us to learn more about ourRegulatory Intelligence and see how we can help you achieve GCP readiness.

References:

The E6 (R3)guideline is available at "ICH, Efficacy Guidelines, E6 Good Clinical Practice E6 (R3)." International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Jan2025

TheICH Reflection Paper is available at “ICH,Reflection Papers, GCP Renovation“.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Jan2017