Over the past six years, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has been working on reinventing the E6 Good Clinical Practice (GCP) guideline that was first introduced in 1996 and revised in 2016. On 06 January 2025, the ICH E6 (R3) guideline reached step four of the ICH process, meaning the revised guideline has been signed off to be implemented. This article will highlight the key points from the new ICH E6 (R3) guideline and how they can be implemented by pharmaceutical and biotechnology companies.
New or updated concepts in ICH E6 (R3)
The ICH E6 (R3) guideline is organised into distinct sections including the GCP principles, Annex 1 and three appendices, with an additional Annex 2 currently under public consultation. At the end of the document, there is a glossary of common terms used throughout the text, which contains a number of new terms which were not included in the previous revision. New terms which have been added to the glossary include: assent, computerised systems validation, data acquisition tool, data integrity, metadata, reference safety information, service provider and signature.
There are 11 principles of GCP listed, the majority of which were also included in ICH E6 (R2), with principles for risk proportionality and roles and responsibilities newly added. The risk proportionality principle requires increased focus on subject safety and reliability of results, with consideration given to risks associated with trial participation compared to standard care. The roles and responsibilities principle requires clarification of activities transferred or delegated by both the Sponsor and Investigator, and maintenance of proper oversight.
Annex 1 includes sections for the Institutional Review Board / Independent Ethics Committee (IRB/IEC), Investigator, Sponsor and Data Governance. The IRB/IEC section includes additional information for submission and communication with IRB/IECs, with language updated to apply globally and details added to reflect the use of new approaches and/or technology in obtaining informed consent. The Sponsor section includes new sections for resources, which highlights the responsibility of Sponsors to ensure sufficient resources are available to conduct the trial, and Sponsor oversight, which outlines oversight measures which should be taken by the Sponsor to ensure the trail is conducted as per the protocol and applicable regulations. The data governance section was a new addition to the guideline, which provides guidance for Investigators and Sponsors for managing the integrity of trial related data.
The appendices provide information about the Investigator’s Brochure, Clinical Trial Protocol and Essential Records for a Clinical Trial. The contents of appendices A and B were previously included in the ICH E6 (R2) guideline, however the language was updated for clarity and additional details were included. Appendix C included new sections on the management of essential records, which provided instructions for filing and retaining essential documents, and the essentiality of trial records, which included details of an assessment to determine whether a document is essential.
Practical applications for Sponsors
For companies acting as a Sponsor or performing activities delegated by a Sponsor, the following changes should be made in order to maintain GCP compliance:
- Put procedures and documentation in place to ensure full oversight of in-house and delegated trial activities, with the extent of oversight measures tailored to the complexity of the trial and the potential risks involved.
- Ensure there is a delegation log and documented process for the delegation of trial activities to Sponsor staff, Investigator(s) and third-party vendor(s).
- Create a list of risks to critical to quality factors to be managed before the trial begins and implement periodic risk assessments throughout the course of the trial to document any new, upgraded or downgraded risks which arise.
- Implement processes for data governance from a Sponsor perspective and ensure these processes are documented, with verifiable outcomes.
- Review procedures for managing, retaining and archiving essential trial records to ensure they comply with Appendix C.
- Perform a gap analysis of the Quality Management System to ensure that any changes made to processes, roles and common terms have been documented.
- Provide training on the revised ICH GCP E6 (R3) guideline to all staff involved in clinical trial activities.
Practical applications for Investigators
For companies acting as an Investigator or performing activities delegated by an Investigator, the following changes should be made in order to maintain GCP compliance:
- Work closely with the Sponsor to ensure that all new processes and practices are followed in compliance with GCP and applicable regulations.
- Clearly document delegation of trial activities from the Investigator to site staff.
- Follow the risk management measures put in place by the Sponsor and report any new, upgraded or downgraded risks promptly to the Sponsor.
- Consider different approaches for obtaining informed consent depending on the nature of the trial, such as using images and videos to inform potential subjects of risks involved.
- Implement processes for data governance from an Investigator perspective and ensure these processes are documented, with verifiable outcomes.
- Review procedures for managing, retaining and archiving essential trial records to ensure they comply with Appendix C.
- Perform a gap analysis of the Quality Management System to ensure that internal procedures comply with the Sponsor’s requirements.
- Provide training on the revised ICH GCP E6 (R3) guideline to all staff involved in clinical trial activities.
Support from Arithmos
Arithmos has a team of experienced GCP auditors and QMS specialists who are able to provide a range of services to ensure your company’s transition from the ICH E6 (R2) guideline to the ICH E6 (R3) guideline is a success. Examples of the services we can provide are included here:
- Gap analysis – One of our GCP experts will review your company’s quality management system against the new GCP guidelines and identify any gaps in processes which require new or updated procedures to be implemented.
- Process audit – One of our GCP auditors will perform an audit of a given process to ensure that internal procedures are followed, and the process is carried out in accordance with the updated GCP guidelines and applicable regulations.
- Mock inspection – Arithmos will form a mock inspection team to prepare for and conduct a mock inspection against the ICH E6 (R3) guideline and applicable regulations, with a detailed report produced which mimics the outputs of a regulatory inspection.
- GCP training – A member of our GCP team will be available to deliver training on topics from the updated ICH E6 guideline including a full GCP induction, GCP refresher training and training on specific GCP related topics such as serious breaches, sponsor oversight, project management and data management.
Choosing to partner with Arithmos will provide you with a team of GxP experts who can provide a fresh perspective on your processes and ensure that your company is both compliant with the new GCP guideline and operating effectively to produce the best outcomes for trial subjects and data.
About the Author
Laura Wilson
GCP Auditor and QMS Specialist
With a degree in Neuroscience and 5 years of experience working to Good Clinical Practice guidelines, Laura Wilson has worked with CROs, NHS sites and academic institutions to promote quality assurance in clinical research.
Laura Wilson works in Arithmos as our GCP Auditor and QMS Specialist.
She has built multiple client Quality Management Systems, delivered GCP training to clients for inspection readiness, and worked on both internal and external audits on behalf of a range of clients.
About Arithmos
With deep expertise in the Life Science Industry, Arithmos supports companies in their digital transformation journey to achieve the best value from technology-enabled solutions and excellence in business operations.
Arithmos team share extensive knowledge of the full GxP regulated environment for both deliveries of services and technologies, and our domains range from Clinical R&D, Quality Assurance, Drug Safety & Pharmacovigilance, Regulatory and Medical Affairs
