As the Life Sciences industry embraces increasingly complex clinical trials to develop innovative therapies, ensuring patient safety and regulatory compliance remains paramount.
To address these evolving needs, the International Council for Harmonisation (ICH) is introducing a revision to its E6 Guideline for Good Clinical Practice (GCP).
In anticipation of the new ICH GCP E6(R3) guidelines, which are due to be implemented in August / September 2024, as Arithmos we would like to discuss the evolution of clinical trial designs and proportional risks.
ICH E6 R3 Guideline on GCP: The Need for Revision
Following the publication of the ICH reflection paper on Good Clinical Practice (GCP) in 2017, a further revision to the E6 Guideline for GCP was proposed. This revision aims to ensure the increasing complexity of trials and advancement of technology are considered within the ICH E8 and E6 guidelines.
The revision was endorsed by the ICH Assembly in June 2019, and the ICH Expert Working Group (EWG) has been working on E6(R3) ever since.
The draft guidelines were released on 25 May 2023, and both the principles and Annex 1 were subject to public consultation between 26 May and 26 September 2023.
Implementation of the principles and Annex 1 is planned for August / September 2024, while implementation of Annex 2 is planned for April / May 2025.
Key changes between ICH E6 (R2) and ICH E6 (R3)
The revised guidance includes reorganised principles of GCP, more focus on proportionality within a risk-based approach, increased public involvement and additional provisions for non-traditional clinical trial designs, including decentralised trials.
The eleven principles of GCP as per ICH E6 (R3) focus on:
- compliance with applicable laws/regulations
- informed consent
- protocol compliance
- “fit for purpose” trials
- adequate staff training
- building quality into trials
- proportionate approaches to trial conduct
- reliable results
- clear documentation of responsibilities
- manufacturing of investigational products to GMP standards.
These principles are supported by Annex 1, which includes considerations for interventional clinical trials such as institutional review board/independent ethics committee oversight, responsibilities for investigators / sponsors and data governance.
There are also appendices which provide further context for the Investigator’s Brochure (IB), protocol and essential clinical trial records.
Annex 2, which is due to be published for public consultation in December 2024 / January 2025, will provide additional considerations for non-traditional interventional clinical trials including trials using real-world data (RWD).
ICH E6 R3 Guideline on GCP: Impact on Sponsors, Sites and Vendors
The changes introduced in ICH E6 (R3) will have a significant impact on everyone involved in facilitating a clinical trial, including Sponsors, Investigators, contract research organisations (CROs) and any other vendors who have been delegated trial-related duties.
- Sponsors and Investigators: Sponsors will need to ensure their Quality Management Systems (QMS) are robust enough to handle the proportional risk-based approach and effectively manage critical trial risks. Investigators will need to update their procedures and documentation to reflect the new focus on proportionality and patient-centricity. Training for clinical trial staff on the revised guidelines will also be crucial.
- Vendors: Vendors performing trial-related tasks will need to ensure their processes are aligned with the new E6 (R3) requirements and that sponsors are providing clear oversight.
For instance, the increased patient focus means that patient-facing documents, including the informed consent form, will require revision to improve understanding of trial expectations and the inclusion/exclusion criteria.
Furthermore, the proportional risk-based approach means that trial risks should be compared to standard care, and that critical to quality risks should be managed proactively, meaning more importance will be placed on documenting and rationalising risk assessments for different trial aspects.
There is also an expectation for enhanced oversight of trials by Sponsors and Investigators, including periodic review of safety information, improved processes for record management and clear, documented oversight of any delegated activities.
How Arithmos can help you adapt
Arithmos offers a comprehensive suite of services to help sponsors, sites, and vendors smoothly transition to the new ICH E6 (R3) guidelines.
Our team of experienced GxP auditors, consultants and quality management system experts can provide the following support:
- Gap analysis and Process mapping Identify areas within your organization that may require adjustments to comply with the revised guidelines.
- Quality Management System development and improvement: Develop or enhance your QMS to effectively implement a proportional risk-based approach.
- ICH E6 (R3) compliance audits: Conduct internal, external, or vendor audits to ensure adherence to the new GCP standards.
- Clinical trial staff training: Deliver customised training programs for your staff on the revised E6 (R3) guidelines and best practices for GCP compliance.
By partnering with Arithmos, you can ensure your clinical trials are conducted in accordance with the latest ICH E6 (R3) guidelines, while prioritising patient safety and regulatory compliance.
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
