Update: As of January 6th, 2025, ICH E6 (R3) reached Step 4 and has been finalized. Please see the updated section at the end of this blog for additional changes and insights.
The revision of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 Guideline, specifically ICH E6(R3), is part of the ongoing GCP Renovation and represents a significant advancement in the conduct of clinical trials.
The public consultation draft was released in May 2023. This draft presented the preliminary changes to the guideline and was open for feedback from industry professionals and stakeholders. The consultation period officially closed in September 2023, and the feedback received was reviewed as part of the process to finalize the guideline.
In addition, Annex 2, released for public consultation in November 2024, focuses on specific Good Clinical Practice (GCP) considerations that arise from the increased use of a broader range of design elements and data sources, such as decentralized trial components, pragmatic elements, and real-world data (RWD). These areas are becoming increasingly prominent in clinical research, and the annex addresses the unique challenges they introduce, providing guidance on regulatory considerations and best practices related to these evolving trial methods.
Now, turning back to the broader updates to the ICH E6(R3) guideline, significant changes have been introduced across several key areas: Data Governance, Sponsor Oversight, and Patient Engagement—all while minimizing risk to participants’ safety and well-being. Below are some of the critical implications for stakeholders:
1. Optimized Data Governance
Data quality and integrity: Organizations are now expected to place a stronger emphasis on ensuring data quality and integrity. This includes implementing robust data management systems, strategies, processes, and policies.
Data transparency and accountability: As part of improving data governance, sponsors must focus on enhancing record management and traceability. Effective procedures will be required to ensure data transparency, trustworthiness, and accountability throughout the clinical trial lifecycle.
2. Strengthened Oversight and Accountability
Clinical trial sponsors are required to increase oversight throughout the trial lifecycle to guarantee that processes implemented are incorporated into a quality-by-design framework. This ensures that quality is built into every stage of the trial process from the outset. Sponsors must apply a risk-proportionate approach to define roles, accountability, and responsibilities for all stakeholders involved in the trial conduct while retaining the ultimate responsibility for the entire trial execution.
3. Patient Engagement and Safety Preservation
Engaging patients early in the planning and protocol development phases can help reduce risk to participants. This collaborative approach improves resource utilization, optimizes protocol
compliance strategies, and enhances data collection, especially in trials using decentralized elements.
Key Steps for Implementing ICH E6(R3)
To achieve these goals and successfully implement ICH E6(R3), biopharma companies sponsoring clinical trials and CROs should consider the following actions:
- Conduct a gap analysis to assess current practices, identify areas for improvement, and define actions needed.
- Update or create Standard Operating Procedures (SOPs) to align with the ICH E6(R3) guidelines.
- Strengthen risk management and data management systems to ensure compliance with the updated requirements.
- Deliver comprehensive organization-wide training to educate all stakeholders on the new processes and the implementation of the updated elements of the guideline.
In summary, the revisions to ICH E6(R3) reflect the evolving landscape of clinical trials, emphasizing the need for robust data governance, enhanced sponsor oversight, and patient-centered approaches. As these updates continue to shape the future of clinical research, leveraging external experts is crucial. Their fresh perspectives on GxP compliance and areas for improvement can help organizations navigate the complexities of these new guidelines, identify gaps, and ensure adherence to the highest standards. By embracing these changes and expert guidance, organizations can not only stay ahead of regulatory requirements but also optimize their clinical trial processes, leading to improved outcomes and greater success.
Update on changes between the ICH E6 R3 draft guideline endorsed on May 19th, 2023, and the final Step 4 guideline document adopted on January 6th, 2025.
In addition to sentence combining, paragraphing, text insertion, renumbering, and styling, the Step 4 guideline document adopted on January 6th, 2025, includes a revision of important pieces for stakeholders, including Appendix C, where Essential Records for the Conduct of a Clinical Trial sits, and Section 4 Data Governance.
In the Essential Records section, three additional paragraphs were added in the Step 4 guideline document, identified as C.2.10, C2.11, and C.2.12. in section 2, Management of Essential Records. Also, the two tables previously included for essential records (Essential Records for All trials and Potential Essential Records) in the draft guideline are now consolidated in one Essential Records table, which provides guidance on “those essential records that should be generally in place prior to the start of the trial”
One additional essential record was incorporated in the Essential Records table:
“Documentation of the assessment of fitness for purpose for non-trial-specific computerised systems used in the trial (e.g., clinical practice computerised systems)”
This record is considered among those essential records that should be generally in place prior to the trial start.
Other changes are seen in section 4 Data Governance. Items 4.2 Data Lifecycle elements, 4.4 Security (formerly named Security of Computerised Systems in the draft guideline), and 4.5 Validation (previously Validation of Computerised Systems in the draft guideline) were adapted using renumbering, insertion, and paraphrasing.
For instance, additional paragraphs were included in 4.2 Data Lifecycle elements under item 4.2.7, “retention aspects,” stressing the need to archive trial data and metadata and ensure their retrievability and non-altered state. Item 4.2.8, “Destruction,” calls for the possibility of destroying trial data and metadata determined by regulatory obligations.
The validation subsection (previously 4.5), now item 4.3.4, is broken down, and the following paragraph was added:
“Periodic review may be appropriate to ensure that computerized systems remain in a validated state throughout the life cycle of the system.”
These changes reflect a more comprehensive and structured approach to these sections but do not change the guideline´s aim in any way.
To learn more about the changes introduced in the updated ICH E6(R3), view the webinar recording presented in December by this blog’s author: Inspection Readiness and the Updated ICH E6(R3): What to Anticipate.
At Allucent, our GxP strategy experts are here to assist you with every aspect of GxP compliance and to support your drug development program. Explore our comprehensive offerings on GxP compliance and inspection readiness.
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