Newsletter

ICH GCP E6(R3) reached Step 4 adoption on January 6, 2025, with EU enforcement starting July 23, 2025, and UK implementation expected by mid-2026. U.S. and global adoption will follow. The revision sharpens expectations for how sponsors manage outsourced trial activities, moving from documentation to demonstrable oversight. Section C.3.3 requires sponsors to show how service providers are selected, managed, and monitored, and to maintain essential records—not just documents—including audit trails and decision rationales. For highly outsourced models, especially in biotech, this marks a significant accountability shift. Celito is actively supporting sponsors in adapting to these new standards with practical, risk-based QA solutions. 

What’s New: Oversight Expectations Under ICH GCP E6(R3) 

• From Essential Documents to Records: Expands oversight scope to include electronic systems data, communication logs, and decision documentation. Evidence of sponsor oversight needs to be maintained within the TMF. (Appendix C) 
• Embedding Quality by Design (QbD) and Risk-Based Oversight: Oversight must focus on critical-to-quality factors and align with risk-proportionate audit strategies (Section 3.10.1.1).  
• Managing Serious Non-Compliance: Section 3.12.2 requires procedures for detecting and reporting non-compliance that affects participant safety or data integrity. 

Barriers to Implementation 

• Legacy Oversight Models: Traditional governance and reactive management fall short under R3. 
• Unclear Ownership of Records: Sponsors often lack visibility and control over records distributed across service providers’ systems. 
• Delayed QA Involvement: QA must be involved early in service provider selection – not post-engagement. 
• Limited Risk-Based Infrastructure: Many sponsors lack tools, processes, or trained staff for risk-based oversight. 
• Restricted Access to SOPs and Metrics: Contracts often miss provisions for accessing service provider SOPs and metrices, as required by Section 3.6.8. 

Practical Steps Sponsors Must Take 

1. QMS Gap Assessment: Benchmark against R3 and implement corrective actions. 
2. Define Records and Roles: Clarify what constitutes essential records, who (Service provider or Sponsor) owns them, and how they’re accessed. 
3. Develop Risk-Proportionate Oversight Plans: Align oversight with QbD principles and study risk. 
4. Qualify Service Providers Diligently: Assess systems, compliance history, and capabilities.  
5. Monitor with Performance Metrics: Use KPIs & metrics to track performance; build document access requirements into contracts. 
6. Leverage Real-Time Tools: Use dashboards and analytics for visibility in service providers’ important trial activities.  
7. Document Oversight: Record decisions, follow-ups, and issue resolution to demonstrate compliance. 
8. Audit Based on Risk: Tailor service provider audit program to risk of outsourced services and past performance of the service provider.  
9. Engage QA Early: Embed QA early in service providers’ selection to proactively identify risks.  

How Celito Supports Sponsors 

Celito provides end-to-end support to help sponsors meet ICH GCP E6(R3) expectations through risk-based, inspection-ready oversight framework and comprehensive service provider qualification and auditing services. With experience supporting 70+ biotech companies and conducting audits in over 50 countries, our team brings deep regulatory knowledge and operational insight. We tailor QA solutions to each development phase, integrate Quality by Design into trial execution, and deliver actionable insights through advanced analytics. Our approach also incorporates cybersecurity best practices, ensuring data protection and regulatory alignment at every stage. 

Conclusion

ICH GCP E6(R3) raises the bar on sponsor oversight—especially in outsourced trials. Sponsors must adopt structured, risk-based oversight and maintain essential records that demonstrate control. With the right strategy and support, these requirements can drive both compliance and trial quality. Celito is here to help sponsors lead this transformation.