Part 2 | ICH E6 (R3) Quality by Design: Transforming Clinical Trial Standards
The recent ICH E6 (R3) update is more than just another revision to Good Clinical Practice, it’s an invitation for the industry to rethink how trials are designed and managed. At the center of this shift is Quality by Design (QbD) and risk-proportionality, two powerful ideas that encourage us to build trials that are smarter, safer, and more flexible.
What Quality by Design Means
Quality by Design means planning for quality from the start, rather than relying on retroactive checks. Under ICH E6 (R3) organizations are encouraged to identify Critical-to-Quality (CtQ) factors, elements essential to participant safety and reliable results, and build safeguards around them during trial planning (ICH Final Guideline).
Mini-Case Example: In a Phase III oncology study, timely reporting of serious adverse events (SAEs) might be identified as a CtQ factor, using QbD principles, the sponsor could implement automated SAE alerts and define streamlined workflows to ensure near real-time reporting, reducing risk and increasing patient safety.
This shift has real advantages:
Quick Start Tips for QbD Implementation:
- Hold a Risk Assessment Workshop: Gather cross-functional stakeholders early in protocol development to identify CtQ factors and rank risks.
- Document Risk Controls: Align SOPs and monitoring plans to focus on the highest-priority risks.
- Leverage Technology: Use RBM and centralized statistical monitoring tools to track key indicators in real time.
Why Risk-Proportionality Matters
Not every trial carries equal risk, so oversight shouldn’t be one-size-fits-all. ICH E6 (R3) encourages tailoring the intensity of monitoring and quality checks to specific risk profile of each trial (FDA Summary of E6 R3, EMA Step 5 Guideline).
It’s about:
Potential Pitfalls:
- Overengineering Risk Plans: Too much complexity can slow implementation
- Lack of Training: Teams need to be familiar with risk assessment frameworks and prioritization.
- Siloed Thinking: Risk-proportionality works best when sponsors , CROs, and sites align early on.
What It Means in Practice
We know this won’t be “business as usual.” Implementing QbD and risk-proportionality will require:
- Rethinking monitoring strategies
- Updating SOPs
- Stronger cross-functional collaboration
- Leveraging technology for real-time risk tracking and oversight
Culture Change Matters: This shift is not just operational, it’s cultural. Organizations must move from a compliance-driven mindset to one of continuous improvement, encouraging teams to focus on what truly impacts participant safety and data quality.
Our View
At VGS, we believe that implementing QbD and risk-proportional thinking won’t just shape how trials are done, it can make them smarter and more resilient. We’ll continue to share perspectives as the industry adapts. The future of clinical trials lies in collaboration, and we’re excited to be part of the conversation.
Guidance To Explore
For those wanting to dive deeper into the details:
ICH E6 (R3) Final Guideline (Step 4, January 6, 2025) – The official reference text.
FDA Overview of ICH E6 (R3) – A clear outline of the changes and their implications.
EMA Step 5 Guideline – European regulatory perspective on implementation.
TransCelerate ICH E6 Asset Library – Practical tools and frameworks to support adoption (TransCelerate).
