Earlier this month, the U.S. Food and Drug Administration released over 200 Complete Response Letters (CRLs) as part of a new transparency initiative. These letters, once confidential, outline the reasons why certain drug and biologics applications were not approved between 2020 and 2024.
While many CRLs cite familiar issues like safety and efficacy, a recurring and less discussed theme stood out: poor quality Chemistry, Manufacturing, and Controls (CMC) documentation. In fact, according to recent analysis, approximately 74% of these CRLs referenced CMC or manufacturing-related deficiencies, underscoring the critical role that clear, consistent, and well-organized Module 3 content plays in regulatory decision making.
One CRL stated:
“Module 3 of your BLA is not well prepared. Submitting a large number of reports with minimal data interpretation did not allow for an efficient review process.”
These letters confirm what regulatory professionals already know: the quality of content in Module 3 matters. Poorly structured or inconsistently interpreted information can slow reviews, trigger additional questions, or even contribute to rejection.
From Clinical to CMC: The Next Phase of Intelligent Automation
Yseop’s Copilot platform is already trusted by leading pharmaceutical companies to generate compliant, scalable content for clinical documents such as study reports and patient narratives. Expanding into CMC is a natural and strategic next step, addressing a growing challenge for regulatory teams working under increasing pressure, shorter timelines, and expanding data volumes.
Clinical and CMC documentation both require precision, traceability, and strict compliance with global standards. They demand close collaboration across scientific, quality, and regulatory functions. Both face the same pressures: limited expert resources and overwhelming documentation loads.
That’s why automation is no longer optional. It’s mission-critical.
Introducing Yseop’s CMC Automation Solution
Yseop’s first CMC-focused offering automates the Quality Overall Summary (Module 2.3), a central component of regulatory submissions that pulls structured insights from Module 3.2.
While the initial offering is centered on the QOS, it ensures consistency and traceability with the related sections in Module 3.2, such as stability and batch analyses, control of the drug substance/drug product. Built in full alignment with ICH M4Q(R1), the solution enables regulatory teams to:
- Generate structured QOS drafts in minutes
- Extract and summarize content from internal source documents that feed into Module 3.2, ensuring alignment without introducing new interpretation
- Update late stage elements like stability and batch data with a single click
- Ensure consistency and traceability across linked sections of Modules 2.3 and 3.2
As the volume and complexity of CMC data continue to grow, manual content generation is becoming increasingly unsustainable. Automation allows teams to scale documentation output, reduce time-to-submission, and stay audit-ready, without sacrificing quality. It directly addresses many of the issues highlighted in the CRLs released by the FDA earlier this summer.
It also significantly reduces the risk of human error, ensuring content is reproduced precisely and consistently, critical when working with high quality, high stakes data. Yseop’s automation integrates seamlessly with existing systems, minimizing manual rework and allowing subject matter experts to focus on value-added tasks like data validation, regulatory strategy, and risk assessment.
Preparing for ICH M4Q(R2)
In May 2025, the International Council for Harmonisation released the draft version of ICH M4Q(R2), a major update to the structure, clarity, and expectations for CMC documentation. Full adoption is anticipated by June 2027.
More than a structural revision, M4Q(R2) represents ICH’s first formal step toward shaping the future of digital transformation in regulatory submission and assessment. It introduces principles that support structured data exchange, future ready content workflows, and enhanced consistency across global submissions.
Yseop is actively preparing for this change. Once the guideline is finalized, we will deliver updated templates and help customers implement workflows that reflect these new standards, helping regulatory teams transition smoothly and confidently.
What’s Next: A CMC Roadmap Shaped by Industry Needs
Following the release of our Quality Overall Summary module, we will expand support to include Stability, Batch Analyses, and additional sections of Module 3. Our long-term vision is to empower regulatory teams to author, update, and manage all CMC documents at scale, with full control and confidence.
This roadmap is being built in close collaboration with regulatory and CMC leaders across the industry. As expectations rise and ICH M4Q(R2) approaches, now is the time to modernize how CMC content is created, reviewed, and maintained.
Built for Life Sciences, Recognized by Industry Leaders
Yseop was recently featured in Gartner’s 2025 Hype Cycle for Life Sciences Manufacturing, under the “Generative AI for Life Sciences” category. This recognition underscores our commitment to regulated content and our deep alignment with industry-specific needs.
If you lead a CMC or regulatory affairs team and are exploring ways to improve documentation quality, reduce cycle times, and prepare for ICH M4Q(R2), Yseop is ready to help. Let’s connect here and shape the future of CMC documentation together
