Integrating the "Collective Unconscious": The Patterns Behind FDA CRLs and How to Break Them

Carl Jung may not immediately spring to mind when you think of Chemistry Manufacturing & Control (CMC) but his insights into the human psyche provide a surprisingly sharp lens for understanding the complexities of pharmaceutical development. While success in our industry depends on seamless scalability and technical precision, the path to market is frequently derailed by Complete Response Letters (CRLs). Avoiding these regulatory setbacks requires more than just a better data set; it demands a fundamental shift in how we manage the "unseen" knowledge within our organizations. 

Drawing an analogy from analytical psychology, we can view a company’s technical expertise as a "collective unconscious". This is a reservoir of shared experience and tacit insights, what some might call "institutional know-how" or "tribal wisdom", that often goes unwritten. A common challenge of R&D and manufacturing activities is that tacit knowledge is difficult to disseminate through documentation alone. A combination of both data and knowledge (explicit or tacit), is critical to ensure the product lifecycle is effectively managed; it helps to ensure quality control, quality risk management, product realization, and support continuous improvement. iAchieve provides context, context that is difficult to capture in documentation.

The Shadow in the Data: Why Knowledge Gaps Trigger CRLs 

When the FDA issues a CRL, they are essentially shining a light on the "shadows" of a CMC submission. Our analysis of over 200 redacted CRLs from 2020–2024 shows that reviewers often flag issues where the narrative does not match the data. These "shadows" represent the missing links in process understanding that the technical team assumes is obvious, but is never explicitly documented. 

This lack of transparency creates significant risks for CMC readiness: 

• Knowledge Stagnation: When insights are trapped in static documents, they cannot be easily retrieved to justify process changes to regulators. 

• The "Brain Drain" Effect: If the scientists who designed the original experiments leave, their tacit knowledge (the why behind the what) disappears. This leaves the company unable to effectively respond to specific FDA queries. 

• Narrative Mismatches: Discrepancies between high-level Module 3 summaries and actual data tables often trigger additional scrutiny.  

Bringing the ‘Unconscious’ to Light with iAchieve® 

Jung believed that self-actualization involved bringing the unconscious to light. For a Tech-CMC company like APC, this means surfacing tacit expertise and merging it with explicit logic using our digital platform, iAchieve®. 

iAchieve® acts as the nexus where these two realms converge. By creating a "living" CMC knowledge ecosystem, we ensure that your CMC readiness is grounded in more than just a snapshot in time: 

1. Absolute Traceability: Decisions and rationale are connected to experimental data in real-time, ensuring that "tribal wisdom" is converted into documented proof¹⁹. 

2. Proven Process Portability: Knowledge packages are "transfer-ready," ensuring performance holds across different sites and scales. 

3. Proactive Risk Mitigation: Digital twins and AI-driven insights allow professionals to predict risks before they result in a CRL. 

Linking experimentation, data analysis, decisions, and ultimately process descriptions in a hierarchical manner, supports the typical CMC workflow. Not only must data be readily available, but the knowledge that contextualizes and homogenizes it as well.  

The Future of CMC: A Harmonious Convergence 

By embracing this Jungian perspective, CMC professionals can bridge operational silos and transform the "collective unconscious" of their technical teams into a strategic regulatory advantage. Integrating documented "know-how" with AI-enabled tools allows for a science-first approach that moves beyond outdated "retrofit manufacturing". 

Ultimately, digitizing tribal wisdom into a single source of truth ensures that your process logic is as robust as the science itself. This precision allows companies to respond to CRLs with confidence, ensuring that life-saving therapies reach patients without unnecessary delay.