Translating Science To Success: CMC Strategies That Drive Market Readiness

By Neha Shah, Ph.D., and Kiran Pedada, Ph.D.

Early decisions in Chemistry, Manufacturing, and Controls (CMC) establish the trajectory for a drug's journey, from first-in-human studies to commercial success. A practical framework for early-phase CMC development must integrate preformulation insights, scalable formulation strategies, Quality by Design (QbD), and proactive risk management to reduce downstream complications.

Strategic early formulation involves balancing constraints like limited Active Pharmaceutical Ingredient (API) with long-term goals of scalability and global registration. Implementing QbD from the outset helps define a robust design space by mapping Critical Quality Attributes (CQAs) and critical process parameters. Furthermore, a phase-appropriate analytical validation strategy and embedding regulatory strategy from day one are crucial for aligning development with long-term approval goals.

Two case studies illustrate this approach: one resolved a complex colonic delivery challenge by leveraging the API's intrinsic gelling properties, and the other overcame a high drug load/poor flow challenge for a virtual client by pivoting to a modular, lower drug load formulation.