Is Your Active Pharmaceutical Ingredient (API) Manufacturable — Or Just Technically Feasible?

By Peter McDonald, Ph.D., Process Development Services (PDS) Director, API (small molecule)

In small molecule drug development, manufacturability is often treated as a secondary concern, addressed only after a synthetic route has been established and the molecule has advanced through early stages. However, by the time processes reach validation, the underlying chemistry is largely fixed, making late-stage changes costly, time-consuming, and potentially risky from a regulatory standpoint. Approaches that appear efficient at the laboratory scale can prove difficult to reproduce consistently or economically under the demands of large-scale production.

At its core, manufacturability is less about theoretical feasibility and more about whether a process can reliably perform under real-world conditions. This requires early evaluation of factors such as scalability, cost and availability of raw materials, process complexity, and potential operational or safety challenges. Addressing these considerations upfront allows for optimization of yields, simplification of workflows, and improved robustness throughout development.

Achieving this level of readiness also depends on strong collaboration across disciplines, including chemistry, analytical development, engineering, and operations. When these functions work in alignment, processes can be continuously refined with practical insights that support smoother transitions from early development through scale-up and beyond, reducing the likelihood of unexpected challenges later on.