Critical API attributes and the major impact they can have on drug product development


Chemical process development of an active pharmaceutical ingredient (API) or drug substance and the pharmaceutical development of the final, formulated drug product from this API are frequently treated as independent activities in the overall process of developing a new drug.

To some extent this is born of necessity, since the drug substance must be generated and made available to pharmaceutical development before any product development activities can commence. As a result, chemical process development is often completed before the requirements of final formulation have been fully defined. However, both activities are intimately linked by the final purification and isolation step of the chemical synthesis and manufacturing process, which for solid APIs, most frequently, is a crystallization process. This final isolation should be carefully crafted to deliver the same solid form, which defines the inherent physical properties of the drug substance as well as process-dependent particle properties for every batch that is manufactured.

No matter how well-designed and robust the crystallization is, if its development lacks consideration for the particle properties required for formulation, the result may be an API that is difficult to handle or requires additional processing before manufacturing the final formulation. Conversely, not all APIs can be manipulated to deliver all attributes required for trouble-free formulation development and manufacturing activities. An integrated approach to product development can serve to avoid common pitfalls and focus efforts to where real issues exist as a result of a mismatch between the API properties and the requirements placed upon the formulated product.