Critical API Attributes And The Major Impact They Can Have On Drug Product Development

By Dr. Peter Poechlauer, Thermo Fisher Scientific and Dr. Matthew Jones, Thermo Fisher Scientific

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.