Chapter 4. Chemistry, Manufacturing and Controls: Active Pharmaceutical Ingredient and Drug Product

Chemistry, manufacturing and controls (CMC) for active pharmaceutical ingredients (APIs) and drug products (DPs) consists in understanding the chemistry behind the manufacturing process, in-process controls, acceptance criteria for drug substances and DPs and supporting stability studies. Guidance documents from the US Food and Drug Administration (FDA) and International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) assist novice readers with how to implement most of the CMC-related activities during development and commercialization activities. The development process for APIs and DPs follows the traditional approach of preclinical, Phase I (safety), Phase II (efficacy) and Phase III (statistical significance over existing therapy) and then final approval after filing a New Drug Application (NDA) by the FDA or marketing approval in the European Union (EU). This chapter (a) summarizes the CMC topics for APIs and DPs in general and (b) narrates the distinct activities required in each phase of development as the molecule progresses from early development to commercialization.