Introduction to CMC

Introduction to CMC

By Cheryl Berkowitz

When new acquaintances learn that I have worked for over 10 years in the Pharma industry, I am frequently hit with a barrage of comments and questions – Why are medicines so expensive? Must medicines be thrown away the day after the expiry date? Do they become dangerous? How are new medicines discovered? Why does it take so long for a newly discovered drug to be marketed as a medicine?

The answers to these questions lie largely in the realm of Chemistry, Manufacturing, and Controls (CMC). What is this world of CMC? CMC is a link that connects clinical batches of a drug (those intended for investigational purposes only, with no requirement for validation of process or analytical methods) to commercial batches (which are characterized by full validation). This ensures that the drug used in clinical studies is the same drug that is eventually marketed commercially and made available to consumers. It provides assurance that the drug sold to the public will have quality attributes in line with those of the drug demonstrated to be safe and effective, assures that the quality of the drug consistently meets appropriate quality standards, and assures that the drug prescribed and administered is the same as the one described on the drug label. CMC provides evidence that the manufacturing process of a drug is under control, control that is vital to quality and consistency. Ultimately, CMC ensures that patients will have access to consistently efficacious, safe, and high-quality pharmaceutical and biopharmaceutical drug products.

CMC is not a “one-size-fits-all” set of processes, nor is it a list of tests that must be performed on every product. Rather, it must be tailored to the specific platform and delivery system of the drug, whether injectable, controlled-release, inhalant, topical, solid dose, oral, etc. In addition, CMC applies to both the drug product (the manufacturing process; quality control release testing; specifications and product stability) and the facility in which a product is manufactured (design; qualification; operation; maintenance). The world of CMC brings together formulation researchers and developers, people who work in the manufacturing facility (“on the floor”), analytical and biological quality control lab personnel, stability coordinators, and, of course, CMC writers who are responsible for preparing the documentation required for submission to regulatory authorities around the world. Drug and health product submissions are submitted in a “common technical document” (CTD), and share a standard format for the technical documentation of clinical trial applications such as an investigational medicinal product dossier (IMPD) in Europe and the Food and Drug Administration’s (FDA’s) investigational new drug (IND) application in the US, as well as EU marketing authorization applications and FDA new drug applications (NDAs) or biologics license applications (BLAs). CMC Module 3 (Quality) is a module—and world!—unto itself.