A Regulatory Perspective for Manufacture of Complex Drug Substances

The quality of chemically synthesized, small-molecule drug substances usually can be characterized by routine analytical testing. In contrast, for drug substances that are polymeric molecules (e.g. peptides), heterogeneous mixtures (e.g. heparins, glatiramer acetate, etc.), or molecular complexes (e.g. iron sucrose), the structure and impurity profile are more complex than small-molecule drugs, and generally cannot be characterized easily by analytical means. As a result of this complexity, quality control of these complex drug substances cannot solely rely on analytical testing. The identity, impurity profile, and content of complex drug substances are highly dependent on their manufacturing process as well as raw material and in-process controls. This presentation will discuss a regulatory perspective for manufacture of complex drug substances in support of both new drug and generic drug applications.