Integrated Approach for Characterization of Highly Heterogeneous Drugs

The transformative evolution of the life sciences field is at an important point of convergence with data sciences, which is another dramatically evolving field. The advances in rapid, sensitive, and high-throughput analytical methods and “big data” approaches (deep sequencing, etc.) have led to an explosion of datasets in life sciences. This rapid accumulation of diverse data necessitates the development of scientific frameworks and concepts borrowing from the evolving data sciences field to make meaningful predictions and practical use of such data. An important practical application of this convergence is providing a scientific framework for regulatory guidance involving characterization of highly heterogeneous molecules that make up active pharmaceutical ingredients of complex drugs. This chapter provides a perspective on developing such a framework for characterization of highly heterogeneous drugs from the standpoint of demonstrating sameness or equivalence with a reference product. Using examples of recently approved generic versions of complex drugs, this chapter presents the concept of “test-points” (terminology used in design of integrated circuit boards) that capture critical relationships between structural attributes of the heterogeneous molecules, the process steps involved in generating the drug product, and the starting reagents or materials.