A Totality-of-Evidence Approach to Ensuring Therapeutic Consistency of Naturally Derived Complex Mixtures

Abstract

Botanicals are naturally derived complex mixtures that may contain multiple active components and considerable batch-to-batch variations (e.g., in chemical composition), and therefore pose a significant drug development challenge from a quality control perspective. To overcome this, the US FDA developed a totality-of-evidence approach. This approach utilizes, in addition to the conventional quality control by analytical testing, other evidence including raw material control, clinically relevant bioassay(s) and other data (e.g., clinical data relating to dose-response, and data generated based on multiple batches) to ensure consistency of product quality. Based on such a comprehensive assessment, the marketed botanical product batches can deliver therapeutic effects consistent with the product batches used in the clinical studies.