US FDA's new guidance on product quality for botanical drugs

Since publication of the Botanical Drug Products guidance for industry in 2004, the U.S. Food and Drug Administration (FDA) has approved two botanical new drug applications (NDAs) and accepted more than 400 botanical investigational new drug (IND) applications and pre-IND requests (2004 – 2013). Like small-molecule drugs, botanical drugs intended to be marketed in the U.S. must show evidence of safety and efficacy and meet standards for quality. While conventional chemistry, manufacturing, and controls (CMC) data remain important quality control measures, botanical products can be complex and their active components may not be known. To address these challenges, FDA developed a science-based regulatory approach that consider “totality-of-the-evidence” pertinent to ensure the consistency of quality for all marketed batches of the product, one of the most critical issues for botanical NDAs. In addition to conventional CMC data, this approach considers information from the raw material control, clinically relevant bioassay(s), and other non-CMC data (e.g., clinical data from multiple doses and product batches). The extent of reliance on this additional information for ensuring the consistency of quality and thereby therapeutic effect will depend on the extent of chemical characterization of the botanical drug.