ABSTRACT
The approvals of first two botanical prescription drugs, Veregen (2006) and Fulyzaq (2012), mapped the framework to developing new therapies from natural complex mixtures in the US. To encourage and facilitate botanical drug development, the Food and Drug Administration (FDA) also published industry guidelines in 2004 and revised them in 2015. Under these regulations, botanical products intended to be marketed as drugs in the US are expected to meet the same standards as non-botanical drugs for quality, safety, and efficacy. While this is relatively straightforward for the clinical efficacy evaluation, botanical product quality and safety assurance require additional evidence-based chemistry, manufacturing and controls (CMC) data for raw materials, batch-to-batch consistency, and early adoption of clinically relevant bioassays. Extensive history of prior human use may reduce the early requirements for nonclinical pharmacology and toxicology for the initial (Phase I and II) clinical studies, but these data will be required for the subsequent Phase III and the final marketing approval. As a result, many botanical manufacturers in the US choose to develop and market their products as dietary supplements (i.e., Estrovera launched in 2010), while maintaining strict evidence-based preclinical and clinical programs to evaluate their safety and efficacy. For many botanical drugs, the path to new drug application (NDA) approval has the initial potential to be cheaper and shorter, but the lack of meaningful exclusivity to existing and less costly botanical dietary supplements is a significant disadvantage to rigorous botanical drug development.
