Botanical New Drugs: From INDs to NDAs

Botanical mixtures, although many widely used around the world for various health care purposes, have, for the most part, not been extensively studied through well-controlled clinical trials to demonstrate their clinical effects. Prior initiating human clinical trials of a botanical product in the US for diagnosis, prevention or treatment of a disease, an Investigational New Drug (IND) application to the FDA is required.

As the FDA's Guidance for Industry-Botanical Drug Products” (2004) has indicated, human experience can be used to expedite early phase clinical trials of a botanical product with a reasonably good safety profile. As the IND for a botanical drug advances to later phases, how to address the consistency of quality and therapeutic effects of the botanical drug for future new drug applications (NDA) is becoming extremely important. A starting point is to establish Good Agricultural and Collection Practice (GACP) and standardize the manufacturing procedures to minimize the naturally chemical variations from raw materials to the botanical drug substance. In addition to employ available qualitative and quantitative analyses for robust quality control of the drug substance, bioassays and multiple-batch clinical trials in phase 3 may be incorporated as part of a comprehensive approach to address the therapeutic consistency issue for a botanical NDA. The two FDA approved NDAs (Veregen 21902 and Fulyzaq 202292) will be used as examples to highlight the importance and challenging issues for bring botanical drug products to the US market.