Scientific and Regulatory Approach to Botanical Drug Development: A U.S. FDA Perspective.

The United States FDA has received over 800 botanical investigational new drug applications (IND) and pre-IND meeting requests (PIND) in the years preceding 2018. The current data show that indications for submitted INDs cover nearly every review division of the FDA. Despite increasing global interest in the investigation of botanical mixtures as drug products, only two botanical new drug applications (NDA) have been approved in the U.S.: Veregen in 2006 and Fulyzaq (also known as Mytesi) in 2012. Given botanicals' chemical and biological complexity, efforts in characterizing their pharmacology, demonstrating therapeutic efficacy, and ensuring quality consistency remain scientific and regulatory challenges. The FDA published a revised document in December 2016 to address developmental considerations for late-phase trials and to provide recommendations intended to facilitate botanical drug development. Herein, we present an analysis of botanical INDs showing their variety of botanical raw materials (e.g., coming from different geographic regions, single vs multiple herbs), the varied levels of previous human experience, and therapeutic areas, as well as provide an overview of experience and challenges in reviewing botanical drugs.