Botanical Drug Development and Quality Standards

The Center for Drug Evaluation and Research (CDER) established the Botanical Review Team in 2003, published a Guidance for Industry: Botanical Drug Products in 2004, and recently revised and published in 2015 a draft Guidance for Industry: Botanical Drug Development. The draft revised botanical guidance provides additional recommendations on quality, nonclinical, clinical, and other unique aspects associated botanical drug development. Most importantly in this guidance, FDA described a “totality-of-evidence” approach that overcomes the limited ability to characterize the entire botanical mixture or its active components by available analytical techniques. In addition to conventional Chemistry, Manufacturing, and Controls (CMC) data, this totality of the evidence approach considers other information including raw material control, clinically relevant bioassay(s), and other data generated based on a multiple-batch and multiple-dose clinical trial of the botanical product. The available evidence is used to ensure that the quality consistency of the botanical product is sufficient to ensure therapeutic consistency. The degree of reliance on these other data for ensuring consistency of quality depends on the extent that the botanical mixture can be characterized and quantified.

Since the publication of the botanical Guidance in 2004, over 400 botanical product INDs have been submitted to the Office of New Drug (OND) at CDER for clinical investigation as treatments for various diseases, such as cancer, infectious diseases, and arthritis, just to name a few. Two NDAs have been approved for marketing botanical products as prescription drugs in the US: Veregen (sinecatechins), a topical drug for the treatment of genital and perianal warts and Fulyzaq (crofelemer), an oral drug for the treatment of HIV/AIDS related diarrhea. These two NDA approvals show that new therapies derived from complex botanical mixtures can be developed to meet modern FDA standards of quality, safety, and efficacy as new drugs.