Review
DOI DOI: 10.65239/botanicaldrugs.2026.02

CMC Challenges and Solutions in Botanical IND & NDA Development

— Lessons Learned from Four Approved Botanical Drugs

Roger Luo1
  1. 1 American Botanical Drug Association, USA

Abstract

Botanical INDs present unique challenges in chemistry, manufacturing, and controls (CMC) and quality assurance that distinguish them from conventional single-molecule drug development. Over more than two decades, the FDA has progressively constructed a fit-for-purpose regulatory pathway through two successive guidance documents (2004, 2016), the establishment of a dedicated Botanical Review Team within CDER, and the review of hundreds of botanical INDs. Central to this framework is the totality-of-evidence approach, which substitutes aggregate evidence from upstream raw material controls, chemical characterization, mechanistic bioassays, and multi-batch clinical data for the molecular certainty required of new chemical entity drugs. This review examines the four FDA-approved prescription botanical drugs, Veregen, Fulyzaq/Mytesi, NexoBrid, and Filsuvez, to illustrate their product-specific CMC challenges and the solutions that enabled their approvals, and the generalizable patterns that collectively define the totality-of-evidence framework as the governing regulatory architecture for botanical drug CMC development.

How to Cite

1.
Luo R. CMC Challenges and Solutions in Botanical IND & NDA Development: — Lessons Learned from Four Approved Botanical Drugs. Botanical Drugs [Internet]. 2026 Apr. 4 [cited 2026 Jul. 12];1:12-20. Available from: https://botanicaldrugs.org/index.php/pub/article/view/7
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