title: Regulatory toxicology perspectives on the development of botanical drug products in the United States.
abstract: Toxicological studies constitute an essential part of the effort in developing a botanical supplement into a drug product. The US Food and Drug Administration recently published a draft guidance and established a special botanical review team to assist academic and industry sponsors to manage this and other regulatory considerations related to this unique group of drug products. In this article, the current state of regulatory viewpoints on issues related to requirements and recommendations of various types of nonclinical toxicity studies in support of advanced phases clinical trials and filing a New Drug Application of a botanical are discussed. Topics include nonclinical pharmacology/toxicology view of previous human experience and initial clinical trial, regulatory perspectives on acute toxicity studies, chronic toxicity studies, mutagenicity studies, reproductive toxicity studies, and carcinogenicity studies on botanicals. Certain regulatory review-related issues are also presented. It is anticipated that through a proactive 2-way communication between the Agency and the sponsor, toxicological development of botanical drug product can be significantly facilitated.
authors.affiliation: The Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, Maryland 20852, USA. wuk@cder.fda.gov
authors.forename: Kuei-Meng
authors.initials: KM
authors.lastname: Wu
authors.forename: James
authors.initials: J
authors.lastname: Farrelly
authors.forename: Debra
authors.initials: D
authors.lastname: Birnkrant
authors.forename: Shaw
authors.initials: S
authors.lastname: Chen
authors.forename: Jinhui
authors.initials: J
authors.lastname: Dou
authors.forename: Aisar
authors.initials: A
authors.lastname: Atrakchi
authors.forename: Anita
authors.initials: A
authors.lastname: Bigger
authors.forename: Conrad
authors.initials: C
authors.lastname: Chen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.forename: Lois
authors.initials: L
authors.lastname: Freed
authors.forename: Hanan
authors.initials: H
authors.lastname: Ghantous
authors.forename: Anwar
authors.initials: A
authors.lastname: Goheer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hausner
authors.forename: Robert
authors.initials: R
authors.lastname: Osterberg
authors.forename: Herman
authors.initials: H
authors.lastname: Rhee
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D002986:Clinical Trials as Topic; D015507:Drugs, Investigational / Q000009:adverse effects*; D006801:Humans; D009152:Mutagenicity Tests; D028321:Plant Preparations / Q000009:adverse effects*; D014116:Toxicology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015507:Drugs, Investigational; D028321:Plant Preparations