Current regulatory toxicology perspectives on the development of herbal medicines to prescription drug products in the United States

Abstract

a b s t r a c tToxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. The US food and drug administration (FDA) published a guidance to assist academic and industry sponsors in the development of this unique group of drug products, and has recently approved an new drug application (NDA) based on green tea extract (Veregen Ò ) for topical treatment of genital and perianal warts. In this article, current regulatory views on issues related to requirements and recommendations on various types of nonclinical toxicity studies in support of clinical trials and filing an NDA for a herbal medicine, including pharm/tox aspects of green tea extract (Veregen Ò ) NDA, are discussed. Topics include nonclinical pharmacology/toxicology perspectives on herbal nomenclature and its identification, previous human experience and initial clinical trial proposal, regulatory aspects of acute toxicity studies, chronic toxicity studies, mutagenicity studies, reproductive toxicity studies, and carcinogenicity studies on botanicals. Certain regulatory reviewrelated issues are also presented. It is anticipated that through a proactive two-way communication between the Agency and the sponsor, toxicological development of botanical drug product can be significantly facilitated.Published by Elsevier Ltd.

Evaluation of subchronic toxicity of the hydroethanolic extract of Tropaeolum majus in Wistar rats

“…In some countries like the United States, herbal medicine products are considered dietary supplements and the company is responsible for the safety of these products, that is regulated by Food and Drug Administration (FDA) (Jordan et al, 2010), but at the same time, when a plant is used for treatment of diseases, this will be classified as a drug, and its manufacturers must provide scientific evidence that the product is effective and safe for the human use (Wu et al, 2008). In the European Union, when natural products are used for therapeutic purposes they are classified as regular medications and their quality, efficacy and safety are regulated by the European Medicines Agency-EMEA (Jordan et al, 2010).…”

Cissus quadrangularis ethanol extract upregulates superoxide dismutase, glutathione peroxidase and endothelial nitric oxide synthase expression in hydrogen peroxide-injured human ECV304 cells

“…According to the US Food and Drug Administration guidance, genotoxicity testing of herbal medicines should be encouraged to avoid undesirable effect (Wu et al, 2008). Quercetin and resveratrol have been referred to induce genotoxicity (Carver et al, 1983;Schmitt et al, 2002).…”

Review of the regulations for clinical research in herbal medicines in USA

“…It provided a path towards development, approval and marketing of future herbal medicines. (54) Several unique issues were extensively discussed and considered by Botanical Review Team (BRT) in the NDA of Veregen. These included how to adequately demonstrate identification and control of the botanical raw material, how to demonstrate adequate characterization of the drug substance, how to ensure the therapeutic consistency of marketing batches, how to name the drug substance, and how to evaluate the pharmacodynamics/pharmacokinetics for a product with multiple active ingredients.…”