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 The US Food and Drug Administration recently published a draft guidance and established a special botanical review team to assist academic and industry sponsors to manage this and other regulatory considerations related to this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.

Toxicological study on Glinus lotoides: A traditionally used taenicidal herb in Ethiopia

“…When botanical formulation is prepared through modern extraction methods, it is helpful to have information on equivalency of the proposed product to that used traditionally or historically in terms of the daily amount and dose recommended (Wu et al, 2004). The traditional mode of administration of Glinus lotoides is to orally consume about 20 g of the whole powdered seeds as suspension in 'tella', the traditional beer made from barely, and this amount is believed to remove the tapeworm completely from the intestine of the patient (Kloos, 1976;Djote, 1978;Endale et al, 1997Endale et al, , 1998.…”

Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats

“…The most essential part in the pre-final stage of product development is to provide all necessary information towards safety and efficacy of the raw material (Schoneker et al, 2003;Wu et al, 2004). In the present investigation, clinical safety is evidenced from the increased body weight and unaltered weight of vital organs, clinical biochemical parameters, serum testosterone and histopathology of vital organs.…”

Morfoanatomia de folhas e caules de Passiflora edulis Sims, Passifloraceae

“…Os nomes comuns podem contribuir na confusão entre espécies vegetais (Wu et al, 2004). Por exemplo, no país, a designação popular 'maracujá' inclui diversas espécies do gênero Passiflora.…”