The Botanical Guidance

It should be emphasized that, in the above new approaches, only different types of information are used in part of the safety assessment. This does not imply that overall standards for quality consistency and clinical efficacy/ safety are more or less stringent than that of nonbotanical drugs. 

As evidence of prior human use, documentation of marketing history (with volume of sales) and review of past and current references, compendia, and literatures should be provided. It is understandable that many of these publications are in variable format and quality, and often do not consist of modern scientific data. In this respect, the Agency will accept all types of documentation for consideration and determine the validity of support in individual cases. 

As noted above, all botanical drugs contain many potentially active molecular entities and many preparations are combinations of multiple 

For details of the Guidance, the readers are referred to the official FDA website for botanical drug review (1). 

BOTANICAL REVIEW TEAM IN CENTER EOR DRUG EVALUATION AND RESEARCH 

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To acquire and consolidate regulatory experiences on botanical drugs, a dedicated BRT has been established in CDER. The BRT will provide scientific expertise on botanical issues to other reviewing staff to ensure consistent interpretation and implementation of the Botanical Guidance and related policies. In addition, the BRT has the following functions ... 

To implement the Botanical Guidance, a new set of review processes for botanical applications have been delineated in a new CDER MAPP (MAPP 6007.1 for Review of Botanical Drug Products). 

As provided in the Botanical Guidance, clinical studies have been permitted for many botanical preparations prior to a complete set of conventional animal toxicity testing. The decisions were not difficult for submissions with substantial and well-documented history of past human use. But some other applicants had not presented an adequate summary of the past human experiences and had failed even to document well-known toxicity of the herbal ingredients. Between these two extremes, how to adjust the requirements of animal toxicity data and substitute that with large quantity but poor quality of human experiences is another big challenge to the regulatory agency in the review of botanical applications. 

The CDER Botanical Review Team website http //www.fda.gov/cder/Offices/ ODE V BRT/default.htm provides links to many useful EDA Guidances and related documents, including the Botanical Guidance and MAPP. 

To implement the new Guidance, the CDER established a new Botanical Review Team (BRT) dedicated to the review of botanical specific issues in new drug applications (NDAs). A new Manual of Policies and Procedures... 

Schilter B, Andersson C, Anton R, et al. Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements. Food Chem Toxicol 2003 41(12) 1625-1649. 

The original edition classified botanical ingredients in four safety classifications to differentiate those that can be safely consumed when used appropriately from those for which some contraindication or other restriction is known, as well as those that should be used only under the guidance of a qualified expert. A handful of entries in that edition were also placed in a separate class if the editors had insufficient data for classification. The revised edition largely retains this safety classification system, except that if the review process did not provide enough information to make a knowledgeable decision on any specific herb, that species was removed from the text. 

Even as the consumer market for herbal supplement products expands and scientific information becomes more accessible, the goals of the second edition of the AHPA s Botanical Safety Handbook are essentially the same as those of the original edition. Companies that market herbal products are bound by federal regulations to disclose known safety concerns that may result from a product s use. Health care providers, especially those lacking in training or experience in the use of herbs, are in need of accurate data if they are to provide guidance to their patients who use herbs. And consumers of herbs and herbal products need readily understandable information to assist them in making safe and appropriate health care... 

Methods and considerations for safety evaluations that are outlined in the U.S. Institute of Medicine s (lOM) Framework for Evaluating the Safety of Dietary Supplements provided guidance in the literature collection and review processes that went into the creation of this text (lOM 2005). This lOM document also highlights the importance of using experts from a number of fields related to dietary supplements. Consistent with this advice, an advisory panel of qualified experts was assembled at the outset of this project. All members were selected for their extensive knowledge and experience in areas such as medicine, clinical herbalism, pharmacology, biochemistry, or traditional herbal medicine systems (e.g., traditional Chinese medicine or Ayurvedic medicine). When knowledge of a particular topic or botanical was not found in the Expert Advisory Council, the experience and opinions of outside experts were solicited. 

We foimd that the making of herbarium specimens was best managed by clear guidance from the trainers. We told which trainees to collect which plants. This allowed us, as a group, to make a significant contributions to our understanding of several botanically poorly known areas. As all the specimens collected by the... 

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