Botanical drug applications

Participates in all phases of reviews, meetings, and decisionmaking processes for all botanical drug applications and submissions as a collaborative scientific discipline, and serves as an expert resource for CDER on all botanical issues. 

BOTANICAL DRUG APPLICATIONS IN CENTER FOR DRUG EVALUATION AND RESEARCH... 

As of April 30, 2004, there are a total of 203 botanical drug applications in CDER, including 167 investigational new drug (IND) applications and 36 pre-IND consultations. At least 75% of the total botanical applications were submitted after 1999, and about two per month were received by the Agency recently. 

In view of the multiplicity of CYPs and the many possible botanical-drug interactions, highly efficient clinical study designs using CYP probe cocktails have been explored. Following successful application to St. John s wort, other botanicals that have been evaluated in this fashion include echinacea (42), saw palmetto (43), garlic (39), peppermint oil, and ascorbyl palmitate (44). The results are summarized in Table 1. Curbicin, a botanical... 

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... 

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). 

What are some considerations influencing a botanical investigational new drug (IND) application A botanical IND application should be filed if the proposed product contains crude plant extracts, partially purified plant extract fractions, or a combination of highly purified compounds from different plants. A botanical IND application should also be filed if a proposed product contains a single herb, multiple herbs, or a botanical alone or with additional active components such as vitamins, minerals, or animal parts. 

NDI status is granted by the BRT (Section 6.2, Botanical Drug Products) when the team does not contest the application submitted by the advocating commercial or private interest. The application must contain evidence ensuring the safety of the NDI. Typically two thirds of the applications are rejected due to unresolved safety and identity issues. The burden of proof of reasonable safety of the NDI falls directly on the applicant. Unfortunately, applicants typically provide only anecdotal safety information. Typically, it is based on folkloric or traditional uses and does not include appropriate or relevant clinical data. 

Is the BCS that was developed with reference to chemically characterized and well-defined synthetic drug substances relevant for application and or adoption to botanical preparations (8) If one assumes, as is reasonable, that bioavailability of the active component(s) in a botanical dosage form depends on both solubility and permeability, the solubility of the botanical extract could be controlled through appropriate formulation technology and dissolution testing. The applicability of the BCS to botanical preparations will certainly be increasingly researched, debated, and discussed in the coming years. 

Collects information, maintains a database of botanical applications, and performs periodic analysis on the status of botanical new drug development. 

These review processes for botanical applications have been tested in CDER with approximately 100 submissions. Collaborations between BRT and the new drug divisions have been smooth and productive. 

A great majority of botanical sponsors have taken advantage of the pre-IND consultation service provided by FDA. As a result, most IND applications were successful with initial submission and few (less than 20) were placed on clinical hold for safety concerns. However, despite the early success, many development programs and research projects have subsequently been suspended for various reasons. As of the above-mentioned cutoff date (April 30, 2004), nearly two-thirds (66%) of INDs still remain active (have not been placed on clinical hold, inactivated by FDA, or withdrawn by sponsor for lack of activities). To date, there have been no submissions of NDAs to FDA for marketing approval of botanical prescription drugs. 

Efforts are under way to make the USP-NF more useful worldwide. Incorporation of monographs for multi-vitamin products, biotechnology-derived products, veterinary drugs, and botanicals and other dietary supplements help. The US AN and USP Dictionary of Drug Names has wide international applicability, thereby making it a repository of International Names Nomenclature (INN) and British Adopted Names (BAN), as well as U.S. Adopted Names (USAN). Pharmacopeial Forum now contains announcements of proposals from the Japanese Pharmacopeia and European Pharmacopeia for revision of standards for international harmonization. 

Among the various prerequisites for a perfect quality proof of these herbal drugs, authentication and safety proof take first precedence. Identification was in former times primarily synonymous with the macroscopic and microscopic botanical authenticity. Since that time, however, chemical composition and particularly the complex entities of the low molecular constituents have become of greater interest for oral medicinal application and thus in evaluating the pharmacological effects and therapeutic efficacy of the plant drug extracts obtained by decoction or other extraction processes. 

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