Botanical Drug Development-Guidance for Industry and Expert Views on Botanical Drug Development in the US / 世界科学技术-中医药现代化

The definition of new drugs in China and the US has no major differences on chemical drugs and biologics.However,Chinese medicines,which are regulated as over-the-counter (OTC) or prescription drugs in China,are mostly regulated as food and/or dietary supplements without FDA approved medicinal use for marketing.The FDA Guidance for Industry-Botanical Drug Products (2004) and the recently revised Guidance for Botanical Drug Development (2016) paved the way for Chinese herbal medicine and other botanical mixtures to be further developed as new drugs through clinical trials and other nonclinical studies.FDA recognizes the value of traditional medicines as part of the previous human experiences to support the safety and speed up early phase clinical trials of botanical products under investigational new drug (INDs) applications.The revised Guidance included addition recommendations for late phase development,like phase 2 trials and new drug applications (NDA),to resolve some of the unique challenges on batch-tobatch consistency (e.g.,a totality of evidence approach,including raw material control,bioassays,multiple-batch and multiple-dose clinical trials,and etc.).The approval of Veregen and Fulyzaq (now Mytesi) are new molecular entity / new chemical entity type of new drugs,treasured fruits from several hundred INDs studying botanicals.With those NDA examples,it is expected that further study of Chinese herbal medicines as new botanical drugs through further clinical and nonclinical development will be fruitful.On the other hand,long-term commitments are universal for new drug development.And it will also be true for bringing Chinese herbal medicines as botanical new drugs to international markets.It still takes time to see whether artesunate tablets can be verified through further clinical trials and achieve the same level of Coartem.

Focuses and difficulties in clinical study of botanical drugs based on revised guidance for Industry by FDA / 药学学报

This paper was prepared to analyze and discuss the main content of the Botanical Drug Development Guidance for Industry by United States FDA's (the draft version of the 2015), especially focused on the guidelines for clinical research (mainly in late-stage clinical studies) recommendations and requirements sectiones. The key and difficult issues in the late clinic study were analyzed and discussed, and a series of countermeasures were proposed in this paper. At the same time, combined with the case of approved botanical drug products, analysis of the guidelines for the development of plant drug regulations, the enlightenment were presented in the last part, to guide the research and development of traditional Chinese medicine and the internationalization of Chinese medicine.

Brief Introduction and Comment on the Final Revised Vision of Botanical Drug Development Guidance for Industry Issued by FDA / 中国药学杂志

Botanical Drug Development Guidance for Industry, replaced the Guidance for Industry on Botanical Drug Products issued in June 2004, was issued at December 2016. With the understanding and experience acquired in the reviews of NDAs and INDs for botanical drugs, specific recommendations have been modified and new sections have been added in this new edition. Compared new version with the old, "loose requirement" policy in early IND on consideration of prior human experience of botanical products was unchanged, but the requirements of quality and the rapeutic consistency on botanical raw material, drug substance and finished product in late-phase development and NDA submission for botanical drugs was very strict, especially, requirement to ensure that different marketing batches, with their variations, have the therapeutic effect consistent with those of the batches used in the phase 3 clinical studies. The new analytical methods, such as"totality of the evidence" approach, biological assays, mass balance of all ingredients, multiple batch analyses and dose-response effect, were introduced to ensure the quality and therapeutic consistency. The manufacturing of botanical drug substance should be in compliance with both GACP and CGMPs may be warranted to cover the way in which the botanical raw material is grown, collected, processed and stored.

European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development / 中国中药杂志

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development.