Key points of toxicology research in international registration of botanical drugs / 中国药理学与毒理学杂志

In recent years, traditional Chinese medicine (TCM) has made great progress in the process of internationalization,but the share of TCM is still insignificant in the international market.One of the reasons is that it is difficult to submit the documents in accordance with the drug registration reguirements of Europe and America. In this paper,the requirements of the international drug registration of botanical drugs are briefly introduced,involving the status of botanical drug international registration, the provisions of toxicological studies on botanical drug registration requirements in the United States and Europe, the difference in toxicological research between China and the United States, and the focus of the international registration of toxicological research.

Regulation and new drug application of botanical drugs in the world / 中国药理学与毒理学杂志

This review summarizes the developmental history of natural products and research status of botanical products in different oversea countries. This paper outlines the regulation for new drug application of botanical drugs from the USA, European Union, and Japan. It also uses the Vergen (the first botanical drug approved by US FDA) as an example to discuss how to meet regulatory require-ments for new drug applications.

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.

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.