摘要
2016年12月美国FDA发布了《工业界植物药研发指南》最新定稿版,通过对美国FDA植物药指南新旧版本的对比发现,尽管FDA认同植物药传统应用经验的历史事实,并在早期临床研究中给予了“宽进”政策,但随着研发的深入,强调了全程质量控制、临床受试样品和原料与上市产品及其原料在质量和疗效上的一致性,保障终产品的“严出”。指南推荐了一批新的方法和思路,如从药材到成品质量控制的“证据链完整性法”、生物测定法、质量平衡法、多批次临床研究设计、剂量-响应效应等技术要求,以确保临床研究用原料、受试样品与拟上市用原料、成品的质量一致性,进而保障疗效的一致性;在监管上同时要求药材的GACP和中间体与成品的cGMP。
Abstract
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.
关键词
植物药研发 /
美国FDA /
指南
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Key words
botanical drug development /
FDA /
industry guidance
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王智民,刘保延,王海南,刘晓谦,高慧敏.
对美国FDA最新版《工业界植物药研发指南》的评述[J]. 中国药学杂志, 2017, 52(11): 905-909 https://doi.org/10.11669/cpj.2017.11.001
WANG Zhi-min, LIU Bao-yan, WANG Hai-nan, LIU Xiao-qian, GAO Hui-min.
Brief Introduction and Comment on the Final Revised Vision of Botanical Drug Development Guidance for Industry Issued by FDA[J]. Chinese Pharmaceutical Journal, 2017, 52(11): 905-909 https://doi.org/10.11669/cpj.2017.11.001
中图分类号:
R284
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参考文献
[1] U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. Botanical Drug Development Guidance for Industry[J/OL]. U.S. 2016,12. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM458484.pdf.
[2] YE Z G, LIU B Y,WANG Z M. Comment on FDA “Guidance for Industry on Botanical Drug Products”[J]. Chin J Inf Tradit Chin Med (中国中医药信息杂志),2001,8(4):1.
[3] WANG Z M,REN Q,YE Z G. In comparison of botanical drug application between FDA and SDA[J]. World Sci Technol/Mod Tradit Chin Med(世界科学技术—中药现代化),2001,3(5):46-49.
[4] U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. Guidance for Industry Q1A(R2) Stability Testing of New Drug Substances and Products[J/OL]. U.S. 2003,11. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073369.pdf.
[5] U.S. Department of Health and Human Services. Guidances (Drugs) [J/OL]. U.S. 2017,4. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
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脚注
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基金
国家食品药品监督管理总局软课题“中药新药研发模式及其注册管理思路研究”;国家中医药行业科研专项(201507002-3)
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