USP+药品质量标准2011.1.15.ppt

1、USP: Quality Standards for MedicinesUSP: 药品质量标准,操洪欣CRM, USP-China,美国与药品标准相关的法律,US Drug Law,Federal Food, Drug, and Cosmetic Act (FFDCA) 联邦食品药品化妆品法 Basic text that governs all pharmaceutical, medical device, food, cosmetics, dietary supplements 管理药品、医疗器械、食品、化妆品和膳食补充剂的基本法律 Includes requirements for ap

2、proval to market a drug 包括对药品上市批准的要求 Portions relevant to USP also apply to biologics 涉及USP的部分同样适用于生物制品 FDA regulations FDA的法规 Developed by FDA under authority granted by FFDCA 在FFDCA法律框架下由FDA建立 FDA guidance FDA指南 Non-binding, but indicates FDAs thinking 非法规，但体现FDA的考虑,Recognition of USP in FFDCA Doc

3、umentary Standards,Section 501(b): A drug is adulterated “if it purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength differs from, or its quality or purity falls below, the standard set forth in such compendium. Such determination as

4、to strength, quality, or purity shall be made in accordance with the tests or methods of assay set forth in such compendium” 以下情况判为假药 “其声称为药典收录的药品名称，而其效力不同于、或其质量或纯度低于药典中所设定的标准。对效力、质量或纯度的判断应当根据药典中所设定的分析方法或测试而得到” Section 501(a)(2)(B): A drug is adulterated if it is not manufactured in accordance with

5、current Good Manufacturing Practices (cGMPs) 若药品未按照cGMP规范生产视为假药 cGMP regulations require testing of each batch of finished drug product to ensure that it meets defined specifications. cGMP法规要求最终产品每批检测，以保证产品符合既定的标准 Section 201(j): The term “official compendium” means the official United States Pharma

6、copeia . . . National Formulary, or any supplement . . .” 术语“official compendium” 意思是法定美国药典国家处方集及其增补本,FFDCA Requirements for Conformance to USP Documentary Standards,Ultimately, the product must conform to the compendial standard. 最终，制剂产品必须符合药典标准。 USP-NF method must be used if the company has commit

7、ted to FDA to use it, or if it is the only appropriate test 以下情况必须使用USP-NF方法：如果生产商向FDA承诺使用，或者USP-NF的方法是唯一恰当的方法 In other cases, manufacturers can use an alternative test method if it is: 其他情况下生产商可以使用替代方法，如果（替代方法）： At least as stringent as the compendial method and 至少和药典方法一样严格，并且 “Scientifically sound

8、.” “科学合理.” Manufacturer must assure conformance to USP standard “by suitable means, including adequate manufacturing process validation and control.” 生产商必须“通过恰当的方式，包括充分的生产工艺验证和控制”保证符合USP标准。 FDA will always use the compendial method as the “referee test.” USP is “regulatory analytical procedure” FDA总

9、是使用药典方法作为“仲裁方法”。USP是“法定分析方法” ORA, CPG Sec. 420.400 Performance of Tests for Compendial Requirements on Compendial Products (CPG 7132.05),FFDCA 2000 drug product monographs; 360 excipient monographs,Example: Pioglitazone Monograph in USP 34举例：吡格列酮各论,收录于USP34,USP标准建立流程,Scientific Liaison performs tech

10、nical review and drafts the monograph (2-3 months) 科学联络人进行技术审核，草拟各论,Monograph is received/development initiated 收到各论，启动流程,Monograph is published for public review and comment (3 months) 发布各论供公众评议,Scientific Liaison submits all comments to Expert Committee 科学联络人向专家委员会提交评议,Expert Committee ballots (1-

11、2 months) 专家委员会投票,Monograph is published in official publication (USP-NF, FCC, etc) (3 months) 各论正式发布,Approved,Not approved,Standards Acquisition标准收集,We identify sponsors that can propose monographs and reference materials to USP for development into standards 确定可以提供分析方法和样品的发起方，与USP合作开发制定标准 Sponsors

12、 are pharmaceutical, food, and dietary supplement industries, manufacturers, government, academia 发起方可以是药品，食品，膳食补充剂生产企业，也可以是政府或科研机构 Collaborate with the sponsors to get the right information test methods, validations, etc. required for standard development 与发起方合作获得标准开发所必需的信息，包括测试方法，验证数据等,Where Are t

13、he Monographs Coming From标准从何而来,USP would like to work with more manufacturers from China USP希望与更多中国生产商合作建立标准,Example: Pioglitazone Monograph in PF36（1）举例：吡格列酮各论,收录于PF36（1）,Reference Standard Development标准品开发,Material is tested and characterized through collaborative testing involving a minimum of t

14、hree labsindustry, FDA, and USP (3 months) 物料在至少3个实验室进行联合标定-企业，FDA和USP,Bulk material is obtained from industry 从企业获取原料,Data from the collaborative study are reviewed by USP staff scientists ( 1week) USP科学人员审核联合标定数据,Compilation of collaborative study is reviewed and balloted by USP scientific teams (

15、3 weeks) USP科学小组审核联合标定汇总数据并投票,Once approved, material subdivided, labeled & QC (1-2 months) 批准后，分装、贴标及QC程序,USP Expert Committees review for suitability for use in USP documentary standards (2 weeks) USP专家委员会审核标准品的适用性,Submit a Reference Standard提交标准品,USP releases about 360 new lots of official Refere

16、nce Standards yearly USP 每年正式发行约360个新批次的标准品 Half are brand new to our catalog, and half are replacement lots for existing standards 其中半数为新加入的标准品，另有一半为现有标准品的更新批次 USP appreciates your support on RS candidates USP 欢迎国内企业提供标准品候选样品,Benefits of Participation参与对于企业的利益,Direct impact in setting the USP speci

17、fications for the donated material/monograph 通过提供样品和方法直接影响USP规格的制定 Competitive advantage, because your standard is used and enforced by regulatory authorities 竞争优势，因为您的标准是官方标准并被强制执行 Public recognition by USP through its Donor Recognition Program 通过USP质量标准合作方认可（表彰）计划获得公众认可 Enhanced corporate citizens

18、hip image 有助于提高企业形象 Copies of the multi-laboratory collaborative testing results with traceability to your reference standard 提供给企业标准品标定的多实验室联合标定结果和可追溯性说明,Donor Recognition Program USP质量标准合作方认可计划,Free workshop registrations 专题学术讨论会免费注册 Free print subscription to either USP-NF, FCC or DSC 免费印刷版USP-NF

19、, FCC 或 DSC Free on-site USP Pharmacopeia Education course 免费现场药典培训 One year, multiple user license of electronic USP-NF 一年多用户电子版USP-NF USP Reference Standards 免费USP标准品 Recognition on the USP Web Site USP官方网站致谢 Recognition in the USP-NF USP-NF出版物致谢 USP Annual Science Meeting Recognition USP年度科学大会致谢,

20、Provide RS Candidates to USP提供标准品给USP,Donors will receive USPs summary data package and a traceability statement after lot release 在批次放行之后，样品提供者会收到由USP颁发的样品联合检测数据汇总报告和可追溯性说明 Traceability provides link between USP standard and in-house standard 可追溯性说明为生产厂家提供了USP标准和生产厂家内部标准之间的相关性,USP Certificate USP 证

21、书,USP Appreciates Your ContributionUSP 感谢您为公众健康的贡献,Evonik Rexim (Nanning) Pharmaceutical 南宁赢创美诗药业,陕西汉江制药,技源科技（中国）有限公司,Status of Rosidlitazone Monograph罗格列酮标准开发状态,USP已经收到罗格列酮标准提案 USP已经收到罗格列酮有关标准品物料的捐赠 罗格列酮 罗格列酮有关物质A 富马酸 马来酸 计划在2011年公布提案,做好准备 参与标准评价？,Identification tests: 鉴别测试 It is preferred to inclu

22、de two orthogonal tests (IR absorption and HPLC retention time comparison) 首选方法包括两个正交试验（红外光谱和液相色谱保留时间的比较） TLC procedures and UV-visible absorption tests are may not always be orthogonal to HPLC procedures 薄层色谱和紫外可见吸收法不一定是高效液相色谱法的正交试验 Colorimetric and wet chemical tests are not preferred since these

23、often involve hazardous reagents or lack specificity 比色法和湿法测试并非首选，因为这些方法往往涉及到危险试剂或缺乏专属性,Current Trends 标准发展趋势,The inclusion of tests for Organic Impurities adds value to monographs 有机杂质测试方法的收录将有助于提高各论的价值 Organic Impurities procedures should be quantitative, selective and stability-indicating 有机杂质测试方

24、法应当是定量的，有选择性的，并且是具有稳定性指示的 HPLC procedures for Organic Impurities are preferred over TLC or spectrophotometric tests 有机杂质的高效液相色谱方法优于薄层色谱或光度法,Current Trends 标准发展趋势,Monograph Modernization各论现代化,Efforts are in process to modernize USP monographs where necessary USP正在努力实现各论的现代化 The following changes are

25、targeted: 目标是完成如下的变化 Replace* TLC procedures with HPLC procedures 用HPLC方法替代TLC方法 Add tests for organic impurities where these are not available 目前没有有机杂质测试方法的地方需要增加该内容 Replace* packed column GC procedures with capillary GC procedures 用GC 毛细管方法替代GC填充柱方法 Replace* titrimetric procedures with HPLC procedures 用HPLC方法替代滴定法 *Note: Need to demonstrate that the new procedure is “equivalent to or better than” the existing procedure,USP General Chapters Guide,USP General Chapters,Official Articles,General Applicable,Noncomplex Active Drug Substances,Biotechnology-derived Drug Sub