USPQualityStandardsforMedicinesUSP药品质量标准

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 LawFederal 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 approval

2、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 regulationsFDA的法规Developed by FDA under authority granted by FFDCA在FFDCA法律框架下由FDA建立FDA guidanceFDA指南Non-binding, but indicates FDAs thinking非法规，但体现FDA的考虑Recognition of USP in FFDCA Documentary StandardsS

3、ection 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 to strength, quality,

4、 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 current Good Manufactur

5、ing 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 Pharmacopeia . . . National Form

6、ulary, 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 StandardsUltimately, 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 committed to FDA to use it, or if it

7、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.” “科学合理.”Manufacturer must assure

8、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总是使用药典方法作为“仲裁方法”。USP是“法定分析方法”ORA, CPG Se

9、c. 420.400 Performance of Tests for Compendial Requirements on Compendial Products (CPG 7132.05) FFDCA & USP Reference StandardsPhysical (Reference) Standards 实物标准（标准品）USP reference standards are developed to conduct compendial tests with legal presumption of suitability. USP标准品开发用来执行药典中的检测，具有法律适用性。

10、No further characterization required as primary standards.作为法定标准品不需进一步的标定（直接使用）FDA guidance requires testing of in-house standard against a primary reference standard (USP or other).FDA指南要求内部标准品要按法定标准品（USP或其它）标定。Introduction to United States Pharmacopeia 美国药典委员会简介8关于USP科学、独立的非营利组织成立于1820年，其出版的美国药典-国

11、家处方集是被联邦法律认可的美国国家药典。 核心工作是为处方药、非处方药、辅料、食品补充剂和食品成分建立质量标准全球各地设有分支机构：美国、巴西、印度、中国和瑞士9USP的使命建立有助于提高药品食品质量、安全性和效用的公共标准及相关方案，以改善全世界人民的健康状况。USP的建立USP 全球分布20102015 届专家委员会13核心药典项目美国药典-国家处方集 (USPNF) 超过4300个各论225章通则食品化学法典(FCC)超过1000个各论150 个通用测试章节食品补充剂标准综合USP-NF和FCC中的相关各论 提供检测方法和标准 提供综合法规信息-FDA, 联邦贸易委员会和产业组织 彩色显

12、微鉴别图，化学结构及色谱图药典论坛其他出版物Type of Article 产品分类Inclusion Criteria 收录标准Therapeutics (drug substances, drug products, biologics)治疗性产品（原料药，制剂，生物制品）USP: approved by US FDA 已被FDA批准Pending： submitted/intended to submit for FDA approval 已递交FDA进行审批或准备提交FDA进行审批的药物Non-US: approved by stringent regulatory authority

13、 other than FDA, for marketing outside USA被FDA之外其它严格的药物管理机构批准，并在美国之外上市的药物Excipients辅料NF: listed on FDAs Inactive Ingredients Database 收录于FDA的非活性成分数据库Dietary Supplements食品和营养补充剂DSC: Listed by FDA as an ODI or NDI (old or new Dietary Ingredient)被FDA列入ODI或NDIFood Ingredients食品成分FCC: Food ingredients le

14、gally marketed in any country with a regulatory food safety agency; Commercially available任何国家经过食品安全机构批准上市的食品成分USP 标准收录范围15USP 标准品可提供超过2,500 种标准品用于支持FDA强制执行的USPNF 中的标准和测试100.0% 纯度保证 (标签另有说明除外)16药典相关项目认证服务 (GMP认证计划)食品补充剂食品补充剂原料药用原辅料药典培训协助美国政府国际援助署（USAID）在发展中国家进行促进药品质量的项目17USP与FDA: 超过一个世纪的合作历史FDA和USP

15、“通过建立和监控用于医药和保健产业的质量标准共同承担促进公众健康的责任。USP标准对FDA而言是非常重要的工具，确保（产品）符合我们的监管标准并保障公众免受假药伤害。” - FDA局长Margaret Hamburg, USP 大会, 2010年4月USP:药品公共标准建立和修订，包括剂量、纯度、质量、包装和标签FDA:执法安全性, 有效性, NDA/BLA/ANDA 上市前审批, GMP生产等.USP-China Activities Update USP中华区总部概况USP-China 成立于 2007年9月 USP-China Site: USP 中国地区总部地址上海浦东张江高科李冰路6

16、7弄11号楼USP-ChinaUSP中华区总部Offer technical assistance to customers that use USP compendial methods and reference materials. 向药典和标准品用户提供技术支持Provide Pharmacopeial Education and training classes in the region 提供药典培训课程Promote a voluntary cGMP USP Verification Program 推广USP cGMP认证项目Work with industry on stan

17、dards and monograph development 与企业界合作开发标准和标准品Coordinate the Collaboration with China Regulatory Agencies 协调与中国官方的合作USP User Forum: USP Free Courses USP 用户论坛: USP的免费课程USP Pharmacopeia Education Courses in ChinaUSP药典培训课程在中国USP and FDA in ChinaUSP与FDA在中国MOU between USP and Official Institutions in Chi

18、naUSP与中国官方机构签署的合作备忘录Chinese Pharmacopoeia Commission 中国药典委员会NICPBP/China中国药品生物制品检定所Shanghai Institute for Food and Drug Control上海市食品药品检验所Beijing Drug Control Institute北京市药检所Zhejiang Drug Control Institute浙江省食品药品检验所Guangzhou Drug Control Institute广州市药检所Shandong Drug Control Institute山东省药检所Photo Food

19、MOU SigningMOU Signing Ceremony between USP and NINFS of CDC中国疾控中心营养与食品安全所与美国药典会合作备忘录签字仪式MOU between USP and Official Institutions in ChinaUSP与中国官方签署合作备忘录USP-ChinaUSP中华区总部Our RS development laboratories are equipped with state-of-art analytical instruments and ISO 9001 and ISO17025 certified that:我们

20、的标准品开发实验室配备先进，通过了ISO9001认证以及ISO17025实验室认可：performs collaborative testing to qualify USP reference material 执行USP标准品的协作标定test samples that were submitted as part of USP Verification Program 对参加USP认证项目的样品进行测试offer 3rd party testing services such as USP-Natural Products Association program 提供第三方测试服务（比如

21、与美国天然产品协会的合作项目）USP-China Laboratory美国药典中华区分部实验室书面标准各论、通则、凡例about 1400 drug substance monographs; 2000 drug product monographs; 360 excipient monographsExample: Pioglitazone Monograph in USP 34举例：吡格列酮各论,收录于USP34USP标准建立流程Scientific Liaison performs technical review and drafts the monograph (2-3 months

22、)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 (1-2 months)专家委员会投票 Monograph is published in official publ

23、ication (USP-NF, FCC, etc) (3 months)各论正式发布ApprovedNot approvedStandards 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 are pharmaceutical, food, and dietary supplement industries, ma

24、nufacturers, 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 the Monographs Coming From标准从何而来USP would like to work with more manu

25、facturers from ChinaUSP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 three 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USPBulk

26、 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 (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

27、-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 Reference 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 hal

28、f 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 candidatesUSP 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 specifications 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, be

29、cause 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 citizenship image 有助于提高企业形象Copies of the multi-laboratory collaborative testing results with traceabili

30、ty 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, FCC 或 DSCFree on-site USP Pharmacopeia Education course免费现场药典培训One year, multiple user license of el

31、ectronic USP-NF一年多用户电子版USP-NFUSP Reference Standards免费USP标准品Recognition on the USP Web SiteUSP官方网站致谢Recognition in the USP-NFUSP-NF出版物致谢USP Annual Science Meeting RecognitionUSP年度科学大会致谢Provide RS Candidates to USP提供标准品给USPDonors will receive USPs summary data package and a traceability statement aft

32、er 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 证书C e r t i f i c a t e o f A p p r e c i a t i o nIn recognition ofYOUfor the donation of a complete monograph for drug

33、or substance name, which may become an official, public USP standard.USP expresses sincere appreciation to company name for its participation in the public standards-setting process in support of the USP mission:To improve the health of people around the world through public standards and related pr

34、ograms that help ensure the quality, safety, and benefit of medicines and food.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

35、案做好准备参与标准评价？Identification tests:鉴别测试It is preferred to include 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Colorime

36、tric and wet chemical tests are not preferred since these 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 q

37、uantitative, selective and stability-indicating 有机杂质测试方法应当是定量的，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 necessaryUSP正在努力实现各论的现代化The following changes are 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