1、USP: Quality Standards for Medicines USP: 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 app
2、roval 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 Documentar
3、y 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 to stre
4、ngth, 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 current
5、 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 Pharmacopeia
6、. . . 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 committed to FD
7、A 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.” “科学合理.”
8、 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总是使用药典方法作为“仲裁
9、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 & USP Reference Standards,Physical (Reference) Standards 实物标准（标准品） USP reference standards are developed to conduct compendial tests with legal presumption of suitability
10、. USP标准品开发用来执行药典中的检测，具有法律适用性。 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
11、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www.usp.org,9,USP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
12、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 彩色显微鉴别图，化学结构及色谱图 药典论坛 其他出版物,USP 标准收录范围,15,USP 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,17,USP与FDA: 超过一个世纪的合作历史,FDA和USP “通过建立和
13、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 UpdateUSP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67
14、弄11号楼,USP-China USP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
15、standards 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 China USP药典培训课程在中国,USP and FDA in China USP与FDA在中国,MOU between USP and Official Institutio
16、ns in China USP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
17、山东省药检所,Photo Food MOU Signing,MOU 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 China USP与中国官方签署合作备忘录,USP-China USP中华区总部,Our RS development laboratories are equipped with state-of-art analytical instruments and ISO 9001 and I
18、SO17025 certified that: 我们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 Assoc
19、iation program提供第三方测试服务（比如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 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 technical review an
20、d 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 (1-2 months) 专家委员会
21、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 are pharmaceuti
22、cal, 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 the Monographs Comi
23、ng From 标准从何而来,USP would like to work with more manufacturers 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 labsindustr
24、y, 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 (3 weeks) USP科学小组
25、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 Reference Standards y
26、early 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 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
27、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 citizenship image 有助于提高企业形象
28、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, FCC 或 DSC Free on-sit
29、e 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 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
30、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 证书,USP Appreciates Your Contribu
31、tion USP 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 include two orthogonal tests (IR abs
32、orption 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 often involve hazardous reagents
33、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 有机杂质测试方法应当是定量的，有选择性的，并且是具有稳定性指示的 HPLC proc
34、edures 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 pro
35、cedures 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 demonstra
36、te 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 Substances,Excipients,Noncomplex Active Drug Products,Biotechnology-der
37、ived Drug Products,Vaccines,Blood and Blood products,Gene and Cell Therapy Products,Dietary Supplement Ingredients,Dietary Supplement Products,Compounding-Substance/Preparation/Practice,Medical Devices, CottonSutures-DiameterSutures-Needle Attachment,Basic Elements, Analytical Instrument Qualificati
38、onPharmaceutical Dosage FormPharmacopeial HarmonizationValidation of Compendial ProceduresVerification of Compendial Procedures,Drug Product Distribution,Microbiology,General Notices 凡例,5.60.20. Residual Solvents in USP and NF Articles All USP and NF articles are subject to relevant control of residual solvents, even when no test is specified in the individual monograph.所有USP和NF中收录的产品都应进行相应的残留溶剂控制，即使产品各论中未要求此测试。,作为一个标准制定机构，USP将继续与全球有关各方紧密合作，与企业、行业协会、政府、采购商、分销商一起努力保障全世界人民获得优质的药品.,结束语,
