FDA药品批准程序简介ppt课件

1、FDA Drug Approval ProcessFDA药品同意程序from Chemistry Manufacturing Controls Perspective化学消费控制(CMC)展望上海宝钜.New Drug Development Process新药的研发过程1. Research & Development (研讨和开发2. Pre-clinical Studies 药理毒理研讨3.Investigational New Drug (IND) Phase I, II, III Clinical Trials 临床实验4.New Drug Application (NDA) 新药恳

2、求5.Post-marketing 新药同意后的市场调查跟踪 Post-approval changes 同意后的消费工艺变卦.New Drug Development Process新药研发程序.New Drug Development Process新药研发程序新化学体有机合成天然产品临床前研讨理化特性生物活性预制剂研讨型新药恳求临床实验 I, II, III阶段新药恳求FDA审核同意前检查FDA操作市场调查跟踪IV阶段临床研讨副作用报告产品缺陷报告产品线扩展同意后CMC变卦研讨：长期动物毒性研讨产品剂型研发消费和控制包装和标签设计.恳求人(药品研发者)新药恳求NDA医学化学药学生物制药学

3、数据统计微生物学CDER审核不立档处置,发回绝信立档处置该恳求吗否是.Generic Drug Development Process非专利药开发过程1. API Process Development 原料药消费工艺开发2.Dosage Form Development 制剂的研发3.Bioequivalent Study 生物等效性实验4.ANDA Review 非专利药的审批- DS & DP manufacturing sites CGMP inspection DS和DP消费现场CGMP检查5.Post-approval Changes 同意后的消费工艺变卦.Drug Applica

4、tion 药品恳求NDA (IND) 新药Chemistry, Manufacturing, & Controls (CMC) 化学性，消费和控制CMCAnimal Studies 动物实验Bioavailability 生物有效性Clinical Studies 临床实验 ANDA 非专利药Chemistry, Manufacturing, & Controls (CMC) 化学性，消费和控制CMCBioequivalence 生物等效性.Bioavailability (BA) 生物有效性21 CFR 320.1(a) Defined as “the rate and extent to

5、which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action.“指“从医药产品中吸收到的，且能在作用位置产生有效作用的活性成分或其部分活性成分的比率和范围.Bioequivalence (BE) 生物等效性21 CFR 320.1(e) Defined as “the absence of a significant difference in the rate and extent to which the act

6、ive ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. 指“活性成分。在经适当设计的研讨中，在类似条件下，当 给药的摩尔剂量一样时，在药品的对应作用位置,其被利用的比率和范围没

7、有明显差别.Generic Drug 非专利药Definition 非专利药的定义A generic drug is identical, or bioequivalent to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use非专利药在药剂方式、平安性、强度、给药途径、质量、性能特征和运用用途上与专利药一样或者生物等效性一样。.Generic Drug Requirement非专利药

8、要求To gain FDA approval, a generic drug must: 要获得FDA的同意，非专利药必需：Contain the same active ingredients as the innovator drug (inactive ingredients may vary) 包括和新药一样的活性成分非活性成分可以有所不同Be identical in strength, dosage form, and route of administration 强度、剂型、和给药途径一样Have the same use indications 运用方法一样Be bioequ

9、ivalent 具有生物等效性Meet the same batch requirements for identity, strength, purity, and quality 符合同批药品在标识、强度、纯度和质量上的要求Be manufactured under the same strict standards of FDAs good manufacturing practice regulations required for innovator products 消费规范与FDA的GMP对于新药的严厉规范一样.Type of ANDA 非专利药恳求的分类No.Type of A

10、pplication申请类型Requirement要求1Paragraph I CertificationI类证书无专利存在2Paragraph II CertificationII类证书专利已过期3Paragraph III CertificationIII类证书专利没过期4Paragraph IV CertificationIV类证书向专利挑战.2002 年全球药品销售分析国家或地域销售US$)销售% 年增长北美203.6 51 12 %欧洲(EU)90.6 22 8欧洲其他 11.3 3 9日本46.912 1亚洲,非洲，澳洲31.6 8 11(日本除外拉丁美洲 16.54 -10总数

11、400 Billion100 % +8%Source: IMS原料药的年销售额估计约在 US$30-35 Billion (300-350亿美圆).2003-2004 年全球药品销售分析国家或地域销售US$)全球市场 年增长U.S. (美国)228.7 46.1% 10%Japan (日本) 55.411.1 3Germany (德国) 27.8 5.6 6France (法国) 26.4 5.3 7U.K. (英国) 18.4 3.7 11Italy (意大利) 17.9 3.6 6Spain (西班牙) 12.8 2.6 11Canada (加拿大) 10.5 2.1 1China (中国

12、) 6.6 1.3 19Mexico (墨西哥) 6.3 1.3 11 Top 10 (总数)410 Billion 82.6 % 9%Source: IMS, for the 12 months ending June 2004原料药的年销售额估计约在 US$40 Billion (400亿美圆).Worldwide Pharmaceutical Market by Sectors ($ Billions)世界药品市场分类单位：十亿美圆 20002001200220032021 增长*Ethical 317.1363.4401.0437.6677.8 9.1处方药Generic 24.0 2

13、7.030.537.064.0 11.6非专利药OTC 70.573.878.582.0101.0 4.3 Biophar-22.126.331.036.558.69.0Maceutical生物药Total433.7490.5541.0593.1901.48.7Source: IMS *Estimated from 2003 to 2021.Top 10 Therapies10大类药物Therapeutic Sale toShare of AnnualClassesJune 2004Global SaleChange药物 截至2004年 全球销售 年度分类 6月的销售额 份额 变化Choles

14、terol & triglyceride胆固醇和甘油三酸酯药物 28.1 5.6% 13%Antiulcerants抗溃疡药 24.9 5.0 5Antidepressant抗抑郁药 20.2 4.1 7 Antipsychotics安定药 13.2 2.6 9Antirheumatic nonsteroidals非类固醇类抗风湿药 13.1 2.6 3Erythropoietins红细胞生成素 11.0 2.215Antiepileptics抗癫痫药 10.4 2.121Oral antidiabetics口服糖尿病药 9.6 1.912Cephalosporins头孢菌素 8.5 1.7

15、2 Top 10 Therapy 150.3 Billion30.2% 10%10大药物 1503亿美圆Source: IMS, for the 12 months ending June 2004 来源：IMS，以2004年六月截至第12个月计.Top 10 Products (2003-2004)10大药品20032004Brand Name MarketerSales Annual(Generic Name)($ Billion)Change品名非专利药名 消费商 销售额十亿美圆 年度变化Liptor (Atorvastatin)辉瑞11.013%Zocor (Simvastatin)默

16、克 6.0 -9Zyprexa (Olanzepine)礼来 4.9 5Norvasc (Amlodipine)辉瑞 4.7 6 Plavix (Clopidogrel)赛诺非安万特 4.337BMSNexium (Esomeprazole)AstraZeneca 4.337Advair (Salmeterol葛兰素史克 4.230 fluticasone)Procrit (Erythropoietin)强生 4.1 0Prevacid (Lansoprazole)Takeda/Abbott 3.9 3Zoloft (Sertraline)辉瑞 3.612 Top 10 Products 10

17、大产品 $51.0 13%Source: IMS, for the 12 months ending June 2004 来源：IMS,截至2004年6月的12个月的数据.Drugs off U.S. Patent by 2007截至2007年美国专利到期的药品Drug NameMarketerSales Off Patent药品称号 消费商 销售额 专利到期日Diflucan (Fluoconazole)Pfizer辉瑞1.2 Billion 12亿2004Neurontin (Gabapentin)Pfizer辉瑞2.7 Prevacid (Lansoprazole)Takeda3.9 2

18、005Zoloft (Sertraline HCl)Pfizer辉瑞3.1 Zocor (Simvastatin)Merck默克6.0Norvasc (Amlodipine)Pfizer辉瑞4.3 2006Paxil (Paroxetine)GSK 葛兰素史克3.3Pravachol (Pravastatin)BMS2.8Resperdal (Risperidone)Janssen杨森2.0 2007Fosamax (Alendronate)Merck默克1.9 Zyrec (Certirizine)Pfizer辉瑞1.3 .Chemistry, Manufacturing and Contr

19、ols (CMC)化学性、消费和控制CMCCMC 的内容包括两大部分：I.Drug Substance 原料药部分a.As Part of CMC Section in an Applicationor Reference to a Drug Master File (DMF) 恳求或参考DMF时作为CMC的一部分b.CGMP Compliance of a Manufacturing Facility 消费车间符合CGMP规范II.Drug Product 制剂部分a.Part of CMC Section 作为CMC的一部分b.CGMP Compliance of a Manufactur

20、ing Facility 消费车间符合CGMP规范.Drug Master File (DMF) 药物主文件DMFTYPES OF DRUG MASTER FILES 药物主文件的分类Type I Manufacturing Site, Facilities, Operating Procedures, and Personnel I类 消费现场、设备、操作程序和人员Type IIDrug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product II类 药品原

21、料、药品原料中间体和配制过程中运用的资料，或者药品Type III Packaging MaterialIII类 包装资料Type IV Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation IV类 赋形剂、着色剂、香料、香精、或配制过程中运用的资料Type VFDA Accepted Reference InformationV类 FDA认可的参考信息.Drug Master File (DMF)药物主文件DMF在 FDA 注册 DMF 的有利之处维护原料药消费的工艺技术和商业有利于原料药消费商

22、寻觅多方面的客户表示原料药消费商已具有 CGMP 预备迈出了开发美国原料药市场的第一步.CGMP Inspection ProcessCGMP检查程序.CGMP Inspection ProcessCGMP检查程序NDA/ANDA恳求CMC审核其他审核规那么符合办公室地域办公室.CGMP Regulation & Guideline有关 CGMP 的文件 A.Code of Federal Regulations 21.210 and 21.211 有关制剂消费的CGMPB.ICH Q7A Good Manufacturing Practice Guidance for Active Phar

23、maceutical Ingredients (August 2001)有关原料药消费的 CGMP.System Based Current Good Manufacturing Practice (CGMP) 基于CGMP的系统Quality System 质量管理系统Material System 原资料系统Facilities and Equipment System消费设备和设备系统Production System 消费系统)Packaging and Labeling System 包装和标志系统Laboratory Control System 实验室控制系统.DMF Prepa

24、rationDMF文件的预备I.Conventional Format 传统方式- Accepted by FDA 被FDA所认可II.The CTD-Format (Module 3) CTD方式模板3- Accepted,Not Required by FDA FDA认可，但没有要求- Accepted by EU 欧盟认可.Drug Substance (API)原料药APIStarting Material原资料- Define starting materials and their specifications 确定原资料及其规格Process Control and Critical Parameters 工艺控制和关键参数 - Identifying critical process parameters 识别关键工