美国FDA顾问药品生产企业验证培训(中英对照).pdf

© Copyright Globepharm, 20051FUNDAMENTALS AND ESSENTIALS OF VALIDATION验证基础及实质验证基础及实质Michael Anisfeld （（Dr.麦克麦克.安斯菲尔得）安斯菲尔得） Globepharm Consulting© Copyright Globepharm, 20052课程安排COURSE SCHEDULEINTRODUCTION + REGULATORY ENVIRONMENT 介绍＋法规环境介绍＋法规环境 VALIDATION BASICS 验证基础知识验证基础知识 VALIDATION MASTER PLANS 验证主文件验证主文件PROCESS VALIDATION 工艺验证工艺验证 UTILITIES VALIDATION 公用系统验证公用系统验证 CLEANING VALIDATION 清洁验证清洁验证 COMPUTER VALIDATION 计算机系统验证计算机系统验证 ANALYTICAL METHOD VALIDATION 分析方法验证分析方法验证CASE STUDY 案例研究案例研究© Copyright Globepharm, 20053HousekeepingCourse Notes 课程注意课程注意 Master List Surveys Are You Lost ? English – American ? Mobile Phone–Beepers-Pagers Restrooms Fire Drill Breaks and Ending Messages from Office Airport ?© Copyright Globepharm, 20054培训期间During this Training SessionIf如果如果: 1. I go too fast我讲的太快我讲的太快 2.I use strange words我使用陌生词语我使用陌生词语 3.I get too technical 我讲的太专业我讲的太专业 Please Interrupt and Ask …. There Is No Such Thing As A Silly Question 请随时打断我，并提问。

请随时打断我，并提问© Copyright Globepharm, 20055请大家自我介绍WHO ARE YOU?Tell Us Your NAME 告诉我你的名字告诉我你的名字 Tell Us Your COMPANY告诉我你的公司告诉我你的公司 Tell Us Your JOB 你的职务你的职务 Tell Us The PRODUCTS YOUR COMPANY MAKES你公司生产的产品你公司生产的产品 Tell Us YourEXPERIENCE WITH VALIDATION有关验证的经验有关验证的经验 Tell Us What SPECIFICALLY YOU CAME TO LEARN你想了解的内容你想了解的内容© Copyright Globepharm, 20056Dr.麦克.H.安斯菲尔得MICHAEL H.ANISFELDIndustrial Pharmacist 执业约师执业约师 Industrial Pharmacy Faculty – University of Illinois毕业于伊利诺伊州州立大学药学系毕业于伊利诺伊州州立大学药学系 Has trained FDA and MCA inspectors培训过培训过FDA ＆＆MCA检查官检查官 Perform audits on behalf of UN agencies and governments代表联合国＆政府部门进行审计代表联合国＆政府部门进行审计 Performs 25 – 35 full scale audits annually每年进行每年进行25－－35个审计个审计 Has audited in 32 countries 对对32个国家的医药企业进行过审计个国家的医药企业进行过审计 Guides clients through FDA, MCA, TGA, HPFBI and other inspections 帮助客户通过帮助客户通过FDA,MCA, TGA, HPFBI及其他官方机构的现场检查及其他官方机构的现场检查© Copyright Globepharm, 20057© Copyright Globepharm, 20058验证VALIDATIONVery Arduous L engthy I nvolved and D etailed Attempt to Test EverythingDefinition 定义非常 辛苦非常 辛苦周期长棘手详细的周期长棘手详细的试图要 测试 所有事务试图要 测试 所有事务© Copyright Globepharm, 20059验证原理及要素FUNDAMENTALS AND ESSENTIALS OF VALIDATIONSREGULATORY ENVIRONMENT法规环境法规环境© Copyright Globepharm, 200510质量QUALITY“a comprehensive system, designed, documented, implemented and controlled, furnished with personnel, equipment and resources, to provide assurance that products will be consistently fit for, and appropriate to, the intended use”一个全面的质量体系， 包含了设计，文件，执行，控制， 以及提供足够的人员、仪器、资源， 为了确保产品能持续达到既定目标。

一个全面的质量体系， 包含了设计，文件，执行，控制， 以及提供足够的人员、仪器、资源， 为了确保产品能持续达到既定目标© Copyright Globepharm, 200511工艺验证PROCESS VALIDATION[FDA]“establishing, through documented evidence, a high degree of assurance that a specific process will consistently produce a product that meets its predetermined specifications and quality characteristics”通过文档记录，建立一个高水平的保证，既在特定的工艺下能生产出符合既定标准的产品通过文档记录，建立一个高水平的保证，既在特定的工艺下能生产出符合既定标准的产品 FDA: Proposed cGMP Rules (21CFR211.3b24), May 1996© Copyright Globepharm, 200512验证目的VALIDATION OBJECTIVEASSURANCE OF CONSISTENCY确保连续性确保连续性 ?Consistency Is Great 连续性很重要连续性很重要?? Inconsistency, or Poor Consistency, Is Terrible 不连续或连续性不好是很糟糕的不连续或连续性不好是很糟糕的© Copyright Globepharm, 200513概念性定义CONCEPTUAL DEFINITIONInstruments Are Calibrated仪器被校验仪器被校验Processes Are Validated工艺被验证工艺被验证Equipment Is Qualified设备被确认设备被确认© Copyright Globepharm, 200514验证不是Validation IS NOT:Validation is not developing the process 验证不是工艺研发验证不是工艺研发 Validation is not an experiment 验证不是试验验证不是试验 Validation is not process optimization 验证不是工艺优化验证不是工艺优化 Validation is not a process capability study 验证不是生产能力研究验证不是生产能力研究 Validation is not “worst case testing” 验证不是最坏条件测试验证不是最坏条件测试 Validation is not writing the SOP 验证不是写验证不是写SOP Validation is not re-inventing the wheel 验证不是彻底重来做验证不是彻底重来做 Validation is not a voyage of discovery 验证不是探索记录验证不是探索记录验证应该是令人很郁闷的！验证应该是令人很郁闷的！© Copyright Globepharm, 200515验证VALIDATION [PIC]“action of proving, in accordance with the principles of GMP, that any procedure, process, equipment, material, or system actually leads to expected results”符合符合GMP原则的校对，既所有程序、工艺过程、设备、物料、系统实际上导致预期的结果。

原则的校对，既所有程序、工艺过程、设备、物料、系统实际上导致预期的结果 Pharmaceutical Inspection Convention GMPs, 1991© Copyright Globepharm, 200516验证VALIDATION [PIC]PIC 5.21“validation studies should reinforce GMP and be conducted in accordance to defined procedures. Results and conclusions should be recorded”PIC 5.21 验证研究应强化验证研究应强化GMP，应遵照既定程序执行所有结果＆结论应进行记录应遵照既定程序执行所有结果＆结论应进行记录 PIC 5.22“when any new manufacturing formula or method of preparation is adopted, steps should be taken to demonstrate suitability for routine processing”PIC 5.22 当新生产配方或制备方法被采用时，应采取措施表明常规操作的适用性。

当新生产配方或制备方法被采用时，应采取措施表明常规操作的适用性 Pharmaceutical Inspection Convention GMPs, 1991© Copyright Globepharm, 200517验证VALIDATION [PIC]PIC 5.23“significant amendments to the manufacturing process, including any changes in equipment or materials which may affect product quality and/or the reproducibility of the process should be validated”PIC 5.23 生。