工艺验证和验证主计划 20120415.ppt

工艺验证与验证主计划 Process Validation and VMP 成都 四川 Chengdu Sichuan, 2012.04.17 汇宇制药 常丰凯 by Chang fengkai, Huiyu Pharma;质量管理工程与GMP 工艺验证 验证主计划 ;质量管理工程与GMP;质量管理工程与GMP;质量管理体系--因素控制 ;质量管理体系;历史背景 50年代的“反应停”（Thalidomide）事件 70年代的注射剂感染事故 美国 GMP published (由美国坦普尔大学6名教授编写，美国FDA以法令形式颁布) 1978 - Current Good Manufacturing Practices 1996 - FDA’s Final Rule - QSR 1997 - Part 11 (Electronic Records) 1998 - New Commissioner of FDA 2002 - Pharmaceutical CGMP for 21st Century Initiative 2006 - Quality systems approach to pharmaceutical CGMP regulations ;WHO 1967年 国际药典 附录 收录 GMP 90年代多次修订 欧共体 1972 GMP总则 1997 修订 2008 修订 其他国家和地区 ;1980s 引入GMP概念 正式颁布GMP 1992 修订GMP 1998 修订GMP 2010 现行GMP GMP是动态的 GMP仅指明要求，而不规定如何达到 GMP仅包括有价值而且可行的要求; VALIDATION - Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product or end result which meet its pre-determined specifications and quality attributes. 有文件证明、具有高置信水平的某工艺过程在符合预设指标及质量属性下能稳定的产出产品或最终结果。 Verification Qualification 工艺验证应当证明一个生产工艺按照规定的工艺参数能够持续生产出符合预定用途和注册要求的产品。 ; Establishing by objective evidence that a process consistently produces a result or product meeting its pre-determined specifications and quality attributes （FDA ） The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a product meeting its pre-determined specifications and quality attributes （EC） Process Performance Qualification， Establishing confidence that the process is effective and reproducible （FDA ） Process Qualification，Showing that the manufacturing processes operate within expected ranges and conditions (and achieve expected results) using challenge test, etc. （Japan Ministry of Health, Control Regulation） ;Requirement Document;常用典型分布 正态分布 二项分布 泊松分布 ;无菌测试 P(x=0)=C200(0.001)0 (0.999)20 =0.9802 P(x=1)=C201(0.001)1 (0.999)19 =0.0196 ;模拟分装 ;职责 物流与采购 工程 生产 研发