精益清洁验证案例分析.ppt课件

1、精益清洁验证 案例分析CLEANING VALIDATIONA LEAN CASE STUDYJPT ConsultingKeith Powell-EvansContent 目录1. Cleaning Strategy p 1 9 清洁策略2. Cleaning Validation p 9 19 清洁验证 A) Objective p 9 目标 B) Scope p 9 范围 C) Approach: 方法: Family/ Grouping p 9 14 族/组 CV Tests/ Limits p 15 清洁验证测试/限度 CV Life-cycle p 16 清洁验证生命周期 Docu

2、ment structure p 17-18 文件结构 Clean Hold Time p 19 清洁持续时间3. Summary p 20 概要Cleaning Strategy 清洁策略Described in SOP- xxx 在SOP-XXX中进行描述COP: Parts washers (incl. COP baths)COP:零件清洗机(包括COP批次)CIP: Cleaning by CIP skids Chromatography cleaning UF/DF cleaningCIP:由在线清洁(CIP) SKID进行清洁色谱清洁UF/DF清洁Equipment 设备Equip

3、ment 设备1) COP LOCATIONS COP位置 COP-001COP-002COP-003COP-0044CIP-008CIP-002CIP-001CIP-005CIP-006CIP-0072) CIP Locations: CIP位置CIP-0095CHR-012CHR-001CHR-004CHR-0113) CIP skids Chromatography & UF/DF: CIP 色谱与UF/DFCHR-010CHR-013FIL-005FIL-014FIL-009FIL-0086Example of CIP circuit：1) Process schematic:CIP管

4、路示例： 1）工艺图ProductVessel产品罐ProductVessel产品罐BufferVessel缓冲罐Example of CIP circuit: 2) Schematic for cleaning CIP管路示例： 2）清洁图ProductVessel产品罐ProductVessel产品罐BufferVessel缓冲罐CIP SUPPLYCIP供应CIP RETURNCIP返回CIP SUPPLYCIP供应CIP RETURNCIP返回CIP SUPPLYCIP供应Cleaning Overview (Continued)清洁概述(续)12456 3Typically 6 cl

5、eaning Phases: 典型的6个清洁阶段:PRE-RINSE PHASE 预先冲洗阶段WASH 1 (Caustic) 洗涤1(碱)3) POST RINSE 后冲洗4) WASH 2 (Acid) 洗涤2(酸)PRE QUALITY RINSE 高质量冲洗FINAL RINSE (hot WFI) 最后冲洗(热注射用水)Cleaning Overview (Continued)清洁概述(续)Specific cleaning procedures 具体的清洁程序= how to prepare to be cleaned systems 如何准备清洁系统= Cleaning Reci

6、pe to be used, which defines: 所使用的清洁方法,其规定:Flows 流量Times 时间Concentration cleaning agents 清洁剂浓度Temperatures 温度Dirty Hold Time/ Clean Hold Time脏东西保持时间/清洁保持时间= defined in SOP- xxx 在SOP-XXX中进行规定Cleaning Validation (CV)清洁验证 VAL-VMP- xxxObjective: Demonstrate cleaning efficiency (incl. Dirty Hold Times) a

7、nd Clean Hold Times目的:证明清洁效率(包括脏东西保持时间)以及清洁保持时间2. Scope: 范围:COP: Parts washers 零件清洗机CIP: Cleaning by CIP skids 用在线SKID清洁 Chromatography SKID cleaning 色谱SKID清洁 UF/DF SKID cleaning UF/DF SKID清洁Cleaning Validation (CV)清洁验证VAL-VMP- XXX3.Approach: 方法: Product (Drug Substance) dedicated产品(原料药)专用 COP: Vali

8、dation of max. loadCOP:最大装量验证 CIP: Family/Groups worst case (see next pages) 族/组最差情况 (见后页)Downstream bufferPreparation下游缓冲制备CV Approach (continued) : CIP Family/Grouping 清洁验证方法(续):CIP族/组 Process Schematic:工艺图Media preparation培养基制备Purification 提纯Harvest 收获Cell culture 细胞培养Final Formulation成品配置Downstr

9、eam bufferPreparation下游缓冲制备Upstream bufferPreparation上游缓冲制备Drug Substance Contact Systems (DSCS) 原料药接触系统Non-Drug Substance Contact Systems (non-DSCS) 非原料药接触系统GROUPING APPROACH 组方法 FAMILY APPROACH 族方法For the DSCS the CV Families are based on:对于原料药接触系统,清洁验证族基于:CIP system (e.g. CIP-00 x, CIP-00y,.) CIP

10、系统Equivalent manufacture and operational functionality (e.g. seed bioreactors vs product vessels)等同制造与操作功能性(如,种子生物反应器与产品罐)Equivalent design (e.g. vessels vs transfer lines)等同设计(如,罐与连管线生产)Equivalent cleaning method 等同清洁方法= cleaning sequence, chemical agents and concentrations, temperatures and minimu

11、m durations during the wash phases (cfr. SOP- xxx) 清洁次序,化学试剂与浓度,温度与在清晰阶段最短时间(参考SOP-xxx)CV Approach (continued) : Family approach worst cases清洁验证方法(续):族方法最坏情况= CV Families are defined 确定清洁验证的族The worst case selection is based on an assessment of:选择最坏情况基于评估:Location = relative CIP distances 位置=相对CIP距离

12、Design = surface area, number of subcircuits设计=表面面积,支路数量Position within manufacturing train 在制造序列的位置= e.g. product vessel used during first DS operations is considered less worst case than an equivalent product vessel used within the last DS operations如,在最早原料药操作中使用产品罐可以考虑比最晚原料药操作中使用产品罐的最坏情况小 CV Appr

13、oach (continued) : Family approach worst cases清洁验证方法(续):族方法最坏情况Remark: worst case product selection is not applicable since systems are product dedicated 注:由于系统专用,不接受最坏情况产品选择For the non-DSCS two groups are identified:对于非原料药接触系统,识别两个组:Media group 培养基组Buffer group 缓冲组Similar manufacture and operationa

14、l functionality and design. 相似的制造与操作方式以及设计Similar cleaning method with regard to cleaning sequence, chemical agents and concentrations, temperatures and minimum durations during the wash phases (cfr. SOP- xxx)在清洁先后次序,化学试剂与浓度,温度与冲洗阶段最短时间相似的清洁方法(参见SOP- xxx)CV Approach (continued) : Family approach wor

15、st cases清洁验证方法(续):族方法最坏情况The worst case selection is based on sound scientific rational:最坏情况选择基于良好的科学原理:MIX systems and worst case media or buffer = most concentrated and highest risk with repect to cross-contaminationMIX系统与最坏情况的培养基或缓冲=交叉污染方面最浓的与最高风险FF Buffer vessel = because of its position within

16、manufacturing train (and risk of a theorethical impurity to end up in the final product bulk)FF缓冲罐=因为其位置在制造序列中(以及理论杂质直到最终原料药中风险)CV Approach (continued) : Family approach worst cases清洁验证方法(续):族方法最坏情况 CV approach (continued): CV Tests / Limits清洁验证方法(续):清洁验证测试/限度 CV approach (continued): CV Tests / Lim

17、its清洁验证方法(续):清洁验证测试/限度CV approach (continued): CV Life Cycle清洁验证方法(续):清洁验证生命周期Family/Group Report implemented= all CV Family/Group members are considered validated族/组报告实施=所有清洁验证族/组成员都认为经过验证 CV approach (continued): Document Structure 清洁验证方法(续):文件结构21 CV approach (continued): Document Structure 清洁验证方

18、法(续):文件结构22CV approach (continued): Document Structure 清洁验证方法(续):文件结构 Data report (per CV member) Family Report (all CV members per CV Family)Sampling (rinse+ swab)Data report worst case CV member implementedCIP performance verification (Flow, Temperature, Conductivity and Time)CIP performance verif

19、ication (Flow, Temperature, Conductivity and Time)-Cleaning recipe verification against worst case CV member23CV approach (continued): Document Structure 清洁验证方法(续):文件结构数据报告(每个清洁验证成员)族报告(所有清洁验证成员,每个清洁验证族)取样(淋洗+擦拭)报告实施的清洁验证成员最坏情况数据CIP性能核实(流量,温度,电导率与时间)CIP性能核实(流量,温度,电导率与时间)-清洁方法根据清洁验证成员的最坏情况进行核实24CV approach (continued): Clean Hold Time 清洁验证