精益清潔驗證案例分析.ppt課件

1、精益清潔驗證 案例分析CLEANING VALIDATIONA LEAN CASE STUDYJPT ConsultingKeith Powell-EvansContent 目錄1. Cleaning Strategy p 1 9 清潔策略2. Cleaning Validation p 9 19 清潔驗證 A) Objective p 9 目標 B) Scope p 9 范圍 C) Approach: 方法: Family/ Grouping p 9 14 族/組 CV Tests/ Limits p 15 清潔驗證測試/限度 CV Life-cycle p 16 清潔驗證生命周期 Docu

2、ment structure p 17-18 文件結(jié)構(gòu) Clean Hold Time p 19 清潔持續(xù)時間3. Summary p 20 概要Cleaning Strategy 清潔策略Described in SOP- xxx 在SOP-XXX中進行描述COP: Parts washers (incl. COP baths)COP:零件清洗機(包括COP批次)CIP: Cleaning by CIP skids Chromatography cleaning UF/DF cleaningCIP:由在線清潔(CIP) SKID進行清潔色譜清潔UF/DF清潔Equipment 設備Equip

3、ment 設備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 色譜與UF/DFCHR-010CHR-013FIL-005FIL-014FIL-009FIL-0086Example of CIP circuit：1) Process schematic:CIP管

4、路示例： 1）工藝圖ProductVessel產(chǎn)品罐ProductVessel產(chǎn)品罐BufferVessel緩沖罐Example of CIP circuit: 2) Schematic for cleaning CIP管路示例： 2）清潔圖ProductVessel產(chǎn)品罐ProductVessel產(chǎn)品罐BufferVessel緩沖罐CIP SUPPLYCIP供應CIP RETURNCIP返回CIP SUPPLYCIP供應CIP RETURNCIP返回CIP SUPPLYCIP供應Cleaning Overview (Continued)清潔概述(續(xù))12456 3Typically 6 cl

5、eaning Phases: 典型的6個清潔階段:PRE-RINSE PHASE 預先沖洗階段WASH 1 (Caustic) 洗滌1(堿)3) POST RINSE 后沖洗4) WASH 2 (Acid) 洗滌2(酸)PRE QUALITY RINSE 高質(zhì)量沖洗FINAL RINSE (hot WFI) 最后沖洗(熱注射用水)Cleaning Overview (Continued)清潔概述(續(xù))Specific cleaning procedures 具體的清潔程序= how to prepare to be cleaned systems 如何準備清潔系統(tǒng)= Cleaning Reci

6、pe to be used, which defines: 所使用的清潔方法,其規(guī)定:Flows 流量Times 時間Concentration cleaning agents 清潔劑濃度Temperatures 溫度Dirty Hold Time/ Clean Hold Time臟東西保持時間/清潔保持時間= defined in SOP- xxx 在SOP-XXX中進行規(guī)定Cleaning Validation (CV)清潔驗證 VAL-VMP- xxxObjective: Demonstrate cleaning efficiency (incl. Dirty Hold Times) a

7、nd Clean Hold Times目的:證明清潔效率(包括臟東西保持時間)以及清潔保持時間2. Scope: 范圍:COP: Parts washers 零件清洗機CIP: Cleaning by CIP skids 用在線SKID清潔 Chromatography SKID cleaning 色譜SKID清潔 UF/DF SKID cleaning UF/DF SKID清潔Cleaning Validation (CV)清潔驗證VAL-VMP- XXX3.Approach: 方法: Product (Drug Substance) dedicated產(chǎn)品(原料藥)專用 COP: Vali

8、dation of max. loadCOP:最大裝量驗證 CIP: Family/Groups worst case (see next pages) 族/組最差情況 (見后頁)Downstream bufferPreparation下游緩沖制備CV Approach (continued) : CIP Family/Grouping 清潔驗證方法(續(xù)):CIP族/組 Process Schematic:工藝圖Media preparation培養(yǎng)基制備Purification 提純Harvest 收獲Cell culture 細胞培養(yǎng)Final Formulation成品配置Downstr

9、eam bufferPreparation下游緩沖制備Upstream bufferPreparation上游緩沖制備Drug Substance Contact Systems (DSCS) 原料藥接觸系統(tǒng)Non-Drug Substance Contact Systems (non-DSCS) 非原料藥接觸系統(tǒng)GROUPING APPROACH 組方法 FAMILY APPROACH 族方法For the DSCS the CV Families are based on:對于原料藥接觸系統(tǒng),清潔驗證族基于:CIP system (e.g. CIP-00 x, CIP-00y,.) CIP

10、系統(tǒng)Equivalent manufacture and operational functionality (e.g. seed bioreactors vs product vessels)等同制造與操作功能性(如,種子生物反應器與產(chǎn)品罐)Equivalent design (e.g. vessels vs transfer lines)等同設計(如,罐與連管線生產(chǎn))Equivalent cleaning method 等同清潔方法= cleaning sequence, chemical agents and concentrations, temperatures and minimu

11、m durations during the wash phases (cfr. SOP- xxx) 清潔次序,化學試劑與濃度,溫度與在清晰階段最短時間(參考SOP-xxx)CV Approach (continued) : Family approach worst cases清潔驗證方法(續(xù)):族方法最壞情況= CV Families are defined 確定清潔驗證的族The worst case selection is based on an assessment of:選擇最壞情況基于評估:Location = relative CIP distances 位置=相對CIP距離

12、Design = surface area, number of subcircuits設計=表面面積,支路數(shù)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,在最早原料藥操作中使用產(chǎn)品罐可以考慮比最晚原料藥操作中使用產(chǎn)品罐的最壞情況小 CV Appr

13、oach (continued) : Family approach worst cases清潔驗證方法(續(xù)):族方法最壞情況Remark: worst case product selection is not applicable since systems are product dedicated 注:由于系統(tǒng)專用,不接受最壞情況產(chǎn)品選擇For the non-DSCS two groups are identified:對于非原料藥接觸系統(tǒng),識別兩個組:Media group 培養(yǎng)基組Buffer group 緩沖組Similar manufacture and operationa

14、l functionality and design. 相似的制造與操作方式以及設計Similar cleaning method with regard to cleaning sequence, chemical agents and concentrations, temperatures and minimum durations during the wash phases (cfr. SOP- xxx)在清潔先后次序,化學試劑與濃度,溫度與沖洗階段最短時間相似的清潔方法(參見SOP- xxx)CV Approach (continued) : Family approach wor

15、st cases清潔驗證方法(續(xù)):族方法最壞情況The worst case selection is based on sound scientific rational:最壞情況選擇基于良好的科學原理:MIX systems and worst case media or buffer = most concentrated and highest risk with repect to cross-contaminationMIX系統(tǒng)與最壞情況的培養(yǎng)基或緩沖=交叉污染方面最濃的與最高風險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緩沖罐=因為其位置在制造序列中(以及理論雜質(zhì)直到最終原料藥中風險)CV Approach (continued) : Family approach worst cases清潔驗證方法(續(xù)):族方法最壞情況 CV approach (continued): CV Tests / Limits清潔驗證方法(續(xù)):清潔驗證測試/限度 CV approach (continued): CV Tests / Lim

17、its清潔驗證方法(續(xù)):清潔驗證測試/限度CV approach (continued): CV Life Cycle清潔驗證方法(續(xù)):清潔驗證生命周期Family/Group Report implemented= all CV Family/Group members are considered validated族/組報告實施=所有清潔驗證族/組成員都認為經(jīng)過驗證 CV approach (continued): Document Structure 清潔驗證方法(續(xù)):文件結(jié)構(gòu)21 CV approach (continued): Document Structure 清潔驗證方

18、法(續(xù)):文件結(jié)構(gòu)22CV approach (continued): Document Structure 清潔驗證方法(續(xù)):文件結(jié)構(gòu) 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 清潔驗證方法(續(xù)):文件結(jié)構(gòu)數(shù)據(jù)報告(每個清潔驗證成員)族報告(所有清潔驗證成員,每個清潔驗證族)取樣(淋洗+擦拭)報告實施的清潔驗證成員最壞情況數(shù)據(jù)CIP性能核實(流量,溫度,電導率與時間)CIP性能核實(流量,溫度,電導率與時間)-清潔方法根據(jù)清潔驗證成員的最壞情況進行核實24CV approach (continued): Clean Hold Time 清潔驗證