【正文】 ersonnel based on this validation protocol按驗(yàn)證方案對(duì)有關(guān)人員進(jìn)行培訓(xùn)252。 Collection, sorting and reviewing of validation data and drafting of validation reports (including the deviation report, if there are any deviations)收集、整理和審核驗(yàn)證數(shù)據(jù)，起草驗(yàn)證報(bào)告（如方案執(zhí)行有偏差，要完成偏差報(bào)告）。n Utility support department 工程服務(wù)部252。 Assistance in implementation of this validation protocol協(xié)助本驗(yàn)證方案的實(shí)施252。 Calibration of instruments related to this validation protocol and providing relevant calibration certificates and quality certificates負(fù)責(zé)校驗(yàn)和本驗(yàn)證方案有關(guān)的儀器、儀表，出具校驗(yàn)報(bào)告并貼合格證252。 Assure normal operation of the utility system保證公用系統(tǒng)的正常運(yùn)行252。 Final report Review 最終報(bào)告的審核n Quality control of quality department 質(zhì)量部質(zhì)量控制252。 Determination of test methods used in this validation protocol負(fù)責(zé)確定本驗(yàn)證方案的檢驗(yàn)方法252。 Validation of the necessary test methods for XXXXX involved in this validation protocol負(fù)責(zé)本驗(yàn)證方案涉及的重組乙型肝炎疫苗（CHO細(xì)胞）原液生產(chǎn)的必要的檢驗(yàn)方法的驗(yàn)證252。 The quality inspections on XXXXX Tablet involved in this validation protocol, and presenting full item certificates of analysis and quality inspection reports and records負(fù)責(zé)本驗(yàn)證方案涉及的重組乙型肝炎疫苗（CHO細(xì)胞）原液生產(chǎn)的質(zhì)量檢驗(yàn)，并出具全項(xiàng)檢驗(yàn)報(bào)告，提供質(zhì)量檢驗(yàn)報(bào)告書(shū)及檢驗(yàn)記錄252。 Providing technical supports and guidance for tests at each of the process steps負(fù)責(zé)各工序檢驗(yàn)的技術(shù)支持和指導(dǎo)252。 Coordinating the plant in the implementation of this validation protocol協(xié)同車間實(shí)施本驗(yàn)證方案252。 Final report Review 最終報(bào)告的審核n Quality assurance of quality department 質(zhì)量部質(zhì)量保證252。 Supervision of validation process, review and approval of this protocol, and ensuring the implementation following this protocol負(fù)責(zé)驗(yàn)證過(guò)程監(jiān)督，方案的審核與批準(zhǔn)，確保按批準(zhǔn)的方案執(zhí)行252。 Sampling at each process steps during the process validation負(fù)責(zé)工藝驗(yàn)證中各工序的取樣252。 Coordination among different departments involved in the validation activities負(fù)責(zé)驗(yàn)證涉及到的各部門之間的協(xié)調(diào)252。 Providing equipment validation reports related to this validation protocol負(fù)責(zé)提供和本驗(yàn)證方案有關(guān)的設(shè)備驗(yàn)證報(bào)告252。 Identification, audit and assessment of suppliers供應(yīng)商的確認(rèn)、審計(jì)及評(píng)價(jià)252。 Assessment and handling of changes and deviations occur during this process validation負(fù)責(zé)對(duì)工藝驗(yàn)證實(shí)施過(guò)程中出現(xiàn)的變更和偏差的評(píng)價(jià)和處理252。 Final report Review 最終報(bào)告的審核4. Regulation and Guidance 法規(guī)和指南252。 EudraLex Volume 4 EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, November, 2008EudraLex 第四卷 歐盟藥品生產(chǎn)質(zhì)量管理規(guī)范指南 醫(yī)藥產(chǎn)品 人用及獸用，2008年11月252。 Final Version of Annex 15 to the EU Guide to Good Manufacturing Practice : Qualification and Validation , September 2001EudraLex 第四卷 藥品生產(chǎn)質(zhì)量管理規(guī)范，附錄15 驗(yàn)證與確認(rèn)，2001年9月252。 EMEA Note for guidance on process validation, September 2001 歐洲藥品管理局 – 工藝驗(yàn)證指南，2001年9月252。 EMEA Annex II to note for guidance on process validation, January 2005歐洲藥品管理局 – 附錄II 工藝驗(yàn)證指南252。 FDA 21 Code of Federal Regulations, Part 211, current Good Manufacturing Practice for Finished Pharmaceuticals, April 2011FDA聯(lián)邦法典第21篇第211部分，現(xiàn)行藥物制劑生產(chǎn)質(zhì)量管理規(guī)范，2011年4月252。 FDA Process Validation: General Principles and Practices , January 2011FDA工藝驗(yàn)證：一般原則和實(shí)踐，2011年01月252。 SFDA Good Manufacturing Practice (2010 Revision), March, 2011SFDA 藥品生產(chǎn)質(zhì)量管理規(guī)范（2010年修訂），2011年03月252。 PIC PIC/S Pharmaceutical Inspection Convention, Pharmaceutical Inspection Cooperation Scheme, “Remendations on Validation Master Plan, Installation and Operational Qualification, Nonsterile Process Validation, Cleaning Validation”, July 2004PIC/S藥品監(jiān)管公約，藥品監(jiān)管合作計(jì)劃，“有關(guān)驗(yàn)證主計(jì)劃、安裝和運(yùn)行確認(rèn)、非無(wú)菌工藝驗(yàn)證、清潔驗(yàn)證的建議”，2004年7月252。 A WHO Guide to good manufacturing practice(GMP) requirements , Part 2 Validation , 1997 WHO 關(guān)于GMP要求的指南， 第二部分：驗(yàn)證，1997年252。 Chinese Pharmacopoeia (CP) 2010 Edition 中國(guó)藥典（CP）2010年版252。 Process Validation of Protein Manufacturing (Technical Report No. 42 Supplement Vol. 59, No. S4 September/October 2005 169。 2005 by PDA)蛋白生產(chǎn)的工藝驗(yàn)證（技術(shù)報(bào)告42，PDA， 2005年版）5. Abbreviations縮略語(yǔ)The abbreviations which will be used in this protocol are listed in the following form.在下面的表格中規(guī)定了本方案中使用的縮略語(yǔ)。表格 1 縮略語(yǔ)Abbreviations縮略語(yǔ)Definition定義APIActive Pharmaceutical Ingredient (or “Drug Substance”)原料藥（或藥品物質(zhì)）CPPCritical Process Parameter關(guān)鍵工藝參數(shù)CQACritical Quality attribute關(guān)鍵質(zhì)量屬性CVCleaning Validation清洗驗(yàn)證IQInstallation Qualification安裝確認(rèn)MFVMedia Fill Validation培養(yǎng)基模擬灌裝試驗(yàn)N/ANot applicable不適用OQOperation Qualification運(yùn)行確認(rèn)PLCProgrammable Logic Controller可編程邏輯控制器PQPerformance Qualification性能確認(rèn)PVProcess Validation工藝驗(yàn)證PWPurified Water純化水QAQuality Assurance質(zhì)量保證RARisk Assessment風(fēng)險(xiǎn)分析SOPStandard Operation Procedure標(biāo)準(zhǔn)操作程序URSUser Requirement Specification用戶使用要求VMPValidation Master Plan驗(yàn)證主計(jì)劃WFIWater for Injection注射用水6. Protocol Description方案說(shuō)明n Using this defined process validation shall be performed for the results of the Process Risk Assessment.本方案實(shí)施的工藝驗(yàn)證，是基于工藝風(fēng)險(xiǎn)評(píng)估結(jié)果的。n Using this defined process validation shall be performed for three consecutive successful runs based on GMP requirements to demonstrate the process control reliability and the repeatability.鑒于XXX的生產(chǎn)已經(jīng)有近20年歷史，本次驗(yàn)證僅是對(duì)生產(chǎn)地址發(fā)生變更后且主要設(shè)備未發(fā)生變化的再驗(yàn)證，考慮到本產(chǎn)品生產(chǎn)周期長(zhǎng)（總生產(chǎn)周期為158天）的原因，本方案實(shí)施的工藝驗(yàn)證將生產(chǎn)1批成功的產(chǎn)品以證明其可靠性。n The determination of the intermediate and final product will implement enterprise internal standard but release finished product should be in accordance with criteria of the item “XXX” in Chinese Pharmacopoeia 2010 Edition.n 半成品、成品按企業(yè)內(nèi)控標(biāo)準(zhǔn)檢驗(yàn)，成品發(fā)放按中國(guó)藥典2010版三部“XXX ”標(biāo)準(zhǔn)執(zhí)行Raw material internal standard原輔料內(nèi)控標(biāo)準(zhǔn)：表格 2原輔料質(zhì)量標(biāo)準(zhǔn)表Quality Standard Doc.質(zhì)量控制標(biāo)準(zhǔn)文件Doc. Number文件編號(hào)Sodium Chloride (BP) Quality Specification氯化鈉（藥用級(jí)）檢驗(yàn)質(zhì)量標(biāo)準(zhǔn)Sodium Dihydrogen Phosphate (BP) Quality Specification磷酸二氫鈉（藥用級(jí)）檢驗(yàn)質(zhì)量標(biāo)準(zhǔn)Crystal Aluminum Chloride AR Quality Specification 結(jié)晶氯化鋁AR檢驗(yàn)質(zhì)量標(biāo)準(zhǔn)Glucose (BP) Quality Specification 葡萄糖（藥用級(jí)）檢驗(yàn)質(zhì)量標(biāo)準(zhǔn)Glutamine Quality Specification 谷氨酰胺質(zhì)量標(biāo)準(zhǔn)Potassium Bromide Quality Specification 溴化鉀質(zhì)量標(biāo)準(zhǔn)Disodium Edetate Quality Specification 乙二胺四乙酸二鈉質(zhì)量標(biāo)準(zhǔn)Sodium Hydroxide (BP) Quality Specification 氫氧化鈉（藥用級(jí)）質(zhì)量標(biāo)準(zhǔn) Disodium Hydrogen Phosphate (BP) Quality Specification 磷酸氫二鈉(藥用級(jí))質(zhì)量標(biāo)準(zhǔn)Merthiolate (BP) Q