【正文】 ruments Calibration Verification 系統(tǒng)和設(shè)備儀表校驗(yàn)確認(rèn) 52 System and Equipment Instruments Calibration Verification 生產(chǎn)相關(guān)驗(yàn)證狀態(tài)確認(rèn) 53 Test Instruments Calibration Verification 測(cè)試儀器和儀表校驗(yàn)確認(rèn) 53 Testing Method Validation Verification檢驗(yàn)方法驗(yàn)證的確認(rèn) 54 Raw Material and Excipient Verification原輔料確認(rèn) 549. Sampling Plan and Evaluation Criteria取樣計(jì)劃及評(píng)估標(biāo)準(zhǔn) 5610. Sample Coding Method樣品編碼原則 7011. Process Validation Test Execution 工藝驗(yàn)證執(zhí)行 72 Liquid Preparation 液體配制 72 Cell Resurrection and Passage細(xì)胞復(fù)蘇及傳代 74 Harvest liquid test 收獲液檢測(cè) 81 Clarification Filtration Efficacy Test 澄清過(guò)濾效果檢測(cè) 83 UF Concentration 1 Efficacy Test超濾濃縮1效果檢測(cè) 83 Ammonium sulfate precipitation efficacy test 硫酸銨沉淀效果檢測(cè) 85 Potassium bromide extraction efficacy test 溴化鉀提取效果檢測(cè) 86 First density gradient centrifugation efficacy test 一次密度梯度離心效果檢測(cè) 87 Second density gradient centrifugation efficacy test 二次密度梯度離心效果檢測(cè) 88 UF Concentration 2 Efficacy Test 超濾濃縮2效果檢測(cè) 89 Chromatography purification product test 層析純化產(chǎn)物檢測(cè) 9012. Bulk Determination原液檢驗(yàn) 9213. Process Validation Summarization工藝驗(yàn)證總結(jié) 9314. PV Report工藝驗(yàn)證報(bào)告 94 Process Validation Report 工藝驗(yàn)證報(bào)告 94 Process Validation Analysis and Evaluation 工藝驗(yàn)證分析與評(píng)價(jià) 9415. Requirements on Execution Records 執(zhí)行記錄要求 9516. Deviation Handling 偏差處理 9517. Change Handling 變更處理 9518. Test Form測(cè)試表 96表格 1 縮略語(yǔ) 9表格 2原輔料質(zhì)量標(biāo)準(zhǔn)表 11表格 3物料消耗表1 21表格 4物料消耗表2 21表格 5所用液體配料表 22表格 6生產(chǎn)車間一覽表 26表格 7主要生產(chǎn)設(shè)備一覽表 29表格 8工藝風(fēng)險(xiǎn)分析表 33表格 9工藝時(shí)間表 49表格 10取樣計(jì)劃表 56表格 11樣品編碼原則 70表格 12配液取樣檢測(cè)信息表 72表格 13復(fù)蘇和傳代取樣表 74表格 14復(fù)蘇和傳代樣品編碼 80表格 15收獲液標(biāo)準(zhǔn) 82表格 16澄清過(guò)濾標(biāo)準(zhǔn) 83表格 17超濾濃縮1標(biāo)準(zhǔn) 84表格 18硫酸銨沉淀標(biāo)準(zhǔn) 85表格 19溴化鉀提取標(biāo)準(zhǔn) 86表格 20一次密度梯度離心標(biāo)準(zhǔn) 87表格 21二次密度梯度離心標(biāo)準(zhǔn) 88表格 22超濾濃縮2標(biāo)準(zhǔn) 89表格 23純化產(chǎn)物標(biāo)準(zhǔn) 90表格 24原液標(biāo)準(zhǔn) 92表格 25測(cè)試表列表 961. Purpose目的This purpose of this process validation is to provide documented evidence to show that the bination of the personnel, materials, equipment, methods, environmental conditions and the other related utilities XXX Co., LTD (XXX) can ensure the consistent production of products conforming to the enterprise internal standards and the national standards, and the processes are reliable and conforming to the GMP requirements. The process validation and the test results are to be documented based on this validation protocol.本工藝驗(yàn)證用于提供文件化的證據(jù)，證明XXX疫苗一室生產(chǎn)XXX原液的人員、材料、設(shè)備、方法、環(huán)境條件以及其它有關(guān)公用設(shè)施的組合可以始終如一的生產(chǎn)出符合企業(yè)內(nèi)控標(biāo)準(zhǔn)及國(guó)家法定標(biāo)準(zhǔn)的產(chǎn)品，工藝穩(wěn)定可靠，符合GMP要求，工藝驗(yàn)證的過(guò)程和檢查的結(jié)果將按照該驗(yàn)證方案進(jìn)行記錄。名稱TitleProcess Validation (PV)2. Scope范圍This protocol is applicable to the process validation of XXX produced by the equipment located XXX.本方案適用于XXX原液生產(chǎn)的工藝驗(yàn)證。 Compile Protocol方案的編寫252。 Assure all the equipment used for validation can be maintained timely保證驗(yàn)證用所有設(shè)備均能按SOP進(jìn)行及時(shí)的維護(hù)和保養(yǎng)252。 Review relevant quality criteria including raw material, intermedia and finished product審核原輔料標(biāo)準(zhǔn)、中控質(zhì)量標(biāo)準(zhǔn)和成品的質(zhì)量標(biāo)準(zhǔn)n Vaccine one Plant 疫苗一室252。n Utility support department 工程服務(wù)部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。 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。 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。 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。 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。 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。 Process Validation of Protein Manufacturing (Technical Report No. 42 Supplement Vol. 59, No. S4 September/October 2005 169。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) Quality Specification 硫柳汞（藥用）質(zhì)量標(biāo)準(zhǔn)Hydrochloric Acid (BP) Quality Specification 鹽酸（藥用級(jí)）檢驗(yàn)質(zhì)量標(biāo)準(zhǔn)Proline (BP) Quality Specification 脯氨酸（藥用）質(zhì)量標(biāo)準(zhǔn)Sodium Bicarbonate (BP) Quality Specification 碳酸氫鈉（藥用級(jí)）檢驗(yàn)質(zhì)量標(biāo)準(zhǔn)DMEM Quality Specification DMEM質(zhì)量標(biāo)準(zhǔn)Formaldehyde Solution (BP) Quality Specification 甲醛溶液(藥用)質(zhì)量標(biāo)準(zhǔn)Ammonium Sulfate AR Quality Specification 硫酸銨AR質(zhì)量標(biāo)準(zhǔn) Glycine (BP) Quality Specification 甘氨酸（藥用）質(zhì)量標(biāo)準(zhǔn)Trypsin (BP) Quality Specification 胰蛋白酶(藥用)質(zhì)量標(biāo)準(zhǔn) New Born Bovine Serum Quality Specification 新生牛血清質(zhì)量標(biāo)準(zhǔn)Methotrexate氨甲喋呤Dimethyl Sulphoxide二甲基亞砜Semiproduct of XXX standard, include the Harvest liquid, the Purification liquid and the Bulk.XXX中間品質(zhì)量標(biāo)準(zhǔn)，包括細(xì)胞收獲液、純化產(chǎn)物、原液（文件號(hào)：XXX）Final product of XXX standard XXX成品質(zhì)量標(biāo)準(zhǔn)：（文件號(hào)：XXX）n The validation procedures, items and contents are divided based on the system process steps. The process steps, validation items, sampling methods, testing methods and acceptance criteria are described for each of the process steps.驗(yàn)證的程序、項(xiàng)目和內(nèi)容中以系統(tǒng)工序?yàn)閱挝?，?duì)各工序中的所涉及的工藝步驟、驗(yàn)證項(xiàng)目、取樣方法、檢驗(yàn)方法和接受標(biāo)準(zhǔn)進(jìn)行了規(guī)定和描述。n Summarize and evaluate the entire process validation based on the validation of each of the process steps and record the evaluation results to the report.在各工序驗(yàn)證的基礎(chǔ)上，對(duì)整個(gè)工藝驗(yàn)證進(jìn)行了總結(jié)評(píng)價(jià)，評(píng)價(jià)結(jié)果記錄到驗(yàn)證報(bào)告中。 Preparation of production cells生產(chǎn)用細(xì)胞制備Take 1 to 2 tubes of cells from the working cell bank (of a same batch No.), resurrect, mix and inoculate them into a 100ml