【文章內(nèi)容簡(jiǎn)介】 uality 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 The process recipe of Bulk of XXX (Registration batch No.: for 20μg: GUOYAOZHUNZI XXX, and for 10μg GUOYAOZHUNZI XXX) is briefly described in this protocol. The contents of the recipe are described and the process flow diagram is listed. The process procedure is conformed to the registration standard.本方案對(duì)XXX原液的工藝處方（注冊(cè)批號(hào)：20μg：國(guó)藥準(zhǔn)字 XXX、10μg：國(guó)藥準(zhǔn)字 XXX）進(jìn)行了簡(jiǎn)介，對(duì)處方內(nèi)容進(jìn)行描述，并且列出直觀化的工藝流程圖。工藝規(guī)程與注冊(cè)標(biāo)準(zhǔn)一致。n This protocol is used to specify the purpose and the scope of this validation and the responsibilities of each of the departments during the implementation of this validation protocol.本方案旨在指明驗(yàn)證的目的、范圍，并規(guī)定了該驗(yàn)證方案在實(shí)施過(guò)程中的各部門(mén)的職責(zé)。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。7. Product And Process Description產(chǎn)品和工藝描述 Product specification(1) Ampoule, one human dose of , containing 10μg of HBsAg (1) 安瓿瓶，含HBsAg 10μg；(2) Ampoule, one human dose of , containing 20μg of HBsAg (2) 安瓿瓶，含HBsAg 20μg；(3) Vial, one human dose of , containing 20μg of HBsAg (3) 西林瓶，含HBsAg 20μg；(4) Vial, one human dose of , containing 10μg of HBsAg (4) 西林瓶，含HBsAg 10μg。 Drug approval No. 20μg：GUOYAOZHUNZI S1096004720μg：國(guó)藥準(zhǔn)字 S1096004710μg：GUOYAOZHUNZI S1096008010μg：國(guó)藥準(zhǔn)字 S10960080 Standard Followed: Chinese Pharmacopoeia 2010 Edition執(zhí)行標(biāo)準(zhǔn)：中國(guó)藥典2010版 Raw Materials and Adjuvants原輔料情況Table 3 Raw Materials and Adjuvants表格 4原輔料信息表Name SpecificationsManufacturerPackaging SpecificationsSodium Chloride BP Tianjin Haiguang Pharmaceutical Industrial Co., Ltd. 1000g/bagDisodium hydrogen phosphate BP Hunan Jiudian Pharmaceutical Co., Ltd. Crystal Aluminum Chloride AP Beijing Yili Fine Chemical Co., Ltd. 500g/bottleGlucose AP Baitaike Bioltechnology Co., Ltd. (filling)500g/bottleGlutamineusp Gradeinvitrogen corporation (Gibco)1kg /drum Potassium Bromide AP Beijing Yili Fine Chemical Co., Ltd. 500g/bottleDisodium Edetate AP Sinopharm Chemical Reagent Co., Ltd 250g/bottleSodium Hydroxide AP Beijing Chemical Factory 500g/bottleMonowater disodium hydrogen phosphate BP Hunan Jiudian Pharmaceutical Co., Ltd. Merthiolate BP (USP/BP/EP)GIHON1kg /drum Hydrochloric acid AP Beijing Chemical Factory 2500ml/ bottleProline Shanghai Xiehe Amino Acid Co., Ltd. 500g/bagSodium bicarbonate AP Beijing Chemical Factory 500g/bottleDMEMGibco6687g/drum Formaldehyde AP Sinopharm Chemical Reagent Co., Ltd 500ml/ bottleAmmonium sulfate AP Beijing Yili Fine Chemical Co., Ltd. 25kg /drum GlycineAP Sinopharm Chemical Reagent Co., Ltd 100g/ bottle Pancreatin BD 500g/bottleGibco100g/ bottle Methotrexate≥%sigmaaldrich（flukaanalytical）100mg/ tube Dimethyl SulphoxideSERVA Electrophoresis GmbH1L/ bottle New born bovine serum Top grade Wuhan Sanli Biotechnology Co., Ltd. 1000ml/ bottleInner Mongolia Jinyuankang Biotechnology Co., Ltd. 500ml/ bottle原輔料名稱(chēng)規(guī)格生產(chǎn)廠家包裝規(guī)格氯化鈉藥用級(jí)天津海光藥業(yè)有限公司1000g/袋磷酸氫二鈉藥用級(jí)湖南九典制藥有限公司結(jié)晶氯化鋁分析純北京益利精細(xì)化學(xué)品有限公司500g/瓶葡萄糖分析純寶泰克生物科技公司（分裝）500g/瓶谷氨酰胺usp Gradeinvitrogen corporation（Gibco）1kg/桶溴化鉀分析純北京益利精細(xì)化學(xué)品有限公司500g/瓶乙二胺四乙酸二鈉分析純國(guó)藥集團(tuán)化學(xué)試劑有限公司250g/瓶氫氧化鈉分析純北京化工廠500g/瓶一水磷酸二氫鈉藥用級(jí)湖南九典制藥有限公司硫柳汞藥用級(jí)（USP/BP/EP）GIHON1Kg/桶鹽酸分析純北京化工廠2500ml/瓶脯氨酸上海協(xié)和氨基酸有限公司500g/袋碳酸氫鈉分析純北京化工廠500g/瓶DMEMGibco6687g/桶甲醛分析純國(guó)藥集團(tuán)化學(xué)試劑有限公司500ml/瓶硫酸銨分析純北京益利精細(xì)化學(xué)品有限公司25kg/桶甘氨酸分析純國(guó)藥集團(tuán)化學(xué)試劑有限公司100g/瓶胰酶BD公司500g/瓶Gibco100g/瓶氨甲喋呤≥%sigmaaldrich（flukaanalytical）100mg/管二甲基亞砜SERVA Electrophoresis GmbH1L/瓶新生牛血清優(yōu)級(jí)武漢三利生物技術(shù)有限公司1000ml/瓶?jī)?nèi)蒙古金源康生物工程有限公司500ml/瓶 Process description:工藝簡(jiǎn)述：216。 Process Cycle 工藝周期Table 5 Process Schedule表格 6工藝時(shí)間表No.序號(hào)Process Steps 工藝步驟Time (Day)時(shí)間（天）1Resurrection 復(fù)蘇12C25 First square bottle incubation C25方瓶第一次培養(yǎng)5~73C26 second square bottle incubation C26方瓶第二次培養(yǎng)5~74C27 Kolle flask incubation C27克氏瓶培養(yǎng)5~75C28 First 3L rotary bottle incubation C283L轉(zhuǎn)瓶第一次培養(yǎng)5~76C29 second 3L rotary bottle incubation C293L轉(zhuǎn)瓶第二次培養(yǎng)5~77C30 third 3L rotary bottle incubation C303L轉(zhuǎn)瓶第三次培養(yǎng)5~78C31 first 15L bottle incubation C3115L瓶第一次培養(yǎng)5~79C32 second 15L bottle incubation C3215L瓶第二次培養(yǎng)5~71020 consecutive harvest 連續(xù)20次收獲液4011Filtration for cell residue removal 去細(xì)胞殘?jiān)^(guò)濾12UF concentration 超濾濃縮13Ammonium sulfate precipitation 硫酸銨沉淀4~514Potassium bromide extraction 溴化鉀提取115First density gradient centrifugation 一次密度梯度離心16Second density gradient centrifugation 二次密度梯度離心17UF concentration 超濾濃縮118Chromatography purification 層析純化119Bulk solution bin