工藝驗證方案模板

1、Process Validation (PV) Protocol XXXXXX工藝驗證方案Written by起 草 人Written date起草日期年 月 日Reviewed by審 核 人Reviewed date審核日期年 月 日Approved by批 準 人Approved date批準日期年 月 日Written department起草部門Effective date生效日期年 月 日Issued by:頒發(fā)部門： Copy number:拷 貝 號： Change record:Revision number變更記載： Date of approval Effect

2、ive date修訂號 批準日期 生效日期 Change reason and goal: 變更原因及目的：Distribution department:分發(fā)部門:所長辦公室 人力資源部 后勤保衛(wèi)部 物資供應(yīng)部 工程服務(wù)部 生產(chǎn)管理部 質(zhì)量保證部 銷 售 部 倉 儲 部 疫苗一室 疫苗二室 疫苗三室 疫苗五室 疫苗六室 生化制品室 細胞因子室 血清制品室 實驗動物室 分包裝室 培養(yǎng)基室 Verification department (department): 驗證科室（部門）： Verify completion date: 驗證完成日期： Validity: 有 效 期： In

3、dex 目錄1.Purpose目的52.Scope范圍53.Responsibility職責53.1AAA responsibilities AAA的職責53.2XXX responsibilities XXX的職責64.Regulation and Guidance 法規(guī)和指南85.Abbreviations縮略語96.Protocol Description方案說明117.Product And Process Description產(chǎn)品和工藝描述147.1Product specification147.2Drug approval No.147.3Standard Followed:1

4、47.4Raw Materials and Adjuvants原輔料情況147.5Process description:167.6Process Recipe工藝處方：217.7List of Production Plants生產(chǎn)車間一覽267.8List of Production Equipment 生產(chǎn)設(shè)備一覽297.9Process Flow Diagram 工藝流程圖337.10CPP Identification CPP確認347.11Validation Plan驗證計劃498.Validation prerequisite驗證先決條件518.1Personal Identi

5、fication人員確認518.2Process Documentation Verification 生產(chǎn)文件確認518.3Training Verification 培訓(xùn)確認528.4System and Equipment Instruments Calibration Verification 系統(tǒng)和設(shè)備儀表校驗確認528.5System and Equipment Instruments Calibration Verification 生產(chǎn)相關(guān)驗證狀態(tài)確認538.6Test Instruments Calibration Verification 測試儀器和儀表校驗確認538.7T

6、esting Method Validation Verification檢驗方法驗證的確認548.8Raw Material and Excipient Verification原輔料確認549.Sampling Plan and Evaluation Criteria取樣計劃及評估標準5610.Sample Coding Method樣品編碼原則7011.Process Validation Test Execution 工藝驗證執(zhí)行7211.1Liquid Preparation 液體配制7211.2Cell Resurrection and Passage細胞復(fù)蘇及傳代7411.3Ha

7、rvest liquid test 收獲液檢測8111.4Clarification Filtration Efficacy Test 澄清過濾效果檢測8311.5UF Concentration 1 Efficacy Test超濾濃縮1效果檢測8311.6Ammonium sulfate precipitation efficacy test 硫酸銨沉淀效果檢測8511.7Potassium bromide extraction efficacy test 溴化鉀提取效果檢測8611.8First density gradient centrifugation efficacy test 一

8、次密度梯度離心效果檢測8711.9Second density gradient centrifugation efficacy test 二次密度梯度離心效果檢測8811.10UF Concentration 2 Efficacy Test 超濾濃縮2效果檢測8911.11Chromatography purification product test 層析純化產(chǎn)物檢測9012.Bulk Determination原液檢驗9213.Process Validation Summarization工藝驗證總結(jié)9314.PV Report工藝驗證報告9414.1Process Validatio

9、n Report 工藝驗證報告9414.2Process Validation Analysis and Evaluation 工藝驗證分析與評價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測試表96表格 1 縮略語9表格 2原輔料質(zhì)量標準表11表格 3物料消耗表121表格 4物料消耗表221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工藝風險分析表33表格 9工藝時間表

10、49表格 10取樣計劃表56表格 11樣品編碼原則70表格 12配液取樣檢測信息表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收獲液標準82表格 16澄清過濾標準83表格 17超濾濃縮1標準84表格 18硫酸銨沉淀標準85表格 19溴化鉀提取標準86表格 20一次密度梯度離心標準87表格 21二次密度梯度離心標準88表格 22超濾濃縮2標準89表格 23純化產(chǎn)物標準90表格 24原液標準92表格 25測試表列表961. Purpose目的This purpose of this process validation is to provide documente

11、d evidence to show that the combination 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 pr

12、ocesses 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)控標準及國家法定標準的產(chǎn)品，工藝穩(wěn)定可靠，符合GMP要求，工藝驗證的過程和檢查的結(jié)果將按照該驗證方案進行記錄。2. Scope

13、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)的工藝驗證。由于工作細胞庫制備的過程并非常規(guī)生產(chǎn)過程，因此，不在本次驗證中進行考察。The labeling and packaging processes are not within the scope of this document since these processes have been validated per PQ protocol (labeli

14、ng) and PQ protocol (packaging), and these processes have minimal impact on finished product quality. 貼標簽和包裝也不在此文件范圍內(nèi)，因為這些工藝已經(jīng)按照PQ方案（貼標簽）和PQ方案(包裝)驗證過，并且這些工藝對產(chǎn)品質(zhì)量極少有影響。3. Responsibility職責3.1 AAA responsibilities AAA的職責 ü Compile Protocol方案的編寫ü Guide Protocol execution, data collection/ Prov

15、ide test data for review upon request by customer指導(dǎo)方案的實施，數(shù)據(jù)的收集/在客戶要求時提供測試數(shù)據(jù)供其審核ü Final report Review/ Analyze and compile data into the summary report最終報告的審核/對數(shù)據(jù)進行分析并將其編輯入總結(jié)報告之中3.2 XXX responsibilities XXX的職責n Production department 生產(chǎn)部ü Review and approve protocol審核并批準驗證方案ü Assure all

16、 the equipment used for validation can be maintained timely保證驗證用所有設(shè)備均能按SOP進行及時的維護和保養(yǎng)ü Assure all the raw materials used for validation can be supplied timely and comply with domestic quality criteria of enterprise保證驗證用原輔包裝材料能按時到貨，并符合企業(yè)內(nèi)控標準n Research and development department 研發(fā)部ü Provide

17、product registration criteria and review whether recipe and process step described in the protocol is complying with registered criteria提供產(chǎn)品的注冊工藝，審核方案中生產(chǎn)處方、工藝與注冊資料的一致性ü Review and make assurance the compliance of raw material supplier with registered supplier審核原輔料供應(yīng)商和注冊資料的一致性ü Review relev

18、ant quality criteria including raw material, intermedia and finished product審核原輔料標準、中控質(zhì)量標準和成品的質(zhì)量標準n Vaccine one Plant 疫苗一室ü Coordination and implementation of this validation protocol協(xié)調(diào)、實施本驗證方案ü Training of personnel based on this validation protocol按驗證方案對有關(guān)人員進行培訓(xùn)ü Collection, sorting

19、 and reviewing of validation data and drafting of validation reports (including the deviation report, if there are any deviations)收集、整理和審核驗證數(shù)據(jù)，起草驗證報告（如方案執(zhí)行有偏差，要完成偏差報告）。n Utility support department 工程服務(wù)部ü Assistance in implementation of this validation protocol協(xié)助本驗證方案的實施ü Calibration of ins

20、truments related to this validation protocol and providing relevant calibration certificates and quality certificates負責校驗和本驗證方案有關(guān)的儀器、儀表，出具校驗報告并貼合格證ü Assure normal operation of the utility system保證公用系統(tǒng)的正常運行ü Final report Review 最終報告的審核n Quality control of quality department 質(zhì)量部質(zhì)量控制ü De

21、termination of test methods used in this validation protocol負責確定本驗證方案的檢驗方法ü Validation of the necessary test methods for XXXXX involved in this validation protocol負責本驗證方案涉及的重組乙型肝炎疫苗（CHO細胞）原液生產(chǎn)的必要的檢驗方法的驗證ü The quality inspections on XXXXX Tablet involved in this validation protocol, and pre

22、senting full item certificates of analysis and quality inspection reports and records負責本驗證方案涉及的重組乙型肝炎疫苗（CHO細胞）原液生產(chǎn)的質(zhì)量檢驗，并出具全項檢驗報告，提供質(zhì)量檢驗報告書及檢驗記錄ü Providing technical supports and guidance for tests at each of the process steps負責各工序檢驗的技術(shù)支持和指導(dǎo)ü Coordinating the plant in the implementation of

23、 this validation protocol協(xié)同車間實施本驗證方案ü Final report Review 最終報告的審核n Quality assurance of quality department 質(zhì)量部質(zhì)量保證ü Supervision of validation process, review and approval of this protocol, and ensuring the implementation following this protocol負責驗證過程監(jiān)督，方案的審核與批準，確保按批準的方案執(zhí)行ü Sampling at

24、 each process steps during the process validation負責工藝驗證中各工序的取樣ü Coordination among different departments involved in the validation activities負責驗證涉及到的各部門之間的協(xié)調(diào)ü Providing equipment validation reports related to this validation protocol負責提供和本驗證方案有關(guān)的設(shè)備驗證報告ü Identification, audit and asse

25、ssment of suppliers供應(yīng)商的確認、審計及評價ü Assessment and handling of changes and deviations occur during this process validation負責對工藝驗證實施過程中出現(xiàn)的變更和偏差的評價和處理ü Final report Review 最終報告的審核4. Regulation and Guidance 法規(guī)和指南ü EudraLex Volume 4 EU Guidelines to Good Manufacturing Practice Medicinal Prod

26、ucts 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ü 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 驗證與確認，2001年9月ü EMEA - Note for guidance on

27、process validation, September 2001 歐洲藥品管理局 工藝驗證指南，2001年9月ü EMEA - Annex II to note for guidance on process validation, January 2005歐洲藥品管理局 附錄II 工藝驗證指南ü 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

28、分，現(xiàn)行藥物制劑生產(chǎn)質(zhì)量管理規(guī)范，2011年4月ü FDA Process Validation: General Principles and Practices , January 2011FDA工藝驗證：一般原則和實踐，2011年01月ü 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ü PIC PIC/S Pharmaceutical Inspection Convention, Pharmaceutical Ins

29、pection Co-operation Scheme, “Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-sterile Process Validation, Cleaning Validation”, July 2004PIC/S藥品監(jiān)管公約，藥品監(jiān)管合作計劃，“有關(guān)驗證主計劃、安裝和運行確認、非無菌工藝驗證、清潔驗證的建議”，2004年7月ü A WHO Guide to good manufacturing practice(GMP) req

30、uirements , Part 2 Validation , 1997 WHO 關(guān)于GMP要求的指南， 第二部分：驗證，1997年ü Chinese Pharmacopoeia (CP) 2010 Edition 中國藥典（CP）2010年版ü Process Validation of Protein Manufacturing (Technical Report No. 42 Supplement Vol. 59, No. S-4 September/October 2005 © 2005 by PDA)蛋白生產(chǎn)的工藝驗證（技術(shù)報告42，PDA， 2005年

31、版）5. Abbreviations縮略語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。表格 1 縮略語Abbreviations縮略語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

32、屬性CVCleaning Validation清洗驗證IQInstallation Qualification安裝確認MFVMedia Fill Validation培養(yǎng)基模擬灌裝試驗N/ANot applicable不適用OQOperation Qualification運行確認PLCProgrammable Logic Controller可編程邏輯控制器PQPerformance Qualification性能確認PVProcess Validation工藝驗證PWPurified Water純化水QAQuality Assurance質(zhì)量保證RARisk Assessment風險分析S

33、OPStandard Operation Procedure標準操作程序URSUser Requirement Specification用戶使用要求VMPValidation Master Plan驗證主計劃WFIWater for Injection注射用水6. Protocol Description方案說明n Using this defined process validation shall be performed for the results of the Process Risk Assessment.本方案實施的工藝驗證，是基于工藝風險評估結(jié)果的。n Using this

34、 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，本次驗證僅是對生產(chǎn)地址發(fā)生變更后且主要設(shè)備未發(fā)生變化的再驗證，考慮到本產(chǎn)品生產(chǎn)周期長（總生產(chǎn)周期為158天）的原因，本方案實施的工藝驗證將生產(chǎn)1批成功的產(chǎn)品以證明其可靠性。n The determinat

35、ion 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)控標準檢驗，成品發(fā)放按中國藥典2010版三部“XXX ”標準執(zhí)行Raw material internal standard原輔料內(nèi)控標準：表格 2原輔料質(zhì)量

36、標準表Quality Standard Doc.質(zhì)量控制標準文件Doc. Number文件編號Sodium Chloride (BP) Quality Specification氯化鈉（藥用級）檢驗質(zhì)量標準Sodium Dihydrogen Phosphate (BP) Quality Specification磷酸二氫鈉（藥用級）檢驗質(zhì)量標準Crystal Aluminum Chloride AR Quality Specification 結(jié)晶氯化鋁AR檢驗質(zhì)量標準Glucose (BP) Quality Specification 葡萄糖（藥用級）檢驗質(zhì)量標準Glutamine Qual

37、ity Specification 谷氨酰胺質(zhì)量標準Potassium Bromide Quality Specification 溴化鉀質(zhì)量標準Disodium Edetate Quality Specification 乙二胺四乙酸二鈉質(zhì)量標準Sodium Hydroxide (BP) Quality Specification 氫氧化鈉（藥用級）質(zhì)量標準 Disodium Hydrogen Phosphate (BP) Quality Specification 磷酸氫二鈉(藥用級)質(zhì)量標準Merthiolate (BP) Quality Specification 硫柳汞（藥用）質(zhì)量標

38、準Hydrochloric Acid (BP) Quality Specification 鹽酸（藥用級）檢驗質(zhì)量標準Proline (BP) Quality Specification 脯氨酸（藥用）質(zhì)量標準Sodium Bicarbonate (BP) Quality Specification 碳酸氫鈉（藥用級）檢驗質(zhì)量標準DMEM Quality Specification DMEM質(zhì)量標準Formaldehyde Solution (BP) Quality Specification 甲醛溶液(藥用)質(zhì)量標準Ammonium Sulfate AR Quality Specificat

39、ion 硫酸銨AR質(zhì)量標準 Glycine (BP) Quality Specification 甘氨酸（藥用）質(zhì)量標準Trypsin (BP) Quality Specification 胰蛋白酶(藥用)質(zhì)量標準 New Born Bovine Serum Quality Specification 新生牛血清質(zhì)量標準Methotrexate氨甲喋呤Dimethyl Sulphoxide二甲基亞砜Semi-product of XXX standard, include the Harvest liquid, the Purification liquid and the Bulk.XXX中

40、間品質(zhì)量標準，包括細胞收獲液、純化產(chǎn)物、原液（文件號：XXX）Final product of XXX standard XXX成品質(zhì)量標準：（文件號：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

41、process steps.驗證的程序、項目和內(nèi)容中以系統(tǒng)工序為單位，對各工序中的所涉及的工藝步驟、驗證項目、取樣方法、檢驗方法和接受標準進行了規(guī)定和描述。n The process recipe of Bulk of XXX (Registration batch No.: for 20g: GUOYAOZHUNZI XXX, and for 10g GUOYAOZHUNZI XXX) is briefly described in this protocol. The contents of the recipe are described and the process flow dia

42、gram is listed. The process procedure is conformed to the registration standard.本方案對XXX原液的工藝處方（注冊批號：20g：國藥準字 XXX、10g：國藥準字 XXX）進行了簡介，對處方內(nèi)容進行描述，并且列出直觀化的工藝流程圖。工藝規(guī)程與注冊標準一致。n This protocol is used to specify the purpose and the scope of this validation and the responsibilities of each of the departments

43、during the implementation of this validation protocol.本方案旨在指明驗證的目的、范圍，并規(guī)定了該驗證方案在實施過程中的各部門的職責。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.在各工序驗證的基礎(chǔ)上，對整個工藝驗證進行了總結(jié)評價，評價結(jié)果記錄到驗證報告中。7. Product A

44、nd Process Description產(chǎn)品和工藝描述7.1 Product specification(1) Ampoule, one human dose of 1.0ml, containing 10g of HBsAg (1) 安瓿瓶，每1次人用劑量為1.0ml，含HBsAg 10g；(2) Ampoule, one human dose of 1.0ml, containing 20g of HBsAg (2) 安瓿瓶，每1次人用劑量為1.0ml，含HBsAg 20g；(3) Vial, one human dose of 1.0ml, containing 20g of HBs

45、Ag (3) 西林瓶，每1次人用劑量為1.0ml，含HBsAg 20g；(4) Vial, one human dose of 0.5ml, containing 10g of HBsAg (4) 西林瓶，每1次人用劑量為0.5ml，含HBsAg 10g。7.2 Drug approval No. 20g：GUOYAOZHUNZI S1096004720g：國藥準字 S1096004710g：GUOYAOZHUNZI S1096008010g：國藥準字 S109600807.3 Standard Followed: Chinese Pharmacopoeia 2010 Edition執(zhí)行標準：

46、中國藥典2010版7.4 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. 0.5k

47、g/bottleCrystal 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 Sin

48、opharm Chemical Reagent Co., Ltd 250g/bottleSodium Hydroxide AP Beijing Chemical Factory 500g/bottleMono-water disodium hydrogen phosphate BP Hunan Jiudian Pharmaceutical Co., Ltd. 0.5kg/bottleMerthiolate BP (USP/BP/EP)GIHON1kg /drum Hydrochloric acid AP Beijing Chemical Factory 2500ml/ bottleProlin

49、e -Shanghai Xiehe Amino Acid Co., Ltd. 500g/bagSodium bicarbonate AP Beijing Chemical Factory 500g/bottleDMEM-Gibco6687g/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.,

50、 Ltd 100g/ bottle Pancreatin -BD 500g/bottleGibco100g/ bottle Methotrexate99.0%sigma-aldrich（fluka-analytical）100mg/ tube Dimethyl Sulphoxide-SERVA Electrophoresis GmbH1L/ bottle New born bovine serum Top grade Wuhan Sanli Biotechnology Co., Ltd. 1000ml/ bottle-Inner Mongolia Jinyuankang Biotechnolo

51、gy Co., Ltd. 500ml/ bottle原輔料名稱規(guī)格生產(chǎn)廠家包裝規(guī)格氯化鈉藥用級天津海光藥業(yè)有限公司1000g/袋磷酸氫二鈉藥用級湖南九典制藥有限公司0.5kg/瓶結(jié)晶氯化鋁分析純北京益利精細化學(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化學(xué)品有限公司500g/瓶乙二胺四乙酸二鈉分析純國藥集團化學(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湖南九典制藥有限公司0.5kg/瓶硫柳汞藥用級（USP/BP

52、/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DMEM-Gibco6687g/桶甲醛分析純國藥集團化學(xué)試劑有限公司500ml/瓶硫酸銨分析純北京益利精細化學(xué)品有限公司25kg/桶甘氨酸分析純國藥集團化學(xué)試劑有限公司100g/瓶胰酶-BD公司500g/瓶Gibco100g/瓶氨甲喋呤99.0%sigma-aldrich（fluka-analytical）100mg/管二甲基亞砜-SERVA Electrophoresis GmbH1L/瓶新生牛血清優(yōu)級武漢三利生物技術(shù)有限公司1000ml/瓶-內(nèi)蒙古金

53、源康生物工程有限公司500ml/瓶7.5 Process description:工藝簡述：Ø Process Cycle 工藝周期Table 5 Process Schedule表格 6工藝時間表No.序號Process Steps 工藝步驟Time (Day)時間（天）1Resurrection 復(fù)蘇12C25 - First square bottle incubation C25-方瓶第一次培養(yǎng)573C26 - second square bottle incubation C26-方瓶第二次培養(yǎng)574C27 - Kolle flask incubation C27-克氏瓶培

54、養(yǎng)575C28 - First 3L rotary bottle incubation C28-3L轉(zhuǎn)瓶第一次培養(yǎng)576C29 - second 3L rotary bottle incubation C29-3L轉(zhuǎn)瓶第二次培養(yǎng)577C30 - third 3L rotary bottle incubation C30-3L轉(zhuǎn)瓶第三次培養(yǎng)578C31 - first 15L bottle incubation C31-15L瓶第一次培養(yǎng)579C32 - second 15L bottle incubation C32-15L瓶第二次培養(yǎng)571020 consecutive harvest 連續(xù)

55、20次收獲液4011Filtration for cell residue removal 去細胞殘渣過濾0.512UF concentration 超濾濃縮0.513Ammonium sulfate precipitation 硫酸銨沉淀4514Potassium bromide extraction 溴化鉀提取115First density gradient centrifugation 一次密度梯度離心1.516Second density gradient centrifugation 二次密度梯度離心1.517UF concentration 超濾濃縮118Chromatography purification 層析純化119Bulk solution combination 原液合并0.5Ø Preparation