【文章內(nèi)容簡(jiǎn)介】 gendaRisk analysis in Filtration Process 過(guò)濾工藝中的風(fēng)險(xiǎn)分析? Filter application and Qualification 過(guò)濾器的應(yīng)用與確認(rèn)? Filter Integrity testing 過(guò)濾器完整性測(cè)試252。Filtration process Validation 過(guò)濾工藝驗(yàn)證? Filtration process review過(guò)濾驗(yàn)證總結(jié)法規(guī)部門(mén)的要求過(guò)濾器驗(yàn)證流程為什么使用者要對(duì)過(guò)濾器進(jìn)行驗(yàn)證？過(guò)濾器驗(yàn)證包括那些項(xiàng)目？再驗(yàn)證周期及條件US GMP 21 CFR Parts 210 amp。 211 美國(guó) GMP? Appropriate written procedures…shall be established and followed. Such procedures shall include validation of any sterilization process　必須建立和跟進(jìn)相應(yīng)的證明性文件 …., ，這些文件中包括所有的除菌工藝的驗(yàn)證文件．EU GMP Annex 1 Sterile Medicinal Products 歐盟GMP 無(wú)菌藥品附錄? All sterilization processes should be validated　所有除菌工藝必須進(jìn)行驗(yàn)證Filter Validation is Required Worldwide by GMP世界各國(guó)ＧＭＰ法規(guī)要求進(jìn)行過(guò)濾器驗(yàn)證Filter Validation is Required Worldwide by GMP世界各國(guó)ＧＭＰ法規(guī)要求進(jìn)行過(guò)濾器驗(yàn)證（續(xù)）Australian TGA GMP 澳大利亞 TGA GMP? Filtration processes used as the sterilizing step for products should be validated　出于除菌目的過(guò)濾工藝應(yīng)該驗(yàn)證Health Canada GMP 加拿大 GMP? Documented evidence is available establishing validation and validity of each sterilization process　每步除菌工藝必須要有驗(yàn)證其有效性的證明性文件Filter Validation in Regulatory and Industry Guidelines 法規(guī)及行業(yè)指南對(duì)過(guò)濾驗(yàn)證的要求FDA Aseptic Processing Guidelines (1987 amp。 2022, ) 　 FDA無(wú)菌工藝指南– Correlate filter performance with filter integrity testing Include microbiological challenges to simulate ‘worst case’ production conditions　 與過(guò)濾器完整性相關(guān)的性能測(cè)試應(yīng)包括：模擬生產(chǎn)條件，在最苛刻生產(chǎn)環(huán)境下進(jìn)行微生物挑戰(zhàn)試驗(yàn)。PDA Technical Report 26 (1998, )– “Early, careful screening of potential filter types and configuration can result in fewer technical and regulatory problems, fewer delays, more efficient product processing, and greater sterility assurance”　 更早地，更細(xì)致地選用過(guò)濾器的規(guī)格和類型可減少技術(shù)和法規(guī)方面的問(wèn)題，避免延誤，更有效的生產(chǎn)，更好的無(wú)菌保障．Filter Validation in Regulatory and Industry Guidelines 法規(guī)及行業(yè)指南對(duì)過(guò)濾驗(yàn)證的要求（續(xù)）ISO/DIS 134082 Aseptic Processing (2022, ) ISO/DIS 無(wú)菌工藝– Filter Preselection shall take into account chemical and physical characteristics of the filter, as established by the filter manufacturer.– Bacterial retention performance of filters shall be validated in a fluidspecific manner or for fluid groups under worst case conditions in production. 選擇過(guò)濾器前向生產(chǎn)商確認(rèn)，仔細(xì)考慮過(guò)濾器的物理，化學(xué)性能。細(xì)菌截留性能驗(yàn)證：１）需要在生產(chǎn)過(guò)程中可能遇到的最差的條件下進(jìn)行，２）使用產(chǎn)品或模擬液進(jìn)行驗(yàn)證。Other Sources of Guidance其它相關(guān)指南FDA 483 and warning letters FDA 483– FOI– Show regulatory trend法規(guī)發(fā)展方向Site Lack of Validation for缺陷常發(fā)生在：? Filter Compatibility with product過(guò)濾器與產(chǎn)品間的兼容性? Filter Extractables過(guò)濾器的析出物? Actual Filtration Process Conditions used實(shí)際過(guò)濾操作條件? Filter Integrity Testing Methods/Fluids過(guò)濾器完整性測(cè)試方法／測(cè)試流體? Equivalency of alternate filters過(guò)濾器的一致性過(guò)濾器驗(yàn)證流程Protocol方案VMP驗(yàn)證總 體 計(jì) 劃AccessQuestionnaire調(diào)查 表Report報(bào) 告ValidationMaster file 驗(yàn)證總 文件除菌過(guò)濾器驗(yàn)證流程定 義 工 藝 條件及流程確定操作條件 ,指定 驗(yàn)證 方案完整性 檢測(cè) 方法析出物，兼容性， 吸附 微生物挑 戰(zhàn)試驗(yàn) ，毒性壓 力，流速，溫度驗(yàn)證 指南產(chǎn)品使用說(shuō)明 最差條件Validation Guide 驗(yàn)證 指南過(guò)濾器驗(yàn)證項(xiàng)目Biological生物性能– Microbial Retention微生物截留? Customized to客戶定制Flow Rate流速Throughput產(chǎn)量Process temperature操作溫度Pressure壓力System Size系統(tǒng)尺寸大小Physical物理性能– Integrity完整性? Product/water BP ratio產(chǎn)品／水起泡點(diǎn)? Diffusion ratio擴(kuò)散流– Binding吸附 Chemical化學(xué)性能w Compatibilityw Extractables兼容性＼析出物Compatibility Testing兼容性測(cè)試化學(xué)兼容性驗(yàn)證A B C A B C酸和堿 汽油 L N R乙酸 (5%) R R R 甘油 R R R硼酸 R R R 己烷 L N R濃鹽酸 R R R 雙氧水 (3%) R R R氫氟酸 R N N 異丁醇 R R R濃硝酸 N N N 異丙酸乙酯 R N R濃硫酸 N N R 異丙醇 R R R氨水 (6N) N R R 煤油 L N R濃氫氧化鈉 N R R 甲醇 R R R溶劑 二氯甲烷 L N R丙酮 N N R 甲乙酮 L N RADurapore CVGL濾 柱B硅膠 O形圈C不 銹鋼過(guò)濾 器外殼ＣＶＧＬ化學(xué)兼容性Filter/Product Compatibility Testing過(guò)濾器與產(chǎn)品兼容性測(cè)試Is the filter membrane patib