除菌过滤器验证(全)

ChineseJournalofNewDrugs2011,20(10)86120112010d[]黄晓龙,男,主要从事药品审评工作联系电话:[phone],Emai:[e-mail]():,,,,,(1国家食品药品监督管理局药品审评中心,北京100038;2颇尔中国生命科学部,上海201203)[]文中介绍了液体除菌过滤和微生物污染水平控制过滤的区别,并结合历史发展阐释了现行法规对液体除菌过滤的定义在此基础上,重点结合国外法规要求,对除菌过滤器的相关验证要求和项目进行了综述[]除菌过滤;除菌过滤器;法规要求;确认;验证[]R95[]C[]1003-3734(2011)10-0861-05Validationofsterilizinggradefilters(I):anoverallreviewofregulatoryrequirementsHUANGXiaolong,DONGWe,iTANGYan,XIETing,HONGHaiyan,CAIQingbo(1CenterforDrugEvaluation,StateFoodandDrugAdministration,Beijing100038,China;2PallChina,LifeSciencesDivision,Shanghai201203,China)[Abstract]Thisarticleintroducedthedifferencebetweensterilizingfiltrationandthefiltrationforcontrollingmicrobialcontamination,alsostatedthecurrentregulatoryidentificationofsterilizingfiltrationinviewofthehistoricaldevelopments.Thisreviewemphasizedontherequirementsofqualification/validationandrelateditemsforsterilizinggradefilteronthebasisofregulationsabroad.[Keywords]sterilizingfiltration;sterilizinggradefilter;regulatoryrequiremen;tqualification;validation,[1],,,,:,,,;,(poresizerating),,,,,,;,(bioburden),,,,,1,,,[2-3],,,[4-5],,,,ChineseJournalofNewDrugs2011,20(10)86220112010d2060,0.45m,,(Serratiamarcescens),,1960,FDAFrancesBowman0.45m,104~106cm-2[6]ASTMF838,,1cm2107CFU(colonyformingunit),(Brevundimonasdiminuta,ATCC19146)[7],,0.2m0.22m,,,:,[5];,0.2m(0.22m),,0.2m(0.22m),2,,,,(EMA),[8],,:,,;,(SAL)/;,,,,,,,,,()(),,,,,,[9],,,,,,/GMP,,[5,10-11]3,GMP,4,:()()[5,10]4,3.1()(),(),,,[1],3.2,,(),,,ChineseJournalofNewDrugs2011,20(10)86320112010d,(),,,,(spiking/spikedstudy),[11],,[1]3.3,,,((),(),,),,GMP,,,,,3.4,,,,,,,,,,,,,,4,GMP:GMP,[3,12-14],,,,,,,,4.1,4.1.1(,)()()/,,,,(USP3388)[15](),ChineseJournalofNewDrugs2011,20(10)86420112010d,pH(,),(NVR)(TOC),(UVVis)(FTIR)(NMR)4.1.2,,,,4.1.3pH,,4.2,,,,,,,,,,,,4.3,,[15],5,,/,[16-19],(worstcase)[17](SOP),,,,,,,,,,[1]6/,,,,[16]7,,,GMP,(harmonization),,,ICH,,;GMPPIC/S,,,,,,,;,,ChineseJournalofNewDrugs2011,20(10)86520112010d,,,(1),,,GMP1()()(),,:pHTOC()[][1]ParenteralDrugAssociation(PDA).Sterilizingfiltrationofliquids,technicalreportno.26[R].2008.[2]EMA.Decisiontreesfortheselectionofsterilisationmethods(CPMP/QWP/054/98)[S].1998.[3]EMA.Annex1,Manufactureofsterilemedicinalproducts,EUguidelinestogoodmanufacturingpractice[S].2008.[4].[S].2010.:,2010:XVII.[5]FDA.Steriledrugproductsproducedbyasepticprocessing,guidanceforindustry[S].2004.[6]BOWMANFW,HOLDOWAKYS.Productionandcontrolofastablepenicillinase[J].AntibiotChemother,1960,10:508.[7]AmericanSocietyforTestingandMaterialsInternational(ASTM).CommitteeD19.F83805standardtestmethodfordeterminingbacterialretentionofmembranefiltersutilizedforliquidfiltration[S].2005.[8]EMA.Decisiontreesfortheselectionofsterilisationmethods[S].1999.[9]FDA.Processvalidation:generalprinciplesandpractices(draft),guidanceforindustry[S].2008.[10]PIC/S.PI0075,validationofasepticprocesses,2009.[11]FDA.Forthesubmissiondocumentationforsterilizationprocessvalidationinapplicationsforhumanandveterinarydrugproducts,guidanceforindustry[S].1994.[12]ParenteralDrugAssociation(PDA).Processvalidationofproteinmanufacturing,technicalreportno.42[R].2005.[13]EUguidelinestogoodmanufacturingpractice[S].Chapter3premisesandequipment,partIbasicrequirementsformedicinalproducts,2008.[14]FDA.Currentgoodmanufacturingpracticeforfinishedpharmaceuticals[S].SubpartDequipment,part211.2010.[15]USP34[S].88Biologicalreactivitytests,invivo,generalchapters.[16]EMA.EUguidelinestogoodmanufacturingpractice[S].Annex15,qualificationandvalidation,2001.[17]PIC/S.PI0063,recommendationsonvalidationmasterplan[S].2007.[18]ICH.Q7GMPforAPI[S].2000.[19]EMA.Noteforguidanceonprocessvalidation[S].2001.编辑:王宇梅/接受日期:2011-04-15ChineseJournalofNewDrugs2011,20(13)116120112013。[e-mail]。。[e-mail]。··11111212012032100038。。3、、、。R95B1003－3734201113－1161－04ValidationofsterilizinggradefiltersIIsterilizationefficiencyXIETing1TANGYan1DONGWei1HONGHai-yan1CAIQing-bo1HUANGXiao-long21PallChinaLifeSciencesDivisionShanghai201203China2CenterforDrugEvaluationStateFoodandDrugAdministrationBeijing100038ChinaAbstractSterilefiltrationhasbeenwidelyappliedinthepharmaceuticalindustry．Choosingappropriatesterilizinggradefilteraccordingtothecharacteristicsofdrugsandvalidatingitsbacteriaretentionefficiencysuffi-cientlyunderdefinedprocessconditionsarethekeypointandnecessaryconditiontoensurethedrugsachieverele-vantasepticguaranteelevel．Inthispaperweoverviewedthethreestagesofvalidationonthesterilizinggradefilterandsterilefiltrationprocessthenecessityofvalidationprincipleandmethodinprocess-specificvalidationaswellasworst-caseconditionsfromthestandpointsofefficacyandsafetyinsterilefiltrationprocess．Keywordsvalidationsterilizinggradefiltersterilizationefficiencybacterialchallengeworstcasecon-dition1。0．2μm。FDA20042。。2－7。13。3ASTMF838-83B．diminuta107CFU。ChineseJournalofNewDrugs2011,20(13)116220112013“”、、pH、。3。。。-pH。“”。。22．1。/。。PDA268。、3。2．22．2．1B．diminuta0．3～0.4μm0.6～1．0μmATCC191469。。、B．diminutaB．diminuta。B．diminutaATCCATCC。SLBFCPB．