无菌检查方案

71STERILITYTESTS无菌测试PORTIONSOFTHISGENERALCHAPTERHAVEBEENHARMONIZEDWITHTHECORRESPONDINGTEXTSOFTHEEUROPEANPHARMACOPEIAAND/ORTHEJAPANESEPHARMACOPEIATHOSEPORTIONSTHATARENOTHARMONIZEDAREMARKEDWITHSYMBOLSTOSPECIFYTHISFACT此章节的某些部份与欧洲药典和/或日本药典的相关内容一致。不一致的章节用（）符号来表示，以标明其事实。THEFOLLOWINGPROCEDURESAREAPPLICABLEFORDETERMININGWHETHERAPHARMACOPEIALARTICLEPURPORTINGTOBESTERILECOMPLIESWITHTHEREQUIREMENTSSETFORTHINTHEINDIVIDUALMONOGRAPHWITHRESPECTTOTHETESTFORSTERILITYPHARMACOPEIALARTICLESARETOBETESTEDBYTHEMEMBRANEFILTRATIONMETHODUNDERTESTFORSTERILITYOFTHEPRODUCTTOBEEXAMINEDWHERETHENATUREOFTHEPRODUCTPERMITSIFTHEMEMBRANEFILTRATIONTECHNIQUEISUNSUITABLE,USETHEDIRECTINOCULATIONOFTHECULTUREMEDIUMMETHODUNDERTESTFORSTERILITYOFTHEPRODUCTTOBEEXAMINEDALLDEVICES,WITHTHEEXCEPTIONOFDEVICESWITHPATHWAYSLABELEDSTERILE,ARETESTEDUSINGTHEDIRECTINOCULATIONOFTHECULTUREMEDIUMMETHODPROVISIONSFORRETESTINGAREINCLUDEDUNDEROBSERVATIONANDINTERPRETATIONOFRESULTS以下程序用来确认药典药品是否按单独记录所列相关无菌测试要求执行。药品的特性允许下，按受检药品无菌测试中的薄膜过滤法来测试药典药品。如果薄膜过滤法不适用，用受检药品无菌测试中的培养基的直接接种指示方法来测试。除设备路径标明无菌外，所有的仪器全用培养基的直接接种指示来测试。测试的物品包含于结果观察资料及说明。BECAUSESTERILITYTESTINGISAVERYEXACTINGPROCEDURE,WHEREASEPSISOFTHEPROCEDUREMUSTBEENSUREDFORACORRECTINTERPRETATIONOFRESULTS,ITISIMPORTANTTHATPERSONNELBEPROPERLYTRAINEDANDQUALIFIEDTHETESTFORSTERILITYISCARRIEDOUTUNDERASEPTICCONDITIONSINORDERTOACHIEVESUCHCONDITIONS,THETESTENVIRONMENTHASTOBEADAPTEDTOTHEWAYINWHICHTHESTERILITYTESTISPERFORMEDTHEPRECAUTIONSTAKENTOAVOIDCONTAMINATIONARESUCHTHATTHEYDONOTAFFECTANYMICROORGANISMSTHATARETOBEREVEALEDINTHETESTTHEWORKINGCONDITIONSINWHICHTHETESTSAREPERFORMEDAREMONITOREDREGULARLYBYAPPROPRIATESAMPLINGOFTHEWORKINGAREAANDBYCARRYINGOUTAPPROPRIATECONTROLS因为无菌测试是一个极其严格的测试，必需确保灭菌程序以求结果的正确诠释，所以对人员进行相应培训以至合格就显得极为重要。无菌测试在无菌条件下进行。为了达到这样的环境，应改变周围的测试环境至无菌测试环境。应采取预防措施避免污染，并且此措施不影响测试中有机体的暴露。无菌测试的工作环境应靠在工作区取样来接受定期监控，同时进行适当控制。THESEPHARMACOPEIALPROCEDURESARENOTBYTHEMSELVESDESIGNEDTOENSURETHATABATCHOFPRODUCTISSTERILEORHASBEENSTERILIZEDTHISISACCOMPLISHEDPRIMARILYBYVALIDATIONOFTHESTERILIZATIONPROCESSOROFTHEASEPTICPROCESSINGPROCEDURES这些医典中的程序并非由自己确定一批药品的无菌性，或者是已经过灭菌的。它主要是由灭菌过程和无菌加工程序认证来确定的。WHENEVIDENCEOFMICROBIALCONTAMINATIONINTHEARTICLEISOBTAINEDBYTHEAPPROPRIATEPHARMACOPEIALMETHOD,THERESULTSOOBTAINEDISCONCLUSIVEEVIDENCEOFFAILUREOFTHEARTICLETOMEETTHEREQUIREMENTSOFTHETESTFORSTERILITY,EVENIFADIFFERENTRESULTISOBTAINEDBYANALTERNATIVEPROCEDUREFORADDITIONALINFORMATIONONSTERILITYTESTING,SEESTERILIZATIONANDSTERILITYASSURANCEOFCOMPENDIALARTICLES1211当通过相应药典中的方法得到的药品中的微生物污染证据，即使另一程序得到不同结果，以此得到的结果为药品不符合无菌测试要求的最终结果。无菌测试的详细信息见COMPENDIALARTICLES的灭菌和无菌保证1211MEDIA培养基PREPAREMEDIAFORTHETESTSASDESCRIBEDBELOW,ORDEHYDRATEDFORMULATIONSMAYBEUSEDPROVIDEDTHAT,WHENRECONSTITUTEDASDIRECTEDBYTHEMANUFACTURERORDISTRIBUTOR,THEYMEETTHEREQUIREMENTSOFTHEGROWTHPROMOTIONTESTOFAEROBES,ANAEROBES,ANDFUNGIMEDIAARESTERILIZEDUSINGAVALIDATEDPROCESS按以下所述为测试准备培养基，或无水配方，当按生产商和销售商指示重新组成，它们符合需氧菌，厌氧性生物，和真菌类助长测试要求。按验证方法对培养基进行灭菌。THEFOLLOWINGCULTUREMEDIAHAVEBEENFOUNDTOBESUITABLEFORTHETESTFORSTERILITYFLUIDTHIOGLYCOLLATEMEDIUMISPRIMARILYINTENDEDFORTHECULTUREOFANAEROBICBACTERIAHOWEVER,ITWILLALSODETECTAEROBICBACTERIASOYBEANCASEINDIGESTMEDIUMISSUITABLEFORTHECULTUREOFBOTHFUNGIANDAEROBICBACTERIA以下培养基适用于无菌测试。液态硫乙醇酸盐培养基主要是用来培养厌氧菌。大豆豆蛋白消化物培养基适用于培养真菌和需氧菌。FLUIDTHIOGLYCOLLATEMEDIUM液态硫乙醇酸盐培养基LCYSTINEL胱氨酸05GSODIUMCHLORIDE氯化钠25GDEXTROSEC6H12O6H2O葡萄糖55/50GAGAR,GRANULATEDMOISTURECONTENTNOTEXCEEDING15琼脂，颗粒状（湿度不超过15）075GYEASTEXTRACTWATERSOLUBLE酵母浸出粉（水溶性）50GPANCREATICDIGESTOFCASEIN酪蛋白胰酶消化物150GSODIUMTHIOGLYCOLLATE硫乙醇酸钠05GORTHIOGLYCOLICACID或者疏乙醋酸03MLRESAZURINSODIUMSOLUTION1IN1000,FRESHLYPREPARED新配制的（1/1000）刃天青钠溶液10MLPURIFIEDWATER水1000MLMIXTHELCYSTINE,SODIUMCHLORIDE,DEXTROSE,YEASTEXTRACT,ANDPANCREATICDIGESTOFCASEINWITHTHEPURIFIEDWATER,ANDHEATUNTILSOLUTIONISEFFECTEDDISSOLVETHESODIUMTHIOGLYCOLLATEORTHIOGLYCOLICACIDINTHESOLUTIONAND,IFNECESSARY,ADD1NSODIUMHYDROXIDESOTHAT,AFTERSTERILIZATION,THESOLUTIONWILLHAVEAPHOF7102IFFILTRATIONISNECESSARY,HEATTHESOLUTIONAGAINWITHOUTBOILING,ANDFILTERWHILEHOTTHROUGHMOISTENEDFILTERPAPERADDTHERESAZURINSODIUMSOLUTION,MIX,ANDPLACETHEMEDIUMINSUITABLEVESSELSTHATPROVIDEARATIOOFSURFACETODEPTHOFMEDIUMSUCHTHATNOTMORETHANTHEUPPERHALFOFTHEMEDIUMHASUNDERGONEACOLORCHANGEINDICATIVEOFOXYGENUPTAKEATTHEENDOFTHEINCUBATIONPERIODSTERILIZEUSINGAVALIDATEDPROCESSIFTHEMEDIUMISSTORED,STOREATATEMPERATUREBETWEEN2AND25INASTERILE,AIRTIGHTCONTAINERIFMORETHANTHEUPPERONETHIRDOFTHEMEDIUMHASACQUIREDAPINKCOLOR,THEMEDIUMMAYBERESTOREDONCEBYHEATINGTHECONTAINERSINAWATERBATHORINFREEFLOWINGSTEAMUNTILTHEPINKCOLORDISAPPEARSANDBYCOOLINGQUICKLY,TAKINGCARETOPREVENTTHEINTRODUCTIONOFNONSTERILEAIRINTOTHECONTAINERFLUIDTHIOGLYCOLLATEMEDIUMISTOBEINCUBATEDAT32525用纯静水将L胱氨酸，氯化钠，葡萄糖，酵母浸出粉，酪蛋白胰酶消化物混合。加热直至形成溶液，在溶液中溶解硫乙醇酸钠或疏乙醋酸，必要时，加入1N的氢氧化钠，在灭菌后，PH值会达到7102。如果有必要过滤的话，加热溶液但不用达到沸点，热气通过潮湿的过滤纸时进行过滤。加入刃天青钠溶液，并搅拌混合，将培养基放入适当的容器中，此容器可以显示一个培养基表面至深度的比率，培育阶段末时，不超过培养基上半部份的指示剂氧化层发生颜色变化。用验证方法进行灭菌。如果要存储培养基，将它存储于一个2和25间的无菌密封容器中。如果超过三分之一的培养基显示粉红色，在水浴或自由流通蒸汽中加热容器直至粉红色消失，并快速冷却，并防止有菌气体产生并进入容器，液态硫乙醇酸盐培养基就在32525下进行培育。ALTERNATIVETHIOGLYCOLLATEMEDIUM可选择疏基醋酸液培养基PREPAREAMIXTUREHAVINGTHESAMECOMPOSITIONASTHATOFTHEFLUIDTHIOGLYCOLLATEMEDIUM,BUTOMITTINGTHEAGARANDTHERESAZURINSODIUMSOLUTION,STERILIZEASDIRECTEDABOVE,ANDALLOWTOCOOLPRIORTOUSETHEPHAFTERSTERILIZATIONIS7102INCUBATEUNDERANAEROBICCONDITIONSFORTHEDURATIONOFTHEINCUBATIONPERIOD按液态硫乙醇酸盐培养基所含成份同样准备一份混合物，除去琼脂和刃天青钠溶液。按以上所示灭菌，使用前允许进行冷却。灭菌后PH值为7102。在厌氧条件下进行培育，以求培育期的持续。ALTERNATIVEFLUIDTHIOGLYCOLLATEMEDIUMISTOBEINCUBATEDAT32525可选择疏基醋酸液培养基应在32525下进行培育。SOYBEANCASEINDIGESTMEDIUM大豆酪蛋白消化物培养基PANCREATICDIGESTOFCASEIN酪蛋白胰酶消化物170GPAPAICDIGESTOFSOYBEANMEAL大豆粉木瓜蛋白酶水化物30GSODIUMCHLORIDE氯化钠50GDIBASICPOTASSIUMPHOSPHATE磷酸氢二钾25GDEXTROSEC6H12O6H2O葡萄糖25/23GPURIFIEDWATER水1000MLDISSOLVETHESOLIDSINTHEPURIFIEDWATER,HEATINGSLIGHTLYTOEFFECTASOLUTIONCOOLTHESOLUTIONTOROOMTEMPERATURE,ANDADJUSTTHEPHWITH1NSODIUMHYDROXIDESOTHAT,AFTERSTERILIZATION,ITWILLHAVEAPHOF7302FILTER,IFNECESSARYTOCLARIFY,DISPENSEINTOSUITABLECONTAINERS,ANDSTERILIZEUSINGAVALIDATEDPROCEDURESTOREATATEMPERATUREBETWEEN2AND25INASTERILEWELLCLOSEDCONTAINER,UNLESSITISINTENDEDFORIMMEDIATEUSE在水中溶解固体，轻轻加热以形成溶液。将溶液冷却至室温，用1N的氢氧化钠来调节PH值，以至在灭菌后其PH值达到7302。过滤，如果有必要进行澄清时，将漏斗放入相应的容器中，并用验证方法来进行灭菌。在一个无菌密封容器中2和25下进行存储，直至使用。SOYBEANCASEINDIGESTMEDIUMISTOBEINCUBATEDAT22525大豆酪蛋白消化物培养基在22525下进行培育。MEDIAFORPENICILLINSORCEPHALOSPORINS青霉素或头孢菌素培养基WHERESTERILITYTESTMEDIAARETOBEUSEDINTHEDIRECTINOCULATIONOFTHECULTUREMEDIUMMETHODUNDERTESTFORSTERILITYOFTHEPRODUCTTOBEEXAMINED,MODIFYTHEPREPARATIONOFFLUIDTHIOGLYCOLLATEMEDIUMANDTHESOYBEANCASEINDIGESTMEDIUMASFOLLOWSTOTHECONTAINERSOFEACHMEDIUM,TRANSFERASEPTICALLYAQUANTITYOFLACTAMASESUFFICIENTTOINACTIVATETHEAMOUNTOFANTIBIOTICINTHESPECIMENUNDERTESTDETERMINETHEQUANTITYOFLACTAMASEREQUIREDTOINACTIVATETHEANTIBIOTICBYUSINGALACTAMASEPREPARATIONTHATHASBEENASSAYEDPREVIOUSLYFORITSPENICILLINORCEPHALOSPORININACTIVATINGPOWERNOTESUPPLEMENTEDLACTAMASEMEDIACANALSOBEUSEDINTHEMEMBRANEFILTRATIONTEST当用受检药品无菌试验测试的培养基直接接种方法来进行无菌试验时，按以下更正液态硫乙醇酸盐培养基和大豆酪蛋白消化物培养基的制剂。在无菌情况下，将足够的内酰胺酶转移到每种培养基的容器中，来钝化试验样品中的抗生素。用以前化验青霉素或头孢菌素钝化力的内酰胺酶制剂来确定需要钝化抗生素的内酰胺酶的量。ALTERNATIVELYINANAREACOMPLETELYSEPARATEFROMTHATUSEDFORSTERILITYTESTING,CONFIRMTHATANAPPROPRIATEAMOUNTOFLACTAMASEISINCORPORATEDINTOTHEMEDIUM,FOLLOWINGEITHERMETHODUNDERVALIDATIONTEST,USINGLESSTHAN100COLONYFORMINGUNITSCFUOFSTAPHYLOCOCCUSAUREUSSEETABLE1ASTHECHALLENGETYPICALMICROBIALGROWTHOFTHEINOCULATEDCULTUREMUSTBEOBSERVEDASACONFIRMATIONTHATTHELACTAMASECONCENTRATIONISAPPROPRIATE另外（在另一个完全与无菌试验无关的领域），确定适当量内酰胺酶混合于培养基中，接着用验证测试中的方法，用不少于100CFU葡萄状球菌（见表1）做为挑战性实验接种的培养菌的典型微生物生长应接受观察，以确定内酰胺酶的浓渡适当。TABLE1STRAINSOFTHETESTMICROORGANISMSSUITABLEFORUSEINTHEGROWTHPROMOTIONTESTANDTHEVALIDATIONTEST表1。促生长试验和验证试验中的可用到微生物菌株AEROBICBACTERIA需氧细菌STAPHYLOCOCCUSAUREUS1金黄色葡萄球菌ATCC6538,CIP483,NCTC10788,NCIMB9518BACILLUSSUBTILIS枯草芽孢杆菌ATCC6633,CIP5262,NCIMB8054PSEUDOMONASAERUGINOSA2铜绿假单胞菌ATCC9027,NCIMB8626,CIP82118ANAEROBICBACTERIUM厌氧细菌CLOSTRIDIUMSPOROGENES3生孢梭菌ATCC19404,CIP793,NCTC532ORATCC11437FUNGI真菌类CANDIDAALBICANS白色念珠菌ATCC10231,IP4872,NCPF3179ASPERGILLUSNIGER黑曲霉ATCC16404,IP143183,IMI1490071ANALTERNATIVETOSTAPHYLOCOCCUSAUREUSISBACILLUSSUBTILISATCC6633可选择杆状菌ATCC6633代替葡萄球状菌2ANALTERNATIVEMICROORGANISMISMICROCOCCUSLUTEUSKOCURIARHIZOPHILA,ATCC9341可选择微球菌ATCC9341代替微生物3ANALTERNATIVETOCLOSTRIDIUMSPOROGENES,WHENANONSPOREFORMINGMICROORGANISMISDESIRED,ISBACETROIDESVULGATUSATCC8482当需要不产生孢子的微生物时，可选择普通拟杆菌ATCC8482来代替梭菌。NOTESEEDLOTCULTUREMAINTENANCETECHNIQUESSEEDLOTSYSTEMSAREUSEDSOTHATTHEVIABLEMICROORGANISMSUSEDFORINOCULATIONARENOTMORETHANFIVEPASSAGESREMOVEDFROMTHEORIGINALMASTERSEEDLOT注释使用种子批培养保护技术（种子批体系），以至接种所用的可繁殖微生物不超过五代而远离原始主种子批SUITABILITYTESTS适用性试验THEMEDIAUSEDCOMPLYWITHTHEFOLLOWINGTESTS,CARRIEDOUTBEFORE,ORINPARALLEL,WITHTHETESTONTHEPRODUCTTOBEEXAMINED所用培养基和以下试验相符合，它在受检产品测试之或与之同时进行。STERILITY无菌性CONFIRMTHESTERILITYOFEACHSTERILIZEDBATCHOFMEDIUMBYINCUBATINGAPORTIONOFTHEMEDIAATTHESPECIFIEDINCUBATIONTEMPERATUREFOR14DAYSNOGROWTHOFMICROORGANISMSOCCURS确定每批消过毒的培养基的无菌性，在特殊的培养温度中培育一部份培养基14天，微生物不生长。GROWTHPROMOTIONTESTOFAEROBES,ANAEROBES,ANDFUNGI需氧菌，压氧菌和真菌类助长试验TESTEACHLOTOFOFREADYPREPAREDMEDIUMANDEACHBATCHOFMEDIUMPREPAREDEITHERFROMDEHYDRATEDMEDIUMORFROMINGREDIENTS1SUITABLESTRAINSOFMICROORGANISMSAREINDICATEDINTABLE1对准备好的每批培养基，和从干粉培养基或混合粉中准备的每批培养基进行试验表1中显示出适宜的微生物类。INOCULATEPORTIONSOFFLUIDTHIOGLYCOLLATEMEDIUMWITHASMALLNUMBERNOTMORETHAN100CFUOFTHEFOLLOWINGMICROORGANISMS,USINGASEPARATEPORTIONOFMEDIUMFOREACHOFTHEFOLLOWINGSPECIESOFMICROORGANISMCLOSTRIDIUMSPOROGENES,PSEUDOMONASAERUGINOSA,ANDSTAPHYLOCOCCUSAUREUSINOCULATEPORTIONSOFALTERNATIVEFLUIDTHIOGLYCOLLATEMEDIUMWITHASMALLNUMBERNOTMORETHAN100CFUOFCLOSTRIDIUMSPOROGENESINOCULATEPORTIONSOFSOYBEANCASEINDIGESTMEDIUMWITHASMALLNUMBERNOTMORETHAN100CFUOFTHEFOLLOWINGMICROORGANISMS,USINGASEPARATEPORTIONOFMEDIUMFOREACHOFTHEFOLLOWINGSPECIESOFMICROORGANISMASPERGILLUSNIGER,BACILLUSSUBTILIS,ANDCANDIDAALBICANSINCUBATEFORNOTMORETHAN3DAYSINTHECASEOFBACTERIAANDNOTMORETHAN5DAYSINTHECASEOFFUNGI用一小部份（不超过100CFU）以下微生物，来接种一部份液态硫乙醇酸盐培养基，以下每种微生物都分别有一部份培养基梭菌，假单胞菌和葡萄状球菌。用小数量的（不超过100CFU）梭菌来嫁接可选择疏基醋酸液培养基。用小数量（不超过100CFU）的以下微生物来接种大豆酪蛋白消化物培养基，以下每种微生物使用单独的培养基黑曲霉菌，枯草芽孢杆菌和白色念珠菌。在细菌的情况下培育不超过3天，在真菌类情况下，培育不超过5天。THEMEDIAARESUITABLEIFACLEARLYVISIBLEGROWTHOFTHEMICROORGANISMSOCCURS如果微生物生长明显出现，培养基适用。STORAGE存储IFPREPAREDMEDIAARESTOREDINUNSEALEDCONTAINERS,THEYCANBEUSEDFOR1MONTH,PROVIDEDTHATTHEYARETESTEDFORGROWTHPROMOTIONWITHIN2WEEKSOFTHETIMEOFUSEANDTHATCOLORINDICATORREQUIREMENTSAREMETIFSTOREDINTIGHTCONTAINERS,THEMEDIACANBEUSEDFOR1YEAR,PROVIDEDTHATTHEYARETESTEDFORGROWTHPROMOTIONWITHIN3MONTHSOFTHETIMEOFUSEANDTHATTHECOLORINDICATORREQUIREMENTSAREMET如果已准备培养基存储于未密封容器中，可使用1个月，使用的两周时间内进行助长试验，指示剂的颜色符合要求，可使用1个月。如果存存储于一个密封的容器中，使用时间的三个月内进行助长试验，指示剂颜色符合要求，培养基可用1年。DILUTINGANDRINSINGFLUIDSFORMEMBRANEFILTRATION薄膜过滤法的稀释液和冲洗液FLUIDA液体APREPARATIONDISSOLVE1GOFPEPTICDIGESTOFANIMALTISSUEINWATERTOMAKE1L,FILTERORCENTRIFUGETOCLARIFY,IFNECESSARY,ANDADJUSTTOAPHOF7102DISPENSEINTOCONTAINERS,ANDSTERILIZEUSINGAVALIDATEDPROCESS溶解制剂将1G动物组织胃蛋白酶消化物加入水中制成1L，如果需要，过滤或者离心直到溶液澄清，并将其PH值调至7102，分配到溶器中，通过验证程序灭菌。PREPARATIONFORPENICILLINSORCEPHALOSPORINSASEPTICALLYADDTOTHEABOVEPREPARATION,IFNECESSARY,AQUANTITYOFSTERILELACTAMASESUFFICIENTTOINACTIVATEANYRESIDUALANTIBIOTICACTIVITYONTHEMEMBRANESAFTERTHESOLUTIONOFTHETESTSPECIMENHASBEENFILTEREDSEEMEDIAFORPENICILLINSORCEPHALOSPORINS青霉素和头孢子菌的无菌配制将一定量的内酰胺酶加入上述所备制剂中，以钝化在试验样品溶液过滤后薄膜上任何残余抗生素活性（见青霉素或头孢菌素培养基）。FLUIDD液体DTOEACHLOFFLUIDAADD1MLOFPOLYSORBATE80,ADJUSTTOAPHOF7102,DISPENSEINTOCONTAINERS,ANDSTERILIZEUSINGAVALIDATEDPROCESSUSETHISFLUIDFORARTICLESCONTAININGLECITHINOROIL,ORFORDEVICESLABELEDAS“STERILEPATHWAY”每1L液体A就加入1ML聚山梨醇酯80，将PH值调至7102，并入配到容器中，通过验证程序灭菌。此液体用于含蛋黄素或油脂的药品，或用于贴着“无菌路径”的仪器。FLUIDK液体KDISSOLVE50GOFPEPTICDIGESTOFANIMALTISSUE,30GOFBEEFEXTRACT,AND100GOFPOLYSORBATE80INWATERTOMAKE1LADJUSTTHEPHTOOBTAIN,AFTERSTERILIZATION,APHOF6902DISPENSEINTOCONTAINERS,ANDSTERILIZEUSINGAVALIDATEDPROCESS将50G动物组织胃蛋白酶消化液，30G浓缩牛肉汁，和100G聚山梨醇酯80溶解制成1L。调节PH值，在灭菌后，达到6902。分配到容器中，通过验证程序灭菌。VALIDATIONTEST验证测试CARRYOUTATESTASDESCRIBEDBELOWUNDERTESTFORSTERILITYOFTHEPRODUCTTOBEEXAMINEDUSINGEXACTLYTHESAMEMETHODS,EXCEPTFORTHEFOLLOWINGMODIFICATIONS按受检产品无菌试验下同样的方法，按以下所述进行试验操作，除以下更改。MEMBRANEFILTRATION薄膜过滤法AFTERTRANSFERRINGTHECONTENTOFTHECONTAINERORCONTAINERSTOBETESTEDTOTHEMEMBRANE,ADDANINOCULUMOFASMALLNUMBEROFVIABLEMICROORGANISMSNOTMORETHAN100CFUTOTHEFINALPORTIONOFSTERILEDILUENTUSEDTORINSETHEFILTER在将容器内溶液或者待测容器中的溶液转移至薄膜后，在用来清洗过滤器最后部份的无菌稀释液里加入（不超过100CFU）小部份可繁殖微生物的培养基。DIRECTINOCULATION直接接种AFTERTRANSFERRINGTHECONTENTSOFTHECONTAINERORCONTAINERSTOBETESTEDFORCATGUTANDOTHERSURGICALSUTURESFORVETERINARYUSESTRANDSTOTHECULTUREMEDIUM,ADDANINOCULUMOFASMALLNUMBEROFVIABLEMICROORGANISMSNOTMORETHAN100CFUTOTHEMEDIUM在将容器内溶液或者待测容器（肠线或其它兽医用的外科缝合用线）中的溶液转移至培养基后，在培养基中加入（不超过100CFU）少量的可繁殖微生物。INBOTHCASESUSETHESAMEMICROORGANISMSASTHOSEDESCRIBEDABOVEUNDERGROWTHPROMOTIONTESTOFAEROBES,ANAEROBES,ANDFUNGIPERFORMAGROWTHPROMOTIONTESTASAPOSITIVECONTROLINCUBATEALLTHECONTAINERSCONTAININGMEDIUMFORNOTMORETHAN5DAYS在两种情况下，按需氧菌，厌氧性生物，和真菌类的助长试验上面所描述，使用同种微生物。执行助长试验作为积极控制。对含有培养基的所有容器进行不超过五天培育。IFCLEARLYVISIBLEGROWTHOFMICROORGANISMSISOBTAINEDAFTERTHEINCUBATION,VISUALLYCOMPARABLETOTHATINTHECONTROLVESSELWITHOUTPRODUCT,EITHERTHEPRODUCTPOSSESSESNOANTIMICROBIALACTIVITYUNDERTHECONDITIONSOFTHETESTORSUCHACTIVITYHASBEENSATISFACTORILYELIMINATEDTHETESTFORSTERILITYMAYTHENBECARRIEDOUTWITHOUTFURTHERMODIFICATION如果培养后，与没有产品的控制容器内相比，或者与在试验条件下不含抗微生物活性的产品相比，或者与活性已消除产品相比，微生物生长明显示，那么无菌试验可在不修改下执行。IFCLEARLYVISIBLEGROWTHISNOTOBTAINEDINTHEPRESENCEOFTHEPRODUCTTOBETESTED,VISUALLYCOMPARABLETOTHATINTHECONTROLVESSELSWITHOUTPRODUCT,THEPRODUCTPOSSESSESANTIMICROBIALACTIVITYTHATHASNOTBEENSATISFACTORILYELIMINATEDUNDERTHECONDITIONSOFTHETESTMODIFYTHECONDITIONSINORDERTOELIMINATETHEANTIMICROBIALACTIVITY,ANDREPEATTHEVALIDATIONTEST与没有产品的控制容器内相比，或者与在试验条件下含抗微生物活性的产品活性未被消化相比，如果受检产品的微生物没有明显的生长，那么更改条件，以消除抗微生物活性，并重复验证测试。THISVALIDATIONISPERFORMEDAWHENTHETESTFORSTERILITYHASTOBECARRIEDOUTONANEWPRODUCTANDBWHENEVERTHEREISACHANGEINTHEEXPERIMENTALCONDITIONSOFTHETESTTHEVALIDATIONMAYBEPERFORMEDSIMULTANEOUSLYWITHTHETESTFORSTERILITYOFTHEPRODUCTTOBEEXAMINEDA当新产品进行无菌试验时，B当测试的试验条件出现变化时,验证执行；验证与受检产品无菌测试可以同时进行。TESTFORSTERILITYOFTHEPRODUCTTOBEEXAMINED受检产品无菌测试NUMBEROFARTICLESTOBETESTED受检药品数UNLESSOTHERWISESPECIFIEDELSEWHEREINTHISCHAPTERORINTHEINDIVIDUALMONOGRAPH,TESTTHENUMBEROFARTICLESSPECIFIEDINTABLE3IFTHECONTENTSOFEACHARTICLEAREOFSUFFICIENTQUANTITYSEETABLE2,THEYMAYBEDIVIDEDSOTHATEQUALAPPROPRIATEPORTIONSAREADDEDTOEACHOFTHESPECIFIEDMEDIANOTEPERFORMSTERILITYTESTINGEMPLOYINGTWOORMOREOFTHESPECIFIEDMEDIAIFEACHARTICLEDOESNOTCONTAINSUFFICIENTQUANTITIESFOREACHMEDIUM,USETWICETHENUMBEROFARTICLESINDICATEDINTABLE3除非此章节或者专论中的其它地方有特别说明，否则按表3详细列出的药品数进行测试。如果每种药品的成份足量（见表2），它们将会被分成适当的小份并被加到每份指定的培养基中。注释进行无菌试验时，运用两到三种指定培养基。如果每种培养基中的每种药品量不足，按表3所示药品用两倍。TABLE2MINIMUMQUANTITYTOBEUSEDFOREACHMEDIUM表2每种培养基所使用的最小量QUANTITYPERCONTAINER每个容器的量MINIMUMQUANTITYTOBEUSED除非另有证明及授权所用的最小量（除非另有证明和授权）LIQUIDSOTHERTHANANITBIOTICS液体（除抗生素外）LESSTHAN1ML少于1MLTHEWHOLECONTENTSOFEACHCONTAINER每个容器的全部量140MLHALFTHECONTENTSOFEACHCONTAINER,BUTNOTLESSTHAN1ML每个容器容量的一半，但不少于1MLGREATERTHAN40ML,ANDNOTGREATERTHAN100ML大于40ML，但不超过100ML20MLGREATERTHAN100ML超过100ML10OFTHECONTENTSOFTHECONTAINER,BUTQUANTITYPERCONTAINER每个容器的量MINIMUMQUANTITYTOBEUSED除非另有证明及授权所用的最小量（除非另有证明和授权）NOTLESSTHAN20ML容器量的10，但不超过20MLANTIBIOTICLIQUIDS液体抗生素1MLOTHERPREPARATIONSSOLUBLEINWATERORINISOPROPYLMYRISTATE其它可溶于水或透汽性油脂的制剂THEWHOLECONTENTSOFEACHCONTAINERTOPROVIDENOTLESSTHAN200MG每个容器的全部容量，不少于200MGINSOLUBLEPREPARATIONS,CREAMS,ANDOINTMENTSTOBESUSPENDEDOREMULSIFIED可溶解制剂，悬浮的或浮化的乳脂和药膏USETHECONTENTSOFEACHCONTAINERTOPROVIDENOTLESSTHAN200MG每个容器的容量，少于200MGSOLIDS固体LESSTHAN50MG少于50MGTHEWHOLECONTENTSOFEACHCONTAINER每个容器的全部量50MGORMORE,BUTLESSTHAN300MG50MG或更多，但少于300MGHALFTHECONTENTSOFEACHCONTAINER,BUTNOTLESSTHAN50MG每个容器体积的一半，但不少于50MG300MG5G150MGGREATERTHAN5G超过5G500MGDEVICES仪器CATGUTANDOTHERSURGICALSUTURESFORVETERINARYUSE肠线和其它用于兽医手术缝合线3SECTIONSOFASTRANDEACH30CMLONG绳的3段（每断30CM）SURGICALDRESSING/COTTON/GAUZEINPACKAGES外科手术敷料/棉花/薄纱（包）100MGPERPACKAGE每包100MGSUTURESANDOTHERINDIVIDUALLYPACKAGEDSINGLEUSEMATERIAL缝合线和其它单独包装使用的材料THEWHOLEDEVICE整个仪器OTHERMEDICALDEVICES其它医疗仪器THEWHOLEDEVICE,CUTINTOPIECESORDISASSEMBLED整个仪器，切成片或拆分TABLE3MINIMUMNUMBEROFARTICLESTOBETESTEDINRELATIONTOTHENUMBEROFARTICLESINTHEBATCH表3。关于一批药品数中受检药品的最小量NUMBEROFITEMSINTHEBATCH一批药的条款项MINIMUMNUMBEROFITEMSTOBETESTEDFOREACHMEDIUM每种培养基的受检的项的最小数除非另有证明及授权PARENTERALPREPARATIONS非肠道注射用药的制剂NOTMORETHAN100CONTAINERS不超过100个容器10OR4CONTAINERS,WHICHEVERISTHEGREATER10或4个容器，选用较大者MORETHAN100BUTNOTMORETHAN500CONTAINERS超过100个容器，但不超过500个容器10CONTAINERS10个容器MORETHAN500CONTAINERS超过500个容器2OR20CONTAINERS,WHICHEVERISLESS2或20个容器，选用较小者FORLARGEVOLUMEPARENTERALS大量非肠道注射用药2OR10CONTAINERS,WHICHEVERISLESS2或20个容器，选用较小者ANTIBIOTICSOLIDS固体抗生素PHARMACYBULKPACKAGES5G散装药20CONTAINERS20个容器PHARMACYBULKPACKAGES5G散装药6CONTAINERS6个容器BULKSANDBLENDS散装药和混合物SEEBULKSOLIDPRODUCTS见固体散装药OPHTHALMICANDOTHERNONINJECTABLEPREPARATIONS眼药和其它非注射制剂NOTMORETHAN200CONTAINERS不超过200个容器5OR2CONTAINERS,WHICHEVERISTHEGREATER5或2个容器，选用较大者MORETHAN200CONTAINERS超过200个容器10CONTAINERS10个容器IFTHEPRODUCTISPRESENTEDINTHEFORMOFSINGLEDOSECONTAINERS,APPLYTHESCHEMESHOWNABOVEFORPREPARATIONSFORPARENTERALUSE如果药品装入单剂型容器中，应用于以上非肠道注射药用方案DEVICES仪器CATGUTANDOTHERSURGICALSUTURESFORVETERINARYUSE非肠道注射用药的制剂2OR5PACKAGES,WHICHEVERISTHEGREATER,UPTOAMAXIMUMTOTALOF20PACKAGES2或5包，选用较大者，至多为20包NOTMORETHAN100ARTICLES不超过200种药品10OR4ARTICLES,WHICHEVERISGREATER10或4包，选用较大者，MORETHAN100,BUTNOTMORETHAN500ARTICLES超过100，但不超过500种药品10ARTICLES10包NUMBEROFITEMSINTHEBATCH一批药的条款项MINIMUMNUMBEROFITEMSTOBETESTEDFOREACHMEDIUM每种培养基的受检的项的最小数除非另有证明及授权MORETHAN500ARTICLES超过500种药品2OR20ARTICLES,WHICHEVERISLESS2或20包，选用较小者BULKSOLIDPRODUCTS固体散装药UPTO4CONTAINERS至多4个容器EACHCONTAINER每个容器MORETHAN4CONTAINERS,BUTNOTMORETHAN50CONTAINERS超过4个容器，但不超过50个容器20OR4CONTAINERS,WHICHEVERISGREATER2或4包，选用较大者MORETHAN50CONTAINERS超过50个容器2OR10CONTAINERS,WHICHEVERISGREATER2或10包，选用较大者IFTHECONTENTSOFONECONTAINERAREENOUGHTOINOCULATETHETWOMEDIA,THISCOLUMNGIVESTHENUMBEROFCONTAINERSNEEDEDFORBOTHTHEMEDIATOGETHER如果一个容器的所装物足够接种两种培养基，此量满足两种培养基所需容器数的量。THETESTMAYBECARRIEDOUTUSINGTHETECHNIQUEOFMEMBRANEFILTRATIONORBYDIRECTINOCULATIONOFTHECULTUREMEDIUMWITHTHEPRODUCTTOBEEXAMINEDAPPROPRIATENEGATIVECONTROLSAREINCLUDEDTHETECHNIQUEOF