1208USpSTERILITY TESTINGVALIDATION OF ISOLATOR SYSTEMS.docx

1208USpSTERILITY TESTINGVALIDATION OF ISOLATOR SYSTEMS.docx

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1208USpSTERILITYTESTINGVALIDATIONOFISOLATORSYSTEMS

1208STERILITYTESTING—VALIDATIONOFISOLATORSYSTEMS

Thischapterprovidesguidelinesforthevalidationofisolatorsystemsforuseinsterilitytestingofcompendialarticles加工配制药物.[note—Inthecontextofthischapter,“decontaminated”净化referstoanitemorsurfacethathasbeensubjectedtoaprocessthateliminates消除viable存活的bioburden微生物量.]

Isolators—devicesthatcreatecontrolledenvironmentsinwhichtoconductPharmacopeialsterilitytests—havebeenusedsincethemid-1980s.AnisolatorissuppliedwithairthroughaHEPAorbetterairfilterandisabletobereproduciblydecontaminated.Closedisolators,whicharesystemswithnodirectopeningtotheexternalenvironment,arenormallyusedforsterilitytesting,althoughopenisolatorswhichallowtheegress出口，外出ofmaterialsthroughadefinedopeningthatprecludes排除theentry进入ofcontaminationbymeansofairoverpressure过压maybeused.Closedisolatorsuseonlydecontaminatedinterfacesorarapid-transferportforthetransferofmaterials.Isolatorsareconstructedofflexibleplastics（suchaspolyvinylchloride）,rigidplastics,glass,orstainlesssteel.

Isolatorsystemsprotectthetestarticleandsuppliesfromcontaminationduringhandlingbyessentiallyeliminatingdirectcontactbetweentheanalystandthetestarticles.Alltransfersofmaterialintoandoutoftheisolatorareaccomplishedinanaseptic无菌的，防腐剂fashionwhilemaintainingcompleteenvironmentalseparation.Asepticmanipulationswithintheisolatoraremadewithhalf-suits,whichareflexiblecomponentsoftheisolatorwallthatallowtheoperatorafullrangeofmotionwithintheisolator,orbyglovesandsleeves.Operatorsarenotrequiredtowearspecialclean-roomclothingforconductingsterilitytestswithinisolators;standardlaboratoryclothingisadequate,althoughapairofsterileglovesisfrequentlywornundertheisolatorglovesasanaddedprecautionagainstcontaminationenteringtheisolatorenclosureandforhygienepurposes.Theinterioroftheisolatoristreatedwithsporicidalchemicalsthatresultintheeliminationofallviablebioburdenonexposedsurfaces.

ISOLATORDESIGNANDCONSTRUCTION构造

AirHandlingSystems

Anisolatorusedforsterilitytestingisequippedwithmicrobialretentivefilters（HEPAfiltersorbetterarerequired）.Atrest,theisolatormeetstheparticulateair-qualityrequirementsforanISOClass5areaasdefinedinISO14644-1through-3*（seeMicrobiologicalEvaluationofCleanRoomsandOtherControlledEnvironments1116）.However,theisolatorneednotmeetClass5conditionsduringanoperationthatmaygenerateparticulates,andnorequirementsforairvelocity速率，高速orairexchangerateexist.Theisolatorshouldbesealed密封wellenoughduringdecontaminationthatthedissemination传播ofsporicidal杀孢子vaporsorgasesintothesurroundingenvironmentiskepttoappropriatelylowlevels.Whendirectopeningstotheoutsideenvironmentexist,constantairoverpressureconditionsmaintainsterileconditionswithintheisolator.Ingeneral,bothopenandclosedisolatorsaremaintainedatpositivepressurerelativetothesurroundingenvironment,andoverpressuresof20Paormorearetypical.Theusershouldneverexceedthemaximumpressurerecommendedbytheisolatormanufacturer.Airflowwithinisolatorsusedforsterilitytestingiseitherunidirectionalorturbulent.

TransferPortsandDoors

Isolatorsmaybeattachedtoa“pass-through”decontaminatorortransferisolatortoenablethedirecttransferofsterilemedia,steriledilutionfluids,andsterilesuppliesfromthedecontaminatorintotheisolatorsystem.Rapidtransferports（RTPs）enabletwoisolators,i.e.,theworkstationandtransferisolator,tobeconnectedtooneanother,sothatsuppliescanbemovedasepticallyfromoneisolatortoanother.AsepticconnectionsbetweentwoisolatorsoranisolatorandanRTP-equippedcontainercanbemadeinunclassifiedenvironmentsusingRTPs.ThenonsterilesurfacesoftheRTPareconnectedusinglockingringsorflanges.Acompressedgasketassemblyprovidesanairtightseal,therebypreventingtheingressofmicroorganisms.

WhenthetwoRTPflangesarelinkedtoformanairtightpassage,anarrowbandofgasketremainsthatcouldharbormicrobialcontamination.Thisexposedgasketshouldberoutinelydisinfectedimmediatelyaftertheconnectionismade,andbeforematerialsaretransferredthroughtheRTP.Goodaseptictechniqueisusedwhentransferringmaterialsandcareistakennottotouchthegasketwiththematerialsbeingtransferredorwiththeglovedhands.

PreventivemaintenanceandlubricationofthegasketassembliesontheflangesisperformedaccordingtotheRTPmanufacturer'srecommendations.TheRTPgasketsarechangedattherecommendedfrequencyandperiodicallycheckedfordamage,becausecutortorngasketscann