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1、GUIDETOINSPECTIONSOFLYOPHILIZATIONOFPARENTERALSNote:ThisdocumentisreferencematerialforinvestigatorsandotherFDApersonnel.ThedocumentdoesnotbindFDA,anddoesnoconferanyrights,privileges,benefits,orimmunitiesfororonanyperson(s).INTRODUCTIONLyophilizationorfreezedryingisaprocessinwhichw
2、aterisremovedfromaproductafteritisfrozenandplacedunderavacuum,allowingtheicetochangedirectlyfromsolidtovaporwithoutpassingthroughaliquidphase.Theprocessconsistsofthreeseparate,unique,andinterdependentprocesses;freezing,primarydrying(sublimation),andsecondarydrying(desorption).Thea
3、dvantagesoflyophilizationinclude:Easeofprocessingaliquid,whichsimplifiesaseptichandlingEnhancedstabilityofadrypowderRemovalofwaterwithoutexcessiveheatingoftheproductEnhancedproductstabilityinadrystateRapidandeasydissolutionofreconstitutedproductDisadvantagesoflyophilizationinclude
4、:IncreasedhandlingandprocessingtimeNeedforsterilediluentuponreconstitutionCostandcomplexityofequipmentThelyophilizationprocessgenerallyincludesthefollowingsteps:·Dissolvingthedrugandexcipientsinasuitablesolvent,generallywaterforinjection(WFI).·Sterilizingthebulksolutionbypassingit
5、througha0.22micronbacteria-retentivefilter.·Fillingintoindividualsterilecontainersandpartiallystopperingthecontainersunderasepticconditions.·Transportingthepartiallystopperedcontainerstothelyophilizerandloadingintothechamberunderasepticconditions.·Freezingthesolutionbyplacingthepa
6、rtiallystopperedcontainersoncooledshelvesinafreeze-dryingchamberorpre-freezinginanotherchamber.·Applyingavacuumtothechamberandheatingtheshelvesinordertoevaporatethewaterfromthefrozenstate.·Completestopperingofthevialsusuallybyhydraulicorscrewrodstopperingmechanismsinstalledinthely
7、ophilizers.Therearemanynewparenteralproducts,includinganti-infectives,biotechnologyderivedproducts,andin-vitrodiagnosticswhicharemanufacturedaslyophilizedproducts.Additionally,inspectionshavedisclosedpotency,sterilityandstabilityproblemsassociatedwiththemanufactureandcontroloflyop
8、hilizedproducts.Inordertoprovideg
