资源描述：
《冻干制剂检查指南 fda》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。
1、GUIDETOINSPECTIONSOFLYOPHILIZATIONOFPARENTERALSNote:ThisdocumentisreferencematerialforinvestigatorsandotherFDApersonnel.ThedocumentdoesnotbindFDA,anddoesnoconferanyrights,privileges,benefits,orimmunitiesfororonanyperson(s).INTRODUCTIONLyophilizationorfreezedryingisaproc
2、essinwhichwaterisremovedfromaproductafteritisfrozenandplacedunderavacuum,allowingtheicetochangedirectlyfromsolidtovaporwithoutpassingthroughaliquidphase.Theprocessconsistsofthreeseparate,unique,andinterdependentprocesses;freezing,primarydrying(sublimation),andsecondaryd
3、rying(desorption).Theadvantagesoflyophilizationinclude:Easeofprocessingaliquid,whichsimplifiesaseptichandlingEnhancedstabilityofadrypowderRemovalofwaterwithoutexcessiveheatingoftheproductEnhancedproductstabilityinadrystateRapidandeasydissolutionofreconstitutedproductDis
4、advantagesoflyophilizationinclude:IncreasedhandlingandprocessingtimeNeedforsterilediluentuponreconstitutionCostandcomplexityofequipmentThelyophilizationprocessgenerallyincludesthefollowingsteps:·Dissolvingthedrugandexcipientsinasuitablesolvent,generallywaterforinjection
5、(WFI).·Sterilizingthebulksolutionbypassingitthrougha0.22micronbacteria-retentivefilter.·Fillingintoindividualsterilecontainersandpartiallystopperingthecontainersunderasepticconditions.·Transportingthepartiallystopperedcontainerstothelyophilizerandloadingintothechamberun
6、derasepticconditions.·Freezingthesolutionbyplacingthepartiallystopperedcontainersoncooledshelvesinafreeze-dryingchamberorpre-freezinginanotherchamber.·Applyingavacuumtothechamberandheatingtheshelvesinordertoevaporatethewaterfromthefrozenstate.·Completestopperingofthevia
7、lsusuallybyhydraulicorscrewrodstopperingmechanismsinstalledinthelyophilizers.Therearemanynewparenteralproducts,includinganti-infectives,biotechnologyderivedproducts,andin-vitrodiagnosticswhicharemanufacturedaslyophilizedproducts.Additionally,inspectionshavedisclosedpote
8、ncy,sterilityandstabilityproblemsassociatedwiththemanufactureandcontroloflyophilizedproducts.Inordertoprovideg
