东富龙_2007_冻干技术与冻干机

.1.20072007551010.2.200720075510101.2.3.4..3.20072007551010.4.200720075510101.2.3.12.5.20072007551010‰¾¾¾¾¾.6.20072007551010.7.20072007551010.8.20072007551010.9.20072007551010.10.20072007551010.11.20072007551010.12.20072007551010.13.20072007551010.14.20072007551010510515.15.20072007551010.16.20072007551010.17.20072007551010.18.20072007551010‰¾.19.20072007551010.20.20072007551010.21.20072007551010601987006105012663-512459560-10259407350-15186355610-20103304230-2560.6253170-3038.0202330-4012.9151700-503.99101220-601.075869-700.26.22.20072007551010‰¾.23.20072007551010‰.24.20072007551010Temp:-50P2=4PaP3Temp:-20P1=103PaPP1P2P=P1-P2-P3‰.25.20072007551010‰.26.20072007551010‰¾.27.20072007551010.28.20072007551010¾‰.29.20072007551010¾‰.30.20072007551010CollapseTemp..31.20072007551010.32.20072007551010‰1.¾.33.20072007551010.34.20072007551010,,,,,,,,.35.200720075510101234567.36.200720075510101.37.20072007551010‰.38.20072007551010+40+200-20-40-6010001001011010-1-2.39.2007200755101025%50%.40.20072007551010‰.41.20072007551010‰.42.20072007551010¾:¾PcTTp¾PcTp.43.20072007551010‰¾¾.44.20072007551010‰.45.20072007551010‰¾¾¾¾.46.20072007551010.47.20072007551010.48.20072007551010CC~1.0C/min1.0C~3.0C/min.49.20072007551010‰¾Lovelock¾¾.50.20072007551010‰¾¾¾¾.51.20072007551010¾¾¾‰.52.20072007551010‰¾¾.53.200720075510101.2.3.4.5.6.7.8.9..54.20072007551010125.55.2007200755101034“”.56.20072007551010506.57.2007200755101078.58.20072007551010910.59.200720075510101.2.3.4..60.20072007551010.61.20072007551010LyophilizerConstructionCondenseRefrigerationSystemSIP&CIPHydraulicCirculationSystemControlSystemVacuumSystemShelvesChamber.62.20072007551010123.63.20072007551010GBASMEPED316L0.5m.64.200720075510100.5mmm/m6020-40-55kg/m21.0kgf/cm2300.1mbar510-3mbar510-3Pa·m3/sec.65.20072007551010GBASMEPED316L0.5mkg10~15mm3020-40-75300.1mbar510-3mbar510-3Pa·m3/sec.66.20072007551010.67.20072007551010•••••.68.200720075510101.IdentificationComponents2.Audittrailfunctionfortrackingrecords3.Electronicsignatureforrecordintegrity4.ElectronicrecordsinPDFformatsystemsPDF.69.20072007551010„„„.70.20072007551010.71.20072007551010„GMP„„()0.35m/s;0.4m/s„BA()„GMPB„1m3=35.3ft3,BABCD0.5µm/m33,5003,500350,0003,500,000GMP1001000100001000000.5µm/m33,5003,5000350,0003,500,000USA-FS209D0.5µm/m33,500350,0003,500,00010,500,0001001000010000030000098GMP.72.20072007551010¾¾¾¾¾¾¾¾¾¾.73.20072007551010‰¾.74.20072007551010SIPCIPSIPCIPUnderSIP&CIPandVacuumConditionSpecial-DesignedGasketEffectivelyPreventWaterGatheringAroundGasketDoorChamberLatchCylinder.75.20072007551010.76.2007200755101012312.77.20072007551010CIP.78.20072007551010VHP.79.2007200755101012VHP3VOP4EO.80.20072007551010CIPSIP.81.20072007551010EndoscopeInspectionOrbitallyWelded.82.2007200755101020.11VentfiltersystemISO1340820.11VentfiltersystemISO13408--1120.11,1Agasfiltrationsystemshallbeusedtobreakthevacuumwhilemaintaininglyophilizerintegrity.20.11.2Thefiltersystemshallbedesignedtoallowsterilization.Note72Filterintegrityshouldbetestedaftereachlyophilizationcycle.Note74Sterilizationandtestingshouldpreferablybeperformed“inplace”,whenpossible,toavoidasepticexchangeoffilters..83.20072007551010.84.20072007551010‰.85.20072007551010‰¾¾∆∆.86.20072007551010.87.20072007551010.88.20072007551010(EDWARDS).89.200720075510101.90.20072007551010‰‰B+A.91.20072007551010.92.20072007551010.93.20072007551010.94.20072007551010FDAGuidetoInspectionofLyophilizationofParenteral‘93.6.95.20072007551010ProcessSimulation„Thisprocesssimulation,alsoknownasamediafill,normallyincludesexposingthemicrobiologicalgrowthmediumtoproductcontactsurfacesofequipment,containerclosuresystems,criticalenvironments,andprocessmanipulationstocloselysimulatethesameexposurethattheproductitselfwillundergo.Thesealedcontainersfilledwiththemediumarethenincubatedtodetectmicrobialcontamination.Resultsaretheninterpretedtoassessthepotentialforaunitofdrugproducttobecomecontaminatedduringactualoperations(e.g.,start-up,sterileingredientadditions,asepticconnections,filling,closing)..96.20072007551010ProcessSimulationObjective:„Theintentofaprocesssimulationstudyistodemonstratethatasepticprocessiscapableofmanufacturingasterileproduct„Thegoalofanyprocesssimulationtrialistogeneratezerocontaminationunitsaftertheincubationperiod„Agivenmanufacturingprocessthatsuccessfullypassestheprocesssimulationtrialsisdeemtobevalidated.97.20072007551010ProcessSimulationStudyDesign„Amediafillprogramshouldincorporatethecontaminationriskfactorsthatoccuronaproductionline,andaccuratelyassessesthestateofprocesscontrol.Mediafillstudiesshouldcloselysimulateasepticmanufacturingoperationsincorporating,asappropriate,worst-caseactivitiesandconditionsthatprovideachallengetoasepticoperations.98.200720075510101.30002.30003.3000.99.20072007551010LyophilizationSimulation„Therearesomelimitationsforperforminganexactreplicationofalyophilizationprocessusinggrowthpromotionmedia„Suchas,manyfreeze-dryingcycleextendseveraldaysduringthedryingphaseitselfundervacuum,whichwouldnotbeconductivetotheproliferationofmicroorganisms.Therefore,act