XXXX4于英伟-工艺放大与技术转移案例

21–22April2014,Shanghai工艺放大与技术转移案例Scaleup&techtransfercasestudy于英伟海正辉瑞制药有限公司ISPECHINAANNUALCONFERENCE2014SCALE-UP&TECHTRANSFEROFTABLETSATechnicalTransferReceivingTeamDocumentationTransferIdentifyAnyKnownRisksAndOpportunitiesTransferStrategyManufacturingSubmissionProjectCharterTechnicalTransferReceivingTeamProjectLeaderQuality/MfgSupportMfgTechnology/ValidationSupplyChainSupportEHS/RAISPECHINAANNUALCONFERENCE2014Documentation商业策略TransferProjectPlanDevelopmentreportQuality/TechnicalAgreement(s)Specification-methodCriticalIn-ProcesschecksheetsMSDSOEB/OELProcessHazardsAnalysisISPECHINAANNUALCONFERENCE2014IdentifyAnyKnownRisksAndOpportunitiesISPECHINAANNUALCONFERENCE2014TechnicalRiskAnalysis•FacilityandEquipment•ManufacturingChange–FormulaandProcesschanges•ChangestoPackagingMaterialsandProcess•CleaningProcessModifications•ChangestoAnalyticalMethodsandLimitsOEB2ISPECHINAANNUALCONFERENCE2014TechnicalRiskAnalysisManufacturing/PackagingFacilitySendingSiteReceivingSiteGaps&RationaleRollercompaction：Compacttheblendusingasmooth(top)andaSerrated(bottom)rollercombination.Passtheblendthroughthescreenmillingsystem.Rollercompaction：Compacttheblend.Passtheblendthroughthescreenmillingsystem.TechnicalRiskAnalysisIBCContainmentValveMeteringVolumeticFeedDeviceHydraulicSystemFloatingRollDesignCompactionRollsSizeReductionUnit(1or2Units)IBCContainmentValvePre-compressionFeedScrew(VPS)MultipleVacuumDe-aerationZones•Volumetriccontroloffeedmaterialtotherollnip(HFS)•Pre-compressionappliedtopowder(VFS)•Rollsurface•Rollspeed•Rollgap(thicknessofcompact)•AppliedrollforceFitzpatrickIR220/IR520TechnicalRiskAnalysisCriticalProcessParameters-RollerCompactionSendingSiteReceivingSiteUnitOperationCritical/Non-CriticalParameterControlSpaceDesignSpaceControlSpaceTransferStrategyDevelopmenttrialswillbecompletedatapproximately10%ofcommercialscaleConversionofblenderspeedCalculationforrotationspeedwhilekeepingtheperipheralspeedconstantCompressionThedwelltimewillbekeptthesameCoatingTransferStrategyStabilityStrategyTransferMilestonesLogisticsandFinancePlanProblems:•Compressibility•Excessfines•Poordissolution•Lowthroughput•Instabilityofribbonortablets•CompactionwithinhopperPossibleSolutions:•Adjustfeedspeed(s)•Rollspeed/pressure•Rollcooling•VacuumDe-aeration•Moisturecontent/ambienthumidity•Adjustformulation•Checksideseals•CompressionSpeedStudy•FeederSpeedStudy•CompressionforceStudy•API•Segregationencounteredduringtabletingstage工序Unitoperation含量Assay(%)润滑Lubrication101.1压片（开始）Compression(start)106.6压片（结束）Compression(end)105.9压片尾料Powderleftinhopperaftercompression102.1趋势Trendingsizeclass(mm)Weight%Assay(%)0.8507.31100.425-0.85015.51130.250-0.42510.01260.180-0.2507.31450.150-0.1806.81340.106-0.15010.51070.075-0.10610.5930.045-0.07518.6540.04513.684筛分含量检测SievecutspotencytestAsthePloughwasnotavailable,powderoutofrotation(lowpotency)inthematerialgrooveofthedieplatecannotbebroughtbacktothedieaspre-filling,whichmightleadtothehighpotencytablets.