符合新版GMP的无菌粉体密闭转移--闫永辉奥星集团2012.4.17

16th–17thApril2012,BeijingContainedsterilepowderhandlingsolutionconformingtonewGMP.符合新版GMP的无菌粉体密闭转移符合新版的无菌粉体密闭转移闫永辉奥星集团AppendixofsteriledrugsbeingamendediniGMPnewversionGMP新版GMP无菌药附录重点SterileAPITransfering无菌粉体转运方案SterileAPIFilling无菌原料药分装方案Casestudy案例分析新版GMP重点修订了无菌药品附录AppendixofsteriledrugsbeingamendedinnewversionGMPAppendixofsteriledrugsbeingamendedinnewversionGMP采用了欧盟和WHO的A、B、C、D分级标准EUandWHOstandardsforA,B,C,andDclassificationareadopted对无菌药品生产的洁净度级别提出了非常具体的要求Veryspecificrequirementsforcleanlinesslevelofsteriledrugsproductionareputforwardforward.悬浮粒子的静态、动态监测Staticanddynamictestingofairborneparticles浮游菌、沉降菌和表面微生物的检测浮游菌、沉降菌和表面微生物的检测Testingofplanktonicbacteria,sedimentatedbacteria,andsurfacemicrobe细化了培养基模拟灌装、灭菌验证和管理的要求Moredetailedrequirementsareputforwardforsimulatedfillingofculturemedia,tilitilidtidtsterilizationvalidation,andmanagement;增加了无菌操作的具体要求Specificrequirementsforsterileoperationareadded;强化了无菌保证的措施强化了无菌保证的措施Measuresforsterilityassurancearestrengthened.非最终灭菌产品严格Non-finallysterilizedproducts洁净度级别Cleanlinessclass非最终灭菌产品的无菌生产示例Exampleofsterileproductionfornon-finallysterilizedproductsB级背景下的A级ClassAunderClassBbackground处于未完全密封(1)状态下产品的操作和转运，如产品灌装（或灌封）、分装、压塞、轧盖(2)等Operationandtransferringundernotfullysealedstate(1),suchasproductfilling(orfillingandsealing)fillingstopperingcapping(2)etcbackgroundandsealing),filling,stoppering,capping(2),etc.灌装前无法除菌过滤的药液或产品的配制Preparationofdrugsolutionorproductsthatcannotbesterilizedandfilteredbeforefilling.直接接触药品的包装材料、器具灭菌后的装配以及处于未完全密封状态下的转运和存放具Assembling,transferringandstorageofpackagingmaterialsandsterilizedapparatusindirectcontactwithdrugsundernotfullysealedstate.无菌原料药的粉碎、过筛、混合、分装ChiiiidfilliftilAPICrushing,screening,mixing,andfillingofsterileAPIs.B级ClassB处于未完全密封(1)状态下的产品置于完全密封容器内的转运Transferringofnotfullysealed(1)productsinafullysealedcontainer;直接接触药品的包装材料器具灭菌后处于完全密封容器内的转运和存放直接接触药品的包装材料、器具灭菌后处于完全密封容器内的转运和存放Transferringandstorageofsterilizedpackagingmaterialsandapparatusindirectcontactwithdrugsinafullysealedcontainer.AppendixofsteriledrugsbeingamendedinnewversionGMPamendedinnewversionGMP新版GMP无菌药附录重点SterileAPITransfering无菌粉体转运方案无菌粉体转运方案ChargepointTransferingαβ阀转运αβ阀转运Processvacuumconveying真空输送工艺真空输送工艺safeandcontainedPowderHandlingintheBulkPharmaceuticalsIndustryintheBulkPharmaceuticalsIndustry原料药行业安全的粉体密封处理Solution1Chargepointtransfering方案一αβ阀转运ActivePassive作HOWDOESCHARGEPOINTWORK?工作原理EQUIPMENTREQUIRED–ChargePointActiveandPassive–ChargePointExcelActiveandPassiveActiveandPassive(PressureRated)ActiveandPassive(PressureRated)SIPPi(P–SIPPassive(PressureRated)–VHPgeneratorgeneratorCOMMONAPPLICATIONS常见用途•IsolatorCharging/Discharging隔离器装料/卸料•ContainedDispensing密闭条件下配料•ContainedDispensing密闭条件下配料•ContainedMilling密闭条件下研磨•ContainedSampling密闭条件下取样pg•ReactorCharging反应器装料•IBC&BulkBagCharging/Discharging采物料转桶或集装袋装料卸料•采用IBC(物料周转桶）或集装袋装料/卸料Filter/Dryer三合一Filter/Dryer三合Milling磨粉Milling磨粉11SterileStoppertransfersolution无菌胶塞转运方案无菌胶塞转运方案1314Solution2Processvacuumconveying方案2真空输送工艺DDihIltDrumsDischargeIsolator桶卸料隔离装置PTSDCSLiquidDCS液体DCS液体Reactor反应釜MPTSPTSFilterDryer过滤干燥机Dischargeglovebox卸料手套箱PFLPowderflexPFL粉体传送软管MillingandMicronizingIsolator研磨和微粉化隔离装置DCS卸料手套箱研磨和微粉化隔离装置DCSDrumContainmentSystemDCS桶密封系统PFLtofillingline,e.g.tabletpress分装压片THEBASICSTHEBASICSTHEBASICSTHEBASICS基本原则基本原则-+ToxicSterileToxic毒性Sterile无菌SterileIsolator+++++STERILETOXIC毒性无菌PRINCIPLESOFVACUUMCONVEYING真空输送原理Transportdirection传送方向Transportdirection传送方向Patm大气压P–负压大气压Riskassessmentofvacuumconveyorsystem无菌真空输送风险分析无菌真空输送风险分析1.Highcontainment系统高密闭性2.Capacity，blockproblem输送能力，堵塞输送能力，堵塞3.Particleseparation颗粒分层Riskofvacumconveyorsystem无菌真空输送风险分析无菌真空输送风险分析4Siliiffil4.Sterilizationforfilter过滤系统灭菌5.Sterilizationforpipe管道灭菌6.Airsterilefiltration无菌过滤7.Sealingandrotationpart密封，转动件Filter过滤器•FDA•specialforPharmaceuticalapplication.专用于制药专用于制药，•Sterelizationwithsteam可蒸汽灭菌可蒸汽灭菌•Material材质：316Ti,316L,PTFE,POMseal36,36,,OseaStainlesssteelfilter不锈钢过滤器Vacumconveyor真空上料Chargepoint阀Freezedryerunloady冻干出料AppendixofsteriledrugsbeingamendedinnewAppendixofsteriledrugsbeingamendedinnewversionGMP新版GMP无菌药附录重点新版GMP无菌药附录重点SterileAPITransfering无菌粉体转运方案无菌粉体转运方案SterileAPIFilling无菌原料药分装方案无菌原料药分装方案Fillingsystem粉体分装形式•Screwfilling螺杆分装螺杆分装•DoubleValve分装阀分装阀•Vibratingtubefilling振动管分装theFillingSystemWithanIsolator带隔离器的分装系统TheDesignisChallengedWiththeMock-隔离系统设计需要建模和风险分析隔离系统设计需要建模和风险分析UpandRiskAnalysis隔离系统设计需要建模和风险分析隔离系统设计需要建模和风险分析IsolatorTechnologygy隔离装置技术Advantages/优点•OperatorcanworkwithoutpersonalprotectionOperatorcanworkwithoutpersonalprotectionequipment•操作员可不用穿戴个人安全防护设备•Controlofatmosphereinisolator隔离装置内有效的空气控制•隔离装置内有效的空气控制•Highcontainment1µg/m3(OEB4,5)•高密封性1µg/m3(OEB4,5)Disadvantages/缺点•Lowflexibility•灵活性低•Highinvestment•投资高•Lowergonomics人机工程学较差•人机工程学较差AutomatedFillingsystem全自动封装系统STERILEDESIGNSTERILEDESIGN灭灭菌菌设计设计灭灭菌菌设计设计ConsiderSterileMETHODOLOGY–VHP,SIP,PARACETICACID,AUTOCLAVE?AUTOCLAVE?考虑灭菌方式-SIP，VHP，过氧乙酸，灭菌柜REMEMBERANISOLATORandsomeequipmentareNOTAPRESSUREREMEMBERANISOLATORandsomeequipmentareNOTAPRESSUREVESSEL注意：隔离器和一些设备是非压力容器注意隔离器和