GMPWaterSystem(cGMP培训系列1)

GMPWaterSystemGMP水系统GMPTrainingModule121DisclaimerThefollowingslidesarecopiedfromWHOpresentationonwatersysteminShanghaionFeb28–March4,2005.声明根据世界卫生组织的有关培训材料改写而成2PartIWaterPre-treatment3水的预处理WaterIntroductionandtreatment水的引入和处理4Objectives目标1.IntroductiontoWaterforPharmaceuticalUse2.ReviewWHOGMPguidance3.Sourcesandtypesofwaterforpharmaceuticaluse4.Storageofbulk,untreatedrawwater5.Pre-treatmentofwater5Principles(1)•Likeanystartingmaterial,watermustconformtoGoodManufacturingPracticenorms•Itmustbe“potable”andcomplywithWHOGuidelinesfordrinking-waterquality原则1必须符合GMP对原料的基本要求必须至少是饮用水标准6Principles(2)1.Potentialformicrobialgrowth2.Systemsmustbeproperlyvalidated3.Waterforparenteralusecouldbecontaminatedwithpyrogensorendotoxins4.Specificationsandperiodictestingisrequired••原则2•微生物生长可能•系统必须被论证•注射用水可能被污染•定期测试7Typesofwaterusedinpharmaceuticalprocesses1.Purifiedwater2.WaterforInjections–PFW&WFI3.SoftenedWater4.WaterforFinalRinse5.Pure,orcleanSteam6.WaterforcoolingAutoclaves原则2微生物生长可能系统必须被论证注射用水可能被污染定期测试8Whypurifyrawwater?水为什么要净化？1.Althoughreasonablypure,itisalwaysvariable2.Seasonalvariationsmayoccurinwater3.Someregionshaveverypoorqualitywater4.Mustremoveimpuritiestopreventproductcontamination.5.Controlmicrobestoavoidcontaminatingproducts9Contaminantsofwater(1)水的可能污染源•Thereisnopurewaterinnature,asitcancontainupto90possibleunacceptablecontaminants•Contaminantgroups:1.Inorganiccompounds2.Organiccompounds3.Solids4.Gases5.Micro-organisms无机，有机，固体，液体，微生物10Contaminantsofwater(2)水的污染源2Treatmentdependsonwater’schemistryandcontaminants,influencedby:1.Rainfall2.Erosion3.Pollution4.Dissolution5.Evaporation6.Sedimentation7.Decomposition雨水，腐蚀，污染，水溶物，蒸发物，沉淀物及分解物11Contaminantsofwater(3)Problemminerals•水的污染物3•矿物质1.Calciumandmagnesium2.Ironandmanganese3.Silicates4.Carbondioxide5.Hydrogensulfide6.Phosphates12Contaminantsofwater(4)Furtherproblemminerals•水的污染物4•重金属1.Copper2.Aluminium3.Heavymetals▫Arsenic,lead,cadmium4.Nitrates13Contaminantsofwater(5)Micro-organisms–Biofilm•水的污染物5•生物膜•水草，原生动物，细菌1.Algae2.Protozoa▫Cryptosporidium▫Giardia3.Bacteria▫Pseudomonas▫Gramnegative,non-fermentingbacteria▫Escherichiacoliandcoliforms14Waterhardnessclassificationmg/LorppmasCaCO3Soft0-60Moderate61-120Hard121-180VeryHard180Waterhardness水的硬度15Sourceofrawwater--水源1.Rainwater2.Surfaceorgroundwater3.Wellorborehole4.Municipalorcivil–“tapwater”5.Purchasedinbulk16Watertreatmentguidance水处理指导Thefollowingshouldbemonitored•Sourcesofwater•Treatmentprocedures•Watertreatmentequipment•Treatedwatertests•Monitoringrecordsrequired17水源处理程序处理设备水测试记录监督Pre-treatmentsteps1.Primaryfiltrationandmulti-mediafilter2.Coagulationorflocculation3.Desalination4.Softening•预处理程序•预过滤，多媒质过滤•凝结•去盐•软化18rawwaterin«S”traptosewerWateriskeptcirculatingTowatersoftener&DIplantPretreatment–schematicdrawingcartridgefilter5micrometersactivatedcarbonfiltersprayballbreaktankairbreaktodraincentrifugalpumpairfilterfloatoperatedvalvesandfilterexcesswaterrecycledfromdeioniser19图表brineandsalttankbrinehardwaterinzeolitewatersoftener-exchanges-CaandMgforNadrainsoftwatertodeioniserbypassvalveWaterSoftener–schematicdrawing软化剂图表20PartIIWaterPurification水净化21ObjectivesToexaminethebasictechnologyandrequirementsfor:1.Watertreatmentsystems2.Storagerequirements3.Samplingandtesting4.Differenttypesofwaterusedinpharmaceuticals5.Microbiallimits,disinfection22目标水处理系统存储要求取样，测试水的种类微生物，消毒Watersystemdesign1.Pipesslopedsowaterdoesnotpoolandcandraineasily2.Sanitaryfittings&connections3.Constructedofsuitablematerialssuchasstainlesssteel4.Circulatethewater5.Incorporatenon-returnvalves(NRV)23水系统测试管子呈一定坡度，以避免回流和方便排放卫生要求不锈钢材料保持循环不回复阀门Furtherwatertreatmentpurificationstagesdownstreamofthepre-treatmentsystem1.Filtration2.Disinfection3.Reverseosmosisorde-ionization4.Distillationorultra-filtration24预处理后的净化步骤过滤消毒反渗透/去离子蒸馏或超净化Watersystemdesign(1)ThereshouldbenodeadlegsWaterscoursdeadlegIfD=25mm&distanceXisgreaterthan50mm,wehaveadeadlegthatistoolong.Deadlegsection2DFlowdirectionarrowsonpipesareimportantSanitaryValveDX25绝对要避免盲管的发生!3.Thewateriscontaminatedasitpassesthroughthevalve2.BacteriacangrowwhenthevalveisclosedWatersystemdesign(2)1.BallvalvesareunacceptableStagnantwaterinsidevalve26球阀不可用1.Sanitarypumps2.ClampsandOringsversusthreadedfittings3.Heatexchangers4.SidearmlevelmeasuringdevicesareunacceptableWatersystemdesign(3)27CationiccolumnAnioniccolumnHygienicpumpOutletsorstorage.OzonegeneratorUVlightHClNaOHEluatestoneutralizationplantAirbreaktosewerDrainlinefromwatersoftenerWatermustbekeptcirculatingTypicalde-ionizerschematic123456123456Returntode-ioniserCartridgefilter5µmCartridgefilter1µm28水必须保持循环rawwaterHighpressureFeedwaterunderpressureRejectwaterSemi-permeablemembranePermeatewaterdrainorrecycleLowpressurePurifiedwaterReverseosmosis(RO)theory29反渗透BranchBranch2ndstagebuffertankCartridgefilter1µmSecondstageROcartridgeFirststagefiltratefeedssecondstageROwithexcessbackto1ststagebuffertank.1ststagerejectconcentrateAirbreaktosewerSecondstagerejectwatergoesbacktofirststagebuffertankSecondstageROwatermeetsPharmacopoeiastandardsOutletsorstorage1ststag