蒸馏水机-多效及热压式蒸馏技术课件

生产WFI的多效及热压式蒸馏技术生产WFI的多效及热压式蒸馏技术1TEST项目LIMIT限度Conductivity电导USP:1.3S/cmat25°CEuPh:1.1S/cmat20°CpHUSP/EuPh:5.0to7.0

AerobicBacteria需氧菌USP/EuPh:≤10CFU/100ml

TOC总有机碳USP/EuPh:500ppmC

BacterialEndotoxin细菌内毒素USP:EU/ml≤0.25EuPh:IU/ml≤0.25Nitrate(NO2)硝酸盐USP:- EuPh:≤0.2ppm

HeavyMetals水重金属USP:-EuPh:≤0.1ppmasPb

Thewaterforinjectionsdidn’talwaysheldthesamecharacteristicsoverthetimeandcountries.SomecountriesstillusePW(from“cold”systemssuchasRO).Othercountrieschangedthisnormrecently,understandingthatthethermaltreatmentsareabsolutelycrucial;forchemicalscut,butoverallfordeepbacteriologicalfall.ThebacteriologicalcontentinPWis10timeshigherthanthe

WFIone,forbothUSPandEuPh.Itshouldbeemphasizedthat:USP(USA):justfrom

ed.27thdefinedtheWFIas

waterpurifiedbyDistillationor(…)superiorindistillationinremovalofchemicals

andmicroorganisms.EUPh(EU):AlwaysconsideredW.F.I.as

DISTILLEDWATER注射用水的标准和定义许多年以来，在不同国家，WFI的特性及标准并不完全相同，有些国家仍采用反渗透类技术所制的纯化水。有些国家近来改变了标准，他们认识到，热处理对去除化学，尤其是微生物相关的杂质至关重要。美国药典及欧洲药典，在纯化水中，微生物类杂质比注射用水高10倍以上。应当强调：美国药典：只是从27版起才优先采用蒸馏作为将水纯化，去除化学及微生物，得到WFI的手段欧洲药典，注射用水只能由蒸馏制得TEST项目LIMIT限度Conductivity2Which

technologiescanproduceW.F.I.?ISPE(InternationalSocietyforPharmaceuticalEngineering),indicates3possibletechnologiestoproduceWFI:Single-Effect(SE)Multiple-Effect(ME)VaporCompression(VC)INLPH4-40095–11.000400–22.000(*)WFITemperaturerange/Options,°C80-10037–100-Ambient-80–100-CombinationAmbient/hot(*)NOTE:Forproductionsover10.000lphissuggestedtosplitthecapacities,notoverpassingthe10tonseachmachine,inordertohaveasaferjob:HavingthepossibilitytoworkwithoneVC,incaseoflowerproductionrequired;withconsequentlowerconsumption.

Notakingrisksofcompleteproductionstop,incasemaintenance,asitwillbepossibletoworkwiththeotherautonomousmachine/s.采用什么技术可以生产注射用水？ISPE指出：有三种制备方法单效蒸馏；多效蒸馏及蒸汽热压法注射用水温度可选范围环境温度；80-100，热的环境温度能力：L/时产量超过1万升时，要考虑能力的划分，为保证安全运行，每个设备不要超过10吨。如果生产量比较的低时，可采用热压式蒸馏水机，它的消耗量也比较小。如因维修要避免停产的风险，也可使用其它独立的设备。Whichtechnologiescanproduce3VCDistillationTechnology;History:TheWATERDISTILLATIONTECHNOLOGYWASININVENTEDIN1908INITALY,andwasbasedonVAPORCOMPRESSION,theusewasmainlyfordesalinationpurposes;justafterWWII,VCfoundapplicationinpharmaceuticalfieldtoo.Untiltheendofthe‘80s,inEuropetheVCtechnologywasnotsubjectedtodevelopments,astheoldfirmswereunabletomeettheimprovedqualityrequirementsofthemarket;indeed,theVCproductionwerestoppedforseveralyears.Inthe‘90s,BRAM-COR®spa,improvedtheoldVCtechnology,withthecreationofanewpatentedmultistagecompressor,reachingthetitleof“LABORATORYOFRESEARCHFORWATERTREATMENTSYSTEMS”givenbytheItalianMinistryOfInstruction,UniversityandResearch.Thehighesttechnologyonthemarket,allowedtheachievementForBRAM-COR®oftheEuropeanleadershipinthistechnology.VCiscurrentlytakingmarketsharesagainsttheMEin

thePharmaceuticalandBiotechcompanies,intheworld,thankstoitslowoperationalcost.热压式蒸馏水技术的历史此技术1908年发明于意大利；它基于蒸汽的压缩，主要用于脱盐；后来发现它还可用于制药行业。在欧洲，热压式蒸馏水技术没有怎么发展，因为一些老的公司无法满足市场对质量的要求，这一情况直到80年代末：热压式蒸馏水技术确实有好几年没有发展在90年代，我们公司改善了热压式蒸馏水技术，有了多步压缩机的专利，获得了意大利建设、大学及研究部颁发的“水处理系统研究实验室”的头衔。.这一技术投放市场，使我们公司在欧洲获得了领先的地位。由于运行费用低，热压式蒸馏水在制药及生物技术领域取得了多效蒸馏水机的市场份额。VCDistillationTechnology;Hi4SomeoldfirmstrytogetbenefitfromBRAM-COR®success,re-enteringthemarketwithjustmarketingoperations,declaring

“NEWVC”stills,whenarenothingmorethanaMIXOFANTIQUATEDANDINEFFICIENTVCmachines,re-assembledwithoutanyaddedvalue.

OtherVCs

areNOTBORNTOBE“PHARMACEUTICAL”,astheHORIZONTAL

(knotty,notnaturalandnotgreen),bornfordesalinizationinthesea-boats.

ItsstructureisinfacttheFORCINGOFTHECIRCULATION,soitrequiresmanyAVOIDABLEDEVICESas;sprays,re-circulationspumps,etc..(subjectedtobreakages,asallmechanisms),consequentlythistypeneedsmorefrequentinterventions,spareschanges,andVERYPUREFEEDWATER(incontrastwiththebenefitthatvctechnologyallowsagainstmestills).

SomeVCsuseVERYFASTCOMPRESSORROTATION(OVER10.000RPM)withtheconsequentSTRESSOFTHEIMPELLERANDSHAFT,thatbecomesubjectedtocriticism,breakagesandreducedlife.

IntheworstcasesVCsalsousetheDIRECTCOUPLING

withLUBRICATINGOILCIRCUIT(DIRTY)ATTHESAMELEVELOFTHECIRCUITOFTHEPS(CLEAN-PHARMACEUTICAL)causingriskofCROSSCONTAMINATION,especiallywhentheVCsaredesignedintheARCHAICVACUUMCONFIGURATION(Inthesemachinesisvisiblea“conduit”intheshaftarea,closedtotheimpeller,todischargetheoilarrivedtotheWFIcircuit)VCDistillationTechnology.Varieties&Types:热压式蒸馏水技术：种类和类型有些老的公司力求从Bram公司的成功中获益，依靠市场运作再次进入市场，他们声称”新的热压式蒸馏水机“，只不过是将陈旧及无效的热压式蒸馏水机混合组装，并无新意。有些热压式蒸馏水机不是药用级的，是用于出海船只非同一级别的它的结构重点是循环，它需要许多可省的部件，如喷雾、循环泵等（因全是机械性的，易损），经常要干预，更换部件，（与多效蒸馏水机相比）供水要求高。有些热压式蒸馏水机采用高速压缩机（超过1万/分），对叶轮及轴造成很大负荷，易成为致命点，损坏/停车及缩短寿命。在极糟糕情况下，热压式蒸馏水机连接器与润滑的回路（脏的）及药用级回路处同一水平上，导致交叉污染的风险，设计采用老式的真空结构，尤其严重。这类设备在轴的位置，靠近叶轮处，油会进入蒸馏水回路。Someoldfirmstrytogetbene5Whythedistillerspre-treatmentisneeded?ExtractsbyISPE:Alldistillationunitsaresusceptibletoscaling(Hardness,Silica),corrosion(Chlorine),iftheappropriatefeedwaterpre-treatmentisnotprovided.VC

operateslightlyaboveatmosphericpressure,andtheremovalofcalciumandmagnesium,bywayofwatersoftening,isnormallyrequired.ME

stillsoperateatamuchhigherpressureandtemperature,andrequirehigherqualityfeedwaterinordertopreventscalingandcorrosion.DistillerfeedingthroughDoublePassRO(orRO+EDI)?Orjustthrough

Softening(orsingleRO)?OR为什么蒸馏水机需预处理？ISPE摘录的内容：热压式蒸馏水机运行稍高于大气压，通常需要通过软化来去除镁、钙。所有的蒸馏水机易结垢（硬度及硅），氯对它有腐蚀。多效蒸馏水机运行的温度和压力要高得多，对水的质量要求也高，以防止结垢及腐蚀。供水通过二级反渗透（或RO+EDI）或只是软化（或一级反渗透I）Whythedistillerspre-treatme6MultipleEffectpre-treatment:Generalpre-treatmentcharacteristicsrequirementsforMultiple-Effect:TDS:≤5-10mg/l,Silica≤1mg/l,Hardness:0,Chlorine:0,Ammonia:0.NOTE:ToreachthiskindofresultitisalwaysrecommendedtousewatertreatedbyRO/ROorRO/EDI.Softenedwaterisnotpossible.RO/EDI(DI)MultipleEffectStillRO/ROSource源水orTypicalpre-treatmentforMultipleEffectStill(ME)多效蒸馏水机典型的处理Softening,Ca,MgRemoval多效蒸馏水机预处理多效蒸馏水机预处理的一般项目总有机碳硅硬度氯氨要达到这一要求始终建议采用反渗透/反渗透或反渗透/电去离子，软化水是不可能达到要求的。软化，去钙镁多效蒸馏水机反渗透/电去离子或反渗透/反渗透MultipleEffectpre-treatment:7Generalpre-treatmentcharacteristicsrequirementsforVaporCompression(VERTICALTYPES–forHorizontalsissuggestedthecompleteoneasperMultipleEffects):TDS:NotConsidered-Silica≤75mg/l,Hardness:<2ppm(CaCO3),Chlorine:0,Ammonia:0.NOTE:Toreachthisresultitispossible,dependingfromtherawwateranalysis,tousetapwaterremovedfromtheChlorine(SodiumMetaBi-Sulphitedosage)andsoftened(Softeners)

asbase;inanycaseabasicsinglepassROisnormallyenoughforVCfeeding.SoftenedwaterorSinglePassROonly,ispossible(MoneySaving!)VaporCompressionpre-treatment:Softening,Ca,MgRemovalVaporCompressionStillSourceChlorineRemovalPossiblepre-treatmentforVaporCompressionStill(VC)热压式蒸馏水机可选的水处理程序热压式蒸馏水机的预处理直立式热压式蒸馏水机对水的预处理要求如下：（水平热压式蒸馏水机则完全与多效蒸馏水机一样）不考虑硅硬度：指折碳酸钙氯铵根据所用源水检验的结果，自来水去氯（焦亚硫酸钠）和软化（软化剂）有可能达到这个结果；在许多情况下，一个单一的反渗透处理，足以向热压式蒸馏水机供水为节约费用，可用软水及一级反渗透源水去钙镁软水脱氯热压式蒸馏水机Generalpre-treatmentcharacte8Vapour

Compression

StillVCisadistillationmethodwherewaterisevaporatedinside,oroutside,abankoftubesarrangedinvertical(NATURALCIRCUIT),orhorizontal(FORCEDCIRCUIT)configuration.TheVERTICALdesignisoftheNATURALCIRCULATIONTYPE(theverticalconfigurationconsentsafirstnaturalseparationbetweensteamandparticlesbygravity).TheHORIZONTALdesignistheFORCEDCIRCULATIONTYPEWITHRE-CIRCULATIONPUMPSANDSPRAYNOZZLES(thehorizontalconfigurationdoesn’tconsentanoptimizednaturalgravityseparation).VCoperatewithplantsteamatonly3Bar(orless).VCcanbeheatedby:Steam,Electricityorboth.Noneedanycoolingwater(noChiller/Towerinvestment,nooperationalcosts).TheWFIcameoutinpressure(ab.1,2barg).热压式蒸馏法有水在内部或外部蒸馏，设置一立式（自然循环）或水平式（强制循环）的多管贮罐直立式设计是自然循环型（粒子与蒸汽之间由重力实现分离）直立式设计是自然循环型（粒子与蒸汽之间由重力实现分离）；水平型是强制循环，有循环泵及喷嘴，难以实现最佳的重力分离热压式蒸馏水机的运行通常的只要3巴（或还可更低些）热压式蒸馏水机的加热方式：蒸汽、电或二者热压式蒸馏水机不需要冷却水及或冷却塔的投资，无此运行成本注射用水的出水压力（绝对压为1.2巴）VapourCompressionStillVCis9ADVANTAGES:Lowindustrialsteam

consumptionLowindustrialpressure(only3barorless)NocoolingwaterMaxflexibility(WFIat

anytemperature/Heatingbysteamand/orelectricity)Efficient

eliminationofincondensable

gasesWFIpressurizedoutput(around1,2bar)Lowfeedwaterpressure(from0,5to1bar)PossibilitytofeedthemachinewithsoftenedorsingleROwater(Dependingfromrawwater)Safedesign(inpressure,norisksofcrosscontamination,asintheold

vacuumdesign)DISADVANTAGES:NoPureSteamproductioninpressure@121°C(Not

completely

true:BRAM-COR®,UNIQUECOMPANYINTHEWORLDTOPROVIDEPS@121°CINPRESSUREFROMVC.Currently

availableonlab.mod).Littlemaintenance(every8-9.000ofwork,2shaft

bearingsw/their

seals

shouldbechanged.Total:4hoursofjobeveryab.2/3years,dependingfromshiftsnumberperday).VaporCompression热压式蒸馏水机优点工业蒸汽消耗低压力低：3巴或更低压力无冷却水灵活性好：任何温度/蒸汽加热或电加热有效去除冷凝水注射用水压出时，约1-2巴进水压力0.5-1巴根据源水情况，可用软水或一级反渗透水安全设计（压力、无老设计中有的无交叉污染）缺点纯蒸汽不要在121度下生产（不完全是这样：BRAM也有世界上独一无二的公司，用热压式蒸馏水机，在121度下生产实验室纯蒸汽的设备，在市场可供选用。ADVANTAGES:VaporCompression热压10ExampleofVCable

toproducealso

COLDWFIVaporCompression

Still热压式蒸馏水机注射用水出进水源水进排放排放工业蒸汽回收冷凝水能生产冷注射用水的热压式蒸馏水机示意ExampleofVCabletoproduce11.DISCHARGEINCONDENSABLEGASESRAWWATERINLETINDUSTRIALSTEAM/ELECTRICITYCONDENSATERECOVERY/ELECTRICITYFEEDWATERINLETWFIOUTLETDISCHARGEVaporCompression

StillWETSTEAMDRYPURESTEAM1°THERMALEXCHANGE2°THERMALEXCHANGE3°THERMALEXCHANGECOMPRESSORROTATIONINCONDENSABLEGASESSTRIPPINGOUTPUMPVC蒸馏水机WFI出进水原水进排水不凝性气体湿蒸汽干蒸汽压缩机工业蒸汽/电冷凝水回收电/蒸汽热交换1热交换2热交换3.DISCHARGEINCONDENSABLEGASESR12NEWBRAM-COR®COMPRESSORTheheartoftheVCtechnologyistheCompressor.BRAM-COR®

hascurrentlythemostdevelopedcompressortechnologyforpharmaceuticalapplicationsinEurope.ThisTopQualityLevel,recognizedbytheItaliangovernment,wasreachedmixingtheknowledgeofouroldengineersgeneration,thatcreatedthefirstVCtechnologyintheworld,togetherwiththeenergyandthemodernattitudeofournewengineers

agegroup,bothcooperatingwithtwoofthemainItalianUniversitiesinthisfield.TheobtainedresultisthemostadvancedVCtechnology,thatconsentedtoBRAM-COR®toearnthetitleof:新的BRAM压缩机压缩机是热压式蒸馏水机的核心BRAM最近开发了压缩机是热压式蒸馏水机的压缩机它的高水平由意大利政府认可，是热压式蒸馏水机老一代工程师及新一代工程师创新精神与这个领域中二个意大利大学合作的结晶。最现代化的热压式蒸馏技术的获得，使BRAM公司获得了“工业研究实验室”的荣誉证书。NEWBRAM-COR®COMPRESSORThehe13VaporCompression:Compressor’s

GearingCURRENTIMPROVEDDESIGN:BELTSTRANSMISSIONEFFICIENT&CLEANOutmoded

OLD

Design:DIRECTCOUPLINGSHAFTSTRESS,RISKOFCROSSCONTAMINATIONTheBELTSTRANSMISSIONbenefitsare:Easymaintenance(simpleaccesstosealsandbearings).Strongest(bearingsonboththeshaft’sedge).

Lessshaftsolicitations(theshaftisheldinboththesides).

Littleroccupiedspace(themotorcanbeplacedunderthecompressor).Littlercompressor(possibilitytosetmechanicallytherotationspeed).Lowerconsumption(littlercompressorandspeedsetting).CleanPharmaceuticalsystem(motorandcompressorcircuitsareinseparatedlevelsNORISKOFCROSSCONTAMINATION.NOOILCLOSEDTOTHEPURESTEAMCIRCUIT.BeltTransmissionDetail热压式蒸馏水机：压缩机的齿轮现行改进设计：皮带传动，有效干净老的设计：直接连接，轴负荷大，有交叉污染风险皮带传动细节易维修，方便处理密封及轴承轴承的二边牢固轴的二侧承负荷占地方小小压缩机（能机械设定转速）接近蒸汽处没有油清洁制药系统，马达及压缩机回路水平分开低消耗（机小，可调速）VaporCompression:Compressor’14Control

Systems-SCADAPharmaceuticalcontrolSCADASUPERVISOR.

SCADA,that

istheacronymfor

Supervisory

Control

AndDataAcquisition,refers

toalarge-scale,distributed

measurement

(andcontrol)system.

SCADAsystems

is

used,inthepharmaceuticals

process

tomonitor,to

control,manage,printandRECORDwatersupply

systems,orother

lines.ThisSUPERVISORis

conform

to

USFDAandCFR21chapter11.

ASCADAsystemincludesinput/outputsignal

hardware,controllers,HMI,networks,communication,databaseandsoftware.Hostcontrolfunctionsarealmostalwaysrestrictedtobasicsiteover-rideorsupervisorylevelcapability(PasswordsLevels).SCADAforeseesstatisticalpagesashistoricaltrendsofconductivity/pressure/T°andtorecordanddisplaybargraph,histogramsandalarms控制系统supervisorycontrolanddataacquisition（system））制药控制监控与数据采集（系统）此系统用于制药工艺控制、管理和打印供水系统及其它生产线的情况符合FDA及CFR2111的要求制药控制监控与数据采集（系统）包括输入/出，硬件、数据库及软件等有主机功能控制管理，密码级别设置等此系统可作统计分析，以不同方式方式显示结果ControlSystems-SCADAPharmac15SCADASUPERVISORonStills:OntheTOUCHSCREENthesoftwareshowsandrecord,forexample,thefollowingdataoftheline:-pressures,-levels,-conductivities,-pharmaceuticalwaterT°,-possiblefaults,T°ofthefeedwater,feedwaterpumpscontrol,-sanitaryvalvescontrol,-heatingsteamtemperatures,-effectivehoursofoperation,-dateandtimeofbeginning/endofsanitationstage,-dateandtimeofstarting/stoppingoftheplant,-capabilitytoadjusttheparameterprintingpauses,-capabilitytoadjusttheplant'ssanitationcycletime,-printingallthealarms,withrelativedateandtime.VCStillMEStill热压式蒸馏水机的监控与数据采集（系统）屏上的在线数据：压力水平电导制药用水可能故障进水温度卫生阀控制加热蒸汽温度有效运行时间清洁开始的日期、时间加热蒸汽温度系统起止时间……SCADASUPERVISORonStills:On16PARAMETERS参数MULTIPLE显著多效EFFECTVAPOUR热压式蒸馏水COMPRESSIONOUPUTFLEXIBILITYfixedoutputcapacitycapacityrangingfrom0tomax.capofthestillTEMPERATUREFLEXIBILITYWFIoutput@90/95°CWFIoutputfromfeedwaterT+10°Ctill85/90°CHEATINGMEDIAFLEXIBILITYindustrialsteamindustrialSteamand/orelectricityCOOLINGWATERhighconsumptiondependingonqtyofcolumnsnocoolingwaterrequiredFEEDWATERSIO2<1ppm,aminesfreeresins(incaseofDI),doublestageROpreferredSIO2<30ppm,SinglestageROorevensoftenedwateracceptableFEEDWATERINPUTmustbehigherthanprimarysteampressure<1barWFIRECIRCULATIONnoyesWFIOUTPUTatmosphericpressure1/1.5barsWFIQUALITY0.2-0.5µS/cm2withFW<5µS0.15-0.4µS/cm2withFW<5µSPREVALIDATION(Endotoxinchallenge)yesyesHEAVVYMETALSfreefree+eliminationofchlorinesolventsSAFETYINCASEOFLEAKAGEnoneWFIcircuitinpositivepressuretowardsFWcircuitMOVINGPARTSCoolingWaterpump,Blowdownpump,feedpumpCompressor,RecirculationPumpPURESTEAMFROM1STCOL.121°Cpossiblemax105°CpossibleSTRESSCORROSIONVeryhigh."Rouging"percentagehigherVerylowCLEANABILITYtough:scaleinsidetubeseasy:scaleoutsidetubes.ManholesSTARTUPSSCADA(15minforsteamh)SCADA(25min,forsteam)SUPERVISORYCONTROLDATAACQUISITIONyesyesVaporCompression/MultipleEffectTechnology

Comparison技术性能参数比较表PARAMETERS参数MULTIPLE显著17VaporCompression/MultipleEffectOperational

Costs

Comparison每小时生产力万升费用比较表VaporCompression/MultipleE18VaporCompression

PhotoShowVaporCompression

StillElectrical

heated

withPureSteamproductionat2.5barand121°C.BRAM-COR®ISTHEUNIQUECOMPANYINTHEWORLDABLETOEXTRACTPURESTEAMFROMVCSTILLS(Currentlyforlabs

models)BRAM是国际上准确生产纯蒸汽的唯一公司VaporCompressionPhotoShowVa19VCStill2200lphwithSCADA,abletoproduceCOLDandHOTWFIVaporCompression

PhotoShow2200L/h热压式蒸馏水机可生产热及冷的注射用水（有数据监控及采集系统）VCStill2200lphwithSCADA,20VCStill1100lphwithSCADA.DetailincondensableGasesStrippingPumpVaporCompression

PhotoShow地100L/h热压式蒸馏水机（有数据监控及采集系统）不凝性气体分离泵细节VCStill1100lphwithSCADA.21生产WFI的多效及热压式蒸馏技术生产WFI的多效及热压式蒸馏技术22TEST项目LIMIT限度Conductivity电导USP:1.3S/cmat25°CEuPh:1.1S/cmat20°CpHUSP/EuPh:5.0to7.0

AerobicBacteria需氧菌USP/EuPh:≤10CFU/100ml

TOC总有机碳USP/EuPh:500ppmC

BacterialEndotoxin细菌内毒素USP:EU/ml≤0.25EuPh:IU/ml≤0.25Nitrate(NO2)硝酸盐USP:- EuPh:≤0.2ppm

HeavyMetals水重金属USP:-EuPh:≤0.1ppmasPb

Thewaterforinjectionsdidn’talwaysheldthesamecharacteristicsoverthetimeandcountries.SomecountriesstillusePW(from“cold”systemssuchasRO).Othercountrieschangedthisnormrecently,understandingthatthethermaltreatmentsareabsolutelycrucial;forchemicalscut,butoverallfordeepbacteriologicalfall.ThebacteriologicalcontentinPWis10timeshigherthanthe

WFIone,forbothUSPandEuPh.Itshouldbeemphasizedthat:USP(USA):justfrom

ed.27thdefinedtheWFIas

waterpurifiedbyDistillationor(…)superiorindistillationinremovalofchemicals

andmicroorganisms.EUPh(EU):AlwaysconsideredW.F.I.as

DISTILLEDWATER注射用水的标准和定义许多年以来，在不同国家，WFI的特性及标准并不完全相同，有些国家仍采用反渗透类技术所制的纯化水。有些国家近来改变了标准，他们认识到，热处理对去除化学，尤其是微生物相关的杂质至关重要。美国药典及欧洲药典，在纯化水中，微生物类杂质比注射用水高10倍以上。应当强调：美国药典：只是从27版起才优先采用蒸馏作为将水纯化，去除化学及微生物，得到WFI的手段欧洲药典，注射用水只能由蒸馏制得TEST项目LIMIT限度Conductivity23Which

technologiescanproduceW.F.I.?ISPE(InternationalSocietyforPharmaceuticalEngineering),indicates3possibletechnologiestoproduceWFI:Single-Effect(SE)Multiple-Effect(ME)VaporCompression(VC)INLPH4-40095–11.000400–22.000(*)WFITemperaturerange/Options,°C80-10037–100-Ambient-80–100-CombinationAmbient/hot(*)NOTE:Forproductionsover10.000lphissuggestedtosplitthecapacities,notoverpassingthe10tonseachmachine,inordertohaveasaferjob:HavingthepossibilitytoworkwithoneVC,incaseoflowerproductionrequired;withconsequentlowerconsumption.

Notakingrisksofcompleteproductionstop,incasemaintenance,asitwillbepossibletoworkwiththeotherautonomousmachine/s.采用什么技术可以生产注射用水？ISPE指出：有三种制备方法单效蒸馏；多效蒸馏及蒸汽热压法注射用水温度可选范围环境温度；80-100，热的环境温度能力：L/时产量超过1万升时，要考虑能力的划分，为保证安全运行，每个设备不要超过10吨。如果生产量比较的低时，可采用热压式蒸馏水机，它的消耗量也比较小。如因维修要避免停产的风险，也可使用其它独立的设备。Whichtechnologiescanproduce24VCDistillationTechnology;History:TheWATERDISTILLATIONTECHNOLOGYWASININVENTEDIN1908INITALY,andwasbasedonVAPORCOMPRESSION,theusewasmainlyfordesalinationpurposes;justafterWWII,VCfoundapplicationinpharmaceuticalfieldtoo.Untiltheendofthe‘80s,inEuropetheVCtechnologywasnotsubjectedtodevelopments,astheoldfirmswereunabletomeettheimprovedqualityrequirementsofthemarket;indeed,theVCproductionwerestoppedforseveralyears.Inthe‘90s,BRAM-COR®spa,improvedtheoldVCtechnology,withthecreationofanewpatentedmultistagecompressor,reachingthetitleof“LABORATORYOFRESEARCHFORWATERTREATMENTSYSTEMS”givenbytheItalianMinistryOfInstruction,UniversityandResearch.Thehighesttechnologyonthemarket,allowedtheachievementForBRAM-COR®oftheEuropeanleadershipinthistechnology.VCiscurrentlytakingmarketsharesagainsttheMEin

thePharmaceuticalandBiotechcompanies,intheworld,thankstoitslowoperationalcost.热压式蒸馏水技术的历史此技术1908年发明于意大利；它基于蒸汽的压缩，主要用于脱盐；后来发现它还可用于制药行业。在欧洲，热压式蒸馏水技术没有怎么发展，因为一些老的公司无法满足市场对质量的要求，这一情况直到80年代末：热压式蒸馏水技术确实有好几年没有发展在90年代，我们公司改善了热压式蒸馏水技术，有了多步压缩机的专利，获得了意大利建设、大学及研究部颁发的“水处理系统研究实验室”的头衔。.这一技术投放市场，使我们公司在欧洲获得了领先的地位。由于运行费用低，热压式蒸馏水在制药及生物技术领域取得了多效蒸馏水机的市场份额。VCDistillationTechnology;Hi25SomeoldfirmstrytogetbenefitfromBRAM-COR®success,re-enteringthemarketwithjustmarketingoperations,declaring

“NEWVC”stills,whenarenothingmorethanaMIXOFANTIQUATEDANDINEFFICIENTVCmachines,re-assembledwithoutanyaddedvalue.

OtherVCs

areNOTBORNTOBE“PHARMACEUTICAL”,astheHORIZONTAL

(knotty,notnaturalandnotgreen),bornfordesalinizationinthesea-boats.

ItsstructureisinfacttheFORCINGOFTHECIRCULATION,soitrequiresmanyAVOIDABLEDEVICESas;sprays,re-circulationspumps,etc..(subjectedtobreakages,asallmechanisms),consequentlythistypeneedsmorefrequentinterventions,spareschanges,andVERYPUREFEEDWATER(incontrastwiththebenefitthatvctechnologyallowsagainstmestills).

SomeVCsuseVERYFASTCOMPRESSORROTATION(OVER10.000RPM)withtheconsequentSTRESSOFTHEIMPELLERANDSHAFT,thatbecomesubjectedtocriticism,breakagesandreducedlife.

IntheworstcasesVCsalsousetheDIRECTCOUPLING

withLUBRICATINGOILCIRCUIT(DIRTY)ATTHESAMELEVELOFTHECIRCUITOFTHEPS(CLEAN-PHARMACEUTICAL)causingriskofCROSSCONTAMINATION,especiallywhentheVCsaredesignedintheARCHAICVACUUMCONFIGURATION(Inthesemachinesisvisiblea“conduit”intheshaftarea,closedtotheimpeller,todischargetheoilarrivedtotheWFIcircuit)VCDistillationTechnology.Varieties&Types:热压式蒸馏水技术：种类和类型有些老的公司力求从Bram公司的成功中获益，依靠市场运作再次进入市场，他们声称”新的热压式蒸馏水机“，只不过是将陈旧及无效的热压式蒸馏水机混合组装，并无新意。有些热压式蒸馏水机不是药用级的，是用于出海船只非同一级别的它的结构重点是循环，它需要许多可省的部件，如喷雾、循环泵等（因全是机械性的，易损），经常要干预，更换部件，（与多效蒸馏水机相比）供水要求高。有些热压式蒸馏水机采用高速压缩机（超过1万/分），对叶轮及轴造成很大负荷，易成为致命点，损坏/停车及缩短寿命。在极糟糕情况下，热压式蒸馏水机连接器与润滑的回路（脏的）及药用级回路处同一水平上，导致交叉污染的风险，设计采用老式的真空结构，尤其严重。这类设备在轴的位置，靠近叶轮处，油会进入蒸馏水回路。Someoldfirmstrytogetbene26Whythedistillerspre-treatmentisneeded?ExtractsbyISPE:Alldistillationunitsaresusceptibletoscaling(Hardness,Silica),corrosion(Chlorine),iftheappropriatefeedwaterpre-treatmentisnotprovided.VC

operateslightlyaboveatmosphericpressure,andtheremovalofcalciumandmagnesium,bywayofwatersoftening,isnormallyrequired.ME

stillsoperateatamuchhigherpressureandtemperature,andrequirehigherqualityfeedwaterinordertopreventscalingandcorrosion.DistillerfeedingthroughDoublePassRO(orRO+EDI)?Orjustthrough

Softening(orsingleRO)?OR为什么蒸馏水机需预处理？ISPE摘录的内容：热压式蒸馏水机运行稍高于大气压，通常需要通过软化来去除镁、钙。所有的蒸馏水机易结垢（硬度及硅），氯对它有腐蚀。多效蒸馏水机运行的温度和压力要高得多，对水的质量要求也高，以防止结垢及腐蚀。供水通过二级反渗透（或RO+EDI）或只是软化（或一级反渗透I）Whythedistillerspre-treatme27MultipleEffectpre-treatment:Generalpre-treatmentcharacteristicsrequirementsforMultiple-Effect:TDS:≤5-10mg/l,Silica≤1mg/l,Hardness:0,Chlorine:0,Ammonia:0.NOTE:ToreachthiskindofresultitisalwaysrecommendedtousewatertreatedbyRO/ROorRO/EDI.Softenedwaterisnotpossible.RO/EDI(DI)MultipleEffectStillRO/ROSource源水orTypicalpre-treatmentforMultipleEffectStill(ME)多效蒸馏水机典型的处理Softening,Ca,MgRemoval多效蒸馏水机预处理多效蒸馏水机预处理的一般项目总有机碳硅硬度氯氨要达到这一要求始终建议采用反渗透/反渗透或反渗透/电去离子，软化水是不可能达到要求的。软化，去钙镁多效蒸馏水机反渗透/电去离子或反渗透/反渗透MultipleEffectpre-treatment:28Generalpre-treatmentcharacteristicsrequirementsforVaporCompression(VERTICALTYPES–forHorizontalsissuggestedthecompleteoneasperMultipleEffects):TDS:NotConsidered-Silica≤75mg/l,Hardness:<2ppm(CaCO3),Chlorine:0,Ammonia:0.NOTE:Toreachthisresultitispossible,dependingfromtherawwateranalysis,tousetapwaterremovedfromtheChlorine(SodiumMetaBi-Sulphitedosage)andsoftened(Softeners)

asbase;inanycaseabasicsinglepassROisnormallyenoughforVCfeeding.SoftenedwaterorSinglePassROonly,ispossible(MoneySaving!)VaporCompressionpre-treatment:Softening,Ca,MgRemovalVaporCompressionStillSourceChlorineRemovalPossiblepre-treatmentforVaporCompressionStill(VC)热压式蒸馏水机可选的水处理程序热压式蒸馏水机的预处理直立式热压式蒸馏水机对水的预处理要求如下：（水平热压式蒸馏水机则完全与多效蒸馏水机一样）不考虑硅硬度：指折碳酸钙氯铵根据所用源水检验的结果，自来水去氯（焦亚硫酸钠）和软化（软化剂）有可能达到这个结果；在许多情况下，一个单一的反渗透处理，足以向热压式蒸馏水机供水为节约费用，可用软水及一级反渗透源水去钙镁软水脱氯热压式蒸馏水机Generalpre-treatmentcharacte29Vapour

Compression

StillVCisadistillationmethodwherewaterisevaporatedinside,oroutside,abankoftubesarrangedinvertical(NATURALCIRCUIT),orhorizontal(FORCEDCIRCUIT)configuration.TheVERTICALdesignisoftheNATURALCIRCULATIONTYPE(theverticalconfigurationconsentsafirstnaturalseparationbetweensteamandparticlesbygravity).TheHORIZONTALdesignistheFORCEDCIRCULATIONTYPEWITHRE-CIRCULATIONPUMPSANDSPRAYNOZZLES(thehorizontalconfigurationdoesn’tconsentanoptimizednaturalgravityseparation).VCoperatewithplantsteamatonly3Bar