环氧乙烷灭菌

EthyleneOxideSterilization环氧乙烷灭菌Topics►Standards标准►PropertiesofEtO/HowdoesEtOKill?环氧乙烷性能及灭菌机理►BasicFactorAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►BarrierstoBiologicalKill影响微生物杀灭的屏障►EtOProcessOverview环氧乙烷灭菌过程概览►Cycledevelopment循环开发►CycleValidation循环确认►EvaluationofProductEtOResidues残留评估►EtOProcessFlow环氧乙烷灭菌处理流程►EnvironmentalConsiderations环境保护Topics►Standards标准►PropertiesofEtO/HowdoesEtOKill?环氧乙烷性能及灭菌机理►BasicFactorAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►BarrierstoBiologicalKill影响微生物杀灭的屏障►EtOProcessOverview环氧乙烷灭菌过程概览►Cycledevelopment循环开发►CycleValidation循环确认►EvaluationofProductEtOResidues残留评估►EtOProcessFlow环氧乙烷灭菌处理流程►EnvironmentalConsiderations环境保护►EtOsterilizationstandards环氧乙烷相关标准ISO11135-1,-2TIR14/TIR15/TIR16/TIR20/TIR28►BIstandards生物指示剂标准ISO11138-1,-2/ISO14161►Microbiologicalstandards微生物标准ISO11737-1,-2/AAMI/ST72►CIstandard化学指示剂标准ISO11140-1►Residualstandard残留标准ISO10993-7►Packagingstandard包装标准ISO11607-1，-2Standards标准Topics►Standards标准►PropertiesofEtO/HowdoesEtOKill?环氧乙烷性能及灭菌机理►BasicFactorAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►BarrierstoBiologicalKill影响微生物杀灭的屏障►EtOProcessOverview环氧乙烷灭菌过程概览►Cycledevelopment循环开发►CycleValidation循环确认►EvaluationofProductEtOResidues残留评估►EtOProcessFlow环氧乙烷灭菌处理流程►EnvironmentalConsiderations环境保护PropertiesofEtO环氧乙烷性能►EthyleneOxideGas(EtO)环氧乙烷气体–Boilingpoint10.4℃沸点10.4℃–Extremelyreactive活跃性强–Highlyexplosive易爆HowDoesEtOKill?环氧乙烷是如何灭菌的?►Killsbyprocesscalled“alkylation”杀灭过程称其为“烷化”►EtOirreversiblybindstokeymoleculesinthecellnucleus环氧乙烷对细胞中分子的作用是不可逆的–DNA脱氧核糖核酸–Proteins(enzymes)蛋白质（酶）Moleculescannolongerfunction分子丧失其作用Cellcannolongerreproduce细胞不再被复制Celldies细胞死亡Topics►Standards标准►PropertiesofEtO/HowdoesEtOKill?环氧乙烷性能及灭菌机理►BasicFactorAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►BarrierstoBiologicalKill影响微生物杀灭的屏障►EtOProcessOverview环氧乙烷灭菌过程概览►Cycledevelopment循环开发►CycleValidation循环确认►EvaluationofProductEtOResidues残留评估►EtOProcessFlow环氧乙烷灭菌处理流程►EnvironmentalConsiderations环境保护9BasicFactorsAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►Fourbasicfactorsinteracttoproductkill影响灭菌的四要素i.EtOconcentration环氧乙烷浓度ii.Humidity湿度iii.Temperature温度iv.Time时间EtOConcentration环氧乙烷浓度►Concentrationscommonlybetween400and1000mg/L浓度通常在400与1000mg/L之间►AsEtOconcentrationincreasesatagiventempandRHmicrobialinactivation(kill)rateincreases在给定的温度与相对湿度条件下,环氧乙烷浓度增加,微生物的灭活率也会增加►Atconcentrationsaboveabout500mg/L,thereislittleincreaseinkillrate浓度大于500mg/L时，杀灭率增加很少►Significantlymoregasaddscostwithoutmuchbenefit值得注意的是EtO的用量越大只会增加成本对灭菌效率益处不大Humidity湿度►Waterisrequiredforethyleneoxidetoreact(alkylationprocess)withthecriticalcellmolecules环氧乙烷与关键细胞分子的反应过程(烷化过程)中需有水–Presentasagasinthesterilizationprocess在灭菌过程中以气体状态存在–GenerallymeasuredasRelativeHumidity通常是指相对湿度Temperature温度►Killrateincreaseswithtemperature杀灭率会随温度的增加而增加►Foreach100Criseintemperature,thesporeinactivationratewillgenerallydouble温度每增加100C,通常孢子的杀活率成倍增加13Time时间•Amountofkillincreaseswithexposure(EtOgasdwell)time杀灭率会随着曝露时间（即EO驻留时间）的延长而增加。Topics►Standards标准►PropertiesofEtO/HowdoesEtOKill?环氧乙烷性能及灭菌机理►BasicFactorAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►BarrierstoBiologicalKill影响微生物杀灭的屏障►EtOProcessOverview环氧乙烷灭菌过程概览►Cycledevelopment循环开发►CycleValidation循环确认►EvaluationofProductEtOResidues残留评估►EtOProcessFlow环氧乙烷灭菌处理流程►EnvironmentalConsiderations环境保护BarrierstoBiologicalKill影响微生物杀灭的屏障►PhysicalBarriers物理屏障–CardboardBoxes纸板箱•Absorbhumidity吸湿•Inhibittemperaturepenetration阻碍温度的穿透–ShrinkWrap缠绕膜•Inhibitstemperatutre,moistureandEtOpenetration抑制温度、湿度和EtO的渗透Gas(N2/EtO/RH/Air)CanEasilyEnterGas(N2/EtO/RH/Air)CanExitGas(N2/EtO/RH/Air)Can’tEasilyEnter16BarrierstoBiologicalKill影响微生物杀灭的屏障►PhysicalBarriers物理屏障–Packaging包装•Inhibitstemperaturepenetration抑制温度渗透•MayinhibitmoistureorEtOpenetration可能抑制EtO和湿气的渗透Mylarcannotbepenetratedbyprocessgases气体不能穿透聚酯薄膜AllprocessgasesentertheproductsthrougheitherTyvekpatches,headersorsides所有气体通过Tyvek进入产品Wrapslikethisbacktablecoverinhibitpenetrationofgases像手术台布的这种包裹方式抑制了气体的渗入Topics►Standards标准►PropertiesofEtO/HowdoesEtOKill?环氧乙烷性能及灭菌机理►BasicFactorAffectingEtOSterilization影响环氧乙烷灭菌的主要因素►BarrierstoBiologicalKill影响微生物杀灭的屏障►EtOProcessOverview环氧乙烷灭菌过程概览►Cycledevelopment循环开发►CycleValidation循环确认►EvaluationofProductEtOResidues残留评估►EtOProcessFlow环氧乙烷灭菌处理流程►EnvironmentalConsiderations环境保护EtOProcessOverview环氧乙烷灭菌过程概览►BatchProcess,typicallywith3phases:主要的3个阶段–Preconditioning–TreatmentofproductpriortothesterilizationcycleinaroomorchambertoattainaspecifiedtemperatureandRH.预处理–灭菌循环前,在房间或柜内,使产品达到一定的温度与湿度.–SterilizationChamber–Enclosedareawhichonlyaccommodatessufficientproducttofillthesterilizer灭菌柜–装载待灭菌产品的一个封闭区域–Aeration–PartofthesterilizationprocessduringwhichEtOdesorbfromthemedicaldevice解析–灭菌过程中医疗器械释放环氧乙烷的阶段.Preconditioning预处理►HeatandHumidityIntroducedtoLoad装载加热加湿►Airiscirculatedtoassistinheat/humiditytransfer空气流通有助于热/湿的转移►Minimumtimegenerallybetween12-24hours.一般至少预热12-24小时►Productcanusuallystayinpreconditioningmuchlonger(2-4daystotal)产品进行预处理的时间一般可以更长(合计2-4天)SterilizationChamber-EtOCycle纯环氧乙烷灭菌工艺0.05.010.015.020.025.030.00100200300400500600Pressure(inHgA)TimefromCycleStart(minutes)GenericEtOCycleLeakTestHumidificationPo