EthyleneOxideSterilization

環(huán)氧乙烷滅菌

TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)EtOsterilizationstandards環(huán)氧乙烷相關(guān)標(biāo)準(zhǔn)ISO11135-1,-2TIR14/TIR15/TIR16/TIR20/TIR28BIstandards生物指示劑標(biāo)準(zhǔn)ISO11138-1,-2/ISO14161Microbiologicalstandards微生物標(biāo)準(zhǔn)ISO11737-1,-2/AAMI/ST72CIstandard化學(xué)指示劑標(biāo)準(zhǔn)ISO11140-1Residualstandard殘留標(biāo)準(zhǔn)ISO10993-7Packagingstandard包裝標(biāo)準(zhǔn)ISO11607-1，-2Standards標(biāo)準(zhǔn)

TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)

PropertiesofEtO環(huán)氧乙烷性能EthyleneOxideGas(EtO)環(huán)氧乙烷氣體Boilingpoint10.4℃沸點(diǎn)10.4℃Extremelyreactive活躍性強(qiáng)Highlyexplosive易爆

HowDoesEtOKill?環(huán)氧乙烷是如何滅菌的?Killsbyprocesscalled“alkylation”

殺滅過(guò)程稱其為“烷化”EtOirreversiblybindstokeymoleculesinthecellnucleus

環(huán)氧乙烷對(duì)細(xì)胞中分子的作用是不可逆的DNA脫氧核糖核酸Proteins(enzymes)蛋白質(zhì)（酶）

Moleculescannolongerfunction分子喪失其作用Cellcannolongerreproduce細(xì)胞不再被復(fù)制Celldies細(xì)胞死亡TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)9BasicFactorsAffectingEtOSterilization

影響環(huán)氧乙烷滅菌的主要因素Fourbasicfactorsinteracttoproductkill

影響滅菌的四要素EtOconcentration環(huán)氧乙烷濃度Humidity濕度Temperature溫度Time時(shí)間EtOConcentration環(huán)氧乙烷濃度Concentrationscommonlybetween400and1000mg/L

濃度通常在400與1000mg/L之間AsEtOconcentrationincreasesatagiventempandRHmicrobialinactivation(kill)rateincreases

在給定的溫度與相對(duì)濕度條件下,環(huán)氧乙烷濃度增加,微生物的滅活率也會(huì)增加Atconcentrationsaboveabout500mg/L,thereislittleincreaseinkillrate

濃度大于500mg/L時(shí)，殺滅率增加很少Significantlymoregasaddscostwithoutmuchbenefit

值得注意的是EtO的用量越大只會(huì)增加成本對(duì)滅菌效率益處不大Humidity濕度Waterisrequiredforethyleneoxidetoreact(alkylationprocess)withthecriticalcellmolecules

環(huán)氧乙烷與關(guān)鍵細(xì)胞分子的反應(yīng)過(guò)程(烷化過(guò)程)中需有水Presentasagasinthesterilizationprocess在滅菌過(guò)程中以氣體狀態(tài)存在GenerallymeasuredasRelativeHumidity

通常是指相對(duì)濕度Temperature溫度Killrateincreaseswithtemperature殺滅率會(huì)隨溫度的增加而增加Foreach100Criseintemperature,thesporeinactivationratewillgenerallydouble溫度每增加100C,通常孢子的殺活率成倍增加13Time時(shí)間Amountofkillincreaseswithexposure(EtOgasdwell)time 殺滅率會(huì)隨著曝露時(shí)間（即EO駐留時(shí)間）的延長(zhǎng)而增加。TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)BarrierstoBiologicalKill

影響微生物殺滅的屏障PhysicalBarriers物理屏障CardboardBoxes紙板箱Absorbhumidity 吸濕Inhibittemperaturepenetration 阻礙溫度的穿透ShrinkWrap纏繞膜Inhibitstemperatutre,moistureandEtOpenetration

抑制溫度、濕度和EtO的滲透Gas(N2/EtO/RH/Air)CanEasilyEnterGas(N2/EtO/RH/Air)CanExitGas(N2/EtO/RH/Air)Can’tEasilyEnter16BarrierstoBiologicalKill

影響微生物殺滅的屏障PhysicalBarriers物理屏障Packaging包裝Inhibitstemperaturepenetration抑制溫度滲透MayinhibitmoistureorEtOpenetration可能抑制EtO和濕氣的滲透Mylarcannotbepenetratedbyprocessgases氣體不能穿透聚酯薄膜AllprocessgasesentertheproductsthrougheitherTyvekpatches,headersorsides所有氣體通過(guò)Tyvek進(jìn)入產(chǎn)品Wrapslikethisbacktablecoverinhibitpenetrationofgases像手術(shù)臺(tái)布的這種包裹方式抑制了氣體的滲入TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)

EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽BatchProcess,typicallywith3phases:主要的3個(gè)階段Preconditioning–TreatmentofproductpriortothesterilizationcycleinaroomorchambertoattainaspecifiedtemperatureandRH.預(yù)處理

–滅菌循環(huán)前,在房間或柜內(nèi),使產(chǎn)品達(dá)到一定的溫度與濕度.SterilizationChamber–Enclosedareawhichonlyaccommodatessufficientproducttofillthesterilizer

滅菌柜

–裝載待滅菌產(chǎn)品的一個(gè)封閉區(qū)域Aeration–PartofthesterilizationprocessduringwhichEtOdesorbfromthemedicaldevice

解析

–滅菌過(guò)程中醫(yī)療器械釋放環(huán)氧乙烷的階段.Preconditioning預(yù)處理HeatandHumidityIntroducedtoLoad

裝載加熱加濕Airiscirculatedtoassistinheat/humiditytransfer

空氣流通有助于熱/濕的轉(zhuǎn)移Minimumtimegenerallybetween12-24hours.

一般至少預(yù)熱12-24小時(shí)Productcanusuallystayinpreconditioningmuchlonger(2-4daystotal)

產(chǎn)品進(jìn)行預(yù)處理的時(shí)間一般可以更長(zhǎng)(合計(jì)2-4天)SterilizationChamber-EtOCycle

純環(huán)氧乙烷滅菌工藝

InitialVacuum初始抽真空Removesairfromtheload

去除裝載中的空氣Airinhibitspenetrationofwater&EtOintothecenteroftheload空氣會(huì)抑制水與環(huán)氧乙烷滲透進(jìn)產(chǎn)品中央Air,whenmixedwithEtO,createsaflammablemixture當(dāng)空氣與環(huán)氧乙烷混合后會(huì)生成一種易燃混合物Deepvacuumscyclehavesomepotentialdrawbacks

深度抽真空循環(huán)具有一些潛在不足Overlydeepvacuumsmaystarttoremovemoisturefromtheload

過(guò)度的負(fù)壓可能使產(chǎn)品脫水Potentialadverseaffectsontheproductand/orpackaging

對(duì)產(chǎn)品和包裝存在潛在的負(fù)面影響

LeakTest測(cè)漏Purposeistodetectcatastrophicchamberleaks

旨在檢測(cè)滅菌柜是否有嚴(yán)重的泄漏Hasnoeffectonkill

對(duì)滅菌沒(méi)有影響Humidification加濕Injectionofmoisture(intheformofsteam)toreplaceanylossduringinitialvacuum

注入濕氣(蒸汽態(tài))以補(bǔ)充初始抽真空階段丟失的濕氣。Typically25to50mBarriseinpressure

通常注入25至50mBar的濕氣Conditioning處理Conditioning(HumidityDwell)isaperiodoftimewheretheproduct“dwells”inthemoistchamberenvironment.

處理(濕氣駐留)指產(chǎn)品駐留在潮濕的滅菌柜環(huán)境中的一段時(shí)間Onlychangeinthe“static”environmentiswhensteamisaddedtokeepthechamberenvironmenthumiditystable.

只有“靜態(tài)”環(huán)境發(fā)生變化，才會(huì)注入蒸汽，旨在保持滅菌柜中濕氣穩(wěn)定Lossofchamberhumidityisduetoloadabsorptionofthehumidity.

滅菌室濕氣的減少是由于產(chǎn)品的吸濕GasInject氣體注入EtOinjectionintothechamber

將環(huán)氧乙烷注入滅菌柜內(nèi)PressureriseassistsinforcingEtOandhumidityintotheload

壓力上升促使環(huán)氧乙烷和濕氣進(jìn)入裝載中GasDwell氣體駐留GasDwellconsistsofaperiodoftimewheretheproduct“dwells”intheEtOladenchamberenvironmentaftergasinjection.

氣體駐留是指注入氣體后產(chǎn)品“停留”在充滿環(huán)氧乙烷的滅菌柜中的一段時(shí)間Onlychangeinthe“static”environmentiswhenEtO(ornitrogen)isaddedtokeepthechamberenvironmentpressureand/orEtOconcentrationstable.

只有當(dāng)“靜態(tài)”環(huán)境才發(fā)生變化時(shí)，才會(huì)注入環(huán)氧乙烷（或氮?dú)猓荚诒３譁缇癍h(huán)境的壓力和/或環(huán)氧乙烷濃度穩(wěn)定LossofchamberpressureisduetoproductabsorptionoftheEtO.

滅菌柜壓力的下降是由于產(chǎn)品吸收了環(huán)氧乙烷GasDwell氣體駐留Dwellprovidestimefor:氣體駐留時(shí)間

- PenetrationofEtOintothemostdifficultportionsoftheload

環(huán)氧乙烷穿透到產(chǎn)品中最難以到達(dá)的位置Killgenerallyoccursslowlyatthestartofdwellduetothefactthat:

殺滅作用在氣體駐留的初期階段會(huì)比較慢的原因：

-

TheEtOhasnotyetdiffusedintothemostdifficulttoreachlocations

環(huán)氧乙烷尚未擴(kuò)散到產(chǎn)品中最難以到達(dá)的位置 - Thetemperatureinthecoreoftheloadisstillrising

產(chǎn)品中心部位的溫度仍在上升TheefficiencyofkillcanbesignificantlyincreasedwithbyinjectingnitrogenontopoftheEtOinthegasinjectionphase.

在氣體注入階段，注入氮?dú)飧采w于EtO上將顯著提高殺滅率AfterVacuum后抽真空RemovesEtOfromthechamberandtheload

去除滅菌柜和裝載中的環(huán)氧乙烷L(zhǎng)oweredchamberEtOconcentrationallowsEtOtobegintooutgasfromsolids(beginningaerationoftheloadinthechamber)

降低柜內(nèi)環(huán)氧乙烷濃度，使EO開(kāi)始從產(chǎn)品中釋放出來(lái)(裝載在柜內(nèi)的初始解析)DeepervacuumsmayhelpremovemoreEtOresidues

深度抽真空有助于去除環(huán)氧乙烷殘留GasWashes洗氣HelpremovehighconcentrationsofEtOfromtheproduct

有助產(chǎn)品去除高濃度的環(huán)氧乙烷Makesthekitssafertohandleaftersterilization

更安全地處理滅菌后產(chǎn)品Mayshortenrequiredaerationtime

可縮短解析時(shí)間

FinalRelease恢復(fù)常壓Bringsthechambertoatmosphericpressuretoallowopeningofthechamberdoor.Thedoorwillnotopenundervacuum.滅菌柜柜門處于常壓下時(shí)才可開(kāi)啟。柜門在真空狀態(tài)下打不開(kāi)。Thechambermustalwaysreturntoatmosphericusingair(toprovideabreathableatmosphereinthechamberwhenthedoorisopened)滅菌室必須通過(guò)注入空氣恢復(fù)常壓(當(dāng)門打開(kāi)時(shí)，在滅菌室內(nèi)提供可以呼吸的大氣)Aeration解析HeatIntroducedtoLoadtodesorbEtO

加熱以去除裝載中的EtOAiriscirculatedtoassistinheattransfer,aswellasdegassingprocess

空氣循環(huán)流通，有助熱量傳導(dǎo)和解析工藝Timegenerally1-5daysforHeatedAeration,typically2days.

通常解析1-5天，典型的為2天Ambientaerationgenerallymuchlonger

自然解析時(shí)間更長(zhǎng)Below:AerationRoomAeration解析FactorsAffectingEtOAeration

影響EtO解析的因素i. MaterialinwhichEtOisdissolved產(chǎn)品材料

SomematerialsgiveupEtOfasterthanothers不同材料釋放EtO的速度不同ii. ThicknessofMaterial材料的厚度

ThickermaterialsholdmoreEtO材料越厚吸附越多的EtO

Longertodiffusetosurfacefromcenter從中心到表面的擴(kuò)散距離長(zhǎng)iii.Temperature溫度

Highertemperaturesproducefasteraerationrates溫度越高解析速率越快iv. Time時(shí)間

Longertimesproducelowerresiduallevels解析時(shí)間越長(zhǎng)殘留越低TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)IdentifyProductFamilies/Classifications識(shí)別產(chǎn)品族/分類

IdentifyPCD識(shí)別PCDIdentify/FinalizePackaging識(shí)別最終包裝IdentifyLoadConfiguration識(shí)別裝載結(jié)構(gòu)SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)IdentifyProductFamilies/Classifications識(shí)別產(chǎn)品族/分類IdentifyproducttobesterilizedintheEtOprocess識(shí)別待滅菌產(chǎn)品Putproductintoproductfamiliesbygroupingsimilarproducts.

將相似產(chǎn)品歸入產(chǎn)品族中productdesignandfunction產(chǎn)品設(shè)計(jì)和功能manufacturingmethod生產(chǎn)方法manufacturingenvironment生產(chǎn)環(huán)境materialofconstruction材料組成packagingmaterials包裝材料density密度sizeand/orsurfacearea,and大小和/或表面積bioburden生物裝載SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)

IdentifyPCD識(shí)別PCDSelectmostdifficulttosterilizefromfamily 從產(chǎn)品族中選擇最難滅菌的產(chǎn)品Highdensity高密度Mosttorturouspathways最多彎曲路徑Longesttubing,smallestlumen最長(zhǎng)的管路，最小的內(nèi)徑Highbioburdenmaterial高生物裝載Forcomplexproductlikecustomkits,therecanbemorethanonetypeofchallengedevice對(duì)于復(fù)雜的產(chǎn)品如手術(shù)包，可能不止一類產(chǎn)品可作為最難滅菌產(chǎn)品IdentifyPCD識(shí)別PCDTherearetwotypesofchallengedevices兩種挑戰(zhàn)器Internal內(nèi)置挑戰(zhàn)器External外置挑戰(zhàn)器SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)InternalChallengeDevice內(nèi)置挑戰(zhàn)器 Generallythemostdifficulttosterilizedevice,isseededwithaBIorliquidsuspensioninthemostdifficulttosterilizelocation.Examplesofinoculationpositionsincludeplaceslike:

通常將BI或孢子懸液接種于最難滅菌產(chǎn)品的最難滅菌位置。如Thecenteroflong,thintubing細(xì)長(zhǎng)管子的中間Betweenthesealsonasyringe注射器密封處SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)

InternalChallengeDevice內(nèi)置挑戰(zhàn)器Packagethechallengeproductinthesamemannerasproductswouldroutinelybesterilized

挑戰(zhàn)性產(chǎn)品的包裝方式同常規(guī)待滅菌產(chǎn)品。Placethepackagedchallengeproductintoasterilizationloadofproduct。將已包裝的挑戰(zhàn)產(chǎn)品置于滅菌裝載內(nèi)。SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)ExternalChallengeDevice外置挑戰(zhàn)器ABIcontainingtestpackthatisareplacementfortheinternalchallengedevice,andgenerallymaybeusedforroutineprocessing

含有BI的測(cè)試包，代替內(nèi)置挑戰(zhàn)器，通常用于常規(guī)生產(chǎn)監(jiān)測(cè)MakesiteasiertoplaceandretrieveBIsduringroutineprocessing 在常規(guī)生產(chǎn)過(guò)程中使得BI的取放更容易。Shouldbeanequalormoredifficultchallengetotheprocessthantheinternalchallengedevice. 對(duì)處理過(guò)程的挑戰(zhàn)性，應(yīng)大于等于內(nèi)置挑戰(zhàn)器Generallydevelopedusingcomparativeresistancestudies 通?？赏ㄟ^(guò)抗力比較獲得SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)Identify/FinalizePackaging識(shí)別最終包裝Productpackaging產(chǎn)品包裝Corrugate,boxthickness瓦楞紙箱，盒子厚度Pouchingmaterials(Tyvek)包裝材料Packingconfiguration(quantity/box)包裝結(jié)構(gòu)（數(shù)量/箱）Mayaffectproduct’sabilitytoabsorbhumidity

可影響產(chǎn)品吸濕的能力Mayaffectproduct’sabilitytoaidtemperaturepenetration可影響產(chǎn)品協(xié)助溫度穿透的能力SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)IdentifyLoadConfiguration識(shí)別裝載結(jié)構(gòu)Palletizingapproach堆垛方式Stretchwrap,cornerboard,netting?纏繞膜、護(hù)角、護(hù)網(wǎng)?Mayaffectloads’abilitytoabsorbhumidity

可影響裝載的吸濕能力Mayaffectloads’abilitytoaidtemperaturepenetration

可影響裝載協(xié)助溫度穿透的能力SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)ProposedParameters建議的參數(shù)Cycleparametersincorporateproduct-limitationinformationfromcustomer

循環(huán)參數(shù)應(yīng)結(jié)合客戶提供的產(chǎn)品局限性信息。Useanexistingcycle(previouslydeveloped)foraproduct

使用已存在的滅菌循環(huán)（以前開(kāi)發(fā)的）Selectageneralcyclethatworksforsimilarproducttypes:

選擇一個(gè)用于相似產(chǎn)品的通用循環(huán)Recommended:IncludeafractionalcycleintheValidation;建議：確認(rèn)過(guò)程包括部分循環(huán)SterilizationCycleDevelopment

滅菌循環(huán)開(kāi)發(fā)ValidationMethod確認(rèn)方法

3recognisedmethodsforEtOvalidation

3種認(rèn)可的方法 Directenumeration直接計(jì)數(shù)法

Fraction-negative部分陰性法 Overkillapproach過(guò)度殺滅法

Directenumeration

直接計(jì)數(shù)法Minimumof5cyclesneeded5次循環(huán)onerunwith0timeexposure

1次曝露時(shí)間為0的循環(huán)onerunwith4SLR

1次SLR下降4的循環(huán)atleastthreerunsbetweeniandii介于i和ii之間的3個(gè)循環(huán)Fraction-negativemethod

部分陰性法

Aminimumof7exposureconditionsshouldbeusedcovering:

至少7個(gè)循環(huán)Atleastonesetofsamplesinwhichalltestedsamplesshowgrowth

至少1次循環(huán)，試樣顯示全部生長(zhǎng)。

Atleast4testsetsinwhichafractionofthesamplesshowgrowth

至少4次循環(huán)，試樣顯示部分生長(zhǎng)。Atleast2testsetsofsamplesinwhichnogrowthisobserved至少2次循環(huán)，試樣顯示無(wú)生長(zhǎng)。Fraction-negativemethod

部分陰性法TheD-value(timeneededtoreducemicrobialcountbyatleast1log)iscalculatedusingtheresultsofthetest.

根據(jù)測(cè)試結(jié)果計(jì)算D值（下降1個(gè)對(duì)數(shù)值所需要的時(shí)間）。Thetheoreticalexposuretimerequiredtoachievethesterilityassurancelevel(SAL)ofthetestorganismiscalculatedfromtheD-value.

通過(guò)D值再計(jì)算得到相應(yīng)無(wú)菌保證水平的理論曝露時(shí)間。Overkillapproach(halfcyclemethod)

過(guò)度殺滅法(半時(shí)循環(huán)法)DeterminesminimumtimeofexposuretoEtOatwhichtherearenosurvivors.(halfcycle)

測(cè)定無(wú)存活菌的最短時(shí)間---半時(shí)循環(huán)3runs(halfcycles)areperformedtoconfirmtheminimumtime.

運(yùn)行3次半時(shí)循環(huán)以確認(rèn)此最短時(shí)間。AllthreerunsshouldshownogrowthontheBI’s.

所有的三次測(cè)試應(yīng)無(wú)BI生長(zhǎng)。Itisrecommendedthatafractionalcyclealsobeperformedtodemonstratetheadequacyoftherecoverytechnique.

應(yīng)運(yùn)行一次短時(shí)循環(huán)以證明復(fù)蘇技術(shù)的充分性。TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)SterilizationCycleValidation

滅菌循環(huán)確認(rèn)Documentedstudy研究工作文件化Validationprotocoltoassurecycleisadequate

確認(rèn)方案以保證循環(huán)是充分的AcceptanceCriteriaagreeduponbeforebeginning

開(kāi)始前應(yīng)認(rèn)可接受標(biāo)準(zhǔn)Proceduresaredocumented程序文件化SterilizationCycleValidation

滅菌循環(huán)確認(rèn)Priortovalidation確認(rèn)前Packagingfinalized產(chǎn)品包裝已確定Loadconfigurationidentified裝載結(jié)構(gòu)已確定ProductFamilieshavebeenidentified(asapplicable)

產(chǎn)品族已識(shí)別（若適用）Bioburden?生物裝載？SterilizationCycleValidation

滅菌循環(huán)確認(rèn)Parameterstobeaddressed待確認(rèn)參數(shù)TransfertimeafterPreconditioning預(yù)處理結(jié)束后的轉(zhuǎn)移時(shí)間Specifiedrangesforsterilizationload(Preconditioning,Chamber,andAeration)滅菌裝載規(guī)定的范圍（預(yù)處理，滅菌柜循環(huán)和解析）VerifyGasSterilantwasadmittedtochamber驗(yàn)證氣體滅菌劑注入滅菌柜Gasweight氣體重量SterilizationCycleValidation

滅菌循環(huán)確認(rèn)Fractional短時(shí)循環(huán)Run1FractionalRuninproductionchamber

在生產(chǎn)用滅菌柜內(nèi)運(yùn)行1個(gè)部分循環(huán)Why?NewstandardstatesthatBIrecoverybetweenprocessfacilityandtestingfacilitymustbedemonstrated

因?yàn)樾聵?biāo)準(zhǔn)要求必須在生產(chǎn)和測(cè)試柜內(nèi)證明BI的復(fù)蘇性。SterilizationCycleValidation

滅菌循環(huán)確認(rèn)HalfCycles半時(shí)循環(huán)Preconditioningtimeshouldbelessthanroutine(fullcycle)time

預(yù)處理時(shí)間應(yīng)小于常規(guī)（全時(shí)循環(huán)）時(shí)間Halfcyclesshouldbesub-nominalforatleastoneparameter

半時(shí)循環(huán)至少有一個(gè)參數(shù)小于常規(guī)TemperatureandHumiditySensorsplacedwithintheload

溫濕度傳感器置于裝載內(nèi)SterilizationCycleValidation

滅菌循環(huán)確認(rèn)HalfCycles半時(shí)循環(huán)Run3totalHalfCycleswithparametersestablishedduringCycleDevelopment

共運(yùn)行3次半時(shí)循環(huán)，使用循環(huán)開(kāi)發(fā)過(guò)程設(shè)定的參數(shù)Removesamplesasdefinedinprocedure

按程序規(guī)定取出樣品SterilizationCycleValidation

滅菌循環(huán)確認(rèn)HalfCycles半時(shí)循環(huán)TestBIs;typically7dayincubation BI測(cè)試，通常7天培養(yǎng)MasterPCD(sporedproductorotherwise)mustshownogrowth.

主PCD（染菌產(chǎn)品或其他）必須顯示無(wú)生長(zhǎng)。ConfirmationofSAL無(wú)菌保證水平確認(rèn)NOPRODUCTTESTINGONHALFCYCLES!!!!

半時(shí)循環(huán)勿進(jìn)行產(chǎn)品無(wú)菌測(cè)試SterilizationCycleValidation

滅菌循環(huán)確認(rèn)FullCycle全時(shí)循環(huán)Runaminimumof1FullCycletoevaluate:

至少運(yùn)行1個(gè)全時(shí)循環(huán)以評(píng)估：Heathistoryofload(loadcontainssensorssameasMPQruns)

裝載加熱歷史記錄（裝載帶有傳感器同MPQ循環(huán)）Aeration/EOResidues解析/EO殘留Product/packagingfunctionality產(chǎn)品/包裝功能測(cè)試SterilizationCycleValidation

滅菌循環(huán)確認(rèn)FullCycle全時(shí)循環(huán)AerationRequirements/EOResidues解析要求/殘留Developdissipationcurvetoestablishreleasetime

開(kāi)發(fā)擴(kuò)散曲線以建立放行時(shí)間SterilizationCycleValidation

滅菌循環(huán)確認(rèn)FullCycle全時(shí)循環(huán)Residualallowablelimitsarebasedonapplicationofproduct

殘留的允許限量是基于產(chǎn)品的應(yīng)用Qualifyreleasetimebasedonthree(3)separatelots(cycles)

基于3次循環(huán)運(yùn)行建立放行時(shí)間SterilizationCycleValidation

滅菌循環(huán)確認(rèn)FullCycle全時(shí)循環(huán)Asecond(2X)FullCycleishighlyrecommended

建議運(yùn)行二次滅菌：Simulatesreprocessingbythefacility模擬再處理TestEOresiduesfor2Xprocessedsamples測(cè)試二次滅菌樣品殘留SterilizationCycleValidation

滅菌循環(huán)確認(rèn)ValidationReport確認(rèn)報(bào)告Reportshallbesignedbypersonsdesignatedresponsibleforpreparing,reviewing,andacceptingthereport

確認(rèn)報(bào)告應(yīng)由指定負(fù)責(zé)準(zhǔn)備、審核、批準(zhǔn)的人簽署。ValidationReportwillcontainspecificationsforEOprocess.

確認(rèn)報(bào)告應(yīng)包含EO過(guò)程規(guī)范。Willincludevalueandtolerancesforthefollowing:

包括以下參數(shù)值和公差：SterilizationCycleValidation

滅菌循環(huán)確認(rèn)ValidationReport確認(rèn)報(bào)告Preconditioning,conditioning預(yù)處理，處理Examples-time,temp,humidity,chambertransfertime

例-時(shí)間，溫度，濕度，轉(zhuǎn)移時(shí)間Sterilization滅菌Examples-chambertemp,exposuretime

例-柜溫，曝露時(shí)間Aeration解析Examples-time,temp例-時(shí)間，溫度Requalification再鑒定Criticalstepinoverallvalidation整個(gè)過(guò)程確認(rèn)的關(guān)鍵步驟Periodicrequalificationstudiesdesignedtodetectinadvertantprocesschanges定期的再鑒定以發(fā)現(xiàn)未注意的過(guò)程變化。

Recommendeduponintroductionofneworsignificantchangesin;

新產(chǎn)品的追加或以下方面有顯著變化建議進(jìn)行再鑒定Product產(chǎn)品Process過(guò)程Packaging包裝Equipment設(shè)備Requalification再鑒定Options:Performone(1)microPQrunineachqualifiedchamber

在已鑒定的柜室內(nèi)運(yùn)行一個(gè)MPQEstablishchamberEquivalencyperTIR28:2009,alongwithreducedPQrequirements

依據(jù)TIR28：2009和簡(jiǎn)化的PQ要求建立滅菌柜室等效性PaperRevalidation:Documentedevaluationofprocesstoverifynoprocessshiftsthroughoutyear.

文件式再確認(rèn)：過(guò)程評(píng)估文件化以驗(yàn)證在過(guò)去的一年中無(wú)過(guò)程偏移。Requalification再鑒定NewRequirement新要求AppropriatenessofBItobeverifiedatdefinedintervals在規(guī)定的時(shí)間間隔內(nèi)驗(yàn)證BI的適合性Makeitpartofperiodicrevalidationschedule將其作為定期再確認(rèn)的一部分TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)EtOResidues殘留3chemicalresiduesassociatedwithEtOprocess

與環(huán)氧乙烷滅菌過(guò)程相關(guān)的3種化學(xué)殘留EtOEthyleneOxide環(huán)氧乙烷ECHEthyleneChlorohydrin氯乙醇EGEthyleneGlycol(a.k.a.,antifreeze)乙二醇EthyleneOxide環(huán)氧乙烷Physicallyabsorbedintomaterialsofconstructionofdevice,essentiallydissolvedintheplastics

醫(yī)療器械產(chǎn)品的材料會(huì)吸收環(huán)氧乙烷，還會(huì)溶入塑料Amountdissolveddependson:吸附量取決于Material-PVCandpolycarbonateamongworstmaterials

材料—PVC和聚碳酸酯吸附量較大ChamberEtOConcentration-Higherconcentrationyieldshigherresiduallevel

滅菌柜內(nèi)環(huán)氧乙烷的濃度—高濃度產(chǎn)生高殘留ContactTime-Longergasdwelltimeyieldshigherresiduallevel

接觸時(shí)間—?dú)怏w暴露時(shí)間越長(zhǎng)殘留越高EthyleneChlorohydrin氯乙醇EtOpluschlorideionorreactivechlorine環(huán)氧乙烷與氯離子的反應(yīng)產(chǎn)物Cannotformunlesschlorideoractivechlorinecompoundpresentinoronmaterial僅當(dāng)材料上存在氯離子或活性氯化物時(shí)方能形成氯乙醇Examples:如PVC聚氯乙烯Cleaningagents(I.e.,bleach)清洗劑（如：漂白劑）EthyleneGlycol乙二醇EtOreactswithwatertoformethyleneglycol

環(huán)氧乙烷與水反應(yīng)形成乙二醇Extentofformationvarieswithmaterial

形成程度取決于所用的材料DeterminationofMinimumAerationTime最小解析時(shí)間確定Typicalmethodistoplotadissipationcurveatdefinedtimeintervals

常用的方法是在規(guī)定的時(shí)間間隔內(nèi)建立一條擴(kuò)散曲線。Recommendedthataminimumof3samplesareeachremovedat3timepoints建議每一時(shí)間點(diǎn)至少測(cè)試3個(gè)樣品Recommendedthat3dissipationcurvesareplotted

建議建立3條擴(kuò)散曲線ShouldassestheaffectsofmultipleEtOexposures

應(yīng)評(píng)估多次滅菌對(duì)殘留的影響ETOAbsorptivityInDeviceMaterials

器械材料ETO吸收率High:PVC聚氯乙烯PVDC聚二氯乙烯Medium:Polycarbonate聚碳酸酯Polyurethane聚氨酯

Polyethylene聚乙烯

Silicone硅膠

Low:Polyamide聚酰胺Cotton棉花

Paper紙No:Metal-Glass–Teflon金屬-玻璃-聚四氟乙烯PatientExposureCategories

根據(jù)與病人接觸時(shí)間分類LimitedExposure短期接觸ProlongedExposure長(zhǎng)期接觸PermanentContacting持久接觸LimitedExposure短期接觸ShortTerm:<24Hours

短期：<24小時(shí)AllowableLimits:允許限量

EO:4mg/day ECH:9mg/dayLimitedExposureExamples短期接觸實(shí)例SyringesSurgicalDrapeProlongedExposure

長(zhǎng)期接觸ExtendedUse:>24Hours&<30Days24小時(shí)＜使用時(shí)間<30天

AllowableLimitsEOECHAVGDailyDose2mg2mg24Hours4mg9mg30Days60mg60mgProlongedExposureExamples長(zhǎng)期接觸實(shí)例CentralVenousCatheterIVDressingPermanentContacting持久接觸Long-Term:>30Days

長(zhǎng)期>30天

AllowableLimitsEOECHAVG0.1mg/day0.4mg/day24Hours4mg9mg30Days60mg60mgLifetime2.5g10gPermanentContactingExamples

持久接觸實(shí)例BoneFiller(Implant)AbdominalAorticAneurysmStentTolerableContactLimit(TCL)

可耐受接觸限量SurfaceContactingDevices表面接觸器械Implants

植入器械A(chǔ)llowableLimits允許限量EO:10μg/cm2ECH:5mg/cm2ContactSurfaceArea-ProvidedbyCustomer接觸表面面積—客戶提供SpecialSituations特殊情況Drapes-IntactSkin-TCLonly

手術(shù)單-接觸完好皮膚-僅TCLIntraOcularLens(IOL):EOLimits眼內(nèi)透鏡：EO限量

Average:0.5μg/lens/day Total:1.25μg/lensCardiopulmonaryBypassProcedures心肺旁路過(guò)程

EO:20mg/dev ECH:9mg/dev

DeterminationofResidualsSuggestedExtractionConditions建議浸提條件DeviceContactDurationPermanentContact持久接觸ProlongedExposure長(zhǎng)期接觸LimitedExposure短期接觸

ExhaustiveExtraction極限浸提SimulatedUse模擬浸提SimulatedUse模擬浸提TopicsStandards標(biāo)準(zhǔn)PropertiesofEtO/HowdoesEtOKill?環(huán)氧乙烷性能及滅菌機(jī)理BasicFactorAffectingEtOSterilization影響環(huán)氧乙烷滅菌的主要因素BarrierstoBiologicalKill影響微生物殺滅的屏障EtOProcessOverview環(huán)氧乙烷滅菌過(guò)程概覽Cycledevelopment循環(huán)開(kāi)發(fā)CycleValidation循環(huán)確認(rèn)EvaluationofProductEtOResidues殘留評(píng)估EtOProcessFlow環(huán)氧乙烷滅菌處理流程EnvironmentalConsiderations環(huán)境保護(hù)

EtOProcessFlow–Conventional

環(huán)氧乙烷滅菌處理流程—傳統(tǒng)放行WhenproductistobesterilizedconventionallybySterigenics,itwillgothroughthefollowingsteps施潔對(duì)于傳統(tǒng)放行產(chǎn)品的處理步驟Receipt收貨Add