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HomeBlogWhenandHowtoRepeatYourEthyleneOxideSterilizationValidation

WhenandHowtoRepeatYourEthyleneOxideSterilization
Validation
PostedbyRobPackardonMarch30,2015
Thisarticlereviewssomeofthefactorstoconsiderwhenyouareevaluatingtheneedtorepeatyour
ethyleneoxidesterilizationvalidation.

ISO111351:2014istheinternationalstandardforsterilizationvalidationforEthyleneOxide(EOor
EtO)sterilizers.ThestandardfullvalidationisrequiredforinitialqualificationofyourEOsterilization
process.Fullvalidationconsistsofthefollowing:
1.ProcessChallengeDevice(PCD)validation
2.Bioburdenmeasurement
3.EOresidualmeasurement(asperISO109937:2008/R2012)
4.FractionalCycle(atleastone)
5.3xHalfCycle
6.3xFullCycle
Inadditiontothefullvalidation,youmightalsovalidatepartialloadsand/orresterilizationofproduct
inthecaseofrework.
Ethyleneoxidesterilizationistypicallyoutsourcedtoacontractsterilizerduetotheenvironmentaland
safetyrequirementsofworkingwithEO.Typicallythecontractsterilizerwillprovideastandard
validationprotocolforfullvalidationthatiscompliantwithISO111351.However,theISO111351
standardrequiresthatmanufacturersperformannualprocessreviewstoevaluatetheneedforre
validationofthesterilizationprocess.Assumingtherehavebeennoproblems,andnochangestothe
productorprocess,thenrevalidationisnotrequiredattheendofthefirstyear.However,most
companiesareexpectedtorevalidatetheprocessaftertwoyears.Sowhydosomecompanies
performrevalidationafterthreeyearsormore?
LongerReValidationCycles
Iftherehavebeennotchangestothesterilizationprocess,theproductorthebiologicalindicators,
thenthemanufacturercanusethisasajustificationforwaitinguntiltwoyearshaveelapsedbeforere
validatingtheethyleneoxidesterilizationprocess.Inaddition,thereshouldbenoevidenceof
sterilizationfailuresorotherproblemswiththevalidatedprocess.However,thataloneisnot
necessarilyenoughtojustifyextendingthedurationbetweenvalidationsbeyondtwoyears.
Companiesthatareabletojustifyintervalsofthreeormoreyearshavemultipleproductsthatare
usingthesamesterilizationprocess.
Inthiscase,themanufacturermayalternateannuallybetweenthree,fourorevenfivedifferent
productfamiliesthatareusingthesamesterilizationprocess.Inthiscase,oneoftheproductfamilies

isbeingrevalidatedeachyearoreverytwoyears,buttheintervalbetweenvalidationsforanyone
productfamilyislonger.Iftheproductsaremadeofsimilarmaterialsandusingthesamesterilization
process,thenthisapproachisvalid.Ifyouonlyhaveoneproduct,thenyouneedtorevalidatethe
sterilizationprocessonceeverytwoyearstoverifytheprocessremainseffective.
MinimumReValidationRequirements
Whenyoudeterminethatitistimetorevalidateyourethyleneoxidesterilizationprocess,youneedto
performthefollowingtestsinordertomeettheminimumrequirementsofISO111351:
1.Bioburdenmeasurement
2.EOresidualmeasurement
3.OneFractionalCycle
4.3xHalfCycle
5.OneFullCycle
Thepurposeof#1istoverifythatbioburdenlevelshavenotchanged.Inpractice,mostcompanies
monitorbioburdenonaquarterlybasisandthereforethisstepshouldberoutine.Step2,EOresidual
measurement,shouldbeperformedinordertoverifythattherehavenotbeenminorchangestothe
productorprocessthatwouldincreasetheconcentrationofEO,EthyleneChlorohydrin(ECH)or
EthyleneGlycol(EG)beyondtheTolerableContactLimit(TCL).Thepurposeofthissecondtestisto
preventlocalizedirritationcausedbyresidualchemicalsfromtheethyleneoxidesterilizationprocess.
Step3oftherevalidationisintendedtoverifythatafullinjectionofEOismorethanrequiredtokill
thebioburdenpresentforthenumberofinjectionsrequiredforahalfcycle.Therefore,ifrequired
minimumconcentrationofEOis2fortwoinjections,twoinjectionsofa3.6EOconcentrationmaybe
usedforahalfcycle.Ideally,theProcessChallengeDevices(PCDs)willbenonsterileaftera
fractionalcycle,whiletheinternalbiologicalindicatorswillbesterile.Afterahalfcycle,allbiological
indicators,includingthePCDs,shouldbesterile.
Thefinalstepistoperformafullcycle.ProductfromthefullcycleistypicallyusedfortheEOresidual
testing.Anyproductfromthefullcyclethatisnotusedfortestingcanbesoldaftersterilitytestingis
complete.
PartialLoads&Rework
Ifyouoccasionallysterilizeloadsthatarelessthanfullloads,thenyouneedtoensurethatyouhave
validatedaminimumloadoraspecificpartialload(e.g.,halfpallet,insteadofafullpallet).Inthecase
ofapartialorminimumload,youmayidentifydifferentlocationsinyourloadthatareconsidered
worstcase.ThesearethelocationsthathadPCDsthatwerenotsterileinafractionalcycle.
Mostcompaniesdonothaveconcernsaboutthecostoftheactualsterilizationrunsduringre
validation,andbiologicalindicatorsaretypicallylessexpensivethanboxesofproduct.Theprimary
costconcernforrevalidationisanyproductthatmustbescrapped.Therefore,manycompanieswill
accumulatedunnage(i.e.,emptypackagingorscrapproduct)overtimeinordertofillasterilizer.This
dunnagemaybeusedtoensurethateveryloadisafullload,oritmaybeonlyusedforrevalidation.
Anotheralternativetousingdunnageforrevalidationistovalidateareworkprocess.Anyproductthat
isexposedtoafractionalcycleorhalfcyclecanberesterilizedinafullcycle.Inordertojustifythe
commercialuseofthatproduct,acompanyneedstovalidatethattheproductwillnotbedamagedby
exposuretotwofullcycles.OneofthekeyacceptancecriteriaforreworkistheEOresiduallevelsin
theproduct.However,themanufactureralsoneedstodetermineiftherehasbeenanydeteriorationof
theproductbyasecondexposuretoEOthatwouldaffectperformance.

OtherConsiderations
Manycompaniesdoapoorjobofreviewingthepotentialimpactofchangestoproduct,packaging
andbiologicalindicators.Ideally,initialvalidationinvolvesdifferentlotsofproduct,packagingand
biologicalindicatorstoassesslottolotvariability.However,manytimes,thepackagingandbiological
indicatorsconsistofonlyonelotduringvalidation.Minorchangestothetolerancesmayreducethe
amountofethyleneoxidethatisabsorbedbytheproductorchangetheresistanceothebiological
indicatortothesterilizationprocess.Therefore,theseminorchangesshouldtriggerarevalidation.
Changesinsupplierswiththesamespecificationcanalsobedifficulttoevaluate.Ifacomponentis
madeofamaterialthatabsorbsEO,thenitmayberecommendedtorevalidatesterilizationforany
changestosuppliersofthosecomponents.Revalidationinthesecasesmayconsistofonlya
fractionalcycleoronlyafullcycletoevaluaterisksassociatedwiththechange.
WhoShouldBeMakingEvaluations
Theevaluationofneedforrevalidationshouldincludeinputofthreetypes:1)microbiological,2)
materials,and3)performance.Inordertomaketheseassessments,typicallyacrossfunctionalteam
isneeded.Someonewithresponsibilityfordesignanddevelopmentcanassessperformanceimpact
ofchanges.Amaterialsengineeristypicallyneededforassessmentofinteractionbetween
componentsandEO.Finally,amicrobiologistisneededtoconfirmthatthereisnoimpactrelatedto
biologicalindicatorsorbioburden.

MedicalDeviceAcademyalsoreleasedanewwebinar
recordingonthetopicofBioburdenFailureAnalysislastweekReadMore
Ifyouneedassistancewithsterilizationvalidationorbioburdenfailureanalysis,pleasecontactmeby
emailatrob@13485cert.comorcallmeat+1.802.281.4381.

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Tags:ethyleneoxide,ethyleneoxidesterilizationvalidation
Postedin:ProcessValidation
LeaveaComment(3)
3Comments

1.
JayasheelHegdeApril5,2015
Averygoodarticle.Itisveryimportanttoconductarevalidationwheneveraproductpackagingis
modifiedorchanged.Youhavemadeitveryclearinthisarticle.
reply

2.
ShreejiIndustriesOctober10,2015
ExcellentArticlepertainingtoneedoftherevalidationofETOSterilizerprocess,especiallyroutine
measurementofbioburdenmeasurementinsteadofquarterlydone.
reply

3.
GiovanniSanchezFebruary27,2016
WhencalculatetheTCLforapermanentdevice,youshouldusetheresultsoftheexhaustive(24hrs
extraction)oryoucanuseanextratestresultswith8hrsextraction?
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