Home>QualifyingPersonneltoVisuallyInspectCleanedEquipment

QualifyingPersonneltoVisuallyInspectCleaned
Equipment
Theauthordiscussesseveraldifferentapproachesforqualifyingpersonnelforvisual
inspection.
Jan02,2014
ByRichardJ.Forsyth[1]
PharmaceuticalTechnology
Volume38,Issue1
Visualinspectionof
pharmaceuticalmanufacturing
equipmentforcleanlinessis
requiredaftercleaningprocedures
arecompletedandisa
prerequisiteforthestartof
manufacturingactivities(1).
Cleaningvalidationdemonstrates
thatthecleaningprocedure
reliablyandconsistentlycleans
pharmaceuticalmanufacturing
equipmenttoanacceptablelevel.
Visualinspectionisanactive
4XIMAGE/GETTYIMAGES
observationofthevisually
accessibleproductcontact
surfacesofthepharmaceuticalmanufacturingequipment.Thevisualinspectionmust
determinethattheequipmentisfreefromanyvisibleresiduesforthecleaningtobe
consideredadequateandtoallowmanufacturingactivitiestocommence.Although
theremaybeothermeasuresofadequateequipmentcleaning,suchasswab
sampling,visualinspectionisthefirstmeasureofequipmentcleanliness.
Visualinspectionsareconductedbyavarietyofsitepersonnel.Equipmentcleaning
personnelroutinelyinspectequipmentduringamanualcleaningprocedureandafter
completion.Theyinspectpartsthathavebeencleanedinapartswasher.They
inspectlargeequipmentaftermanualcleaningorcleaninplace(CIP)procedures.
Finally,theyinspectclosedsystemequipmentthatiscleanedusingacleaningskid
thatpumpscleaningagentsthroughpipingtotheequipment.Equipmentcleanliness
isdocumentedinthecleaningrecordfortheequipment
Inadditiontotheequipmentcleaningpersonnel,visualcleanlinessofcleaned
equipmentisroutinelyconfirmedanddocumentedinthecleaningrecordbya
secondperson.Priortomanufacturingofthesubsequentbatch,equipmentis
routinelyinspectedforvisualcleanlinessbymanufacturingpersonneland
documentedinthemanufacturingbatchrecord.Qualityandvalidationpersonnel
alsoinspectcleanedequipmentperiodicallyaspartoftheirworkfunction.
Trainingofpersonnelforvisualinspectionofcleanedequipmenthistoricallyhas
consistedofonthejobtrainingconductedbyexperiencedpersonnel.
Documentationofthetrainingwastypicallynotinaunique,separatetrainingrecord,
butaspartofgeneraltrainingforcleaning,operations,orquality.
Aspartofacleaningvalidationprogram,personnelwhotakeswabsampleshave
beenroutinelyqualifiedtodeterminethattheycanadequatelyrecoverresiduesfrom
equipmentsurfaces.Laboratorypersonnelarequalifiedfortestingofthecleaning
samples.Cleaningandtestingproceduresarevalidatedtodemonstrateconsistent
execution.Aqualificationcriterionforvisualinspectionofcleanedequipmentby
personnelisalogicalextensionofthisphilosophyaspartofacleaningvalidation
execution,andqualificationofallpersonnelthatvisuallyinspectcleanedequipment
wouldbeanexpectedoutcome.
Implementationofavisual
inspectionqualificationprogramata RELATEDCONTENT
sitepresentssomelogistical
complications.Qualificationof
RuggednessofVisibleResidueLimitsfor
validationpersonnelforcleaning
Cleaning(PartII)[2]
validationproceduresisusually
conductedforasmallgroupandcan
bedoneinalaboratorysetting.For
RuggednessofVisibleResidueLimitsfor
qualificationofallnecessary
Cleaning(PartIII):VisibleResidueLimitsfor
personnelforvisualinspection,
DifferentMaterialsofConstruction[3]
however,itwouldbemorepractical
tobringthevisualtestingtothe
MoreGMPs/ValidationTopics[4]
personnelinageneralmeeting
roomortrainingarea.Aviewing
stationwiththedriedsamplesmountedforviewingdisplayedonatableorhungona

wallwouldbeideal.
Qualificationparameters
Testingparametersforvisualinspectionqualificationshouldbebasedonthe
viewingparametersofcleanedequipmentatasite.Forequipmentthatismanually
cleanedorcleanedinapartswasher,inspectionsaregenerallyinthe12ftrange.
Theviewingangleisunrestricted,andtheinspectionisconductedunderambient
light.Forlarger,stationary,CIPequipment,theviewingdistanceisincreasedthe
viewinganglewillberestricted,andthelightinglevelcouldbelowerontheinterior
surfacesofthecleanedequipment.Anevaluationofthesiteequipmentandfacility
shoulddrivetheviewingdistance,viewingangle,andlightingconditionsofthe
viewingparametersforvisualqualification.Suggestedparameterguidelinesinclude:
<10feetviewingdistance>30viewingangleand>200luxlightinglevel(2).
Thematerialsofconstruction(MOC)forthevisualinspectionqualificationshouldbe
themostprevalentMOCatthesite,whichinmanycaseswillbestainlesssteelas
showninFigure1.OtherrepresentativeMOCcanbeincludedasdeemed
appropriate,andtheirviewingcharacteristicsshouldbeconsidered.Theoptimal
viewingparametersforglass,forexample,provideadditionalchallengesforavisual
inspectionqualification(3).Optimalviewingconditionsforglassinvolveholdingthe
glassandlookingthroughitataslightlyoffsetanglefromthelightsource.OtherMOC
suchasTeflon,whichmakeitmuchmoredifficulttodiscernresidues,arenotvalue
addedforvisualinspectionqualification.TheseMOCsneedtobeaddressedina
differentformat,suchascleanability.ConcernsforvisualinspectionofMOCneedto
beaddressedeitherexperimentally(4)orduringonthejobtraining.

Figure1:Usingcouponstorepresentequipmentmaterialsofconstruction
forvisualqualification.
Theresiduesforvisualinspectionqualificationshouldincludeallproducts
manufacturedatthesite.Asubsetofthesitesproductportfolioresiduescanbeused
withjustificationbasedonexperimentalevidenceofsimilarityofresidueappearance.
Ifavailabledatashow(5)thattheVRLoftheAPIisaslowasthatoftheformulation,
thenAPIresiduesamples,whichareofteneasiertoprepare,couldbeusedforthe
qualification.Theresiduestestedforthevisualinspectionqualificationshouldbe
indicativethatthequalifiedinspectorwillbeabletodetectresiduesonthe
manufacturingequipmentduringavisualinspectionbothaftercleaningandagain
beforemanufacturing.
Theresiduelevelsforvisualinspectionqualificationshouldbebasedonthevisible
residuelimits(VRL)oftheAPIsorproductsinthesitesmanufacturingportfolio.Ata
minimum,theVRLmustbeestablishedforalloftheproductsmanufacturedatthe
siteusedforqualification.AmorethoroughevaluationwouldestablishseparateVRL
forallproducts,APIs,excipients,anddetergentsusedinmanufacturingorcleaning
atthesite(5).
Approaches
Thereareseveralalternativeapproachesforqualificationofpersonnelforvisual
inspection.Thefirstandmostobviousoptionistopresentstainlesssteelcoupons
spikedwithanumber(e.g.,10)ofrepresentativeproductsattheVRLmixedinwith
anequalnumberofblank,unspikedcouponsandpresentedinarandomorderfor
qualificationasshowninFigure2.Thenumberofproductswoulddependonthesite
productportfolio,butideallyallproductsresidueswouldbepresented.The
personnelwouldeitherseetheresidueonthespikedcouponsornotseeresidueon
theblankcoupons.Theadvantageofthisapproachisthatitisthemoststraight
forwardandpresentsspikedcouponsandblanksinapassorfailsituation.

Figure2:Visualinspectionqualificationusingrandompresentationof
couponsspikedwithrepresentativeproductsatthevisibleresiduelimit
(VRL).
Thisapproach,however,doesnottrainpersonnelontheappearanceofresiduesas
theirconcentrationnearstheVRL.Personnelundergoingqualificationcould
misidentifyaspikedcouponasblankorablankcouponasspiked.Avariationonthis
approachwouldpresenttheAPIsaswellastheproductsforsituationswheretheAPI
issolelyinvolvedinoneormoreofthemanufacturingstepsorwherethesiteproduct
portfolioislimitedtoonlyafewproducts.AnothervariationcouldincludeVRLson
additionalMOCcoupontypesifthisweredeemednecessary.Finally,asitewitha
limitedproductportfoliocouldpresentmultiplespikedcouponsofthesameproduct
tocompletethequalificationarray.
Asecondalternativewouldbetopresentspikedcouponsindecreasing
concentrationtomimicaVRLdetermination.Thespikedcouponswouldbemixed
withblankcouponsandrandomlypresentedforqualificationasshowninFigure3.
Thisapproachwouldgivepersonnelanideaofwhatresidueslooklikeathigher
concentrationsandthepassorfailcriterioncouldbebasedontheVRLofthe
productorthespikedcouponatthenexthighestleveltotheVRL.Thenumberof
couponsrequiredwouldbemuchgreaterorthenumberofproductstestedwouldbe
limited.AvariationonthisapproachwouldpresenttheVRLcouponsandthe
concentrationsapproximately25%abovetheVRLorpresentthe25%higher
concentrationforqualification.ThisisalowriskapproachwhentheestablishedVRL
issignificantlylowerthantheallowableresiduelimit(ARL)basedonpatientsafety
concerns.

Figure3:Visualinspectionqualificationusingmultiplespikelevelsto
mimicavisibleresiduelimitdetermination.
ThisapproachhasbeenusedtoestablishVRLlevels(6).Couponswerepresented
inbothaserialorderfromhightolowandinarandomorderforVRLdetermination.
Dataconcludedthattheorderofpresentationhadnoimpactontheobserversability
todiscerntheVRL.Theobserversinthatstudy,however,hadpreviousexperience
withVRLdeterminations.
UsingspikelevelsgreaterthantheVRLforvisualinspectionqualification,whether
multipleorsinglelevel,isdifficulttojustifyiftheestablishedVRLsarerugged.VRLs
areestablishedsothatthereisalevelofconfidencethatallpersonnelwillbeableto
seetheVRLlevel.Usingmultipleresiduelevelsforvisualinspectionqualification
clearlyindicatesalackofconfidenceintheestablishedVRLsortheabilityof
personneltodetectthem.
Qualificationacceptancecriteria
Thelogicalacceptancecriteriaforvisualinspectionqualificationisthatthetrainee
identifiesallofthespikedcouponsasvisibleandalloftheblankcouponsasblank.If
atraineemisidentifiesacoupon,eitherspikedorblank,shouldtheynecessarilyfail
thequalification?Foraspikedcoupon,amisidentifiedcouponwouldhavetobe
consideredasaqualificationfailure.Forablankcoupon,amisidentifiedcoupon
wouldnotnecessarilyhavetobeconsideredasaqualificationfailure.Ablank
coupondeemedvisibleisamistakeonthesideofcautionandcouldbetolerated.
Identifyingmultipleblankcouponsasvisiblecouldbeproblematicinthatitmight
leadtounnecessaryinvestigationsintoproperlycleanedequipmentbeingdeclared
notvisiblyclean.Theacceptancecriteriaforvisualinspectionqualificationcould
allowoneormoreblankcouponstobemisidentifiedasvisible.Theacceptable
numberofallowablemisidentifiedblanks(e.g.,03of10blanks)wouldbedecidedat
thesitebasedonariskassessmentoftheVRLruggednessanditsrelationtothe
allowablesafetycleaninglimit.ThegreaterthedifferencebetweentheVRLandARL
levels,thegreatertheassuranceonehasthatvisuallycleanpharmaceutical
manufacturingequipmentissufficientlycleanandthelowertheriskofacleaning
failureasaresultofaninadequatevisualinspection.
Trainingforvisualinspectionqualification
Qualificationforvisualinspectionsofcleanedequipmentisjustonepartofthe
trainingrequiredtoassurereliable,thoroughvisualinspectionofcleaned
pharmaceuticalmanufacturingequipment.AsshowninTableI,adequatetraining
shouldstartwithareviewofthevisualinspectionandthevisualinspection
qualificationSOPs,whichdescribetheprocessforinspectionanddocumentationof
cleanedequipmentandthevisualinspectionqualificationprocessrespectively.If
available,equipmentdiagramsshowingdimensionsandswablocationswith
associatedjustificationcanbereviewedtofamiliarizetraineeswiththe
manufacturingequipmentandproblemareasforcleaning.Priortoqualification,
trainingonVRLdeterminationshouldconsistofseveralexamplesofVRL
determinationsinordertoacquaintpersonnelwiththeappearanceoflowlevelsof
residuesforcleaning.TrainingforVRLsondifferentMOCsshouldbeincludedif
therearemultipleMOCsatthesiteandtheyarepartofthequalification.Ifpersonnel
areinvolvedindeterminationofVRLs,thentheVRLexamplereviewmightnotbe
necessary.AdiscussionoftherelationshipoftheVRLtothecleaninglimitorARL
andtherelationshipofthecleanabilityofthedifferentresiduesfromthevarious
MOCswouldimpartanunderstandingoftheconfidencelevelinthecleaning
procedureandthevisualinspection.Onthejobtrainingshouldconsistofsupervised
inspectionofthemanufacturingequipment,includingthehardtocleanlocationsand
thoselocationsmostlikelytohaveproductbuildup,foreachpieceofcleaned
equipmentasidentifiedforcleaningvalidation.Thefinalstepaftertrainingand
qualificationshouldconsistofamonitoredvisualinspectionofacleanedpieceof
equipment,ensuringthattheproperproceduresarefollowed,athoroughvisual
inspectionisconductedfortheequipment,andthevisualinspectionisproperly
documented.

Step

Training

Reviewstandardoperatingprocedure(SOP)forthevisualinspection
ofcleanedmanufacturingequipment

ReviewSOPforqualificationofpersonnelforthevisualinspectionof
productcontactareas

Reviewequipmentdiagramsshowinghardtocleanareasandareas
ofproductbuildup

Reviewvisibleresiduelimit(VRL)examples

DiscussVRLvs.cleaninglimit

Conductonthejobtraining

TableI.Trainingforvisualinspectionqualification.
Conclusion
Qualificationofpersonnelforvisualinspectionofcleanedpharmaceutical
manufacturingequipmentsproductcontactsurfacesisanecessarycomplementto
bothacleaningvalidationprogramandthemanufacturingoperationsatasite.
Visualinspectionqualificationisjustonefacetofanoveralltrainingprogramto
assurethatpersonnelareequippedtoprovideaconsistent,thorough,andaccurate
evaluationofcleanedsurfacesforongoingpharmaceuticaloperations.
References
1.CFRTitle211.67(GovernmentPrintingOffice,Washington,DC).
2.R.J.ForsythandV.VanNostrand,Pharm.Tech.29(10)152161(2005).
3.R.J.Forsyth,K.Bader,andK.Jordan,Pharm.Tech.37(10)8691(2013).
4.R.J.Forsyth,K.Bader,andK.Jordan,CleanabilityofPharmaceuticalSoilsfrom
DifferentMaterialsofConstruction,inpress.
5.R.J.Forsyth,Pharm.Tech.33(3)102111(2009).
6.R.J.Forsyth,Pharm.Tech.35(3),122128(2011).
AbouttheAuthor
RichardForsythisaprincipalconsultantwithForsythPharmaceuticalConsulting,
907ShamrockCt,Royersford,PA19468,tel.484.535.1688,
forsythpharmaconsulting@gmail.com.
2016AdvanstarCommunications,Inc.Allrightsreserved.Reproductioninwholeorinpartisprohibited.Pleasesendanytechnicalcommentsorquestionstoourwebmasters.

SourceURL:http://www.pharmtech.com/qualifyingpersonnelvisuallyinspectcleanedequipment
Links:
[1]http://www.pharmtech.com/richardjforsyth
[2]http://www.pharmtech.com/pharmtech/article/articleDetail.jsp?id=711294
[3]http://www.pharmtech.com/pharmtech/Analytics/RuggednessofVisibleResidueLimitsforCleaning/ArticleStandard/Article/detail/825126
[4]http://www.pharmtech.com/gmps_validation