11/19/2016 LifeCycleRiskAssessmentofHPLCInstruments

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LifeCycleRiskAssessmentofHPLCInstruments
Feb01,2015
ByPaulSmith[1] ,R.D.McDowall[2]
LCGCEurope
Volume28,Issue2,pg110117

Whatdoesriskassessmentinthecontextofthelifecycleofahighperformance
liquidchromatography(HPLC)instrumentreallymean?Thisinstalmentof
"QuestionsofQuality"willlookatproblemswithanoperationalliquid
chromatographtoseeiftheycanbepickedupintheperformancequalification
(PQ)orpreventedintheoperationalqualification(OQ).Therelationshipbetween
PQandOQandthedesignqualification(DQ)phasesofthelifecyclearealso
explored.

RegulatedGxPlaboratoriesmustqualifytheirchromatographstodemonstratethat
theyarefitforpurpose.Aqualificationprocessbasedonthe4Qsmodelistypically
usedtoqualifyliquidchromatographs.The4Qsmodel,enshrinedinUnitedStates
Pharmacopoeia(USP)<1058>(1)consistsoffourinterlinkedphases:design
qualification(DQ),installationqualification(IQ),operationalqualification(OQ),and
performancequalification(PQ).Wewilldiscusslifecycleriskassessmentofhigh
performanceliquidchromatography(HPLC)instrumentsinthecontextofthe4Qs
model.Inthisdiscussion,wewillnotconsiderchromatographydatasystems(CDS)
butthereistheunderlyingassumptionthattheinstrumentiscontrolledbythis
software.

WewilllookatlifecycleriskassessmentofHPLCinstrumentsfromtheperspectiveof
whatcangowrongwithaqualifiedliquidchromatographduringtheoperational
phase(PQphase).Howcanidentificationofproblemsherebeusedtohelpus
manageandmitigateriskinotherphases?Fromthisperspectivewewilllookathow
systemsuitabilitytestsandtheirlinkagebetweenDQandOQcanmitigatesome,but
notall,theinstrumentproblems.

PerceptionsofRiskAssessment

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Overthepastdecade,riskmanagementandriskassessmenthavebecomepartof
thepharmaceuticallexicontheyarethesubjectofanICHQ9paperonqualityrisk
management(2).However,whatdoesthismeanforregulatorsandtheindustry?

Fromtheregulator'sperspective,industryshouldundertakeriskassessmentsto
identifythemostcriticalpartsofanactivityorprocessandfocusmitigationefforts
there.Itisameansofputtingscarceresourceswheretheyaremostneededandof
identifyingimprovementsinqualityriskmanagement(3).Generally,fromthe
industry'sperspectiveitcanbeameanstojustifydoingless.Wewillexploresomeof
thesepointsinthiscolumn.

WhatCanGoWrong?

FeaturesthatcangowrongwithanoperationalHPLCsystemisthestartingpointfor
ourdiscussion.ThisisillustratedinFigure1wherealiquidchromatographconsists
offourmodules:pump,injector(autosampler),columnoven,andthedetector.We
haveomittedthecolumnfromthefigureasouraimistolookatanLCinstrument's
qualificationratherthanmethodperformance.Underneatheachmodulearelisted
themainfailuresthatcouldoccur.Notethatthislistisnotexhaustiveandsomeofthe
failurescouldbebrokendownfurther.However,tokeepthediscussionsimplewe
havedecidedtolookatthisproblemfromahighlevelperspective.Somefailures
maynothappeniftheinstrumentinyourlaboratorydoesnothaveaparticular
feature,forexample,foranisocraticpumptherewillnotbegradienterrors.

Figure1:HPLCinstrumentshowingthepossiblefailuresforeachmodule.

Nowwehavelistedthemainfailures,weneedtoconsiderthecircumstancesunder
whichthesemightbedetectedinaOQorPQ,asshowninTable1.ThePQisbroken
downintothreeareas:systemsuitabilitytest(SST),aninstrumentdetectingthe
problem,andagroupcalledextraSSTwhereparameterscanbemeasuredifthe
SSTisdesignedtoincludethem.

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Table1:PossibleLCinstrumentfailuresandtheabilitytodetecttheminoperationalqualification
(OQ)orperformancequalification(PQ).

WhatisanInstrumentPerformanceQualificationPart1?

Asourdiscussionisfocusedontheoperationalphaseofaninstrumentlifecycle,we
alsoneedtoconsiderthePQ.OneofthecurrentambiguitiesassociatedwithUSP
<1058>relatestoOQandPQ.Specifically,whattheyshouldcontainandwhohas
responsibilityforthem?Historically,beforeUSP<1058>wasfirstimplementedin
2008,the1987USFoodandDrugAdministration(FDA)guidanceforprocess
validation(4)wasadaptedandappliedtoanalyticalinstrumentqualification.This
guidancewasinterpretedindivergentwaysbylaboratoriesandserviceproviders.
Thisdivergenceisrecognizedin<1058>,whichstatesintheinformationunderTable
1(1):

Performingtheactivityisfarmoreimportantthanthephaseunderwhichtheactivityis
performed.

Andelsewhere:

Whenaninstrumentundergoesmajorrepairsormodifications,relevantOQand/or
PQtestsshouldberepeated[so,inthiscontext,OQandPQmightbeconsidered
interchangeable].

However,USP<1058>alsoprovidesthefollowingdefinitionsofOQandPQ:

Operationalqualificationisthedocumentedcollectionofactivitiesnecessaryto
demonstratethataninstrumentwillfunctionaccordingtoitsoperationalspecification
intheselectedenvironment.

Performancequalificationisthedocumentedcollectionofactivitiesnecessaryto
demonstratethataninstrumentconsistentlyperformsaccordingtothespecifications
definedbytheuser,andisappropriatefortheintendeduse.

Therefore,althoughthereisambiguity(andfromtheexperienceoftheauthorsquite
alotofuncertaintyinlaboratories),anOQandaPQservecompletelydifferent
functions.

TheOQisrelatedtotestingtheinstrumentunderstandardizedconditionsso
thatthecorrectoperationoftheinstrumentinthelaboratoryversustheDQ
canbeconfirmed.
ThePQaddressesthesuitabilityoftheinstrumentunderactualconditionsof
useinbetweenrepetitionoftheOQ.

ThepotentialroleofSSTinPQhasbeendiscussedpreviouslyinthiscolumn(5).
Partofthechoicethatsomelaboratoriesmaymakerelatestotheconditionsunder

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whichanOQoraPQmayberequiredtoberepeated.Intheopinionoftheauthors,
anOQandaPQmustbeperformedonany"new"instrumentbeforeitisusedto
generateGxPdata.WithinstrumentationpurchasedforGxPuse,thesuitabilityofthe
instrumentfortheworkitwillbedocumentedinitiallyintheDQ.Thiswilldefinethe
intendeduseoftheinstrumentandwhentheOQisperformedwillshowwhythe
instrumentisfitforpurpose.

ADifferentViewofthe4QsModel
Typically,theinstrumentqualificationlifecycleisdepictedorimpliedasalinear
model,especiallyinUSP<1058>(1)whereitispresentedinatable.However,to
fullyunderstandthe4Qsmodelitisbetterifthefirstthreephasesarepresentedin
theformofaV,asshowninFigure2.

Figure2:Depictionofthe4QsmodelasaV.

InthissimplifiedVmodel,itismucheasiertoseetherelationshipbetweenthe
stagesofthe4Qs.TheOQverifiesthespecificationasoutlinedinthedefinitionofOQ
inUSP<1058>(1)providedwhoeverperformstheOQknowsthecontentofthe
DQorthattheDQhasactuallybeenwritten.

Thereisalsoanongoing,dynamic,requirementtomanagetheDQ.Thisisinpart
dependentonhowtheDQisdefined(forexample,ifthisreferencesaveryspecific
pharmacopeiarequirementorchaptertheneachtimethepharmacopeiaisupdated
theDQfortheinstrumentwillneedtobereviewed).Instead,itismoreefficientto
addressanyhighlevelcomplianceintheproceduresthatsupporttheDQandtolimit
theDQrequirementstoinstrumentusage(rememberthatwearefocusingonlyon
theinstrument).

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Thisdiagramalsohighlightsthatwhereaninstrumenthasamajorupgrade(because
thereisawidedivergenceofopinionthisislefttoanindividuallaboratorytodefine)
orisusedwithnewmethodsnotpreviouslyconsidered,thereisaneedtoreviewthe
DQforsuitability.Withoutthisfeedbackloop,thereisarisktheinstrumentisnot
suitableforanewapplication.Inaddition,becauseoftherelationshipbetweenthe
DQandOQ,itwillalsohighlightifdifferentsetpointsneedtobeincludedintheOQ
totesttherangeofuse.IntermsofourdiscussionofrisktheOQcancover:

Qualificationofanewinstrument
Requalificationofanexistinginstrumentfollowingadefinedtimeperiod
typicallylinkedwithapreventativemaintenanceservice
Requalificationfollowingamajorrepair
Extendingtheoperatingrangeofaqualifiedinstrumentbecauseofan
upgradeornewapplicationthatoperatesoutsideoftheexistingrange
Significantmoveofaqualifiedinstrumentwiththejustificationfortheextentof
OQtestingdocumentedinariskassessment.

TheOQisintendedtodemonstratethatatafixedtimepointtheinstrumentoperates
tothespecificationsintheDQandcanthereforedemonstratethatitmeetsthe
intendedpurpose.AtthispointitisworthrepeatingthestatementfromUSP<1058>
thatroutineanalyticaltestsdonotconstituteOQtesting(1).

WhatisanInstrumentPerformanceQualificationPart2?
LetusreturntotheOQversusPQdiscussion.ThedifferentrolesofOQandPQneed
tobefulfilledandsupportedonanongoingbasisduringthelifetimeoftheinstrument
andthereareoptionsforhowthiscanbeachieved.SummarizingfromUSP<1058>
(1)foranHPLCinstrument,PQtestsshould:

DefineuserspecificationsforPQteststodemonstratetroublefreeinstrument
operationfortheintendedapplications.
Verifytheacceptableperformanceoftheinstrumentforitsintendeduse
(parameterslistedinTable1underExtraSST).
Betypicallybasedontheapplicationsoftheinstrumentinyourlaboratory.
Bebasedongoodscienceandreflectthegeneralintendeduseofthe
instrument.
Beperformedconcurrentlywiththetestsamples(SST)todemonstratethat
theinstrumentisperformingsuitably.

ThereisadirectrelationshipbetweentheDQandPQbecausethelatterneedsto
demonstratethattheongoinginstrumentoperationisconsistentwiththeintended
userequirementsintheformer.

OneoftheOQversusPQuncertaintiesrelatestodefininghowoftenqualification
functionsshouldbeperformedduringthelifecycleoftheinstrumentandwhat
triggersqualificationrequirements.Intheabsenceofblackandwhiteguidance(in
USP<1058>[1],GAMP[6],orother),generallyforHPLCsystems,annual
requalificationisoftenperformed,andthistiestheinstrumentmaintenancetothe
qualificationwork.Oneconsequenceofthistieinisthepotentialperceptionthatan
instrumentmayhaveafaultcorrectedduringmaintenancethatwasnotpreviously

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detected,butbecauseofthemaintenance,thisfaultiscorrectedandthereforenot
evaluatedinthesubsequentqualificationtestingordetected.

Insomeinstances,thishasresultedinadiscussionof"asfound"measurement
(testinganinstrumentparameterbeforeanyadjustmentsaremade),particularly
wherealaboratorymayusethewordcalibrationasadescriptivelabelforthe
qualificationwork.Thisquestionisattheheartofthispaperandtheconsiderationof
howaninstrumentmightfailandifthatfailureisdetected.But,beforeconsidering
thisfurther,itisfundamentalthatanyregulatedlaboratoryunderstandstheplanned
maintenanceworkperformedandexactlywhatwasdone.

MostHPLCmaintenanceworkisassociatedwithwearrelatedtousageand
thereforethemaintenanceproceduredefinesreplacementofconsumablepartssuch
aspumpseals.Anyotherpartreplaced(suchaspumppistonsfollowingavisual
inspection)arelistedintheservicereport(typically,becausetheyarechargeablebut
thisdependsonthecontract).Firmwareupgradesmustbepreapprovedbefore
installationandariskassessmentcarriedoutusingtheavailableinformationfrom
themanufacturerorserviceagenttodeterminethelevelandextentofrequalification.
Inaddition,anytestingperformedduringpreventativemaintenance(PM)and
visibilityofanytestfailureshouldbeincludedinthePMreportandthelaboratory
shouldactonthisinformation.Typicaltestsmightincludeleaktestsortemperature
testsbutthiscanbedependentontheinstrumentmanufacturerorserviceprovider.
Alwaysensurethattheworkperformedduringaplannedmaintenanceorinstrument
repairisfullydocumentedandunderstoodbeforebeingsignedoff.

Withthisinmind,theriskthatanyPMactivitywillcorrectafailurebeforeitisdetected
isusuallysmall.Therefore,requestsforanasfoundtestforaninstrumentas
complexasanHPLCsystemaremeaninglessbecausethereisvisibilityofwhatwork
isperformed,whattestsaredone,andtheoutcomeofthose.Infact,theonlywayto
providea100%checkwouldbetoperformaprePMOQ,thenaPM,thenapostPM
OQ,whichisnotthesmartestwaytowork!

LeanSigmaVersusScientificallySoundSSTs
Itisalwaysgoodtochallengeabusinessprocessbuttodoitwithoutfullknowledge
oftheregulationsisfoolhardy.Sometimesthisiswhereriskmanagementfallsinto
theClintEastwoodcategoryof"I'mfeelinglucky".Afacilitatorwillchallengewhatis
doneandwilltypicallyask"Wheredoesitsaythatintheregulations?"Sometimes
thiscanvergeonaninterrogationandfailuretoidentifyaregulatoryrequirementcan
resultinataskbeingdiscarded.

Takeanassaywhereeachinjectiontakes30minandthesystemsuitabilitytest
includes5replicatestandardinjectionsandablanksample:Wheredoesitexplicitly
sayineithertheGMPregulationsorthepharmacopoeiasthatyouneedablank?
Nowhere.Theresultisthattheblankinjectioncanendupbeingdiscarded,savinga
vital30min.Highfivesallaround!

BUT....Haveyoureadtheregulations?USGMP(21CFR211.160[a])requiresthatall
activitiesbescientificallysound(7)USP<1058>(1)requiresaPQtesttobebased
ongoodscience,asnotedabove.Isablankinjectionofanyvalue?Moreimportantly,
isitscientificallysound?Ablankinjectioncandeterminethebaselineflatnessand

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noiselevelandifthereisanycarryoverfromtheautosampler(seeTable1).Yes,you
candroptheblankinjection,butifproblemswerefoundbeforethesampleswere
committedthiswouldsavemuchtimelaterinlaboratoryinvestigationsbutonlyif
youhaveablanksampleintheSST.

Letusbeclearhere,ifyouaregoingtoredesigntheprocessitisimportantto
understandtherisksthatyouwillcarrywheneliminatingtasks.Saving30minfora
singleinjection(whichinallprobabilityisminimalasmostoftheLCinjectionsoccur
overnight)needstobeweighedagainstthetimespentonlaboratoryinvestigations
lookingforanassignablecauseaftertheruniftherunfails.Similarconsiderations
needtobemadefortheinclusionofanapprovedandwellcharacterizedcontrol
sample,particularlyforimpuritycharacterization(11).Itisnotuncommoninapost
leanlaboratoryforchromatographicmethodsnottoincludeastandardtoserveasa
comparisonfortherun.Giventhefactthatchromatographyisacomparative
analyticaltechnique,thiscouldbeseenasstupidityonstilts.Thechoiceandtherisks
youcarryormitigateareyours.Areyoufeelinglucky?

AssessmentofOngoingInstrumentPerformance
DesignedtosatisfypharmacopeiarequirementssuchasUSP<621>(8),SSTsplaya
pivotalroleindocumentingtheperformanceofthechromatographysystem(atthe
analyticalrunlevel).AnaturalevolutionofthisistoconsiderhowSSTscansupport
ongoingPQrequirements(aftertheinitialPQtomovetheinstrumentintothe
operationalphase).Previousconsiderationofthis(5)identifiedthatadditionaltests
needtobeaddedtothoseroutinelydefinedinUSP<621>(8).Thisrequirementhas
notchanged,butconsiderationofthewaysaninstrumentmightfailaddsadifferent
perspective.Thiscanpotentiallybequiteapainfulprocess,becausetheimplication
isthatinthepostleanlaboratorytheremaybesomefailuresthatarenotcurrently
detected.Attheheartofthisdocumentisthequestionhowmightaninstrument
failandwouldthatfailurebedetectedinyourlaboratory?

Inpractice,thisapproachmeansthatlaboratorieshavetoreviewtheinformation
showninTable1(howaninstrumentmightfail)againsttheSSTstheycurrently
includeintheirchromatographicmethods(forexampleattheSSTsdefinedineachof
theiranalyticalmethods).Oneofthecorestrengthsofthisfundamentalapproachis
thatitevolvesthethinkingwithinthelaboratorymanagementawayfromleanand
backtowardsscientificallysound.Inparticular,inanerawhereregulatorssuchas
theFDAareconsideringdataintegrityfromafraudulentpracticesperspectiveyour
approachshouldbedefendablefrombothascientificsoundnessanddataintegrity
perspective.Thisthoughtprocesshelpslaboratoriestoidentifypotentialgapsintheir
regulatorydefence.So,insteadofthinkingpurelyfromatheoreticalperspective:
"Whatwouldhappenif",makethesituationreal:"Ifthishappened,whatwouldthe
potentialperformanceimpactbeandhowwouldwedefenditinanaudit?"

TheOQcolumnofTable1showsthattheOQshouldbedesignedtoevaluateand
detectallthesepotentialhighlevelfailuremodes.However,inoperationaluse,some
ofthefailuremodesmaynotbedetected.Itisinpartdependentonhowthe
laboratoryisusingtheinstrument(forexampletheinstrumentshouldinitiatea
wavelengthdiagnosticcheckwhenturnedon,usingwellcharacterizedlamp
emissionlines,soistheinstrumentturnedoffandon?).Whileothers,suchasthose
whichmightbedetectedbyretentiontimedifferences(flowrateandtemperaturefor

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example)aredependentonchromatographypracticeswithinthelaboratory(for
example,formalizingacceptancecriteriaassociatedwithpeakidentification
windows).

Ultimately,ongoingmonitoringofSSTs,includinganyadditionalrequirements
identifiedtohelpdetectfailuremodeslistedinTable1,mustbeintegratedintothe
controllingCDSsoftware,sothatitcanbeperformedandtrendedinasemi
automatedmanner.PeriodicreviewofthisSSTdatawouldthensupportcompliance
withtherequirementsofFDAdraftguidanceonmethodvalidation(9)and,inpart,be
analogoustoperiodicreviewrequiredforsoftware.

Anotherbenefitofdevelopingthisapproachisthatitprovidesariskframeworkthat
canbeappliedtosupportadditionalcompliancedecisions,suchasmovingfrom
maintenanceorqualificationbasedonafixedannualrequirement,towards
compliancemodelsthatcouldbebasedonusage.Thishasbeensuccessfully
appliedoutsideofthelaboratoryarea(10),becausethemethodbasedrisk
assessmentframeworkalreadyconsidersfailuremodesandthedetectabilityof
potentialfailure.

Carealsoneedstobetakenwithinjectingsamplestoevaluatetheperformanceofa
chromatographbecauserecentFDAguidance(11)wantstoavoidusingsample
injectionsasameansoftestingintocompliance.Thereforeallworkneedstobe
includedindocumentedproceduresandthegenerateddatareviewed(11).

WhatDoIDoWhen...?
Whenaninstrumentfaultisdetected,theinstrumentmustberemovedfromservice
(topreventusebyanotheranalyst)andthelaboratoryprocedureforconsideringthe
potentialimpactoftheinstrumentfailureonpreviousanalyticalresultsinitiated.
Typically,theinstrumentisrepairedandanappropriatelevelofrequalificationwork
mustbeperformedbeforeitisreturnedtouse.

Dependingontheservicecontractforaninstrument,minorrepairscouldbe
performedbylaboratorypersonnel(forexample,changeseals,checkvalvesor
lamp),whilemajorrepairsaretakenonbytheserviceagent.Regardlessofwho
doesit,itisimportantthataconsistentapproachisappliedtoanyrequalification
workdonefollowingrepairandbeforetheinstrumentisreturnedtouse.Sometimes,
minorrepairsperformedbythelaboratorymighthaveadifferentapprovalprocessto
majorrepairsperformedbytheserviceagentandthisrepresentsapotentialrisk.
Inconsistencyisalwaysanareaoffocusduringanaudit.

Aqualificationtestmatrix,eitherinthelaboratoryorserviceagentsdocumentation,
shouldbeapprovedthatdefinesandliststheinstrumentrepairsperformedandthe
requalificationworkrequiredforthechromatograph.Withoutthis,inprinciple,a
laboratorymightbeexpectedtoperformafullinstrumentrequalificationifthepump
sealsarereplaced,whenapumpflowtestisallthatisrequired.Ifanyrepairworkis
performedthatisnotdetailedintherequalificationtestmatrix(whichessentiallypre
approvesthequalificationwork),thentheserviceagentmustagreethere
qualificationworkperformedwiththecustomer.Formajorrepairsitcanbemore
efficientfromadecisionmakingandworkflowperspectivetoperformafull

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requalification,becausethetimetodiscuss,agree,andjustifyanythinglesscan
extendtheinstrumentdowntime.

OperationalQualification
ThedefinitionofOQfrom<1058>waspresentedearlier,andtheopinionofthe
authorsisthatthisdefinitiondoesnotrequiremodification.TheOQphaseprovidesa
controlledwayoftestingtheperformanceoftheinstrumentandtheintendeduse(for
example,the"setpoints"neededtocovertheintendedrangeofuse).Fortestssuch
astemperatureandflow,thesecanbemeasuredasmetrologytestsusingan
appropriatelycalibrateddevice,whileothertestsincludetheuseofareference
materialandaremoreholisticintheirnature.Generally,wavelengthisevaluated
usingasuitablereferencematerialsuchascaffeineorholmiumoxideinperchloric
acid.Thismeansthatthewavelengthsthatcanbeevaluatedaredependentonthe
availabilityofsuitablereferencematerials,whichcancauseaproblemforusersof
detectorswhohavetooperateat200nm,5nmbelowthe205nmpeakofcaffeine.
Here,ajustificationisrequired,whichthesupplierorserviceprovidermaybeableto
helpwrite.

TheOQteststhefunctionaloperationoftheinstrumentunderstandardconditions,
whichshouldmatchtheoperationalrangeofuse.Sometests,suchasinjection
precision,areincludedintheOQ,thePQ,andongoinginstrumentperformance
evaluation(SST).Thereisanimportantdistinctiontobemadehere,becausesome
tests,suchasinjectionprecisionandcarryover,areapplicationspecific.Therefore,
thelimitsappliedintheOQarerelatedtothestandardizedmethodusedtomeasure
thisintheOQ,whileanyinjectionprecisionlimitsappliedwhicharerelatedtothe
analyticalmethodsarebestevaluatedinthePQandongoingSSTrelatedtothe
pharmacopeiarequirements(8).WhereaPQisperformed,thechromatography
methodusedshouldberelatedtothemethodsandapplicationsappliedinthe
laboratory.NotethatthiswouldalsobeafeedbacktotheDQ.

UnderstandingtheclearanddistinctroleoftheOQandPQrelativetotheinstrument
useisfundamentaltogoodcompliancepracticeandrobustinstrumentdefence.
Whereareferencematerialisused,thisshouldbetraceableandappropriateforthe
intendedusethereshouldbedocumentedjustificationofthesuitabilitywhena
methodthatisnewtotheinstrumentissetup,thisshouldbeanautomatictriggerto
reviewtheDQtoOQlinktodecideifdifferentsetpointsarerequired.

Summary
RepresentingthelifecycleprocessasamodifiedVmodelmoreclearlyillustratesthe
relationshipbetweenthestagesofthe4Qsmodelandmakesitconceptuallysimpler
tounderstand.Inparticular,thatthelaboratorydefinestheusageoftheinstrumentin
theDQstageandthatthisistestedattheOQstageusingstandardizedmethods
whichcouldpotentiallybeindependentofthemakeandmodeloftheinstrument.The
methodsandrangeofoperationdefinesthesetpointsthatneedtobeconsideredso
thattheOQteststherangeofuse.Therefore,ifmethodsarechangedoradded,this
becomesanautomatictriggertoreviewthecurrentDQtoOQrelationshipany
differentwavelengths,temperatures,orflowinthenewmethodstriggeranupdateto
thestandardizedqualificationtestssetpointsintheOQ,sothattheOQisnotstatic
butdynamicallyconfiguredtosatisfytheongoingOQrequirementsofthelaboratory.
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Theprotocolapprovalprocessneedstobeappropriatelystructured(applicationof
LeanSigmaprinciples)tosupportamoredynamicandresponsiveapproach.

Thedetailsoftheriskassessmentconsideringhowaninstrumentfailuremightbe
eitherdetectedand/ordefended,hastobeperformedinthelaboratory,againstthe
actualSST'sandworkingpracticescurrentlyusedinthelaboratory.Onthefaceofit,
thisapproachmayseemlikealotofworkwithlittlebenefit.However,oncethework
isdone,theongoingmanagementoftheriskbasedmatrixismuchsimplerandthe
benefitsincludethedevelopmentofstrongercompliancedefenceinthelaboratory,
bothintermsofjustificationofthepotentialimpactofaninstrumentfailureonresults
andreductionofrisksbecausethepossibilityofanundetectedinstrumentfailurehas
beensignificantlyreduced.Atatimewhenregulatorsacrosstheglobearefocusing
ondataintegrityandexchangingauditriskinformation,thishastobeagoodthing.

Finally,byaugmentingtheSSTsdefinedinUSP<621>(8),theSSTscanbeusedto
supportthedemonstrationoftheongoingconsistentperformanceoftheinstrument
(PQ)ratherthanbeingusedtotestcompliance(11).

PaulSmithisGlobalStrategicComplianceProgramManageratAgilent
Technologies.Afterinitiallyspecializinginspectroscopyandapplicationof
chemometricstospectroscopicdata,Pauldevelopedhiscomplianceexpertiseina
varietyofqualityandmanagementroleswithinthe17yearshespentinthe
pharmaceuticalindustry.Paulworkedasanindependentconsultantanduniversity
lecturerbeforemovingintolaboratorycomplianceconsultancyandproductivityroles.

"QuestionsofQuality"editorBobMcDowallisDirectoratR.D.McDowallLtd,
Bromley,Kent,UK.HeisalsoamemberofLCGCEurope'seditorialadvisoryboard.
Directcorrespondenceaboutthiscolumnshouldbeaddressedtotheeditorinchief,
AlasdairMatheson,atamatheson@advanstar.com[3]

References
(1)UnitedStatesPharmacopeia,<1058>,AnalyticalInstrumentQualification.

(2)ICHQ9QualityRiskManagement,step4,2005(www.ich.org[4] ).

(3)KevinO'Donnelletal.,PDAJPharmSciandTech66,243261(2012).

(4)FDAGuidanceforIndustryGuidelinesonGeneralPrincipalsofProcess
Validation,May1987.

(5)LukasKaminskietal.,LCGCEurope24(8),418422(2011).

(6)GAMPGoodPracticeGuide,ARiskBasedApproachtoGXPCompliant
LaboratoryComputerizedSystems,(SecondEdition,ISPETampa,Florida,USA,
2012).

(7)CodeofFederalRegulations,21CFRpart211.160(a).

(8)UnitedStatesPharmacopeia,<621>,Chromatography.

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(9)FDADraftGuidanceforIndustryAnalyticalProceduresandMethodsValidation
forDrugsandBiologicals,SectionVIIILifeCycleManagementofAnalytical
Procedures,February2014.

(10)I.H.Afefy,Engineering2,863873(2010)

(11)Item7,
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
[5]

2016AdvanstarCommunications,Inc.Allrightsreserved.Reproductioninwholeorinpartisprohibited.Pleasesendanytechnicalcommentsorquestionstoourwebmasters.

SourceURL:http://www.chromatographyonline.com/lifecycleriskassessmenthplcinstruments

Links:
[1]http://www.chromatographyonline.com/paulsmith
[2]http://www.chromatographyonline.com/rdmcdowall
[3]mailto:amatheson@advanstar.com
[4]http://www.ich.org/
[5]http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm

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