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CAPA and Root Cause Analysis

RecentFDAWarningLettershavecitedinsufficientcorrectiveandpreventiveaction(CAPA)programs
asmajorcomplianceweaknesses.HowdoesoneensureonesCAPAisontherighttrack?Doug
BartholomewinterviewsindustryQAprofessionalsandleadingconsultantsfortheanswers.
ByDougBartholomew,ContributingEditor
Jul20,2006

Investigatingthecauseofaqualityfailureorotherproductionproblemissomethingthatallpharmaceutical
companiesmustdosomemorefrequentlythanothers.Themorecomprehensiveandstructuredthe
investigationprocessis,themoreeffectiveitwillbe.
Thatstheconsensusofconsultantsandotherexpertsinthecorrectiveandpreventiveaction(CAPA)field.While
CAPAishandleddifferentlyatmanypharmaceuticalmanufacturers,bestpracticesforhandlingcomplaintsand
investigationsrevolvearoundcertaincoreactivities,abasicprocessand,moreoftenthannot,someenabling
technology.
TheCAPAcomplaintrootcauseinvestigationprocessisparamount.HavingasuccessfulCAPAismoreacultural
thingforacompanythanmerelyhavingthetechnologyforCAPA,saysSimonJacobson,researchanalystfor
manufacturingoperationsatAMRResearchinBoston.
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InJacobsonsview,mostlargepharmaceuticalcompanieshavemoretroublebreakingdownthesilosinwhich
theymighthaveseveraldifferentCAPAprocessesandtechnologiesbeingusedindifferentdepartmentsand
plantstoachieveasinglemanagedviewoftheprocess.Manypharmaceuticalcompanieshaveinstalledseveral
CAPAsolutions,butthereisnocommonwayforthemtodotrendingandputpreventiveactioninplaceacrossthe
company,hesays.
Surprisingly,smallerpharmaceuticalfirmsoftentakeamoresystematicapproachtohandlingCAPAcomplaints
thanlargercompanies.Atsinglesiteoperations,peoplearemoreinclinedtoworktogether,sothat,forinstance,
theR&Dchiefknowsthemanufacturingguy,Jacobsonobserves.Butwiththebiggercompanies,therearemore
silosandthereisagreaterneedforacommon,systematicapproachtoCAPA.
Often,CAPAproblemscanbetracedtothelackofconsistentprocessrequirementsandwrittenprocedures.
Becauseoftheseinconsistenciesacrosssites,companiesmayhavetochasethesamecomplaintatmultiple
facilities.T hisispreventingorganizationsfromhaltingwhatcouldbesystemicinefficiencies,Jacobsonsays.In
addition,hesays,T helackofanorganizationwidesystemicmanagementprocesspreventsacompanyfrom
successfullyauditingtheirprocessesandtakingeffectivepreventiveactions,suchastrendingacrossmultiple
sites.
The four-step method
Inmostcases,aCAPAinvestigationissetinmotionbyaneventeitheralaboratoryinvestigation,a
manufacturinginconsistency,aregulatoryorinternalaudit,oracustomercomplaint.Anyoftheseinvestigation
recordsareenteredintoaCAPAsystem,whichcanspawnarelatedCAPAinvestigation,explainsRobert
Fetterman,presidentofTechnicalBusinessSolutions(RoyersFord,Pa.).
hemajorityofcompaniesinitiatetheirCAPAprocessesonceacomplaintorfieldfailureisdiscovered,says
T
AMRsJacobson.T hisisnotonlytoolatebecausethepatientisalreadyatrisk,butcompaniesarehardpressed
tocomplywiththeFDAsCAPArequirementsbecausetheylackinsightintotherootcauseofthedevice
malfunction.
TheCAPAprocess,ofcourse,isbroaderthanjusttheinvestigationofcomplaints.Butinvestigationoftheroot
causeofproblemsliesatitscore.AsJacobsonsays,AttheheartofasuccessfulCAPAisadefinitionofthe
problemandanassessmentofwho,whatandwhereisatrisk,aswellasthepotentialimpactontheorganization
shouldtheproblemgrow.
Ingeneral,CAPAexpertsrecommendthatrootcauseinvestigationsfollowafourstepprocess:
1.Identify
theproblem.

1.Evaluate
itsmagnitude,whichincludesassessingrisk.

1.Investigate
andassignresponsibility.
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1.Analyze
anddocumenttherootcauseoftheproblem.
Tracking best practices
FettermanisnearlycompletionofaprojecttoinstallaCAPAsolutiongloballyatamajorpharmaceuticalfirm.
Weredevelopingthesystemandrollingitouttoalltheir30sitesworldwide,hesays.ThefirmisusingSparta
Systems(Holmdel,N.J.)TrackWisequalitymanagementsoftwarepackagebecauseitiseasilycustomized,
Fettermansays.Itlendsitselftoquickconfigurationofworkflowsandmodificationstomeetthebusinessneeds.It
alsorunsontheOraclesystemsthatareinuseatmanypharmaceuticalcompanies,hesays.
WithanyCAPAinvestigation,havingaprescribedworkfloworsetofactivitieswithdesignatedpeopleassignedto
carrythemoutisessential.YoucantrackaCAPAeventandthemultipleactivitiesrequiredthroughoutthe
workflowprocess,Fettermansays.EachCAPArecordislinkedtotheoriginalparentqualityevent,sothata
supervisorormanagercancheckthesystemandquicklyseethattheeventhasbeentrackedthroughtoclosure,
orifnot,exactlywhereitisstalledorheldup.
hisisimportanttoCAPAcomplaintinvestigation,thattherebeasystemtomakesurethattheseproblemsare
T
trackedallthewaythroughtocompletion,Fettermansays.T hisway,theplantmanagerknowsthatappropriate
actionsweretaken...andthatthecorrectiveactionstakenare,infact,solvingtheproblem.
Thesoftwaresworkflowcapabilityhelpstoensurethateachstepistakeninatimelyfashion.Thesystemassigns
investigationtaskstoteammembers,trackingeachtaskthroughtocompletion.Eachinvestigatordocumentshis
orherfindingsinthesystem,withresultsandattachmentselectronicallyincluded.Theleadinvestigatorisnotified
aseachstepiscompletedor,conversely,undulydelayed.
Unfortunately,manycompanieshaveyettocomputerizetheirCAPAcomplaintsandinvestigations.Thedangerof
manuallydocumentingCAPAprobleminvestigationsisthatithasproventobeunreliable,Jacobsonpointsout.
T heFDAhasaddressedCAPAasthenumberonegoodmanufacturingpractice(GMP)deficiency,hesays.And
theFDAismoreinsistentthaneverthatmanufacturersmaintainconsistentfilesandproceduresacrosstheir
organizationsandembedFDAregulationsintocompanystandardoperatingproceduresregardingtheCAPA
process.
SomecompanieshaveimplementedelectronicsolutionsforpiecesoftheCAPAprocess.Butveryfew
pharmaceuticalfirmshaveimplementedacomprehensiveprocessliketheoneFettermanisinstallingforhis
currentclient,hesays.T heyhadatotallymanualprocessbefore,headds.
People issues
InFettermansexperience,itisextremelydifficulttogetpeopleacrossallsitestofollowtheCAPAcomplaintand
investigationprocessinthesameway.T hebiggestchallengewehadwiththisglobalrolloutwascomingupwitha
consistentandreliableapproachtohandlingCAPAcomplaintsandinvestigationsworldwide,hesays.
Toestablishconsistency,companiesmusthaveastrongdirectivefromseniormanagementfortheproject,anda
commitmentbytheorganizationthatthisisthewaywearegoingtohandleit,hesays.Youjustdontwanttohave
separateworkflowsfordifferentsites.
Ofcourse,eventhebesttechnologiesandprocessesareonlypartofthesolution.Theculturalissueofgetting
peopleintheorganizationtoperformtheirCAPAresponsibilitiesisthekeytoanysuccessfulprogramfordealing
withCAPAcomplaintsandinvestigations.Howtoincentemployeestoworkonthesamepageisimportant,says
AMRsJacobson.T hetechnologyistheenablingcomponent,butsomeonehastoownresponsibilityforthe
process.Alotofcompanieshaveputtogethercrossfunctionalteams.

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FDAcertifiedconsultantswhospecializeinCAPAcanfacilitateitsacceptance,Jacobsonsays.Havingacredible
outsidevoicetocomeinishelpful,hepointsout.
ThisisespeciallytrueforpharmaceuticalcompaniesthatplantoinstallaspecificsoftwarepackageforCAPA.F or
asystemlikeTrackWise,youdoneedspecificexpertiseonhowtoconfigureit,Fettermansays.
ButCAPAtechnologyandconsultantswilltakeacompanyonlysofar,saysWadeSpeir,seniorconsultantinthe
lifesciencespracticeatKepnerTregoe,Inc.,aPrinceton,N.J.consultingfirm.T hesoftwareisonlyapartofthe
solution,hesays.T herearetheprocessissues,whichoftenrequirechangingpeoplesbehaviors.
The bearer of bad news
ThemostdifficultaspectofCAPAproblemsolvingisgettingasharpfixonexactlywhatconstitutestheproblemat
issue,Speirsays.Byfarthehardestpartofproblemsolvingisgettingaclearconsensusofwhattheproblemis,
hesays.Youneedtoidentifywhatsactuallyhappeningaswellaswhatisexpectedtohappen.
Forexample,pillsoftenshowsiliconecontaminationfromtheproductionprocess.Themanufacturerneedsto
knowexactlyhowmuch,ifany,siliconewasexpectedtoappearinthepillunderoptimalcircumstances.Though
drugcompaniesmaynotadmitit,T heresalwayssomecontaminationfromallthevalvesandmachinery,Speir
says.Knowingtheproperbaselinewhetherthereiszeroorthemostminuteamountofcontaminationis
essentialtodetermininghowmuchactualdeviationexists.
ToidentifytherootcauseofaCAPAproblem,themanufacturermustfirstspecifywhattheproblemis,whereit
occurs,howoften,andhowbigtheproblemis.Itmustalsotestpossiblecausesagainstthefactsofthe
occurrence.Theideaistoseewhichcauseexplainstheproblem.Atthesametime,thisprocessalsoshould
pointoutthepossibleproblemsthatcouldoccurandwhytheyarenot.
heideaistobeabletoexplainwhythisbatchwasbad,aswellaswhytheprecedinglotandtheoneafterthe
T
badonewereokay,Speirsays.Oncethecompanyhasahypothesisforwhatcausedtheproblem,thenextstep
istotestiteitherbyexperimentation,orbyfixingitandseeingifthissolutionworks.
CompaniesneedtobesurethattheirCAPArootcauseanalysisinvestigatesallpossiblecausesandteststhe
suspectedonetomakesureitis,infact,therealcauseoftheproblem.Itsimportanttodistinguishbetweenthe
observedsymptomsofaproblemandthefundamentalorrootcause.Youwanttobesurepeoplearefixingthe
rightissueandaddressingtherightcause,saysJohnMcLaughlin,principalconsultantatTaratecDevelopment
(Bridgewater,N.J.).Youdontwantanengineerputtingafixonaproblemwithoutaddressingtheunderlying
issues.
Therootcauseanalysisinvolvesansweringabatteryofquestionsthataskwhywiththegoalofdiggingdeepuntil
thereasonfortheproblemisidentified.Sometimesthecauseoftheproblemmayonlybeasymptomofamore
pervasiveissue.Forexample,ifapoorlytrainedoperatorwastheimmediatereasonfortheproductionofabad
batch,therootcauseanalysisshoulddelvedeepertodetermineiftheplantstrainingprogramitselfisatfault.The
questionshouldbeasked,couldotheroperatorsbepoorlytrainedinthefuture?
harmaceuticalfirmsshouldbelookingacrosstheorganizationtoseeifalargerproblemexists,adds
P
McLaughlin.T hegoodnewsisalwaysgreattohear,butthebadnewsiswhatyoureallywanttohear.Companies
shouldrememberthat,attheendoftheday,theCAPAprocessissupposedtohelpthem.
AllthisactivitymustbedocumentedtoprepareafullinvestigationreportfortheFDA.Muchofthisinformationcan
bedrawnfromthebatchrecord,whichinmanyinstances,canbefoundinbindersofinformation.F ormany
companiesthisisquiteachallengingeffort,Speiradds.Andusuallythepeopledoingitarenotthehighestpaidin
theorganization.
IdentifyingtherootcauseofaCAPAeventisonlypartoftheoverallCAPAactiontobetaken.Theotherhalfof
SHOWMORECONTENT
theprocessisdeterminingwhatactionscanbetakenbothtocorrectandpreventsuchoccurrences.
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