Download - DATA INTEGRITY THE FOUNDATION OF GOOD S … · FDA has defined data integrity as the completeness, consistency and accuracy of data3. Complete, consistent and accurate data have the

TRUSTEDADVISORSTOHEALTHCAREANDLIFESCIENCEEXECUTIVES

©2017Axendia,Inc.

DATAINTEGRITY-THEFOUNDATIONOFGOODSCIENCEDATAALONEISNOTGOODENOUGH

By:EllynMcMullin,ResearchAssociate&SandraK.Rodriguez,MarketAnalyst

ABSTRACT

Sounddataisthefoundationtogooddecisionsandgoodscience.IntheLife-Scienceindustrypatientoutcomes,productquality,safetyandefficacyallrelyuponvastamountsofdatathatisgeneratedthroughouttheproductlifecycle.Thismeansthatpatients,brandequityandreputationshavethepotentialtosuffergreatlywithoutastrongdataintegrityfoundation.Inrecentyears,regulatorsaroundtheworldhaveincreasinglyobservedcGMPviolationsinvolvingdataduringinspections.AccordingtoFDA’sdata,14of23warninglettersissuedbytheOfficeofManufacturingQualityreferenceddataintegrityintheperiodfromJanuary2015toJanuary20161.Dataintegrityfindingshaveledtowarningletters,importalertsandconsentdecrees.OneFDAwarningletterspecificallycalledout,“seriousCGMPviolationsdemonstratingthatyourqualitysystemdoesnotadequatelyensuretheaccuracyandintegrityofthedatageneratedatyourfacilitytoensurethesafety,effectiveness,andqualityofthedrugproductsyoumanufacture.2”Thisisproofthatthelackofdataintegrityhasthepotentialtocallintoquestionanorganization’sentirequalitysystem.TheMedicinesandHealthcareproductsRegulatoryAgency(MHRA)hasalsoreportedthatdataintegrityhasbeenatoppriorityfortheLifeScienceindustryintheUKoverthepasttwoyears.Noteworthyistheoftenmisconceivednotionthatactsofdeliberatefraudaretherootcauseofdataintegrityissues.However,theMHRAInspectoratehasdeterminedthatbadpractices,poororganizationalbehaviorsandweaksystemshavecreatedopportunitiesfordatamanipulation.Toaddressthesetypesofissues,companiesshouldconsiderleadingfromthetopandempoweringfrombelow,understandingthedatalifecycleandgivingspecialconsiderationstoorganizationalandtechnicalcontrolswithinthequalitysystemleveraging the technologies provided by the industry.

1 http://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm504306.pdf 2 http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm432709.htm

©2017Axendia,Inc.2

DATAINTEGRITY–THEFOUNDATIONOFGOODSCIENCE

“Bythemselvesthey(data)aremeaningless;onlywhenweaddcriticalcontextaboutwhatisbeingmeasuredandhowdotheybecomeinformation…”

RobertM.Califf,M.D.FMRFDACommissioner

WHATISDATAINTEGRITY?

FDAhasdefineddataintegrityasthecompleteness,consistencyandaccuracyofdata3.Complete,consistentandaccuratedatahavethefollowingattributes(usingtheacronymALCOA):

Attributabledatameansknowingwhoputthedatain,where,whenandwhatsystemitcamefrom

Legibledataensureswhoeverneedstoreadorinterpretthedata,caneasilyandclearlydoso

Contemporaneouslyrecordeddataincludesthetimedatawasgathered,recordedand/orlookedat

Original,firstrecordingofdata,raworsourcedata,oracertifiedtruecopy Accuratedataiscorrectincludingcontext/meaning(e.g.,metadata)andedits

IS160DEGREEPORRIDGETOOHOT,TOOCOLDORJUSTRIGHT?

Answer:Itdependsonthecontext.Adatavaluebyitselfismeaninglesswithoutadditionalinformationaboutthedata.Metadataisoftendescribedasdataaboutdata.Metadataisstructuredinformationthatdescribes,explains,orotherwisemakesiteasiertoretrieve,use,ormanagedata.Todeterminewhetherthedataisreliable,additionalquestionsregardingthemetadatamustbeconsidered(seetheInfographic“WhatGoldilocksandLife-SciencesCompanieshaveinCommon?)

Whenwasthetemperaturetakenandwhotookit? Howwasthedatarecorded?Isitlegible? Wasthetemperaturemeasuredcorrectly? Wastherighttoolusedtomeasureit? Wasthethermometerproperlycalibrated? Wasthecalibrationineffectwhenthemeasurementwastaken?

Wasthetemperaturewithinspecification? Weretherighttemperatureunitsused?

3 Source: FDA Data Integrity and Compliance with CGMP, Guidance for Industry. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm495891.pdf >

AttributableLegibleContemporaneouslyrecordedOriginaloratruecopyAccurate

©2017Axendia,Inc.3

DATAINTEGRITY–THEFOUNDATIONOFGOODSCIENCEDatabyitselfisnotenough.FromaGMPstandpoint,metadataisalloftheadditionalinformationaboutthedatathatisusedtoreconstructthecGMPactivity.Assumingallthequestionswereansweredsatisfactorily,Goldilockswouldfindthat:

RobertM.Califf,M.D.,FMRFDACommissionerstated,“Bythemselvesthey(data)aremeaningless;onlywhenweaddcriticalcontextaboutwhatisbeingmeasuredandhowdotheybecomeinformation…Thatinformationcanthenbeanalyzedandcombinedtoyieldevidence,whichinturn,canbeusedtoguidedecision-making4.”

HOWDOESDATAINTEGRITYENABLEGOODDECISIONMAKING?

Dataintegrityisafoundationalrequirementforastrongandreliablequalitysystemthatenablessounddecisionsbasedonscientificfacts.Thisappliesequallytomanual(paper)orelectronicsystems-regardlessofwherethedatacamefrom.Thepursuitofdataintegritypromotesaqualityculturewithinanorganization.Itrequiresparticipationandcommitmentbyallstafflevelsaswellassuppliernetworksanddistributors–fromsuppliersofrawmaterialstotheenduser.Finally,dataintegrityenablesseniormanagementtoassessdataintegrityrisksformitigationandcommunicationinaccordancewiththeprinciplesofqualityriskmanagement.DataIntegritystartswithseniormanagementcommitmentbutpermeatesthroughouttheentirevaluechain.

WHOISRESPONSBILEFORDATAINTEGRITY?DataintegrityisultimatelytheresponsibilityofSeniorManagement.5Thereneedstobeamasterdatamanagementsystemthatsupportsgovernancearounddatainordertosupportitsintegrity.Howeverforthesystemtohavevalue,participationandcommitmentbystaffatalllevels(bothinternalandexternalresources)isnecessary.Thetoolsto

4 Source: http://blogs.fda.gov/fdavoice/index.php/2015/12/what-we-mean-when-we-talk-about-data/?source=govdelivery&utm_medium=email&utm_source=govdelivery 5http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000027.jsp&mid=WC0b01ac05800296ca#section16

©2017Axendia,Inc.4

DATAINTEGRITY–THEFOUNDATIONOFGOODSCIENCEsupportdataintegrityincludemanagementcommitment,policiesandprocedures,educationandtechnicalcontrols.

SOMUCHDATA,SOLITTLEINTELLIGENCE

CompaniesregulatedbytheFDAareobsessedwithcollectingdata,retainingandhoardingittomeetstatutoryandregulatoryrequirements.Unfortunately,mostcompaniesdonotharnessthisdatatoproducebetterqualityproducts.Asaresult,companiesaredatarichbutIntelligencepoor.Anexampleofdatapointstypicallycollectedthroughoutaproduct’slifecycleinclude:

concept prototype designtransfer manufacturing non-conformances postmarketsurveillance adverseevents

VastamountsofdataaregeneratedbyamultitudeofsystemsbutunfortunatelyverylittleIntelligenceisavailableregardinghowthisinformationcanbeharnessedtoproduceabetterqualityproduct.TheintegrityofthisdataisvitaltoshowingFDAacompany’scommitmenttocompliance.However,complianceandqualityarenotthesame!FDAISSHIFTINGFOCUS

TherearenewFDAinitiativesbeingpromulgatedtoindustrysuchastheCaseforQuality(see: http://mdic.org/cfq/) to consider compliance as a baseline and quality as aninvestment.Collectingdocumentedevidenceofcompliancewithregulatoryrequirementsisanoverheadcost–itdoesnotaddvalue.Beinginbusinesstobecompliantisdifferentfrombeing in the compliance business. Life Science companies are in business tomakehighquality,life-sustainingproducts,notdocuments.Qualityistheinitiativethatdrivesimprovements,tostreamlineprocessesresultinginoperationalefficienciesandreducedwaste.Therefore,investinginimprovingproductqualitycanactuallylowercostsandimproveprofitability.TosupportthistransitionfromcompliancetoQuality,itisnecessarytotransformdataintoTruth.WiththeimplementationofFDASIATitleVIISection7066,theFDAisshiftingitsfocustorequestinginformationinadvanceof,orinlieuof,aninspectionineitherelectronicorphysicalform.Thisshifttoe-Inspectionsofdrugmanufacturersrequiresmassiveamounts

©2017Axendia,Inc.5

DATAINTEGRITY–THEFOUNDATIONOFGOODSCIENCEofdataandinformationthatcanonlybeasgoodasthequalityofavailabledataandanalytictoolsused.Aspartofthisshiftinfocus,FDAintendstotakeacloselookatacompany’scommitmenttoQuality.HowardSklamberg,J.D.,CommissionerRegulatoryOperations&PolicyatUSFDAstated:

Wewillalsocollectdata,or"qualitymetrics”thatwillhelpusmeasureafirm’scommitmenttoquality.

Ourevaluationofafirmwouldbeanchoredbydatathatprovethattherisksofmanufacturingproblemsinacertainfacilityareminimal.

Webelievethatbyimprovingtheinspectionprocessinthisway,future“metrics”thatdefinequalitywillbeunderstoodandaspiredtobymanufacturers-nomatterwheretheyareintheworld.

Tosupportthiseffort,theagencyhasreleasedaguidancedocumentontheSubmissionofQualityMetricsData7.Theseinclude:

LotAcceptanceRate(LAR) ProductQualityComplaintRate(PQCR) Invalidated Out-of-Specification (OOS) Rate (IOOSR)

WHYSHOULDYOUFOCUSONDATAINTEGRITY?Theproblemisnotthatwedon’thaveenoughsystemsbutthattherewehavetoomanysystems.Asaresult,managingdataacrossmultiplesystems–seekingasinglesourceoftruth–becomesachallenge.Havingaplatformthatallowsyoutoensuredataintegrity,connectthedotsandturningthatdataintoknowledge,iscriticaltosupportthisprocess.ToachieveDataIntegritycompaniesneedtohavecontrols(whetherelectronicorpaper)overthesystem,validationandsupportingevidence.TechnicalControlsincludeaccesscontrol/passwords,audittrails,metadataandsupportingevidence.Digitaltransformationandcontinuity-theabilitytotransformprocesses-shouldnotbeconfusedwithdigitalization.Simplydigitizingapoorprocessdoesnotimproveitorachievetheintegrityneeded.Infactitexacerbatesitbyproducingmoresubstandardoutputmorequickly.

In“InnovationThroughDigitalContinuity”wediscusshowmostpeopletoday,consumedataasstaticdocuments.Thesedocuments,however,oftenrepresentdynamicprocesseswheredatacanbemanagedandparameterscanbedefined.

7 http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm455957.pdf

©2017Axendia,Inc.6

DATAINTEGRITY–THEFOUNDATIONOFGOODSCIENCE

“..dataintegrityproblemsarenotalwaysintentional;sometimestheyresultfrompoorlycontrolledsystems.”

PaulaKatzDirectorofManufacturingQuality

GuidanceandPolicyStaffCDEROfficeofCompliance

Aconnectedsystemisadynamicsystemprovidingdigitalcontinuitytoallowpeopleto“followthedrug,notthedocuments”,permittingfulltraceability.

Thefirststeptowardstransformationisinformationefficiencyandtransitioningfromtheoldparadigmofmanagingstaticdocumentstothenewparadigmwheredocumentsarethegraphicalrepresentationofthedata…nottheendinandofthemselves.Inthenewparadigm,onecanusetheintegratedsystemstointerpretdata,getranges,tolerancesandothermetricsinacontextthatisrelevanttothedecisionbeingmade.

Dataanddatamodelscanbemanagedtosupportdigitalcontinuityandpromotevisibilitytosupportcontinuousimprovementacrosstheproductlifecycle.Aconnectedsystemisadynamicsystemprovidingdigitalcontinuitytoallowpeopleto“followthedrug,notthedocuments”permittingfulltraceabilitydownstreamorupstream(i.e.rawmaterialstopatienttooutcome).ItcanalsobeusedtosupportRegulatorychangestoenablemoreefficientadoptionofinnovativetechnologies,regulatoryevaluation,bothinreviewandinspection,andovertheproductlifecycle.Dataintegrityisthefoundationthatsupportsgoodscience.WHATARETHECOMPONENTSOFANOPTIMALSOLUTION?AccordingthePaulaKatz,DirectorofManufacturingQualityGuidanceandPolicyStaffatCDEROfficeofCompliance,“dataintegrityproblemsarenotalwaysintentional;sometimestheyresultfrompoorlycontrolledsystems8.”Asaresult,theoptimalsolutionwillincludeadataintegritystrategy.Dataintegrityneedstobeconsistentacrosstheentiredomainandthroughouttheproductlifecyclefromresearchanddevelopmenttoqualityandmanufacturing.Aplatformapproachallowsacompanytointegratedataapplications,processesandpeopleacrosstheorganizationaswellasexternalorganizations.Datasourcescanbeintegratedwithdataconsumingapplicationsfromthebusiness,manufacturing,laboratoryandqualityareas.Thiswillallowusersacrossthevaluechaintoaccess,organize,analyzeandsharescientific,qualityandprocessdatawithfullconfidenceoftheirintegrity.Atthesametime,thesolutionshouldhavethecapabilitiesforenterprisequalityanddatamanagement,laboratoryinformaticsanddataanalytics.Thisapproachsupportsdigitalcontinuity-theabilitytomaintainthedigitalinformationofacreatorinsuchawaythat 8 http://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm504306.pdf

©2017Axendia,Inc.7

DATAINTEGRITY–THEFOUNDATIONOFGOODSCIENCEtheinformationwillbeavailable,asneededandwhereneeded.Itfocusesonmakingsurethatinformationisunaltered,complete,availableandthereforeusable.CONCLUSION

Forsounddatatobethefoundationforgooddecisionsandgoodscience,therecanbenoquestionswithregardstoitsintegrity.Patientoutcomes,productquality,safetyandefficacyofproductsrelyuponvastamountsofdatathataregeneratedthroughouttheproductlifecycle.Muchofthisdataisoftenproducedbyamultitudeofdisconnectedstand-aloneorredundantsystemsthatweregenerallyimplementedbyfunctionalareastoaddressspecificneeds.Thisdisconnectcanresultinalackofdataintegrityandconsistency.Thereforepatients,brandequityandreputationshavethepotentialtosufferwithoutastrongfoundationfordataintegrity.Bytakingaplatformapproach,companiescanintegratedataconsumingapplicationsthatsupportbusiness,manufacturing,laboratoryandqualityareas.Dataintegrityisultimatelytheresponsibilityofexecutivemanagement.Theseteamsmustbecommittedtoensuringthatamasterdatamanagementsystemsupportsgovernancearounddatainordertosupportitsintegrity.However,forthesystemtohavevalue,participationandcommitmentbystaffatalllevels(bothinternalandexternalresources)isnecessaryinordertosupportasinglesourceoftruth.Isyourcompanydoinggoodscience?Withoutdataintegritytheresultsofthatsciencecanbeinquestion. This white paper was written by Axendia, Inc. and was sponsored by BIOVIA, a brand of DassaultSystèmes. TheopinionsandanalysisexpressedinthisresearchreflectthejudgmentofAxendiaatthetimeofpublicationandaresubjecttochangewithoutnotice.Informationcontainedinthisdocumentiscurrent as of publicationdate. Information cited is notwarrantedbyAxendiabuthasbeenobtainedthrough a valid research methodology. This document is not intended to endorse any company orproductandshouldnotbeattributedassuch. AboutAxendia:Axendia,Inc.isaleadingtrustedadvisortotheLife-ScienceandHealthcareindustries.WeprovidetrustedcounseltoindustrystakeholdersonBusiness,RegulatoryandTechnologyissues.Formoreinformation,[email protected]

ReadAxendia’sblog:Life-SciencePanoramaathttp://LSP.axendia.com

FollowusonTwitterattwitter.com/axendiaandLinkedInatlinkedin.com/company/axendia-inc. ©2017Axendia,Inc.AllRightsReserved.ThispublicationiscopyrightedbyAxendiaInc.andprotectedbyUnitedStatescopyrightlawsand international treaties. Thisdocumentmaynotbe reproducedorpostedon anotherweb sitebeyond the sponsors’withoutpriorwrittenconsentfromAxendia.Unauthorizedreproductionofthispublicationoranyportionofitbyotherpartiesmayresultinseverecivilandcriminalpenalties,andwillbeprosecutedtothemaximumextentnecessarytoprotecttherightsofthepublisher.

PublishedFebruary2017