DATA INTEGRITY THE FOUNDATION OF GOOD S … · FDA has defined data integrity as the completeness,...
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TRUSTED ADVISORS TO HEALTHCARE AND LIFE SCIENCE EXECUTIVES © 2017 Axendia, Inc. DATA INTEGRITY - THE FOUNDATION OF GOOD SCIENCE DATA ALONE IS NOT GOOD ENOUGH By: Ellyn McMullin, Research Associate & Sandra K. Rodriguez, Market Analyst ABSTRACT Sound data is the foundation to good decisions and good science. In the Life-Science industry patient outcomes, product quality, safety and efficacy all rely upon vast amounts of data that is generated throughout the product lifecycle. This means that patients, brand equity and reputations have the potential to suffer greatly without a strong data integrity foundation. In recent years, regulators around the world have increasingly observed cGMP violations involving data during inspections. According to FDA’s data, 14 of 23 warning letters issued by the Office of Manufacturing Quality referenced data integrity in the period from January 2015 to January 2016 1 . Data integrity findings have led to warning letters, import alerts and consent decrees. One FDA warning letter specifically called out, “serious CGMP violations demonstrating that your quality system does not adequately ensure the accuracy and integrity of the data generated at your facility to ensure the safety, effectiveness, and quality of the drug products you manufacture. 2 ” This is proof that the lack of data integrity has the potential to call into question an organization’s entire quality system. The Medicines and Healthcare products Regulatory Agency (MHRA) has also reported that data integrity has been a top priority for the Life Science industry in the UK over the past two years. Noteworthy is the often misconceived notion that acts of deliberate fraud are the root cause of data integrity issues. However, the MHRA Inspectorate has determined that bad practices, poor organizational behaviors and weak systems have created opportunities for data manipulation. To address these types of issues, companies should consider leading from the top and empowering from below, understanding the data lifecycle and giving special considerations to organizational and technical controls within the quality system leveraging 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
Transcript of DATA INTEGRITY THE FOUNDATION OF GOOD S … · FDA has defined data integrity as the completeness,...
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
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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
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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
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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
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PublishedFebruary2017
