How to build win-win relationships with CROs?biophia.com/wp-content/uploads/2019/06/Win-win... ·...
Transcript of How to build win-win relationships with CROs?biophia.com/wp-content/uploads/2019/06/Win-win... ·...
Howtobuildwin-winrelationshipswithCROs?
ShreekantKarmarkar,Ph.D.May22,2019
Topics
� Transactionalvs.StrategicCROrelationship◦ DrivingtransactionalCROrelationshiptosuccess
� Win:WinstrategicCROrelationship◦ DuediligenceinCROselection◦ Qualitymanagement:FDAandICHguidances◦ Clarityleadstosuccess,ambiguitytofailure◦ Buildthetrust,andnotusvs.them◦ Empowerment◦ Simplifyingthecomplex◦ Relevantmetrics◦ Operationalexcellence
� Summary� Q&A
Background,firstsomeacronyms
• CRO• Contractresearchorganization• Clinicalresearchoutsourcing
• CMO:Contractmanufacturingorganization• CDMO:Contractdevelopmentandmanufacturingorganization• CTO:ContracttestingorganizationThetermCRO,usedinthispresentation,ismeantforcontractresearchorganizationinmind.However,Ithinktheconceptsleadingto“win:winrelationship”wouldapplytoalloutsourcedcontractworkwithlong-termstrategiesinmind.
Background
• PharmaceuticalandbiopharmaceuticalcompaniesextensivelyuseCROstomeettheirchallengingneedsinresearchanddevelopment,manufacturingandstability.• Forexample,Approximately33%ofdrugsinthepipelinesofthetop
tenpharmaceuticalcompanieswereinitiallydevelopedelsewhere,accordingtoa2014WSJarticlebyJonathanD.Rockoff.
• BothsmallandlargepharmacompaniesextensivelyuseCROs.• ThesponsorcompanyneedstodecidewhethertoengageaCROon
atransactionalbasisorastrategicrelationshipbasis.• Stakesarehighforpharmaceuticalandbiopharmaceutical
companiestomakesureCROworkissuccessful.• AsuccessfulCROrelationship,evenwithareputedCRO,isnota
given.SponsorcompanyandCROcandrivetoasuccessfulrelationshipbyimplementingthekeystrategiesdiscussedhere.
References
� JonathanHughesandStuartPrice,ThePerilsandPromiseofStrategicPartneringwithCROs,PharmaceuticalOutsourcing,March2016.
� AnthonyMire-Sluis,JuliaEdwards,JeffreyStaecker,QiaoBobo,PatriciaHughes,StephenLiewbowitz,ShawnNovick,SiddharthJ.AdvantandBernardHuygheEffectiveManagementofContractOrganizations:KeepingtheProductPipelineMoving,Compliant,andAvailable,BioProcessInternational,October2015.
� Syngene’swhitepaper,2018https://pink.pharmaintelligence.informa.com/emails/weekly-partnered-content?utm_campaign=Pink%20Sheet&utm_source=emdigest&utm_medium=email
� FDAguidancedocument,Contractmanufacturingarrangementsfordrugs:Qualityagreements,November2016
� Section2.7,Managementofoutsourcedactivitiesandpurchasedmaterials,ICHQ10,Pharmaceuticalqualitysystem,2008
Transactionalvs.Strategic
Transactional• Shortdurationprojects• Commitmentbyboththe
clientandtheCROonlyfortheSOWproject
• CROaswellasclientwouldshyawayfromanybiginvestment,continuousimprovementorinnovation
• Atarms-length.Simplyanaugmentationofresources
• Examples:Verificationstudy,Validationstudy,Synthesis
Strategic• Longdurationprojects• Long-termcommitments
byboththeclientandtheCRO
• CROaswellasclientwouldwanttomakebiginvestment,continuousimprovementandinnovation
• Ideallybasedonmutualrespectandtrust
• Examples:Stabilitystudies,Referencestandards,Clinicalstudies
MetricsfortransactionalCROs
AretherewaystomaximizetheoutcomefromtransactionalCROs?� Asimpleansweris“Yes”!� Forexample,considerimplementingthefollowingmetrics:◦ On-timecompletioninpercentage.AquantitativeKPI
◦ Qualityofwork:Itcanbemeasuredintermsofiterationsforreviewofprotocol,report,oranyinvestigations.Theoutcomecanbemeasuredintermsofiterations:
◦ Valuesof5:minimumiterations(e.g.,2-3),Valueof3:medium(3-5),andValueof1:major(greaterthan5iterations).
� Overthecourseofyearortwo,thenumbersdoaddup.ThemetricsthenbecomesapowerfultoolinevaluatingCROperformance.
0
25
50
75
100
0 2 4 6
On-tim
ecompletion
Quality
PerformanceassessmentofCROs
Starperformers!
Eitherdropthemornegotiatelowerrateuntilperformanceimproves!
CreatebubbleplotwithbubblesizeproportionaltoannualspendwiththeCROforimpactassessment
StrategicrelationshipswithCROs
StrategicrelationshipwithCROs
Strategicrelationship◦ WhensponsorandCROactivelyworktogethertohelpeachother
achievetheirrespectiveobjectives.
Afewthingstoconsider◦ UnderstandingofdifferentbusinessmodelsforsponsorsandCROis
importantindevelopingmutuallybeneficialrelationship.◦ Knowingthattherelationshipsarenotmonogamoushasimportancein
afewaspects,e.g.,firewall&applyingbestdemonstratedpractices.◦ Itismoreofstrategicrelationship,butitmaynotgotothelevelof
partnership.
Benefitsofstrategicrelationship
� Improvedoperationalefficiency◦ Accesstoinfrastructurewithouthavingtomakecapitalinvestment◦ Resourceflexibility:Rampingupanddown
� Continuousimprovement,innovation,andlearningwithandfromCROs
� In-houseresourcescanbeleveragedtobusinesscriticalprojectneeds
� PossibleopportunitiestopenetrateintoanewmarketsegmentwhentheCROisfromalocationwherethesponsorcompanylacksanypresence.
Examplesofstrategicrelationships
� SyngeneInternational,Bangalore,India◦ Amgen◦ BaxterHealthcare◦ Bristol-MyersSquibb◦ GSK◦ Herbalife◦ Novartis
� Parexel◦ EliLilly
Formingastrategicrelationship
Define
• Definewhatworkstaysin-houseandwhatisoutsourced• Definekeydrivers;speed,cost,workcomplexity
Duediligence
• Technicalassessments• Supplierqualityaudits
MSAandQA
• Masterserviceagreement(MSA)&Qualityagreement(QA)withtheselectedCRO(s)• Addresstechnical,business,andqualityaspects
Cadences
• Workinitiation,includingtransferwork• Establishingengagementandgovernancecadences
Followthrough
• Qualityaudits• MSAandQArenewals
WhatareFDAguidelinesonqualityagreement?
FDA’sguidance,“Contractmanufacturingarrangementsfordrugs:Qualityagreements”
• Guidancedocument,November2016• FDA’sregulationsrecognizethatownerscommonlyusecontractfacilitiestoperform
somedrugmanufacturingactivities.• AlthoughtheguidanceisforCMO,manyoftheprinciplesdescribedinthisguidance
couldbeappliedinpre-commercialstagesofthepharmaceuticallifecycle.
• Whenanownerusesacontractfacility,theowner’squalityunitislegallyresponsibleforapprovingorrejectingdrugproductsmanufacturedbythecontractfacility,includingforfinalrelease.Theregulationsrequirethatthequalityunit’sresponsibilitiesandproceduresbeinwritingandthattheybefollowed.
• OwnerscanuseacomprehensivequalitysystemmodeltohelpensurecompliancewithcGMP.Acomprehensivequalitysystemscallsforqualityagreementsbetweenownersandcontractfacilities.
• OwnerstoevaluatecontractfacilitiestoensurecGMPcomplianceforspecificoperations.
FDAandthequalityagreement• Qualityagreement:
• Qualityagreementsshouldclearlydescribethematerialsorservicestobeprovided,qualityspecifications,andcommunicationmechanismsbetweentheownerandcontractfacility.
• ShouldexplainhowtheCROwillreportmanufacturingdeviations,deviationswillbeinvestigated,documented,&resolvedincompliancewithcGMP.
• Definesandestablisheseachparty’smanufacturingactivitiesintermsofhoweachwillcomplywithcGMP.
• FDArecommendsthatqualityagreementsbeseparatedocuments,oratleastseverable,fromcommercialcontractssuchasmasterservicesagreementsorsupplyagreements.Qualityagreementsmaybereviewedduringinspections.
• Twocriticalpieces:• Manufacturingactivities(Qualityunit,Facilitiesandequipment,Materials
management,Productspecificconsiderations,Laboratorycontrols,anddocumentation)
• Changecontrols
Thebuckstopswiththesponsor
• Nomatterwhoteststheproducts,theowners’qualityunitsareultimatelyresponsibleforensuringthattheproductsaremanufacturedinaccordancewithcGMP.Aqualityagreementdoesnotchangethat.FDAcouldcitetheownersforfailingtoevaluate,qualify,audit,andmonitortheircontractfacilities.
• ICHguidanceforindustryQ10PharmaceuticalQualitySystemstatesthat,aspartofapharmaceuticalqualitysystem,theownerisultimatelyresponsibleforensuringthat“processesareinplacetoassurethecontrolofoutsourcedactivitiesandqualityofpurchasedmaterials.”
Howtheendgamemaylooklike?
SponsorWinSponsorLoseCRO
Win
CROLose
• Sponsor:TimelyandQualityoutput,costsavings,resourcemgmt.
• CRO:Growthinrevenueandprofits,capabilitiesfornewbusiness
• Sponsor:Short-termwin.• CRO:Unsustainable
partnership
• Sponsor:andCROwanttoendtherelationship
• Sponsor:workoutputeitherlate,notofquality,overbudgetandresourcedrain
• CRO:Revenueandprofitgrowth,andcapabilitiesfornewbusiness
Keystrategiesforwin:winrelationship
Win:WinStrategies
Continuousimprovement
CROselection
Qualitymanagement
Clarityinexpectations
Buildthetrust
Empowerment
Simplifyingthecomplex
Metrics
Solidfoundation
Softfactors
ProjectManagementExcellence
Roadtowin:winrelationship
CROselection• Defineoutsourcedwork• Qualitytrackrecord• IPandconfidentiality• Capabilities:depthandbreadth• Resourcepoolinthelocalarea• Financials• Managementteam
Qualitymanagement• Qualityagreement• Qualitysystemalignment• Qualitytraining• Rolesandresponsibilitiesfor
investigations,OOS,FAR• Frequencyinreviewoforiginaldata• Qualitymetrics
Buildthetrust• Meetingcadencesandtransparency:
Senior,midandoperationallevel• Feedbacksessions(CROto/from
Sponsor)andactingonthem• Accountabilityonbothsides• Openbook,e.g.,FilesonSharepoint
Clarityleadstosuccess• Clarityisamusttoovercometime,
distance,&culturaldifferences• SOWisthevehicle• Frequentteleconferences• Useoftemplates• Lessonslearnedsessions
Roadtowin:winrelationship
Empowerment• ConsiderCROasanextension:Coaching
andmentoring• Culturaltraining• Trainingandeffectivenesscheck• SMEvisit• ShowCROthebigpicture
Simplifyingthecomplex• Feasibilitystudiespriortoformalones• Identifyfailuremodes• Templatesforprotocolsandreports• Audio-visuals,e.g.,telepresence,skype• Earlysuccessenablers• Issueescalationcadence
Relevantmetrics• Identifyrelevantmetricstoevaluate
strategicandtacticallevelstatus• Review&course-correctmetricsasthe
collaborationmatures:Establishment;efficiency,&productivity
Continuousimprovement• Don’tsitonyourlaurels• IdentifyKPIstomonitorstatus• UseGreenBelttooltominimize
defectsandLEANtoeliminatewaste• Explorevisualtools
It is a journey and not a destination!
ExamplesofrelevantKPIs
KPI Frequency Purpose
On-timeSOWcompletion,% Quarterly
MeasuresofefficiencyFirsttimeright,% Monthly
Labexecutionerrors,% Quarterly
Logistics,e.g.,shipment,receiptofchemicals Monthly Measureofefficiency
Productivity,studyoutput/FTE/year AnnualMeasuresofproductivity
Productivity,tasks/FTE/yearQuarterly
Regrettablelosses Measureofworkenvironment
“ Not everything that counts can be counted, and not everything that can be counted counts” – Albert Einstein
Illustrativescenarios
Scenario Discussion
CROneedstosubcontractpartofservice
• CROneedstoauditthesubcontractedCROtoensurecGMPcompliance.
• WorkaccountabilityisstillwiththeCRO
Inaccuratedocumentationofmanufacturingsteps
• Contractfacility’sbatchrecordsdidnotaccuratelyreflecttheactualmanufacturingprocessbecausethebatchrecordsdidnotdocumenttheadditionofreclaimedpowder.Batchrecordswassponsorresponsibilityperthequalityagreement.
• AqualityagreementcannotexemptownersorcontractfacilitiesfromstatutoryorregulatoryresponsibilitiestocomplywithapplicablecGMP.TheCROviolatedcGMPbyusingabatchrecordthatdoesnotaccuratelyreflectthemanufacturingprocess,eventhoughthebatchrecordwasconsistentwithwhatwassetoutinthequalityagreement
Illustrativescenarios
Scenario Discussion
Parentcompanyreceives483sorwarningletter
• AlthoughtheparentcompanyandCROhaveseparatequalitysystemsandthereisafirewallbetweenthetwoentities,thequalityculturecanessentiallybethesame.TheCROshouldsharewhatwouldbethenecessarychangestheyneedtoimplementbasedontheparentcompany’sauditfindingswiththesponsor.
Leastsuccessfulvs.mostsuccessfulstrategicrelationship
Leastsuccessful• Bothsideshaveunclearandunrealistic
expectationsofoneanother• Amindsetof“Youworkforus/weworkfor
you”prevails• CROshavelimitedvisibilityintoSponsor
developmentplansandtimelines• Lackofclarityandalignmentaround
policiesandprocedures;lackofclearlydefinedanddifferentiatedrolesandresponsibilities
• WorkiseithermicromanagedbySponsorsor“thrownoverthefence”toCROs
• Problemsareoftennotaddresseduntiltheymetastasize,finger-pointinganddefensivenessarecommon
• Lackofcontinuousimprovement
Mostsuccessful• Differencesarejointlymanaged• Amindsetof“Wearecolleagues”prevails• Sponsorsprovideahighdegreeof
transparencytoCROsregardingdevelopmentpipelineandplans,enablingmoreefficientresourcedeploymentandmanagementbyCROs
• Processes,policies,andproceduresareclearlydefinedandwell-integrated.
• Rolesandresponsibilitiesforexecutionandoversightareclearlydistinguished
• Potentialproblemsarespottedandaddressedearly;bothsidesexplorerootcausesanddeveloppotentialsolutionstogether
• ContinuousimprovementwithGB,LEAN
Summary
• StrategicCROrelationshipcanindeeddeliversubstantialbenefits.• However,asuccessfulCROrelationship,evenwithareputedCRO,isnota
given.• ImplementationofkeystrategiesinCROselection,qualitymanagement,
buildingtrust,drivingclarityandempowerment,simplifyingcomplex,relevantmetrics,andcontinuousimprovementcanleadtheCROcollaborationtosuccess!
• HowcanIhelpyouinstartingthestrategiccollaborationtherightwayorturningaroundanineffectivecollaboration?
Acknowledgments
� NumerousBaxtercolleaguesandmanagers� Syngeneemployeesandmanagement� EdMoore,RichJohnson,JeffStacker,andBioPhiacolleagues� MATTER
Thankyouforyourtime!