Drug-Safety

1、PharmacovigilanceandDrugSafety:Top10IssuesfacingComplianceandLegalPharmaceuticalRegulatoryComplianceCongressandBestPracticesForumNovember8th2007WashingtonDCChrisHolmesPrincipal,WCIConsultingLtdContents•Pharmacovigilance(PV)environment•BestPracticesForum•Top10issues•Currentindustryresponses•ConclusionsPharmacovigilanceenvironment•Movebeyondcompliancetoproactive,medicallydrivensafetyriskmanagement•Constantlyevolvingregulatoryenvironmentwithincreasedenforcement•Increasedinterestindrugsafetybystake。

2、holders,desireformoretransparency•IncreasingworkloadIndustryresponsetocurrentenvironmentExistingFutureAnIndustryForumhasbenchmarkedcurrentpracticesanddevelopedfuturepractices•12largepharmaceuticalandbiotechnologycompanies,since2001•HeadsofPharmacovigilance•26mediumsizedcompanies,inc.Rx,OTC,Devices,Generics•HeadsofPharmacovigilance•12largeandmediumpharmaceuticalcompanies•In-houselawyersTop10PVIssues*1.QP-PVroleandresponsibilities2.Contractualarrangements3.Governance&QualityManagementSystem4.Incre。

3、asedenforcementofRegulations5.FormalisedSignalManagementprocess6.SubmissionofRiskManagementPlans(RMPs)7.DevelopingRMPsacrossproductlifecycle8.AligningPVorganisationtoenableproactivesafety9.IndividualreportingofICSRs10.MaintainingefficientPVprocess*Source:pvnetMembers,notprioritized1.QP-PVroleandresponsibilitiesClarifiedinEUVolume9a,January2007•Establish/maintain/manageMAHPVsystem•Overviewofsafetyprofiles,emergingsafetyconcerns•SinglecontactpointforAuthorities•EnsureexecutionofPVobligations:•coll。

4、ectionofADRsatonepointintheEU•preparationofreportse.g.PSUR,PASS•continuouspost-authorizationPVevaluation•EnsurethatrequestsfromAuthoritiesareansweredfully&promptly1.QP-PVroleandresponsibilitiesIndustryResponsibilitieshavebeenclarifiedinVol.9a•Provideoverviewof,anddirectaccessto,informationregardingsafetyprofiles,emergingsafetyconcerns•Ensureadequaterepresentationinmedicalgovernance•AssignsufficientauthoritytoactivelymanagePVsystem•DevelopPerformanceMgttosupportsafetyobjectives•Increaseemployeeaw。

5、arenessofsafetyresponsibilities,ensureeffectivemechanismsinplacetoenableissuestobecaptured2.Contractualarrangements•MAHmusthave“detailedandcleardocumentedcontractualarrangements”inplace•MAHmustprovideauthoritieswith“informationonsucharrangements”•Closercollaborationwithlegalandcommercialfunctionsrequiredforcompliance•DefinedprocessforearlyinvolvementofPVinportfoliodecisionsandduediligence3.Governance&QualityManagementSystem•DetailedDescriptionofPharmacovigilanceSystem(DDPS)requiredforsubmissions。

6、inEU•MoretransparencyofhowMAHPVsystemworks•TemplatebasedonVolume9aexpectations•Emerginggoodpractice,keydocumentforInspections•NeedtoalignandsimplifySOPsacrossPVandoperatingcompanies•Create‘PVHandbook’forinspectionreadinessinallaffiliates•EstablishOperationalRiskManagementframework•Proactive,systematicapproachtoidentifyingandmitigatingcompliancerisks3.SingleglobalQualityManagementSystemOperations&ComplianceframeworkAnalysePrioritise&PlanControl&ReportMonitorIdentifyTechnologyGovernanceStructureFa。

7、ilure,Effect,Cause,RiskindexFECRFECRFECR4.IncreasedenforcementofRegulations•RecentshifttowardsstricterenforcementofstricterEUrules•EUinspectionsbecomingroutine•EachMemberStateresponsibleforinspections•Needforclearandconsistentinspectionstandards•Needtokeepabreastof‘HotTopics’asinspectionstandardsandfocusvaries•NewEUPenaltieslegislation(July,2007)•Appliestocentrallyauthorizedproducts•FinancialpenaltiestoMAHsinrespectofinfringements•Financialriskassociatedwithnon-compliance:upto5%oftotalEUannualtu。

8、rnoverperannum5.Formalisedsignalmanagementprocesses•SignalManagementbecomingmoreproactiveandformalised•pvnetbenchmarkdatashowsmaturingapproachNothingformalbeyondPSUR/ASRreportsLimitedsignaldetectionSOPsUseofsomeadhocreportsprimarilylookingatAEcountsandfrequenciesConsistentlocalSDSOPsUseofregulatorymethodologies(e.g.,EBGM)andthresholdsUseofexternaldatasourcesforbackgroundvaluesGlobalSDSOPsUseofmodelingtoolstoexplore“what-if”scenariosElectronictrackingofsignallife-cyclefromdetectiontoresolutionSDp。

9、rocessesintegratedwithriskmgtplansFulldatawarehouseincorporatingcross-organizationaldata(e.g.,marketing,etc.)ThoughtleaderinSDapproaches&methodologiesEstablishedcommunicationplanbetweenstakeholders1-Basic2345-Maturepvconnectpvnet5.FormalisedsignalmanagementprocessesBenchmarkfindingspvconnectpvnetHaveSOPsdescribingsignaldetectionandevaluationprocesses73%(11/15)93%(13/14)Treatinquiriesfromregulatoryagencies/DSMBsassignalsources73%(8/11)86%(12/14)Specifytimelinestoensuretimelyevaluationofsignals46%。

10、(5/11)50%(7/14)Documentactionstakenforsignalsthatprogresstofurtherevaluation80%(12/15)79%(11/14)Documentactionstakenforsignalsthatdonotprogresstofurtherevaluation80%(12/15)29%(4/14)Havesignaldetectionprocessesintegratedintoriskmanagementplans13%(2/15)36%(5/14)5.FormalisedsignalmanagementprocessesIndustryresponses•SignaldetectionSOPsintegratedintoSafetyRiskManagementprocesses•Consistentresponsibilitiesandaccountabilityforsignaldetectionandmanagement,especiallybetweenpre-andpost-marketing•Benefit-r。