Regulatory Aspects of Product Development ICH Process Q8, Q9, Q10.ppt

regulatoryaspectsofproductdevelopmentichprocessq8 q9 q10whoworkshop october2007 sultanghani directorbureauofpharmaceuticalsciencestherapeuticproductsdirectorate healthcanada focusofpresentation ichprocessichq8 q9 q10pharmaceuticaldevelopment ich backgroundichestablishedin1990asjointindustry regulatoryprojecttoimprovethroughharmonizationtheefficiencyoftheprocessfordevelopingandregisteringnewmedicinalproductsthefourthinternationalconferenceonharmonization ich4 brussels 1997marksthecompletionofthefirstphaseitwasagreedthatthesecondphaseofharmonizationcontinuetoensurethefutureactivitiesofich ich futureofichacontinuationofharmonizationactivity mechanismtoharmonizenewtechnicalrequirementsprocessforupdatingandsupplementingthecurrentichguidelinespreventfuturedisharmonythroughearlycollaborationandexchangeofinformation ich ichstructurefoundingmembers europeeuropeancommission ec europeanfederationofpharmaceuticalindustriesassociations efpia japanministryofhealthandwelfare mhw japanpharmaceuticalmanufacturersassociation jpma u s a u s foodanddrugadministration fda pharmaceuticalresearchandmanufacturersofamerica phrma ich ichstructure cont d othermembers observersworldhealthorganization who therapeuticproductsprogramme tpp europeanfreetradeassociation efta extendedworkinggroupmemberspharmacopoeialauthoritiesgenericindustryassociationnon prescriptionpharmaceuticalindustrysecretariattheinternationalfederalofpharmaceuticalmanufacturersassociation ifpma thefivestepsintheichprocessforharmonizationoftechnicalissues risk based conceptsandprinciplesofich newerawithnewchallenges q8 q9 q10 ref ich pharmaceuticaldevelopmentpaths designspaceforcontinuousimprovement q8isnotyetfinalizedbyich ich svisionofthefuture adaptedfromefpia pattopicgroup 2005 qbd awellknownconceptofthe50 sref outofcrisis 1986 w edwardsdeming dependingoninspectionisliketreatingasymptomwhilethediseaseiskillingyou theneedforinspectionresultsfromexcessivevariabilityintheprocess thediseaseisthevariability ceasingdependenceoninspectionmeansyoumustunderstandyourprocessessowellthatyoucanpredictthequalityoftheiroutputfromupstreamactivitiesandmeasurements toaccomplishthisyoumusthaveathoroughunderstandingofthesourcesofvariationinyourprocessesandthenworktowardreducingthevariation ceasingdependenceoninspectionforcesyoutoreducevariability ref http deming eng clemson edu pub den files varman txthttp deming eng clemson edu pub den files varman txt traditionalpdversusqbd traditionalproductdevelopment limiteddevelopmentandscale upworkfinalconfirmationbyvalidationof3batches worst case scenariossupposedtobeincludedmarketrecallsandunderutilizationofcapacityindicatethisapproachhashadlimitedsuccess qbd completeunderstandingofprocessandmonitoringofallcriticalsteps correctiveactionsaretakentopreventproductfailure acceptablequalityoftheproductisensured norecallsinnovationencouragedmaximizeutilizationofcapacity qualitybydesign traditionalprocessvalidationestablishdocumentedevidencewhichwillprovideahighdegreeofassurancethataspecificprocesswillconsistentlyproduceaproductmeetingitspredeterminedspecification qualitybydesign traditionalprocessvalidation cont d processvalidationprotocolthreelotsextensiveandfrequentsamplingmorethanroutinetestingprovenhomogeneitywithinalotconsistentproductqualitybetweenthreelots qualitybydesign traditionalprocessvalidation cont d welldocumentedprotocolandreportwellprepareddemothatproductcanbeproducedthreetimesresolutionofalldeviationinvestigationreportwithjustificationreviewandapproval qualitybydesign traditionalproductdevelopment complexmultivariatephysiochemicalsystemtreatedasuni variatesystem onefactoratatime materialsnotwellcharacterizedprocessfactorsnotwellunderstoodtimecrunchreluctantforpostapprovalchanges qualitybydesign traditionalestablishmentofproductspecificationcompendial mostly criticalprocessparametercanberelatedtoproductsafetyandefficacyasperclinicaltrialsbasedonprocesscapabilityliteratureexperience designspace qualitybydesign qualitybydesign definitiondesignofexperiment doe mechanisticunderstandingofhowformulationandprocessfactorsaffectproductperformanceandquality qualitybydesign definitionprocessanalyticaltechnology pat asystemofdesigning analyzingandcontrollingmanufacturingthroughtimelymeasurements duringprocessing ofcriticalqualityattributesofin processmaterialsandprocesseswiththeobjectiveofensuringendproductqualityineachlot qualitybydesign definitionriskmanagement systematicprocessfortheidentification assessmentandcontrolofrisktothequalityofpharmaceuticalacrosstheproductlifecycle fmea astructuredprocessforidentifyingthewayaproductorprocesscanfail qualitybydesign definitioncriticalqualityattributes cqa propertyofamaterial productoroutputofaprocessthatiskeytotheprocessperformance criticalprocessparameters cpp aprocessparameter e g temp time speed whenvariableitcanaffectthecqaofaproductorprocess causeandeffectanalysis c e aninvestigationaltooltofindandquantifythecauseandeffectrelationshipforaprocessorproductfailure qualitybydesign gooddoerequiresscientificunderstandingofhowformulationandprocessfactorseffectproductperformanceunderstandingandidentificationofcppandtheireffectsoncqaexperimentbasedontheprinciplesofstatisticsidentifyingandstudyingtheeffectandinteractionofproductandprocessvariablesuseofthemultivariatedataanalysis qualitybydesign riskassessmentprocessofriskassessmenttomitigaterisksidentifytherootcausesofprocessfailurehelppreventproblemsfromhappeningquantitativeprioritizationofpotentialfailureimprovequalityandreliabilityofproductdocumentedproofofactiontakentoreduceandeliminateriskskeyinputsofriskassessment qualitybydesign traditionalonlinecontrol qainspection statisticalandprocesscontrolsappliedatmanufacturingstage hardworkaftertheexamination futureofflinecontrol qualitybydesign statisticsandprocessengineeringapplicationatdesignphaseoftheproduct qualitybydesign establishmentofproductspecificationprovideassurancetomaintainproductqualityspecificationtoconfirmthequalityvscharacterizationlinkedtomanufacturingprocessaccountforthestabilitylinkedtopreclinicalandclinicalstudieslinkedtoanalyticalprocedures qualitybydesign theoutcomeprovisionofgreaterunderstandingofpharmaceuticalandmanufacturingsciencescreatesabasisforflexibleregulatoryapproachestablishingameaningfulproductspecification q6 andtherisk basedapproach q9 cancreateflexibilityforthecontinuousimprovement e g post approvalchanges withouttheneedforpriorapprovalsupplementindustrycanassistthecmcreviewerandgmpinspectorsbyprovidingtheoptionalinformationinctd qualitybydesign theoutcome cont d givesindustrytheopportunityviaaharmonizedstandardtorealizethefullpotentialofq8andtoutilizeq9encouragesandmotivatesindustrytoimproveandoptimizeprocesses equipment facilities systemsandproceduresgivesregulatorstheconfidencethatindustrycanberesponsibleforgreaterself managementofimprovementsandchangescompanieswithgoodqualitymanagementsystemswellcontrolledprocessesandproducts futurevisionisdrivenbyichq9 managerisktopatient basedonscience product processandfacilityrobustnessofqualitysystemrelevantcontrolstoassess mitigaterisklevelofoversightrequiredcommensuratewiththelevelofrisktopatientfor marketingauthorizationapplicationspost approvalchangereviewgmpinspections ref ich qualityriskmanagement quality degreetowhichasetofinherentpropertiesofaproduct systemorprocessfulfillsrequirements risk definedasthecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm management systematicprocessfortheassessment control communicationandreviewofriskstothequalityofthedrug medicinal productacrosstheproductlifecycle pharmaceuticaldevelopment todesignaqualityproductanditsmanufacturingprocesstodelivertheintendedperformanceoftheproducttoprovidescientificunderstandingtosupporttheestablishmentofdesign specificationsandmanufacturingproductdevelopmentstudiesformabasisofqualityriskmanagement pharmaceuticaldevelopment qualitycannotbetestedintheproduct itshouldbebuiltinbydesigndesignspaceproposedbyapplicantissubjecttoregulatoryassessmentandworkingwithinthespaceisnotachangemovementoutofdesignspaceisconsideredtobeachangeandrequirespost approvalchangeprocess pharmaceuticaldevelopment criticalaspectofdrugsubstances excipients containerclosuresystemandmanufacturingprocessshouldbedeterminedopportunitiesexisttodevelopmoreflexibleregulatoryapproach e g risk b