影音下載電影電視劇使用幫助

02四月2024影音下載電影電視劇使用幫助02四月2024影音下載電影電視劇使用幫助1CharlesDiLibertiV.P.GlobalPharmacokineticsandBioequivalence,BarrLaboratories,Inc.CharlesDiLibertiV.P.GlobalP2“CommercialOpportunitiesandChallengesforFollow-onBiologics”“CommercialOpportunitiesand3PresentationOverviewGenericBiologicsCommercialOpportunities&SavingsScience&TechnologyChallengesRegulatory&IntellectualPropertyIssuesSummaryPresentationOverviewGenericB4CommercialOpportunities&SavingsCommercialOpportunities&Sav5BenefitsofGenericCompetitionSignificantCostSavingOpportunitiesSavingsforconsumersandtaxpayersGenericCompetitionWillFuelInnovationBrandcompanieswillhavetheincentiveneededtovigorouslypursuenewbiologics

BenefitsofGenericCompetitio6IncreasingSignificanceofBiologicProductsUSBiologicRevenues1997:$17.4Billion2007:$65.2Billion*400Biologics&VaccinesCurrentlyinClinicalTrialsTargeting>200Diseases**Between2003and2006,biologicsrepresented24%ofallnewchemicalentitiesapprovedbytheUS***

SalesofbiotechproductsintheUSshowedanannualgrowthrateof20%between2001and2006comparedwith6%to8%inthepharmaceuticalmarket****Ernst&Young**BiotechnologyIndustryOrganization***JournalofAmericanMedicalAssociation,October22,2008IncreasingSignificanceofBio7HighCostofBrandBiologicsAnnualCostperPatient

Enbrel(Arthritis)

$20,000*Cerezyme(GaucherDisease)$200,000**

Remicade(Arthritis)$35,000-$66,000***GenericCompetitionWillReduceTheseCosts*BaltimoreSunJanuary28,2007**BloombergJanuary11,2007***PhiladelphiaInquirerSeptember19,2006HighCostofBrandBiologicsAn8SignificantCostSavingsOpportunityGenericBiologicsRepresentSignificantCostSavingsOpportunitiesandStimulateInnovationEpogenMarketBeforeGenericLaunch:$2.5Billion*Brand/YearToday:$9,000**GenericSavings/Yearassuming50%savings:$4,500EnbrelMarketBeforeGenericLaunch:$2.7Billion*Brand/YearToday:$20,000***GenericSavings/Yearassuming50%savings:$10,000*ABNAMROFebruary2008**NationalJournalFebruary10,2007***BaltimoreSunJanuary28,2007SignificantCostSavingsOppor9GenericCompetition

PriceDropsasNumberofManufacturersIncreasesGenericCompetitionPriceDrop10MarketSizeforSelectBiologicProductsSource:ABNAMROFebruary2008MarketSizeforSelectBiologi11MarketSizeforSelectBiologicProductsSource:ABNAMROFebruary2008MarketSizeforSelectBiologi12Perspective:

HistoricalGrowthinSubstitutionSource:IMSHealth,BancofAmericaSecuritiesLLCestimatesPerspective:

HistoricalGrowth13GenericBiologics

OpportunityGenericPharmaceuticals-AVitalPartinHealthCareSystemApproximately67%ofthePrescriptionsDispensedintheUSAreGenerics*BiologicsWorldwideMarketEstimatedaround$75Billion*PerPatientCostforBiologicProductsCanExceed$100,000PerYearGenericBiologicsUSConsumersCouldSave$43BillionBetween2011and2020**EstimatedValueofBiologicsthathavealreadylostPatentProtection:$10Billion***EstimatedValueofBiologicstolosePatentProtectionintheNextTenYears:$20Billion****IMSHealth**CitizensAgainstGovernmentWaste(CAGW)Release,May2,2007***ABNAMROFebruary2008GenericBiologics

OpportunityG14Science&TechnologyChallengesScience&TechnologyChallenge15ScientificChallengesforGenericBiologicsCharacterizationSafetyAssessmentTherapeuticEquivalenceManufacturingControlsScientificChallengesforGene16GenericBiologicsGenericbiologics,sometimescalledfollow-onbiologics(FOBs),areproteinproductsthatarepharmaceuticallyandtherapeuticallyequivalentGenericbiologicsdonotutilizethereferenceproduct’sproprietaryprocess,specificationsorclinicaldataForestablishedproducts,therapeuticequivalencecanbedemonstratedusingInvitrostudiesand/orPharmacokineticsand/orSurrogatemarkersand/orClinicaloutcomes dependingonthecharacteristicsoftheproteinGenericBiologicsGenericbiolo17Interferon2804atomsMonoclonalAntibody21112atomsrDNATechnologyDrugs:Filgrastim(G-CSF)2659atomsBiologics

SizeDoesMatter...Azithromycin124atomsChemicalDrug:InterferonMonoclonalrDNATechn18MisinformationCampaignAboutGenericBiologicsMyth:Rawmaterialsofbiologicoriginarehardtosourceandonlybrandbiotechsknowwheretofindthem.Reality:Rawmaterialsareavailabletodayformanygenericbiologicsincludinginsulin,G-CSF,erythropoietin,interferons,etc.MisinformationCampaignAbout19MisinformationCampaignAboutGenericBiologicsMyth:Biologicsaretoocomplicatedtobecharacterized.Reality:Numeroushighlysophisticatedanalyticalmethodshavebeendeveloped,permittingcompletecharacterization.Moreadvanceswillbeachievedeachyear.MisinformationCampaignAbout20MisinformationCampaignAboutGenericBiologicsMyth:Genericcompanieslackthemedical,scientific,andtechnicalabilitytoproducesafeandeffectivebiotechproducts.Reality:Genericcompaniescananddomakesafeandeffectivebiologics.ManysafeandeffectivebiologicscurrentlyaremadeincontrolledenvironmentsandmarketedbygenericcompaniesoutsidetheU.S.

MisinformationCampaignAbout21GenericBiologics(Biosimilars)intheEUTheabilitytomakegenericbiologicsisfarfromatheoreticalpossibility.In2004EUissuedEMEADraftGuidelinesforfourclassesofgenericbiologics,referredtoasbiosimiliarsintheEU.Since2004,theEUhasapprovedseveralbiosimilarproducts.GenericBiologics(Biosimilars22EUBiosimilarApprovals DRUG EUMARKETAUTHORIZATIONDATESandoz’sOmnitrope?

(somatropin) April12,2006

BioPartners’Valtropin?

(somatropin) April24,2006

Sandoz’sBinocrit?Medice’sAbseamed?HexalBiotech’sEpoetinalfaHexal?

(recombinanthumanerythropoietinalfa) August28,2007StadaArzneimittel’sSilapo? Hospira’sRetacrit? (epoetinzeta) December18,2007Teva’sTevagrastim? Ratiopharm’sRatiograstim?Ratiopharm’sFilgrastimratiopharm?CTArzneimittel’sBiograstim? (humanG-CSF) September15,2008currentthroughSeptember25,2008EUBiosimilarApprovals DRUG 23FDAApprovesSandoz’sOmnitropeTherehasbeensomemovementintheUStoapprovegenericbiologics.FDAapprovedOmnitropeinMay2006.FDAstated,however,thatthisapprovaldoesnotcreateapathwayforallgenericbiologics.Omnitropereferencedabrandproduct(Genotropin)approvedundertheFDCA.FDAApprovesSandoz’sOmnitrop24MisinformationCampaignAboutGenericBiologicsMyth:“TheProductistheProcess.”Reality:“Oldmodelsandmantrasareinhibitingprogress–theproductisnolongertheprocess.”(StatementofMathiasHukkelhoven,Ph.D.,SeniorV.P.,GlobalHead,DrugRegulatoryAffairs,Novartis,Sept.14-15,2004).MisinformationCampaignAbout25MisinformationCampaignAboutGenericBiologicsReality(continued):Biotechproductscanbefullycharacterizedandcomparedanalytically.BiotechFirmsroutinelyjustifytheirownprocesschangesviaFDAapprovedcomparabilityprotocols.MisinformationCampaignAbout26Developmentof

GenericBiologicsStrictlyControlledProcess(Validated)ExtensiveAnalyticalComparability(Characterization)ComparableBiologicalActivity(InVitro/InVivo)Non-ClinicalComparability(Safety,Immunogenicity...)Comparablepharmacokinetics(bloodconcentrationprofile)ComparableClinicalEfficacyandSafetyDevelopmentof

GenericBiolog27DevelopmentConsiderationsProductComplexityFromDevelopmentToClinicalCharacterizationBiosynthesis,In-ProcessandFinishedProductNomenclatureLackofStrictDefinition,INNIssueHighCostofDevelopmentMarketingRequirementsandCostPost-MarketingSafetySurveillanceIPStrengthDevelopmentConsiderationsProd28Regulatory&IntellectualPropertyIssuesRegulatory&IntellectualProp29ChallengesforGenericBiologicsRegulatoryCongressneedstocreateanabbreviatedapprovalpathwayIntellectualPropertyBrandexclusivityGenericexclusivityResolutionofpatentlitigationpriortogenericlaunchChallengesforGenericBiologi30RegulatoryIssuesRegulatoryFrameworkComplicatedByExistenceofTwoLawsForBiologicsFDCAforNDAProductsPHSAforBLAProductsNDAProductsGenericPathwayExits,ButFDAImplementationIsUnclear BLAProductsThreeIssuesNeedToBeResolvedMechanicsofApprovalPathwayNeedToBeDefinedBrand/GenericExclusivityAnEfficientPatentDisputeResolutionMechanismRegulatoryIssuesRegulatoryFr31AbbreviatedGenericPathwayUnderPHSAAGenericPathwayShould:GiveFDAAuthorityToDecideApprovalRequirementsForGenericProductsAdoptExclusivityProvisionsNoGreaterThanThoseFoundInHatch-WaxmanPermitPre-LaunchAdjudicationofCertainPatentDisputesAbbreviatedGenericPathwayUn32AbbreviatedGenericPathwayUnderPHSAFDAshouldbepermittedtodecidewhattests/dataarenecessaryforapprovalasacomparableorinterchangeablegeneric.Congressshouldnotimposeunnecessarybarrierstogenericapprovals,e.g.,mandatoryguidanceorrule-makingrequirements;mandatoryclinicaltrials;requirementthatgenericsseekapprovalforallapprovedbranduses.AbbreviatedGenericPathwayUn33AbbreviatedGenericPathwayUnderPHSACongressshouldcarefullyconsideranynew,additionalexclusivitiesawardedtobrandbiologics.Considerableincentivesalreadyexistforbrandbiotechcompanies.AbbreviatedGenericPathwayUn34ExistingIncentivesforBrandBiotechCompaniesExistingIncentivesforBrand35AbbreviatedGenericPathwayUnderPHSAIfCongressdecidestogiveadditionalexclusivitiestobrandcompanies,Hatch-Waxmanestablishesthemaximumlengthandnumberofexclusivitiesthatcanbejustified:

-5yearsfortrulynew,innovativeproducts -3yearsforcertainimprovementstoalready-approvedbrandproductsAbbreviatedGenericPathwayUn36AbbreviatedGenericPathwayUnderPHSAUnliketheincentivesthatalreadyexisttodevelopnewbrandbiologics,noincentivesexisttodevelopgenericbiologics.Genericbiologicslegislationshouldincludeanincentive,justasHatch-Waxmandoesforsmallmoleculedrugs,forthedevelopmentofgenericbiologics.AbbreviatedGenericPathwayUn37AbbreviatedGenericPathwayUnderPHSAEffectivegenericbiologicslegislationwillincludeamechanismforexpeditiousresolutionofpatentdisputes.Hatch-Waxmanhasshownthatpatentmechanismscanbeabusedtodelaygenericmarketentry.AbbreviatedGenericPathwayUn38AbbreviatedGenericPathway