中美仿制药研发和申报流程--涂家生.ppt
- 文档编号:18691138
- 上传时间:2023-09-14
- 格式:PPT
- 页数:59
- 大小:4.24MB
中美仿制药研发和申报流程--涂家生.ppt
《中美仿制药研发和申报流程--涂家生.ppt》由会员分享,可在线阅读,更多相关《中美仿制药研发和申报流程--涂家生.ppt(59页珍藏版)》请在冰点文库上搜索。
中美仿制药研发和申报流程,涂家生,Ph.D.中国药科大学药剂学教授Tel:
025-83271305Email:
2011.11郑州,我国仿制药申报、审评和研发对策,主要内容,中美关于原研药和仿制药的背景,美国仿制药:
申报、基于问题的审评和研发对策,展望,1,2,3,4,CompanyLogo,3,药物经济学催生美国仿制药制度,美国社会安全制度导致政府赤字严重SSA已经破产:
如何破局?
降低医疗费用成为必然Hatch-Waxman法案出台美国FDA药品注册申请:
新药(两类)、仿制药和非处方药申请,1984年后,NewDrugApplications(NDAs),AbbreviatedNewDrugApplications(ANDAs),“FullReports”ofSafetyandEfficacyInvestigationsApplicanthasrightofreferencetoessentialinvestigations?
DuplicateofanalreadyapprovedproductNosafety/efficacydatapermitted(onlybioequivalence),505(b)
(1),505(b)
(2),505(j),NDA的研发和申报,505(b)
(1)新药申报资料内容,IndexSummaryChemistry,ManufacturingandControlSamples,MethodsValidationPackageandLabelingNonclinicalPharmacologyandToxicology,6.HumanPharmacokineticsandBioavailability7.Microbiology(foranti-microbialdrugsonly)8.ClinicalData9.SafetyUpdatereport(typicallysubmitted120daysaftertheNDAssubmission),10.Statistical11.CaseReportTabulations12.CaseReportForms13.PatentInformation14.PatentCertification,505(b)
(2):
历史过程,HatchWaxman法案:
1984ParkmanLetterPhantomANDAFDADraftGuidanceforIndustry(1999)FDAResponsetoCitizensPetition(2003)可以降低研发的费用和审评力量的浪费,505(b)
(2)的关键:
可靠性,Whatis“Reliance”Bywhom?
Onwhat?
RelianceandExclusivityMarketvs.DataExclusivitySafety/EfficacyDatavs.CM&CdataFDAProcessforDeterminingRelianceWho,whenandhow?
505(b)
(2)的意义,介于全创新药物和仿制药之间具有专利保护,且不存在产权纠纷和仿制药不同,无替换的要求应有突破,505(b)
(2)范围,NewChemicalEntity(rarely):
我国1.1-1.3Newdosageform:
我国5类Newdosingregimen:
我国补充申请Newstrength:
我国补充申请Newrouteofadministration:
我国2类Newindication:
我国1.6,505(b)
(2)情形,Newactiveingredient(differentsalt,ester,complex,chelate,clathrate,racemate,orenantiomerofactivemoiety)NewinactiveingredientthatrequiresmorethanlimitedconfirmatorystudiesRxOTCswitchNewCombinationProducts“Genericbiologics”,505(b)
(2)排他性,Exclusivitiesavailablefor505(b)
(2)productsNCEExclusivity(5years)NewProductExclusivity(3years)OrphanDrugExclusivity(7years)Pediatricexclusivityextensions(6months)PatentIssues505(b)
(2)drugscanhaveOrangeBook-listedpatents,andenjoy30-monthstayprotectionagainstgenericcompetitorsBut,505(b)
(2)NDAsmayalsobeblockedbypatentsonReferenceDrugs,505(b)
(2)新药的成功例子,NCEThalomid(thalidomide)(1998)MarketedunapproveddrugsLevothyroxine(2000)Guaifenesinextendedrelease(2002)Quininesulfate(2005)NewDosageFormTramadolorallydisintegratingtablets(2005)Ondansetronoralspray(filed2006),505(b)
(2)新药的例子,NewDosingRegimenTramadolextendedreleasetablets(2005)NewStrength/FormulationAntara(micronizedfenofibratecaps)(2004)(130mgisBEtoTricor200mg)NewFormulation/InactiveIngredientAvita(tretinoingel)(newemollient)(1998)Abraxane(cremaphor-freepaclitaxel)(2005)Oxy-ADF(oxycodoneformulatedtoreducedrugabuse)(indevelopment),505(b)
(2)新药的例子,NewActiveIngredientPexeva(paroxetinemesylate)(newsalt)(2003)NewRouteofAdministrationEmezine(prochlorperazine)(newbuccal/transmucosaldelivery)(NDApending)Oralamphotericin-B(pre-clinical)RxOTCSwitchAlavert(loratadine)(2002),505(b)
(2)新药的例子,“GenericBiologics”Omnitrope(rHGH)(2006)Glucagen(glucagonrecombinant)(1998)Hyaluronidase(variousapprovals2004-05)Fortical(calcitoninsalmonrecombinant)(2005)*Examplesbasedonpubliclyavailableinformation,FDANDA审评过程,FDA可以使用已有数据用于审评NDA吗?
Hatch-Waxman之前,国会限制FDA在审评NDAX时应用NDAY的数据:
“NodatainanNDAcanbeutilizedtosupportanotherNDAwithoutexpresspermissionoftheoriginalNDAholder.”FDA“FinkelMemorandum”(1978,1981)Hatch-Waxman解除只适合ANDAs:
ANDAprocessallows“genericproducerofthefullytesteddrugtorelyonthesafetyandefficacydataofapriorapplicant.”505(b)
(2)doesnotauthorizesuchdatarelianceMerelysetsconditionsforcertainNDAsRequires“fullreportsofinvestigations”establishingsafetyandeffectiveness21USC355(b)
(1)(A),(d)
(1),美国仿制药,Agenericdrugproductisonethatiscomparabletoaninnovatordrugproduct(alsoknownasthereferencelisteddrug(RLD)productasidentifiedintheFDAslistofApprovedDrugProductswithTherapeuticEquivalenceEvaluations)indosageform,strength,routeofadministration,quality,performancecharacteristicsandintendeduse.,Genericdrugapplicationsaretermed“abbreviated”inthattheyaregenerallynotrequiredtoincludepreclinical(animal)andclinical(human)datatoestablishsafetyandeffectiveness.Theseparameterswereestablishedupontheapprovaloftheinnovatordrugproduct,whichisthefirstversionofthedrugproductapprovedbytheFDA.,FDA审评仿制药程序,二、美国仿制药的申报、审评和研发对策,由FDA的OGD审评审评方式采用QbR申报资料采用CTD资料内容也针对问题,OfficeofGenericDrugs,如何保证审评质量和效率?
StructuredProductLabeling(SPL)MakeslabelingavailableonInternetviaNationalLibraryofMedicine(NLM)ReviewEfficienciesEarlyDMFreviewClusterreviewsproductspecialistsSupplementtriagingatteamleaderlevelDBETruncatedReviewQuestionbasedReview(QbR)Willhaveaverypositiveimpact,NewresourcesdevelopedDissolutionDatabaseIndividualProductBioequivalenceInformationEncouragedtheuseoftelephoneinreviewprocessIncreasedthenumberof1stcycleapprovalsDecreasedthetotalnumberofreviewcyclesTotaltimetoapprovaldidnotincreaseinspiteofincreasedworkload,ben,ThisguidancecontainsanInternetlinktoalistingofdrugproducts,eachlinkedinturntoacorrespondingbioequivalencerecommendation.Clickingonaproductnameinthatlistwillbringupthebioequivalencerecommendationsforthatspecificproduct.Recommendationshavebeendevelopedforseveraldrugsthatarenotyeteligibleforgenericcompetition(i.e.,newlyapprovedproducts)andsomeolderproductsforwhichinformationhaspreviouslybeenprovided.Asadditionalrecommendationsaredeveloped,thosewillbepostedontheWebsite.Whenthisguidanceisfinalized,thelistingwillbeavailablethroughtheAgencysWebpage.,QbR:
从提出到完善,1/20052/2005:
Question-basedReviewDrafted3/20054/2005:
DivisionDirectorsDiscussion5/20056/2005:
TeamLeadersDiscussion7/20058/2005:
ReviewersDiscussion9/20051/2006:
ModelPharmaceuticalDevelopmentReportandQualityOverallSummary2/200512/2005:
DiscussionswithStakeholdersandUpperManagement1/200512/2006:
GradualImplementation1/2007:
FullImplementation,QbR的内涵,Question-basedReviewisageneralframeworkforascienceandrisk-basedassessmentofproductqualityQuestion-basedReviewcontainstheimportantscientificandregulatoryreviewquestionsto关键制备工艺及其质控产品的工艺、处方是否有设计缺陷强调QbD,ANDAsUnderQbR(Continued),FutureGenericApplicationsgenericsponsorssubmitgenericapplicationsbasedontheformatofICHCTD,preferably,electronicallyModule1:
AdministrativeInformationModule2:
QualityOverallSummaryandClinicalSummaryModule3:
QualityPharmaceuticalDevelopment;QualitybyDesignModule4:
NonclinicalModule5:
Clinical(Bioequivalence),新药申报(NDA)和仿制药申报(ANDA)的比较,NDArequirements,ANDArequirements,美国仿制药申报,FDA仿制药部(OGD)鼓励申请人根据ICH对于人用药物的注册技术要求,即通用技术文件(CTD)的格式,提交ADNA。
包括以下模块:
OGDQBRThequestionbasedreview(QBR)servesasageneralframeworkfortheCMCassessmentofANDAsthatfocusesoncriticalpharmaceuticalattributesofproductquality.Withjustification,deviationsoralternateapproachestothisframeworkcanbeutilize,asnecessary,toensuretheadequacyoftheassessmentofproductqualityForeaseofdiscussion,asimpledosageformisdefinedasasolutionoranimmediaterelease(IR)solidoraldosageform.,QBR:
DrugSubstance,DescriptionandCharacterizationWhatarethenomenclature,molecularstructure,molecularformula,andmolecularweight?
WhatarethepKa,aqueoussolubility(asfunctionofpH),partitioncoefficient,polymorphism,hygroscopicity,andmeltingpoints?
ControlofDrugSubstanceAppearanceandIdentificationArethespecificationsforappearanceandidentificationappropriate?
AssayIstheproposeddrugsubstanceassaylimitacceptable?
Istheanalyticalmethodvalidatedandstability-indicating?
ImpuritiesandResidualSolventsAreallthepossibleimpuritiesaccountedfor?
Whatisthejustificationfortheimpurityacceptancelimits?
Aretheanalyticalmethodsvalidatedandsuitablefortheirintendedfunction?
AdditionalSpecificationsBasedonthereviewofthedrugproductandmanufacturingprocessarespecification(s)requiredonparticlesize,solidstateform,moisturecontent,orotherpropertiesofthedrugsubstanceandwhy?
Foreachadditionalspecification:
Whatisthejustificationfortheacceptancelimit?
Isitsuitableforitsintendedfunction?
QBR:
DrugProduct,DescriptionandCompositionWhatarethecomponentsandcompositionofthefinalproduct?
Whatisthefunctionofeachexcipient?
DoanyexcipientsexceedIIGlimitsinthecontextofmaximumdailydoseandrouteofadministration?
IfproductisanNTIdrugoranon-simpledosageformAretheresignificantdifferencesbetweenthisformulationandtheRLDthatpresentpotentialconcernswithrespecttoproductperformance?
ControlofExcipientsWhatarethespecificationsfortheinactiveingredientsandaretheyappropriatepertheirintendedfunction?
SimpleDosageForm:
EitherasolutionoranIRsolidoraldosageform,QBR:
DrugProduct(Continued),ManufactureForallproductsDoesthebatchformulaaccuratelyreflectthedrugproductcomposition?
Ifnot,whatarethedifferencesandthejustifications(e.g.potencyadjustment,overage,excesscoatingsolution,etc.)?
IfproductisnotasolutionWhatarethekeyunitoperationsinthedrugproductmanufacturingprocess?
Arein-processtestsidentifiedbythesponsorappropriate?
Whatisthedifferenceinsizebetweencommercialscaleandbiobatchanddotheyusethesameunitoperations?
IfproductisanNTIdrugoranon-simpledosageformWhatarethecriticalstepsinthemanufacturingprocess?
Whatarethein-processtests/controlsthatensureeachcriticalstepissuccessful?
Intheproposedscaleupprocesswhatoperatingconditionswillbeadjustedtoensuretheproductmeetsallin-processandfinalproductspecifications?
Whydoyoubelievethesponsorhas
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 中美 制药 研发 申报 流程 涂家生