1029-19c国际生物制药工厂的趋势与未来王家麒GE

生物制药工厂的趋势与未来Oct2014生物制药工厂的趋势与未来Oct2014GEHealthcareLifescienceEnterpriseSolutionSalesManagerJeffWanggƒ全球生物制药概况及需求ƒ全球生物制药概况及需求ƒ生物制药的历史与演进生物制药的历史与演进ƒ不锈钢vs一次性ƒ工艺设计和厂房设计策略Whereisthecapacity?Reference:“TheStateofMammalianCellCultureBiomanufacturreportpreparedbyBioprocessTechnologyConsultants(BPTC),2100,000LSelectedmanufacturingsitesRoche,VacavilleI:150,000LRoche,SSF:96,000LPfizer,GrangeCastle:75,000LBiogenIdec,DK:90,000LLonza,Portsmouth:100,000LAmgenBioNext135000L,50,000L10,000LAbbott,PuertoRico:62,000LAmgen,PuertoRico:80,000LBIP,Biberach:180,000LRoche,Basel/Penzberg:95,000LLonza,Porriño:40,000LNovartis/Sandoz:120,000LBIP,Fremont:32,000LRoche,NIMO:90,000LAmgen,BioNext,135,000LBMS,Devon:120,000LEliLilly,BB50:110,000LBiogenIdec,RTP:100,000LSignificantfacilitiesmothballed:RhVillII200000L(2010)Celltrion,Incheon:50/140,000LChugai,Utsunomiya:80,000LLonza,Singapore:85,000LRoche,Singapore,80,000L•Roche,VacavilleII:200,000L(2010),re-opening•Roche,Penzberg:75,000L(2010)•Amgen,BioNow:64,000L(2007)•EliLilly,BB36BranchburgNJ:30,000L(2010)•GenMab,BrooklynParkMN:20,000L(2009)Affordabilityversusdemandelsewhere!100,000LSelectedmanufacturingsites,50,000L10,000LEmergingmarketsdemandbuild-upoflocalbilicapability:•Brazil•Russia•India•China•MiddleEast单抗Mab市场概况及预估单抗市场概况及预估Mabsusage10g/100000population25%CAGR•ProjectionfromEvaluatePharmaconsideringglobal10g/100,000population10–200g/100,000population200–1000g/100,000populatio25%CAGRjggacceptanceofbiosimilarin2015onwards•BiosimilarmAbstoaccountfor8%oftotalmAbssalesin2018Source•EvaluatePharma2018•SkyQuest四种单抗BiologicMoleculename(Qtyandsalesin2011)ClinicalKeyPatentexpiryHerceptin-RocheTrastuzumabEarlystageHER2-positivebreastcancer,advancedstomachcancer2014EU,Japan;2019USRoche($5.7Bn)~961kgHumanizedRituxan-RocheRituximabNon-Hodgkin’slymphoma,RA,FollicularEnd2013EU,2018US($7.8Bn)~1360kglymphomaGoldstandardforNHLChimericAvastin-RocheBevacizmab($6.3Bn)MetastaticcolorectalcancerAdvancednon-smallcelllungcancer,AdvancedbreastcancerAngionesisinhibitorUS/EU2019*()`1200kgAngionesisinhibitorHumanizedErbitux-MerckkGACetuximabMetastaticcolorectalcancerheadandneckcancer.2014kGA($2Bn)`460kgEGFRinhibitorChimericSource:•IMSHealthDatabase2011•Citeline:BiosimilarMonoclonalAntibodiesinthePipeline:MajorPlayersandStrategies,•Citeline:Drug-Development-Overview-Biosimilar-Monoclonal-Antibodies-16-May-2012.pdf•四种单抗未来市场预估四种单抗未来市场预估Additional~3000-9000kgofmAbsarerequiredin2020~202520202025Source:IMSHealthdata2009-2013formAbsdemandin2013生物制药的历史与演进历史演进100%StainlessFixedSystems,SilPdtSSSystems,DisposablesforTODAYIntegrated,singleusemodular,portableSingleProductMedia,BuffersMid90s,pFlexFactory™1980’s20022002100%StainlessFixedSystems,Multi-Product哺乳细胞培养演进Producttitre哺乳细胞培养演进Slightlyre-writtenhistory…ofanotherwisefantasticdevelopment50-1,000mg/L1,000-5,000mg/LacceptabletogoodefficiencyProducttitre…5-50mg/Lbarelyjustifiableglargelyinefficient…matchingneedforMabs5,000mg/Lquestionable1982-19852005-20101985-2005questionablebenefits2010tPAIfanalternativehadexisted(andmAbs&EtanerceptThelowproductivityofcellcultureLegacymAbsTechnologyisheretoproduce“any”FutureprocessesAt5g/La4x1,000Lfacilitycanproduce350kg*)700withthecurrentviewoncost),mammaliancellculturewouldnothavebeenchosencellculturestartedthetrendtobuildextremelycostly,huge6to12-kbittoproduceanyrealisticquantityofproteintherapeutics.Legacyupstreamproduce350kgmAbannually*).Goodfitwithavailablesingle-usereactors,0kgwith4xhavebeenchosentoproduceglycosylatedbiopharmaceuticalspackbioreactorfarmswitheconomicissuesuntiltodayinefficienciesnowcreatebarriersforimprovement&changeofprocessandfacilitypurificationsteps,andmarketdemand.Moretitermightbeless…x2,000LfacilityCHO细胞株已可达到3-6g/L…细胞株可达到g/Goodtitersenablesmallscale,economicalproductionmAb1mAb2ProduceenoughANDlbexperimentalLargesurplusofANDlearnaboutprocess(3runs)materialin1run,expensivelearningMammaliancellcultureproductivityisnoweconomicallyviable:•LegacyprocessesforRAandcancermAbsoftendeliveredbelow1/Ldibhllbidil1g/Lproducttiter,buthavegenerallybeenimprovedinlateryears•Manymodernprocessesreach4-5g/Lproducttiterorevenhigher•Experimentalbatcheshaveachieved7g/Lrecently,longbatchtime(!)()纯化技术演进纯化技术演进MonoclonalAntibodiesin15,000Lbioreactors,10%lossinharvestingScaleproportionalScaledecoupledUpstreamtechnologypptoproductmasspfromproductmassDownstreamtechnologyNxtgenproductionrateCelllevelpurificationPurifyduringharvestDecoupleDSPDepthfiltersVariousplantfitCurrentgenproductionrateDepthfiltersFlow-throughmodeMultimodalresins3rdvirusclearanceMbSltSRimprovements1stgenproductionrateContinuousprocessingCombinedunitoperationsIn-linebuffer/adjustmentMabSelectCaptoMabSelectSuReMabSelectSuReLXCaptoCaptoImpResPlantfitlimits不锈钢vs一次性不锈钢vs次性优势与劣势优势与劣势工业生产对一次性产品观点产对次性产品观点•Lowercapitalinvestment•Lowervalidationcost(egSIPCIPmethods)•Lowervalidationcost(e.g.SIP,CIPmethods)•Lowercleaningcosts–personnel,productchangeover,water,steamandchemicals•Standardizeandmodularize–lesscosttochangeandoperate