1、创新药物研发创新药物研发北京到新泽西的路北京到新泽西的路程有多远？程有多远？2011年3月23日孟凡强 博士，总裁北京翰博瑞强医药科技有限公司H&J CRO International,Inc.2022-12-41内容提要内容提要中国是药品消费大国，但在国际上是创新药品研发小国。知耻近乎勇。我们与美国新泽西的药物研发中心有较大差距，具体表现在以下几个方面：药品研发技术和CRO公司的整体水平低下 v.s.十分成熟的研发技术和CRO公司IT技术整体低下，不足以支撑创新药物研发 v.s.Linux Version Control 等IT技术，使得所有研究数据可以溯源临床试验操作不规范，关键证据(TM
2、F)漏洞百出 v.s.临床试验各环节认真负责，临床医生自我约束力高，文件管理严谨，数据证据链完整数据管理和统计分析技术低下，专业人才缺乏 v.s.专业的、高度职业化的DM和SA研发企业与CRO未形成风险共担的系统，两者是简单的雇佣关系 v.s.伙伴关系新药研发法规滞后 v.s.对研发的政策法规支持大众对知识产权保护普遍缺乏 v.s.对知识产权的尊重研发者急于求成的态度偏差 v.s.极力证明“可能不行”我们有学习的目标，努力的方向，国家的大力支持，研发企业的努力，大量“海归”人才，相信在不远的将来，达到世界先进水平！2022-12-42China:New Silicon Valley of R&
3、D?Pharmaceutical sales:l2010 +27%,2011+24%(938.8 Billion RMB)lOTC 2009,World Number 2,2nd to USAR&D InvestmentlChina invested 6 Billion RMB 2009lR&D China invested 7 Billion lShandong:1.2 Billion R&D PlatformlChengdu:Bio-valleylWuxi:Huishan Life-parklTianjin:2022-12-43Our R&D AchievementThousands of
4、“Mimic Drug”not“Generic”So called“New Drug”,actually notGenerics apply marketing in US,the game played by India company for more than 10 yearsNDA with international patent=02022-12-44How far from BJ to NJ2022-12-45How far from BJ to NJR&D Technology&CRO Professional LevellInformation TechnologylClin
5、ical Trial Operation(TMF)lData Management and StatisticslMutual support between Sponsor and CROR&D Policy&RegulationsPublic Conscious of IP protectionR&D Conception2022-12-46Information TechnologyItemsChinaUSAServer Operating SystemWindows Unix or LinuxOperation PlatformLocal computersCentral Server
6、Server ManagementMost companies delegate their servers to professional IT company for managementHave an independent department for IT service and server managementNetwork Speed2 Mbps15MbpsData BackupBackup data in IT vendor or backup data in local diskMost companies use RAIDIT Specialist collocation
7、13 IT specialist(s)in a companyUsually every 10 employees have 2 IT specialists 2022-12-47IT InfrastructureFirst Domestic CRO with qualified IT support 5 IT staff(1 EDC,1DM,1Web/Mail,2 Security)Disaster Backup in NJDM/SAS on server Version control VPN remote desktopLinux Operation System2022-12-48Cl
8、inical Trial OperationSponsorItemsChinaUSAVendor SelectionPrefer cheaper vendorsPrefer vendors with good history on cooperation and qualityBudget$500,000 commonlyDifferent budget on different trial phaseInvestigational ProductFocus on Generic Drugs and Listing Drugs New Drugs,also have Listing Drugs
9、 Trials TypeMost of Phase IV trials or Post-marketing studiesMost of Phase I to III for RegistrationExpectation on ResultHave a good result on trial objectsResult presented on true data2022-12-49Compare on Clinical Trial Operation2InvestigatorItemsChinaUSASite ScaleHospitals in Medical Center Level
10、Private clinics or Regional HospitalsAttitude for TrialsMost of Investigators dont care their trialsPay more attention to the trials he/she participatesPerformance on TrialsProtocol or SOPs Deviations/Violations appear commonlyGood compliance with Protocol and SOPsCooperation with CRAHave an arrogan
11、t attitude to CRAsTake a good cooperation with CRACorrespondences between Investigators and CRAsA few of Investigators answer the Emails/Fax from CRAMost of Investigators answer the Emails/Fax from CRA if CRA requires2022-12-410Compare on Clinical Trial Operation3Contract Research Organization(CRO)1
12、ItemsChinaUSACRO Scale10100 employee commonly501000 employeeDescriptionProvide a full services on trialDivide the trial for different steps and provides a very professional service on one step among those,e.g.just for Data ManagementCRA QualificationMost of CRAs are trained by GCP and SOPs but have
13、little experience on monitoringWell-trained and also have abundant experience2022-12-411Compare on Clinical Trial Operation4Contract Research Organization(CRO)2ItemsChinaUSASOP SystemHave SOP framework and have SOPs on critical trial steps Have very detailed and systemic SOPs on every steps on the t
14、rialsSOP OperationCan follow SOPs but SOP Deviations/Violations appear usuallyFollow SOPs strictly and every SOP Deviations/Violations can be record carefullyTrial Data QualityMost of data on CRFs can be SDVed by CRAs,but there also have some fraud on trialsCRO and Investigators take an honest perfo
15、rmance on trials,and also collect data by protocol/SOPs requires 2022-12-412Compare on Clinical Trial Operation5Contract Research Organization(CRO)3ItemsChinaUSASubjects Protection on TrailsTake informed consent action and get signed ICF.A few of trials can provide indemnification Take informed cons
16、ent action strictly and get signed ICF.Most of trials can provide indemnification 2022-12-413Compare on Data Management and Statistics1Data Management1ItemsChinaUSAData Management SOPsA few companies have SOPs on this section,also with poor complianceHave professional companies in this section and t
17、hose companies have systemic SOPs Database Formatone OBS is in one line.And without uniform format for submission to SFDARaw Data is saved as SDTM-Like.And should be submitted to FDA by SDTM formatStandard for Database Design and CRF Design NoCDASH2022-12-414Compare on Data Management and Statistics
18、2Data Management2ItemsChinaUSAElectronic Data StorageLocal computersData can be stored in Central Servers and have more than two backup servers in different areasData TransmittalBy Email or flash diskBy Central ServerDocument(Paper version)StorageStored in cabinet with lockHave an individual room to
19、 store document and the room must have function on fire-proof and so on2022-12-415Compare on Data Management and Statistics3Statistics1ItemsChinaUSAData FormatWithout uniform formatCDisc(SDTM/ADAM)Programming QC ProgressNoIndependent double programming(IDP)Analysis ProcessGet result directlyFirst gi
20、ve an Analysis Dataset and than get the TFLDocumentsNo recordAll record for whole progressReport GenerationCopy and paste results into reportGenerate TFL directly from SAS program into a word file2022-12-416How far from BJ to NJR&D Technology&CRO Professional LevellInformation TechnologylClinical Tr
21、ial Operation(TMF)lData Management and StatisticslMutual support between Sponsor and CROR&D Policy&RegulationsPublic Conscious of IP protectionR&D Conception2022-12-417Difference on Regulations and Laws ChinaUSADrug Administration Law of the Peoples Republic of ChinaCode of Federal Regulations（CFR）T
22、itle 21Food and DrugsRegulations for the Implementation of Drug Administration Law of the PRCChinese Good Clinical PracticeICH-GCPComparing to Chinese GCP,US regulations give more detailed and more humanized guidance on trial performance.In some special situations,the Chinese government would interv
23、ene in the progress of new drug clinical trials 2022-12-418How far from BJ to NJR&D Technology&CRO Professional LevellInformation TechnologylClinical Trial Operation(TMF)lData Management and StatisticslMutual support between Sponsor and CROR&D Policy&RegulationsPublic Conscious of IP protectionR&D C
24、onception2022-12-419How far from BJ to NJR&D Technology&CRO Professional LevellInformation TechnologylClinical Trial Operation(TMF)lData Management and StatisticslMutual support between Sponsor and CROR&D Policy&RegulationsPublic Conscious of IP protectionR&D Conception2022-12-420Gap on ConceptionIt
25、emsChinaUSAConception of SponsorMeans for marketing or promotion,just a few for researchMost of trials are held on purpose of researchConception of InvestigatorBurden of leaders delegated or means to increase revenue Also a way to increase revenue but its a voluntary choiceConception of CROVulnerable groups in trials,have lower status than Sponsors and Investigators.Have harsh competition in the industry with low profitEqual status with Sponsors and Investigators.Also have more choice to select Investigators to finish the trial2022-12-4212022-12-422Thank you for you attention2022-12-423
