我国药物临床试验的科学监管田少雷课件

1、我国GCP的实施及药物临床试验的科学监管GCP Implementation and Regulation In China 田少雷Tian Shaolei 国家食品药品监督管理局药品认证管理中心SFDA，CCD1我国GCP的实施及药物临床试验的科学监管GCP Imple 临床试验监管历史回顾 相关法规和部门 我国GCP和相关要求的特点 临床试验监管的思路和措施内容 Content2 临床试验监管历史回顾内容 Content2 1986年,我国开始了解国际上GCP发展信息 1992年,派人员参加WHOGCP指南定稿会 1993-94年,收集各国GCP及指导原则,邀请外国专家介绍GCP,举办GC

2、P研讨会和GCP知识培训 2019年,成立了5位临床药理专家组成的GCP起草小组 In 1986，world GCP information was investigated. In 1992,WHO-GCP conference were attended. In 1993-94，GCP guidelines was collected, GCP workshops and trainings were sponsored.In 2019, GCP subscribing group including 5 experts was organized.历史回顾 History Review3

3、 1986年,我国开始了解国际上GCP发展信息历史回顾 Hi2019年3月中国卫生部发布了GCP（试行版）2019年8月中国国家药品监督管理局组建，执法主体转移至SDA2019年9月SDA颁布实施GCP（2019版）2019年12月SDA对原“卫生部临床药理基地”进行确认并更名为“国家药品临床研究基地”In Mar.2019，Ministry of Public Health (MPH) issued GCP (trial ed.) In Aug.2019，SDA was organized and took the place of MPH as the regulation authori

4、ty of drug administration in China.In Sept.2019,SDA issued and initialed implementation of GCP (2019 ed.)In Dec.2019,SDA re-confirmed original “Clinical pharmacology Bases of MPH” as “State Drug Clinical Trials Bases” 历史回顾 History Review42019年3月中国卫生部发布了GCP（试行版）历史回顾 Hi2019年3月中国修订中华人民共和国药品管理法,将GCP明确为法

5、定要求2019年9月SFDA重新修订并发布实施GCP（2019版）2019年2月，SFDA会同MPH发布药物临床试验机构资格认定办法（试行）并于3月1日开始受理有关申请.In Mar. 2019 Chinese government issued revised Drug Administration Act and GCP was incorporated into the revised Act as the state legal requirementIn Sep. 2019, SFDA issued and implemented revised GCP (2019 ed.)In F

6、eb. 2019, SFDA, together with MPH, issued “Regulation for Qualification Accreditation of Clinical trial Agency” and began to accepted related applications.历史回顾 History Review52019年3月中国修订中华人民共和国药品管理法,将GCP 临床试验监管历史回顾 相关法规和部门 我国GCP和相关要求的特点 临床试验监管的思路和措施内容 Content6 临床试验监管历史回顾内容 Content6中华人民共和国药品管理法（2019.

7、3）中华人民共和国药品管理法实施条例（2019.8）药物临床试验质量管理规范（GCP）（2019)药品注册管理办法(2019)药物临床试验机构资格认定办法（试行）(2019)药品临床研究的暂行规定（2000）药物研究监督管理办法（待颁发）药物临床试验有关的法律法规（Law and regulation)7中华人民共和国药品管理法（2019.3）药物临床试验有关SFDA药品安全监管司：主管资格认定、GCP实施情况的监管SFDA药品注册司：主管临床试验、新药注册的审批SFDA药品认证管理中心：资格认定的资料审核和现场检查、GCP实施情况的现场检查SFDA药品审评中心：新药注册的审评SFDA药品评价

8、中心：上市后ADR的监测PFDA：资格认定、临床试验、新药注册的初审及日常监管药物临床试验有关监管部门(RA)8SFDA药品安全监管司：主管资格认定、GCP实施情况的监管药 临床试验监管历史回顾 相关法规和部门 我国GCP和相关要求的特点 临床试验监管的思路和措施内容 Content9 临床试验监管历史回顾内容 Content9中国GCP共13章70条。主要参考WHO、ICH、欧盟等国际GCP原则制订。基本内容和原则与国际GCP要求一致。在细节方面充分考虑了中国的国情和法律法规。Chinese GCP includes 13 chapters with total 70 articles.Fo

9、rmulated with reference to the International GCP guidelines，mainly WHO, ICH and EC guidelines.The general aspects and basic principles are compatible with international GCP.In detail the Chinese special situation and related laws and regulations were considered.中国GCP的特点 Features of Chinese GCP10中国GC

10、P共13章70条。中国GCP的特点 Features相似点 Similarity of Chinese GCP and ICH GCP 定义相同 With the similar definitionICH：临床试验的设计、开展、实施、监查、稽查、记录、分析和报告的标准。An standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials。Chinese: 有关临床试验全过程的标准规定，包括方案设计、组织、进行、监查

11、、稽查、记录、分析总结和报告。A standard regulation of the entire process of clinical trials, including protocol design, organization, performance, monitoring, auditing, recording, analyses, summarizing and reporting。11相似点 Similarity of Chinese GCP 相似点 Similarity of Chinese GCP and ICH GCP宗旨相同 With the same purpos

12、es for implementationICH: a. 保证试验数据和报告的结果可靠和准确。provides assurance that the data and reported results are credible and accurate. b. 保护试者的权益、完整性和隐私。that rights, integrity and confidentiality of trial subjects are protected.Chinese: a. 保证临床试验的过程规范，报告的结果科学、可靠。Provides assurance that the processes of cli

13、nical trial are standard and the reported results are science sound and credible. b. 保护受试者的权益和生命安全。Protect subjects rights and safety.12相似点 Similarity of Chinese GCP 相似点 Similarity of Chinese GCP and ICH GCP原则相同 With same principlesICH的13条基本原则均被贯穿在我国的GCP中。All the 13 principles of ICH GCP are adopted

14、 into Chinese GCP13相似点 Similarity of Chinese GCP 相似点 Similarity of Chinese GCP and ICH GCPGCP基本原则临床试验的实施应依据赫尔辛基宣言中的伦理原则，同时应符合GCP及现行管理法规。在试验开始前，应权衡可预见的风险和不便，并比较每名试验受试者的风险和社会预期获得的受益。临床试验只有在预期的益处大于其风险时才能予以启动和继续。受试者的权益、安全和健康应是首要的考虑，并应胜过科学及社会的利益。一种试验用药品应有充足的临床及非临床资料来支持提出的临床试验。临床试验应具有良好的科学性，并应在试验方案中明确、详细地

15、描述。 临床试验的实施应与已被机构审查委员会或独立伦理委员会给予批准或同意的试验方案相一致。 给予受试者医疗保障，以及为受试者做出医疗决定是合格的医生或牙医的责任。14相似点 Similarity of Chinese GCP 相似点 Similarity of Chinese GCP and ICH GCPGCP基本原则每位参与实施试验的人员均应在教育、培训和经验方面具有资格来完成其任务。应在每位受试者参加试验前获得其自愿给出的知情同意。全部临床试验资料应以能确保其被准确报告、解释及核对的方式来记录、处理和保存。应对可识别受试者的保密性记录进行保护，并遵从现行管理法规中有关隐私权及保密性的规

16、则。 试验用药品应依据现行的GMP进行生产、管理和保存。应根据被批准的试验方案使用试验用药品。应建立并实施能够确保试验各方面质量的程序系统。 15相似点 Similarity of Chinese GCP 相似点 Similarity of Chinese GCP and ICH GCP 适用范围相同 With the same application ranges 凡进行各期药物临床试验、人体生物利用度或生物等效性试验，必须执行GCP。The clinical trials of all drugs, including phase I to IV and human bio-availab

17、ilities and bio-equivalence studies, must be performed according to GCP.16相似点 Similarity of Chinese GCP 相似点 Similarity of Chinese GCP and ICH GCP 内容相似 With similar contents有关人员的资格和职责 临床试验的条件、程序及方案 试验资料的记录、报告、处理和存档 试验用药的准备、分发、使用和回收 SOP的制订和遵循 多环节的质量保证体系,包括质量控制、监查、稽查和检查。Qualification and responsibiliti

18、es of related parts, including IEC, investigator, and sponsorConditions, procedures and protocol of clinical trialPreparation, distribution, storing，using and recycling of investigational productsRecording, reporting, handling and archiving of trial data and documentationFormulating of and complianc

19、e with SOPsQuality assurance system including QC, monitoring, audit, and inspection17相似点 Similarity of Chinese GCP QC monitor audit inspectionMonitorAuditorSFDA/PFDAInspectorSponsorInvestigatorQuality Documen-tationSOPsQuality Assurance System18 QC monitor audit 不同点 Difference Between Chinese and IC

20、H GCP 临床试验的批准 IND approval在美国，不需要临床试验的书面批文。In USA, “no news is good news”. If a sponsor dont get any information regarding to its IND application from FDA within 30 days, then the trial can be initialed.在中国，临床试验开始前必须得到SFDA的书面批文。IN China, a sponsor must get a written approval from SFDA prior to clini

21、cal trial 19不同点 Difference Between Chinese不同点 Difference Between Chinese and ICH GCP 研究者InvestigatorsICH：PI可以是医生或得到有经验医生的支持。 In ICH countries, a principal investigator (PI) should be a physician or dentist himself/herself or get the support from an experienced physician.在我国，PI必须在医疗机构具有任职行医资格。In Chin

22、a, a PI must be a qualified physician or dentist who currently works for a hospital.20不同点 Difference Between Chinese不同点 Difference Between Chinese and ICH GCP 研究机构 Institution在其他国家无需官方的资格认定，临床试验机构不无须一定是医疗机构 In other countries, a clinical trial institution may be either a hospital or a special resear

23、ch institution, and it needt any qualification accredited by the RA (although inspection is necessary) 在我国承担临床试验的单位及相关专业必须是医疗机构而且该机构及相关专业必须具有官方认定的资格。In China, a clinical trial institution and related field must be a hospital which have been accredited by the RA (SFDA and MPH).21不同点 Difference Betwee

24、n Chinese不同点 Difference Between Chinese and ICH GCP Ethics Committee在ICH国家，IRB或IEC往往是独立于临床研究单位的第三方。In ICH countries, IRB or IEC is completely independent to investigator or institution of a clinical trials.在我国，伦理委员会一般设置在临床研究机构内，其独立性通过参与一项临床试验的研究者不得作为审核该临床试验的伦理委员会的委员参与表决来体现。In China, EC is typically

25、established within a clinical trial institution. However, the investigator of a clinical trial cannot be the member of the committee which responsible for reviewing the trial.22不同点 Difference Between Chinese不同点 Difference Between Chinese and ICH GCP试验方案Protocol 在其他国家，试验方案一般由申办者制订，然后经研究者确认后，双方签字。In o

26、ther courtiers, the protocol of a trial usually formulated by the sponsor, then confirmed by investigators and subscribed by both parts. 在中国，许多申办者，特别是国内企业通常委托研究者来起草试验方案，然后双方签字认可。In China, many sponsors, especially local pharmaceutical companies usually trust PI selected by themselves to formulate pr

27、otocol for them, then confirmed by themselves and subscribed by both parts.23不同点 Difference Between Chinese不同点 Difference Between Chinese and ICH GCPSAE的报告时间The time for reporting SAE在ICH国家，仅致死或危及生命的SAE需要在24小时内向官方报告，而其他SAE的报告期限则长至1周(5个工作日)。In ICH countries, such as USA, only SAEs resulting in death

28、or being life-threatening are required to reported to regulatory authority within 24 hours, other types of SAEs may be permitted to reported to regulatory authority within longer time, such as 1 week.在中国，所有试验过程中发生的SAE均应在24小时内向官方报告。In China, all SAEs happened in the process of a trial should be repor

29、ted to SFDA and PFDA within 24 hours.24不同点 Difference Between Chinese不同点 Difference Between Chinese and ICH GCP 试验资料保存时限 Storing period of trial documentationICH: 研究者需保存的文件应保存至该药品在ICH成员国范围内获得最后上市许可后或再没有决定做出至少2年，或临床试验中止后至少2年。The investigator/institution specific essential documentation should retaine

30、d until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. 申办者保存资料的时间同上。 Same pe

31、riod is required for sponsor to keep its specific essential documentation.25不同点 Difference Between Chinese不同点 Difference Between Chinese and ICH GCP 试验资料保存时限 Storing period of trial documentation在中国， In China：我国研究者保存资料的时间为试验结束或中止后面至少5年。, Investigator/institution specific essential documentation shou

32、ld be retained until at least 5 years after the completion or discontinuation of clinical development of the investigational product. 申办者保存资料的时间为获得药品注册后至少5年。Sponsor specific essential documentation should be retained until at least 5 years after the marketing approval is issued by SFDA. 26不同点 Differ

33、ence Between Chinese 临床试验监管历史回顾 相关法规和部门 我国GCP和相关要求的特点 临床试验监管的思路和措施内容 Content27 临床试验监管历史回顾内容 Content27临床试验监管的重点受试者的权益得到了很好的保护临床试验的过程是规范的（符合GCP和现行法规）数据和结果是科学的、可靠的28临床试验监管的重点受试者的权益得到了很好的保护28科学监管的思路分步实施，稳步推进资格准入，强化监督市场选择，打破垄断动态管理，优胜劣汰29科学监管的思路分步实施，稳步推进29资格认定 Qualification Accreditation for clinical tria

34、l institution根据药品法要求，开展临床试验的机构及相关专业必须具备经主官部门依法认定的资格。药品法实施条例进一步规定由SFDA会同卫生部制定。2019年2月“临床试验机构资格认定的办法”发布，并于3月1日开始受理并认定。30资格认定 Qualification Accreditati资格认定的意义 Significance of qualification accreditation for clinical trial institution管理部门 药品管理法及实施条例的要求 是我国特色的监管举措 进一步推动我国GCP的实施保护受试者的安全和权益保证临床试验数据的质量For r

35、egulatory authorityRequired by China Drug Administration ActAn important measure to monitor clinical trials.Promote the implementation of GCP in China Ensure the quality of clinical trial data supporting drug registration.Protect the safety, rights and well-being of subjects.31资格认定的意义 Significance o

36、f qualif资格认定的意义 Significance of qualification accreditation for clinical trial institution对申办者扩大临床试验机构的选择范围 减小选择研究者的盲目性 增加选择研究者的主动性 改善临床试验开展的条件 减少对研究者的培训投入 获得高质量的临床试验数据 缩短临床试验的周期 降低临床试验的风险和投入For sponsorsLower blindness on selecting investigatorsImprove conditions for clinical trialsDecrease the inpu

37、t for investigator trainingShorten clinical investigation periodGet high quality data and credible resultsMinimize risk and financial input32资格认定的意义 Significance of qualif资格认定的意义 Significance of qualification accreditation for clinical trial institutionFor Investigators/institutions More doctors and

38、 more chance to perform clinical evaluation of safety and efficacy of new drugs Rise the research level and increase their chance to participate international co-operationPromote rational medicine use and higher quality of clinical practiceHelp to perform ADR monitoring and PMSPromote the developmen

39、t of evidence based MedicineEnhance the management level of hospital对研究者参与新药安全性、有效性评价提升科研水平，开展国际合作促进合理用药，提高医疗质量开展ADR监测和药物警戒学研究开展医疗器械临床试验提升医院的管理水平促进循证医学的发展33资格认定的意义 Significance of qualifProcedures for qualification accreditationRe-inspectionRe-correction within limited timeQualifiedRe-correction nee

40、dedUnqualifiedQualificationCertificateRegular InspectionDisqualificationUnqualifiedAnnouncementApplicationPrimary reviewFilingSiteinspectionDoc.review34Procedures for qualification a资格认定的基本要求 Requirements for Qualification Accreditation for clinical trial institutionBe medical institution (hospital)

41、With management organizationQualified staff and suitable training of GCP, and clinical trial knowledgeSufficient conditions, facilities and instruments Enough Subject sources Formulation of and compliance with SOPs Retaining, archiving of documentation 医疗机构（医院）组织管理机构合格的人员并经GCP、临床试验技术培训足够的试验和急救设施和仪器设

42、备充足的受试者来源 制订并遵循SOP 试验资料的保管设施和制度试验药物的保管实施和制度35资格认定的基本要求 Requirements for Qua 资格认定的进展情况(至06年9月底)机构数量专业情况原基地专业新申请总数申 请32758622922872已 检 查26149119122403公告通过158-1035限期整改8-待 检 查479537747236 资格认定的进展情况(至06年9月底)机构数量专业情况原基药物临床试验机构的监督管理定期报告：获得资格认定的医疗机构须于每年3月底前向SFDA报送上年度承担药物临床试验的情况。监督检查：SFDA对通过资格认定的医疗机构进行随机检查、有因检查以及专项检查.定期复查：SFDA对已取得药物临床试验机构资格的医疗机构每3年进行一次资格认定复核检查。对复核检查不合格的医疗机构，取消其药物临床试验机构的资格并予以公告。飞行检查：对药物临床试验项目进行抽查，严重违规项目将不予接受作为新药注册资料。同时对相关单位进行处理。违规查处：SFDA在监督检查中发现药物临床试验机构未按规定实施GCP，将依据药品管理法及其实施条例等对其进行处理。对严重违反GCP的，取消其药物临床试验机构资格，同时予以公告。且自公告之日起，3年内不受理其资格认定的申请。37药物临床试验机构的监督管理定期报告：