我国药物临床试验的科学监管.ppt

Click to edit Master title style,*,SFDA,CCD,TSL,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,1,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,Content,2,1986年,我国开始了解国际上,GCP,发展信息,1992年,派人员参加,WHO,GCP,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,GCP,研讨会和,GCP,知识培训,1995,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 1996,GCP subscribing group including 5 experts was organized.,历史回顾,History Review,3,1998年3月中国卫生部发布了,GCP（,试行版）,1998年8月中国国家药品监督管理局组建，执法主体转移至,SDA,1999,年9月,SDA,颁布实施,GCP（1999,版）,1999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.1998，Ministry of Public Health(MPH)issued GCP(trial ed.),In Aug.1998，SDA was organized and took the place of MPH as the regulation authority of drug administration in China.,In Sept.1999,SDA issued and initialed implementation of GCP(1999 ed.),In Dec.1999,SDA re-confirmed original,“,Clinical pharmacology Bases of MPH,”,as,“,State Drug Clinical Trials Bases,”,历史回顾,History Review,6,中华人民共和国药品管理法（2001.3）,中华人民共和国药品管理法实施条例（2001.8）,药物临床试验质量管理规范（,GCP）（2003),药品注册管理办法,(2002),药物临床试验机构资格认定办法（试行）,(2004),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,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),8,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,Content,9,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.,Formulated 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 GCP,10,相似点,Similarity of Chinese GCP and ICH GCP,定义相同,With the similar definition,ICH：,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、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 and ICH GCP,宗旨相同,With the same purposes for implementation,ICH: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 clinical 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 and ICH GCP,原则相同,With same principles,ICH,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 into Chinese GCP,13,相似点,Similarity of Chinese GCP and ICH GCP,GCP,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 and ICH GCP,GCP,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 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-availabilities and bio-equivalence studies,must be performed according to GCP.,16,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 responsibilities of related parts,including IEC,investigator,and sponsor,Conditions,procedures and protocol of clinical trial,Preparation,distribution,storing，using and recycling of investigational products,Recording,reporting,handling and archiving of trial data and documentation,Formulating of and compliance with SOPs,Quality assurance system including QC,monitoring,audit,and inspection,QC,monitor,audit,inspection,Monitor,Auditor,SFDA/PFDAInspector,Sponsor,Investigator,Quality,Documen-,tation,S,O,P,s,Quality Assurance System,18,不同点,Difference Between Chinese and ICH 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 don,t 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 clinical trial,19,不同点,Difference Between Chinese and ICH GCP,研究者,Investigators,ICH：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 China,a PI must be a qualified physician,or,dentist who currently works for a hospital.,20,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 research institution,and it need,t 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 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 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 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 other,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 protocol for them,then confirmed by themselves and subscribed by both parts.,23,不同点,Difference Between Chinese and ICH GCP,SAE,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 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 reported to SFDA and PFDA within 24 hours.,24,不同点,Difference Between Chinese and ICH GCP,试验资料保存时限,Storing period of trial documentation,ICH:,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 retained 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 period is required for sponsor to keep its specific essential documentation.,25,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 should 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,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,Content,27,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,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,资格认定,Qualification Accreditation for clinical trial 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。,2004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,资格认定的意义,Significance of qualification accreditation,f,or 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,regulatory authority,Required by China Drug Administration Act,An 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 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,sponsors,Lower blindness on selecting investigators,Improve conditions for clinical trials,Decrease the input for investigator training,Shorten clinical investigation period,Get high quality data and credible results,Minimize risk and financial input,32,资格认定的意义,Significance of qualification accreditation for clinical trial institution,For,Investigators/institutions,More doctors and 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-operation,Promote rational medicine use and higher quality of clinical practice,Help to perform ADR monitoring and PMS,Promote the development of evidence based Medicine,Enhance 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,Procedures for qualification accreditation,Re-inspection,Re-correction within limited time,Qualified,Re-correction,needed,Unqualified,Qualification,Certificate,Regular Inspection,Disqualification,Unqualified,Announcement,Application,Primary review,Filing,Site,inspection,Doc.,review,34,资格认定的基本要求,Requirements,for,Qualification Accreditation for clinical trial institution,Be medical institution(hospital),With management organization,Qualified staff and suitable training of GCP,and clinical trial knowledge,Sufficient 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,327,586,2292,2872,已 检 查,261,491,1912,2403,公告通过,158,-,-,1035,限期整改,8,-,-,-,待 检 查,47,95,377,472,36,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,在中国开展临床试验的优势,Advantages of conducting clinical trial in China,丰富的受试者资源。,Abundant subjects resource,.,一大批富有经验的研究者。,Lots of investigators with rich experience of carrying out clinical trials,even international multi-center clinical trials.,相对低廉的临床试验费用。,Lower expense on clinical trials compared to other countries.,中国,GCP,的强制实施提高了我国临床试验的规范和学术水平，并逐渐宿小与,ICH,成员国的差距。,The GCP implementation is required legally by Chinese government rise the level of both standardization and scientific technique of clinical investigations carried out in China and smoothly minimize the regulatory and academic gap between China and ICH countries.,38,在中国开展临床试验的优势,Advantages of conducting clinical trial in China,临床试验机构的资格认定制度方便了国外企业在中国选择研究者。,T,he qualification accreditation program for clinical trial institution make it,s relatively easier for foreign sponsors to select qualified investigators in China.,国外企业已在中国开展的临床试验为研究者提供了资金、技术和先进的管理经验。,Many foreign enterprises carrying out their clinical trials provide fund,technique and advanced management experience for GCP development in China.,中国,GCP,和,ICHGCP,原则的相似性使得在我国开展的临床试验的结果能够得到发达国家的认可。,The similarity of Chinese GCP and ICH GCP make it possible that the results of clinical trials conducting in China are accepted by the RA of developed countries.,39,多谢指正,Thank you for your attention!,67188037 67102284-31 sltian2,