美国食品和药物管理局对临床试验申办者现场核查情况分析

目的为加强和促进对我国药物临床试验申办者的监管提供借鉴。方法收集美国食品和药物管理局(FDA)网站上公布的生物研究监查(BIMO)项目2007—2014财政年度工作情况报告、科学调查办公室(OSI)工作情况更新报告及FDA 2010—2016财政年度预算报告中相关数据,分析FDA对临床试验申办者现场核查的比例、结果分级及FDA对药物临床试验核查的情况等。结果 2007—2011财政年度,FDA对临床试验申办者的现场核查比例逐年上升,自2012年降至中间水平后呈现平稳波动,同时自2009年起FDA对此类核查中发现的问题采取官方行动的比例明显下降。FDA药品审评和研究中心(CDER)组织实施的药物临床试验核查数量超过BIMO项目各中心GCP核查总数的一半,其未对所有新药申请和生物制品许可申请的申办者进行现场核查,受委托承担部分申办者职责的合同研究组织(CRO)亦是此类核查的重要内容。结论针对申办者的现场核查是药物临床试验监管的重要组成部分,借鉴国外成熟的监管经验建立符合我国国情的药物临床试验申办者和CRO的监管制度并开展相关的现场核查势在必行。     

疫苗临床试验申办者质量体系现状及思考

本文通过对疫苗临床试验申办者质量体系中存在的缺陷情况的分析,提出了进一步完善疫苗临床试验申办者临床试验的质量控制和质量保证系统的建议,为疫苗临床试验的监管提供参考。     

合同研究组织在临床试验中的作用与存在的问题

本文将合同研究组织的特点、产生的背景、发展状况、在新药临床试验中的优势与存在的问题进行了阐述与分析,寄期待合同研究组织在今后的新药临床中发挥更大的作用.     

新药临床试验中GCP实施的问题与对策

现阶段“药品临床试验管理规范”(GCP)的实施中存在诸多问题，笔者通过对新版GCP的学习，分析目前临床研究中存在的问题，并探讨相应的对策。且响应国际新形势下对GCP的要求，深切感受到现阶段我国药品临床研究中实施GCP的必要性和重要性。     

合同研究组织进行临床试验的风险分析及防范策略

目的 分析合同研究组织(CRO)运营和管理临床试验项目的关键流程及其中的风险因素,为临床试验的质量管理和风险管理提供参考.方法 以某跨国CRO公司为例,总结CRO公司运营和管理临床试验项目的整体流程,并以该公司近3年内发生的与研发服务相关的问题为数据来源,使用风险矩阵法识别关键流程.结果 识别到"人类遗传资源管理相关事...     

新药临床和审批过程中FDA与药品申办者的会议沟通机制

目的对FDA在新药临床和审批过程中与药品申办者的会议沟通机制进行介绍,为我国提供相应的参考。方法查阅FDA的相关法律法规以及一系列的指南文件。结果与结论该会议机制以其法制化、规范化、透明化的特点,确保了新药审评的效率及质量,值得我国借鉴。     

药物临床研究阶段申办者和生产场地变更研究五:申办者和生产场地不同组合方式的风险评估和风险控制研究

目的：对新药临床试验阶段申办者和临床试验药物生产场地的境内外不同组合方式开展风险评估和风险控制研究,为进一步完善我国临床试验阶段申办者和生产场地的跨境管理提供参考。方法：采用失效模式与效应分析及风险指数法,针对申办者和生产场地的境内外不同组合方式进行风险的识别、分析和评估。结果与结论：在新药临床试验阶段,“申办者在境内、生产场地在境外（供全球）”和“申办者在境外、生产场地在境内”是两种风险较低的跨境情形,且可通过适当措施对潜在风险进行管控,可优先考虑打通这两种跨境情形的注册路径。     

药物临床研究阶段申办者和生产场地变更研究二:欧盟药物临床试验及临床试验期间变更管理要求对我国完善监管体系的启示

目的：通过法规比较研究分析,为完善我国药物临床试验及临床试验期间变更管理,特别是临床试验期间申办者变更、生产场地变更及其变更管理提供参考。方法：对欧盟药物临床试验申请及临床试验期间变更管理的法规监管要求和实施情况进行研究整理,与我国当前相关监管法规建设和实施现状进行比较分析并提出建议。结果与结论：欧盟允许临床试验申办者和临床试验药物生产场地分属境内、外的临床试验注册申请及变更申请。欧盟临床试验管理制度相对成熟完善,比如其统一的临床试验申请门户网站及临床试验信息数据库、一体化的科学和伦理双重审查并行的审评程序,对申办者及其法定代理人的资质和责任要求、对临床研究用药品生产场地及其变更的监管和风险控制等监管措施,对我国有参考价值。     

药物临床研究阶段申办者和生产场地变更研究一:日本药物临床试验及临床试验期间变更管理要求对我国完善监管体系的启示

目的：研究日本药物临床研究期间变更管理的法规监管要求和实施情况,并与我国当前相关监管法规建设和实施现状进行比较,为完善我国药物临床研究期间申办者和生产场地变更管理的监管体系提供参考。方法：对日本临床研究期间申办者和生产场地变更的监管法规进行系统的梳理研究,结合我国临床研究期间变更管理情况提出建议。结果与结论：日本允许临床试验申办者和临床试验药物生产场地分属境内、外的临床试验注册申请及变更申请。日本监管体系中“履职承责的境内代理人制度、全面高效的咨询服务、全程全球的监管检查”等监管措施,对我国有参考价值。     

美国食品和药物管理局对临床试验中学术行为不端的监管

临床试验中的行为不端不仅仅是学术腐败,它使得临床试验的受试者安全受到威胁,临床试验的过程失去可信度;使得申办者提交数据的有效性和公正性大打折扣,失去公信力。美国食品和药物管理局对临床试验中的欺诈行为实施零容忍,研究者将面临取消研究资格和执业资格,甚至涉及罚款、监禁和法律诉讼。必须对药物临床试验中的行为不端,采取积极预防措施,实施严厉行政监管。     

Food and Drug Administration monitoring of adverse drug reactions

Food and Drug Administration requirements for reporting adverse drug reactions (ADRs), processing of ADR reports, and actions in response to these reports are described. FDA requires that drug manufacturers report ADRs to the FDA Division of Epidemiology and Surveillance; 90% of the ADR reports received are from manufacturers. Of the remaining 10%, one third are from pharmacists. FDA regulations were revised in 1985 to specifically define reportable ADRs and procedures for reporting; manufacturers are required to report within 15 days reactions that are serious and unlabeled. For newly approved drugs, reports on ADRs must be submitted quarterly for three years; subsequently, annual reporting is required. Any increase in the frequency of serious, labeled reactions must be reported. Serious reactions not listed in the product labeling must be reported for products marketed before 1962 for which new drug applications or abbreviated new drug applications were not filed. ADR information received by FDA is coded into standard terms and entered in a computerized database for evaluation by reviewers. If an important reaction is suspected, the report is entered in a tracking system for further monitoring. ADR reports may result in requirements for changes in product labeling, "Dear Doctor" letters, requirement of further study by the manufacturer, or withdrawal of the product. Information about ADRs is communicated to health-care practitioners in product labeling and in the literature. Pharmacists are encouraged to report suspected serious and unlabeled reactions to FDA so that the medical community and the public can benefit from current information about drug safety.     

开展药物临床试验以促进临床科研工作的发展

开展药物临床试验不仅在完善临床专业学科建设,规范临床诊疗等方面有巨大推动作用,对提升临床科研能力也具有一定促进作用。本文将从科研队伍人才培养,医学伦理学意识、科研作风培养,科技信息获取、科研思维启发,科研质量管理意识强化,多学科协作建立及团队合作意识提升等方面进行分析,并结合本院相关临床专业在开展药物临床试验前后科研立项、专业重点实验室建设等情况,探讨开展药物临床试验对临床科研的促进作用。     

2009年SFDA批准注册的国产化学药品统计分析

目的了解和分析2009年我国新注册的化学药品分布情况。方法全面检索国家食品药品监督管理局数据库和相关资源,登记2009年注册的国产化学药品的名称、批准文号、药物化学治疗分类、是否属国家基本药物等,然后运用Excel进行分类汇总分析。结果 2009年共注册国产化学药品1 583个,涉及通用名药物489个,药品批准文号数量排序前三位的依次为抗微生物药物、作用于中枢神经系统的药物和作用于消化系统的药物。结论 2009年国产化学药品注册依然存在药品注册与需求不完全一致、个别药品"一药多号"、抗微生物药物生产竞争激烈等问题,同时也出现基本药物注册小高峰等新迹象。     

United States Food and Drug Administration approach to risk evaluation and risk management for foods

The Food and Drug Administration (FDA) is developing a comprehensive program on risk evaluation and risk management related to foods and food ingredients. Various groups view the FDA differently in terms of potential food hazards, but the regulatory agency is required to follow the laws that reflect a set of social judgments about permissible risks and benefits. The traditional agency approaches to risk management are reviewed and recent plins to consider structural changes in the basic food statute that could lead to greater administrative flexibility are presented. The proposed tentative suggestions discussed embody basic principles that the public health and trust remain the focus of food safety laws. Public confidence in the present system must be retained, it must be a credible system, embody valid scientific data, and the regulatory actions must be taken by FDA scientists who are recognized for their scientific competence. All the proposed actions need to be taken without placing unnecessary economic burdens on industry. The scope of this program is reviewed.     

2018年美国食品药品监督管理局批准的新药

<正>2018年美国食品药品监督管理局(Food and Drug Administration, FDA)共批准了43个新分子实体(new molecular entity,NMEs)和23个新生物制剂(biologic license applications,BLAs),该数字较2017年的56个,增加了10个(17. 9%)。按照药物作用分类,抗肿瘤药物18个(27. 3%),心血管系统药物12个(18. 2%),呼吸系统药物2个(3.0%),神经系统用药8个(12. 1%),内分泌用药9个(13.6%),抗感染药9个(13.6%),其他药物7个(10. 6%)。     

Regulatory science: a special update from the United States Food and Drug Administration: Preclinical issues and status of investigation of botanical drug products in the United States

A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products.