美国上市后药品风险管理及启示

简述上市后药品风险管理的目的和风险来源,并通过查阅文献资料,介绍了美国上市后药品风险管理体系,旨在借鉴先进经验以加强和完善我国药品风险管理体系。     

从美国药品撤市看药品安全风险管理

目的 分析美国上市药品的撤市原因,明确上市药品风险管理对保证公众健康的重要意义.方法 通过检索文献和美国FDA网站,收集和分析美国药品撤市信息.结果 1964～2009年期间美国实际撤市的产品为72个,撤市的主要安全性问题为:心血管毒性、致癌风险、肝毒性、血液毒性、皮肤损害、中枢神经系统损害、肾毒性等.结论 风险管理应贯穿于药品研发到使用的全过程,而上市后的风险管理尤为重要,药品撤市是上市后安全风险管理的终极手段.     

浅析我国药品上市后风险管理中存在的问题

结合国外药品上市后风险管理经验,浅析我国药品上市后风险管理工作中存在的不足,提出相关建议,为完善我国药品上市后风险管理工作提供参考。     

美国药品上市后风险管理剖析

风险管理是当今全球药品监管最热门的话题,药品风险管理为在药品生命周期内,用于优化药品的效益/风险比的一个反复持续的管理过程。美国是最早将风险管理引入药品监管的国家,并在风险管理上做出大量的创新,积攒了丰富的经验。本文对美国风险管理发展历程及相关文件进行了简要介绍,着重探讨了药品上市后风险管理的方法,旨在促进风险管理在我国药品监管中的全面发展。     

加拿大的药品上市后风险管理

药品上市后风险管理是全世界各国药品管理部门面临的严峻挑战。通过对加拿大药品上市后管理部门机构设置、职能及特点的阐述与分析,为我国药品上市后风险管理提供参考。     

美国药品风险管理指南与案例分析

目的 简介药品风险管理的概念和方法,并附实例说明.方法 利用文献资料采取综述的方法,介绍药品风险管理概念在美国、欧盟的发展和药品风险管理的内容.结果 药品的风险管理是一个运用多学科方法来记载、监控、评价和干预药品不良反应的科学系统方法.它适用于药品从前体化合物筛选、新药审批、上市后监控直至撤出市场的整个生命周期.结论 国际药品风险管理的经验对我国药品安全管理工作具有借鉴意义,我国在药品风险管理方面应逐步与国际接轨,提出符合我国国情的药品风险管理指导方案以进一步改善药品安全管理.     

嵌合抗原受体T细胞(CAR-T)药品信息可及性的国内外对比与启示

目的：为我国嵌合抗原受体T细胞(CAR-T)上市产品的药品信息可及性管理提供参考。方法：通过梳理CAR-T类药品的临床试验及批准上市情况,检索美国、欧盟、日本和中国药品监管官方网站已上市CAR-T类药品的药品信息,对比分析各国披露的信息类别。结果：目前在美国、欧盟、日本和中国上市的CAR-T类药品均可以在上市国家药品监管网站上查找到药品说明书和上市审评报告。美国和欧盟有专门面向患者的信息页面和风险管理文件,日本公布了上市公司提交的申请资料和最佳使用推广指南。我国缺乏面向患者的信息页面和风险管理文件,不利于全面了解药品信息。结论：我国需进一步提高药品信息的可及性,加强药品风险管理,以促进药品的安全合理使用以及公众对于CAR-T类药品的正确认识。     

国际药物警戒开展现状对我国药品风险管理的启示

本文就世界卫生组织药物警戒合作项目和欧盟、美国药物风险管理现状进行分析。以期对我国药物警戒系统的建立和药品风险管理提出一些建议。国际药物警戒已将药品风险管理从单纯的不良反应监测扩大到与疾病预防治疗相关的领域．变被动监测为主动警戒,以防患于未然。我国建立药物警戒体系需要在组织体系、交流沟通．人员培训及制药企业主动进行药品上市后风险管理等方面多加完善与改进。     

我国疫苗风险管理模式探讨

药品风险管理是围绕药品安全性问题开展的,通过上市前研究或上市后不良反应监测,完成药品风险评估、风险控制、风险审核和风险沟通的系统过程.疫苗作为一种特殊的药品,其风险管理尤为重要.本文分析了我国疫苗不良反应监测的现状及存在的问题,并参考国际先进经验,对我国疫苗风险管理模式进行了探讨.     

刍议美国FDA对口服磷酸钠制剂上市后安全风险的监管

目的:为我国上市药品安全风险监管提供参考和借鉴。方法:从美国食品与药品管理局(FDA)对口服磷酸钠制剂(OSP)上市后安全风险管理全过程入手,详细回顾并深入解析FDA对上市后药品安全风险评估和控制的具体措施,重点分析了FDA对上市后药品安全风险管理的特点。结果与结论:上市阶段是药品全生命周期安全监管的重要阶段。FDA对OSP上市后二次风险评估及控制措施基本反映了其对上市药品安全风险管理的概貌,可以为我国加强上市后药品安全风险监管的薄弱环节提供有益的借鉴。     

希美加群药品风险管理的案例简析

药品风险管理适用于药品从前体化合物筛选、新药审批、上市后监控以及药品撤出市场的整个过程。通过介绍阿斯利康公司生产的新一代抗凝血药物希美加群（Exanta。）从新药审批上市到撤出市场的风险管理相关事件,以期为我国抗凝药物的监测和安全管理工作提供借鉴,从而更好地规范我国的药品市场。     

Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products

With a New Drug Application (NDA) innovative drug therapies are reaching the market in a specific dosage form for one or more clinically proven indications of which after expiration of the patent or the data exclusivity copies are launched using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged from launched molecules during their product life-cycle have gained considerable attention as clinical practice provides evidence for additional therapeutic values, patient centric delivery systems show improved therapeutic outcomes or emerging technologies offer efficiency gains in manufacturing or access to emerging markets. The USA and European regulatory framework has set reasonable regulations in place for these "Supergenerics" or "hybrid" applications. While these regulations are relatively recent the pharmaceutical industry is just starting to use this route for their product development and life-cycle management. From a clinical perspective the potential for advanced product development have been demonstrated. Yet, there is still a lag of common understanding between the different stakeholders regarding the development, application process and commercial incentive in developing enhanced therapeutic entities based on existing drug products for the market.     

Liposomal Drug Product Development and Quality: Current US Experience and Perspective

Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug’s pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.     

A 'demand side' estimate of the dollar value of the cannabis black market in New Zealand

The dollar value of an illicit drug market is an important statistic in drug policy analysis. It can be used to illustrate the scale of the trade in a drug; evaluate its impact on a local community or nation; provide an indication of the level of criminality related to a drug; and can inform discussions of future drug policy options. This paper calculates the first ever demand side estimates of the New Zealand cannabis black market. The estimates produced are calculated using cannabis consumption data from the Alcohol & Public Health Research Unit's (APHRU) 1998 National Drug Survey. The wholesale value of the market is estimated to be $81.3-104.6 million a year, and the retail value of the market is estimated to be $131.3-168.9 million a year. These demand side estimates are much lower than the existing supply side estimates of the market calculated using police seizures of cannabis plants. The retail figure is four times lower than the lowest national supply side estimate ($636 million) and seven times lower than the highest national supply side estimate ($1.27 billion). The demand side estimates suggest a much smaller cannabis economy to fuel organized criminal activity in New Zealand than previous estimates implied.     

企业如何开展药品风险管理工作

通过介绍药品风险管理概念及内容，比较美国药品风险管理系统与我国药品风险管理的不同，提出关于国内制药企业进行药品风险管理工作的建议。     

CDER Risk Assessment Exercise to Evaluate Potential Risks from the Use of Nanomaterials in Drug Products

The Nanotechnology Risk Assessment Working Group in the Center for Drug Evaluation and Research (CDER) within the United States Food and Drug Administration was established to assess the possible impact of nanotechnology on drug products. The group is in the process of performing risk assessment and management exercises. The task of the working group is to identify areas where CDER may need to optimize its review practices and to develop standards to ensure review consistency for drug applications that may involve the application of nanotechnology. The working group already performed risk management exercises evaluating the potential risks from administering nanomaterial active pharmaceutical ingredients (API) or nanomaterial excipients by various routes of administration. This publication outlines the risk assessment and management process used by the working group, using nanomaterial API by the oral route of administration as an example.     

Pharmaceutical industry perspective on risk evaluation and mitigation strategies: manufacturer take heed

INTRODUCTION: Enactment of the Food and Drug Administration Amendments Act of 2007 (FDAAA) authorized the FDA to require manufacturers to submit Risk Evaluation and Mitigation Strategy (REMS) when it was deemed necessary to ensure that a drug's benefit outweigh its risk. REMS apply to new drug applications (NDAs), abbreviated new drug applications (ANDAs) and biologics license applications (BLAs). The objective of this review is to describe the impact of REMS requirements on the pharmaceutical industry. AREAS COVERED: Articles were identified in MEDLINE searches through October 11, 2011, using the MeSH terms and keywords pharmaceutical industry, risk management, United States Food and Drug Administration, REMS, ETASU, and Medication Guide in various combinations. EXPERT OPINION: The new powers ascribed to the FDA are notable, as they add enforceability to safety strategies that were not part of FDA's prior risk management tools, risk minimization action plans (RiskMAPs). Failure to comply with REMS can lead to financial penalties up to $10 million, and a drug could be deemed misbranded if the REMS is not followed. The new approach to risk management via FDAAA has elevated the rigor with which manufacturers must fulfill postmarketing safety commitments.     

Examination of risk evaluation and mitigation strategies and drug safety in the US

BackgroundThe Food and Drug Administration Amendment Act of 2007 (FDAAA 2007) enabled the US Food and Drug Administration (FDA) to require risk evaluation and mitigation strategies (REMS) for a drug or biologic to ensure that its benefits outweigh the risks.ObjectiveThis study sought to evaluate REMS approved and released by the FDA since the program inception in 2008, to assess the characteristics of REMS approved and to calculate the time lag between FDA drug application approval and REMS approval.MethodsData were derived from Approved Drug Products with Therapeutic Equivalence Evaluations, Approved REMS and Drugs@FDA. Data included generic availability, application type and approval date, therapeutic class and FDA review class, orphan designation, priority review and market status.ResultsThe FDA approved REMS for 259 marketing applications (217 new drug applications -NDAs, 10 abbreviated NDAs, and 32 biologic license applications) in the study period. The FDA granted orphan designation to 11.4% of active ingredients with REMS and priority review to 38.4% of the NDAs with REMS. The largest number of REMS approvals was for nervous system products (31.8% of total approved REMS) and antineoplastic and immunomodulating agents (15.3%).ConclusionsThe FDA approved REMS for one in three biologics and one in thirteen chemical entities available in the market. A pharmaceutical product can be in the market for an average of 14 years before the FDA identifies and evaluates the risk problems that warrant the approval of a REMS.