国外药政部门采用溶出曲线评价口服固体制剂内在品质情况简介

美国FDA药品审评中心的仿制药办公室属下的生物等效部于2004年1月起，推出了采用溶出曲线来评价药品内在质量，即延伸至仿制药与原研药是否生物等效的情况；其中详细罗列了溶出度试验各参数以及取样时间点，并规定采用f2因子对溶出曲线的一致性进行评估（f2因子需大于50）；该做法与1998年日本实施至今的“薬品品臂再评俩工程”具有相同的出发点。故建议我国对于仿制药的研发、审评以及内在质量的评价，也能从国家的层面参照以上两国的做法，采用溶出曲线的方式来评价，并同时提高溶出度试验标准、严格溶出度试验参数，从而切实有效地提高国产仿制药的品质，力争使其具有与进口原研药相同的生物等效性，并最终得以促进我国工业药剂学的发展，为国产仿制药打入国际市场奠定基础。     

药物制剂生物利用度和生物等效性试验指导原则(草案)

参考国际上的相关指导原则,对《中国药典》2015年版药物制剂生物利用度和生物等效性指导原则提出了修改草案。包括前言,常释制剂生物等效性试验的设计、实施和评价,调释制剂和透皮吸收制剂的生物等效性试验,试验报告,与生物等效性试验相关的体外溶出度检查,对不同剂型的生物等效性要求,以及基于生物药剂学分类系统的生物豁免。与现行药典指导原则相比,把生物样品定量分析方法的内容分离出去,对试验药品的规格、参比制剂选取、测试原形药物还是代谢物、高变异性药品生物等效性等提供了新的建议,强调溶出度实验的意义,并引入了生物试验豁免的相关内容。     

国内外特殊注射剂生物等效性指导原则的介绍分析

制剂生物等效性试验是评价仿制药内在质量的关键之一。美国食品药品监督管理局和欧洲药品管理局颁布的"单项品种生物等效性指导原则"中,对特殊注射剂如何进行生物等效性试验进行了推荐和相应要求,本文对其要点包括试验设计、检测指标、受试者选择、生物豁免原则、体外方法等进行总结分析,以对我国正在开展的仿制药质量与疗效一致性评价工作起到借鉴和指导意义。     

缓释制剂体内研究有关问题的思考

文中对缓释制剂体内研究涉及的有关问题进行了分析讨论,重点讨论了缓释制剂的生物利用度及生物等效性研究的基本要求、多规格缓释制剂体内研究的考虑、缓释制剂临床试验的基本研究思路,强调了食物对生物利用度影响研究及餐后生物等效性试验在缓释制剂体内研究中的重要性,并对体内研究与药学研究的关系以及如何结合体内外研究结果开展进一步工作进行了阐述。     

溶出曲线相似性的评价方法

介绍了日本厚生劳动省颁布的<仿制药生物等效性试验指导原则>与<固体制剂处方变更后生物等效性试验指导原则>中对溶出曲线评价的具体操作细则.     

各国生物类似药命名原则的比对研究及完善我国生物类似药命名原则的建议

对生物类似药名称进行规范管理不仅有利于医生处方和患者用药的准确性,更重要的是利于药品上市后不良反应的可追溯。对美国、欧洲、日本、韩国等国家或地区以及WHO生物类似药命名方式、命名技术要求进行比对研究,尽管各国生物类似药的命名方式有所不同,但"可区分"是各国共同遵循的原则。在对比研究的基础上,结合我国命名、处方管理相关要求、问卷调研和专家研讨,提出完善我国生物类似药命名原则的建议。     

基于药物基因组学的药物流行病学研究设计概述

摘要：药物基因组学在新药临床试验及个体化用药中发挥着重要作用。基因组水平的生物标志物可用在药物流行病学研究的设计中,用于识别个体对药物疗效有差异的原因,以及有药物毒性风险的个体。本文介绍了药物基因组学生物标志物的筛选方法,以及举例介绍了如何用药物流行病学的方法开展药物基因组学研究,包括临床随机对照试验和观察性研究。     

各国生物类似药沟通交流机制及生物类似药可互换性对比研究及建议

药品注册中的沟通交流对于控制风险、提高研发注册效率具有重要作用。对美国、欧盟、日本、韩国等国家生物类似药沟通交流机制进行对比研究,结合我国沟通交流的现状,问卷调研和专家研讨,提出完善我国生物类似药沟通交流机制的建议。各国对生物类似药的"可互换性"有着不同的界定和管理。对美欧等国家生物类似药的"可互换性"进行研究,结合问卷调研和专家研讨,提出完善我国生物类似药可互换性的建议。     

改进溶出度评价方法, 提高固体药物制剂水平(溶出度研究系列二)

全面阐述了我国目前药品内在品质方面的现状及与进口药的差距所在，提出了切实可行的解决办法，旨在呼吁业内人士应充分重视对溶度度试验的深入研究，从而推动药物制剂技术的不断进步，使我国尽快成为药物制剂强国！     

生物等效性评价的统计分析方法

生物等效性试验用于评价试验药(T)与注册药物(R)的生物等效性，以确定其效应相当。目前生物等效性平均、群体、个体生物等效性三种。平均生物等效性只评价观察指标的平均水平，而不考虑个体间的变异；而群体生物等效性既考虑了平均水平，又考虑了个体间的变异；个体生物等效性除考虑平均水平和个体变异。还考虑个体与药物间的交互作用。本文介绍了评价三种生物等效性的统计学原理，准则，等效性界值的确定，以及应用中的注意事项。并以实例说明。     

Recessions and the participation of youth in the selling and use of illicit drugs

Background

There has been limited research on how recessions (or more generally, the strength of the economy) affect drug use and the related outcome of drug selling. This is especially important, given the current economic crisis. This paper aims to use a conceptual framework, previous research, and new research to predict how the current economic crisis may be affecting youth drug selling and drug use.

Methods

A conceptual framework to understand how a recession could affect youth drug selling and drug use is presented, along with a review of the literature on empirical investigations on how the strength of the economy affects these behaviours among teenagers. In addition, new analyses for young adults are presented.

Results

The conceptual framework postulates that a recession would have direct positive effects on the prevalence of youth drug selling but ambiguous direct effects on youth drug use. The conceptual framework also postulates that drug selling and drug use are inter-connected at the individual level and the aggregate level. Thus, any effect of a recession on one would likely affect the other in the same direction. The limited empirical evidence indicates that both drug selling and drug use among youth are higher when the economy is weaker.

Conclusions

The current economic crisis will likely increase both youth drug selling and drug use relative to what they would have otherwise been.     

Evaluation of the microbial growth potential of pharmaceutical drug products and quality by design

The microbial growth potential of a pharmaceutical drug product refers to the ability of microorganisms to survive and proliferate in the product. Each drug formulation possesses a different potential for supporting or inhibiting microbial growth. Understanding this microbial growth potential can have a significant effect on the development and design of the drug manufacturing process. This article describes how this attribute can exert this effect on manufacturing process development and design through real examples and case studies obtained from the regulatory review of new drug and biologics license applications. In addition, this article describes how understanding the microbial growth potential of a pharmaceutical drug product is an element of the Quality by Design paradigm and how this understanding can simplify the drug development process and lead to better process design. LAY ABSTRACT: The microbial growth potential of a pharmaceutical drug product refers to the ability of microorganisms to survive and proliferate in the product formulation. Each drug product formulation possesses a different potential for supporting or inhibiting microbial growth depending on its components. Understanding this microbial growth potential can have a significant effect on the development and design of the drug manufacturing process. This article describes how this attribute can affect manufacturing process development and design through real examples and case studies obtained from the regulatory review of new drug and biologics license applications. In addition, this article describes how understanding the microbial growth potential of a pharmaceutical drug product is an element of the Quality by Design paradigm and how this understanding can simplify the drug development process and lead to better process design.     

The State of Support for Research on the Epidemiology,Prevention, and Treatment of Drug Use and Drug Use Disorders in the USA

This article describes the challenge of sustaining a balanced agenda for drug use research in the USA to advance understanding of the nature and extent of drug use and drug use disorders in a population; the processes and mechanisms that underlie onset, continuing, and stopping drug dependence; how to effectively prevent the onset of and early drug use as well as the social and health consequences of such use; and how to treat and maintain those with drug use disorders. This review concludes with recommendations to achieve sustained stability of funding for and to promote the progress of epidemiologic, prevention, and treatment policy research.     

Conceptions of Risk in the Lives of Club Drug-Using Youth

This paper describes current patterns of club drug use and local conceptions of risk among New York City area youth. The data is drawn from a NIDA-funded ethnographic study of club drug initiation among “Bridge and Tunnel” youth. The paper entails an examination of the harmony and discontinuity between folk models of risk within this population and professional models of risk. The author explores how club drug-using youth conceive of risks related to club drug use, specifically ecstasy, and how such conceptions compare and contrast with current professional models of risk. These conceptions of risk are crucial to understand, as they form an informal logic by which club drug practices are guided. Ultimately, the author examines how the relationship between folk models and professional models might inform health promotion efforts targeting youth.     

The use of kinetic-dynamic interactions in the evaluation of drugs

Deterred by the complexity of the mathematics, pharmacologists and clinical pharmacologists have only recently appreciated the usefulness of pharmacokinetics in drug development. Now unfortunately, although the vernacular of the science is known, often the meaning behind the words is lost. It is often assumed that drug levels are linearly related to drug action. Frequently they are not. This review shows, with reference to psychotropic drugs, how, in simple terms, it is possible to relate pharmacokinetics with pharmacodynamics, and how such relationships may provide a greater insight into drug activity and enhance drug development. Assuming that an equilibrium exists between the drug in plasma levels, and at the site of action, the same Michaelis-Menten equations used to relate effect to drug receptor binding can be used for drug level-dynamic interactions. A number of these relationships have been published and are discussed in terms of their derivation and their limitations. The graphical and computerised methods to create completeE _max curves are described and how the parameters of maximal effect, potency, variability and slope can be measured. When the drug is not in equilibrium with its site of action, hysteresis occurs and drug levels are out of phase with activity. Anticlockwise hysteresis, that is, activity increasing with time for a given drug level, can be caused by uptake into an active site, active metabolites, cascade activity, and sensitisation whilst clockwise hysteresis, in which activity decreases with time, can be caused by tolerance, active antagonistic metabolites, learning effects and feedback regulation. Attempts to relate simultaneously kinetics and dynamics by Link models can be difficult and not always necessary. It is assumed in therapeutic drug monitoring that individuals will show the same response for a given drug level. On the contrary, differences in individual subject sensitivity to drugs measured by kinetic-dynamic relationships may provide a greater understanding of the disease itself.     

Marriage, mortgage, motherhood: what longitudinal studies can tell us about gender, drug 'careers' and the normalisation of adult 'recreational' drug use

Through a consideration of quantitative and qualitative data obtained from young women aged 18-28 in the later years of the North West England Longitudinal Study, this paper explores how women's drug careers develop, progressing the authors' normalisation thesis of 'recreational' drug use from adolescence into adulthood. Longitudinal studies are here compared with repeated cross-sectional surveys more usually favoured and funded by governments. The authors argue that firstly, in relation to methodology, longitudinal studies provide a unique opportunity to elucidate how drug careers develop across the life course and to chart the various impacts of life events and transitions on these careers and vice versa. Secondly, through this exploration of gender differences in drug careers and life transitions, we develop an age and gender-sensitive understanding of how recreational drug use fits into women's adult lives. The paper concludes that the challenge for policy makers is how to address adult women's 'normalised' recreational drug use, in the face of a regime focused on educational provision aimed at adolescent prevention; public health information designed for teenagers; and treatment resources focused on predominantly male and non parenting problem drug users, and the links between addiction and acquisitive crime.     

对药物临床试验档案管理若干问题的探讨

建设科学的档案管理,规范档案管理员的素质,对保障药物临床试验质量至关重要。本综述基于我院药物临床试验中的相关经验,着重探讨如何建立科学的药物临床试验档案管理体系规范,以保证药物临床试验质量。     

医院药师做好药品不良反应监测工作的体会

目的 探讨医院药师如何做好药品不良反应监测工作.方法 总结在实际工作中的体会,多方面分析减少药品不良反应的有效方法.结果与结论 只要严格把控合理用药的各个环节,即能实现药品不良反应的最低化.     

Conceptions of risk in the lives of club drug-using youth

This paper describes current patterns of club drug use and local conceptions of risk among New York City area youth. The data is drawn from a NIDA-funded ethnographic study of club drug initiation among "Bridge and Tunnel" youth. The paper entails an examination of the harmony and discontinuity between folk models of risk within this population and professional models of risk. The author explores how club drug-using youth conceive of risks related to club drug use, specifically ecstasy, and how such conceptions compare and contrast with current professional models of risk. These conceptions of risk are crucial to understand, as they form an informal logic by which club drug practices are guided. Ultimately, the author examines how the relationship between folk models and professional models might inform health promotion efforts targeting youth.     

Toward the institutionalization of quantum computing in pharmaceutical research

Innovative pharmaceutical companies have started to explore quantum computing (QC). In this article, we provide a collective industry perspective from QC domain leaders at leading pharmaceutical companies. There are immediate nonfinancial benefits in engaging with QC, some likely financial returns in the short term in drug development, manufacturing, and supply chain, and potentially large scientific benefits in drug discovery long term. We discuss the required activities for institutionalizing QC: how to create an understanding of QC among researchers and management, which and how to deploy external resources, and how to identify the problems to be addressed with QC. If (and once) deployable, QC will likely have a similar trajectory to that of computer-aided drug design (CADD) and artificial intelligence (AI) during the 1990s and 2010s, respectively.