加强对药品生产企业GMP认证后的日常监管

目前一些药品生产食业在生产管理中对GMP实施不力的问题突出。“齐二药”假药事件教训惨痛，不仅给所有约品生产企业敲响了警钟，也给了我们药品监督管理人员一个重要启示：药品监管无小事。对GMP认证后企业的日常监督必须适应监管形势的变化。     

美国药品安全风险管理最终指南对我国药品安全风险管理的启示

从"万络事件"和"欣弗事件"中,探寻中美两国对药品风险管理手段的差异,从中为我国药品安全管理提出可行性建议。通过例证法分析两国在药品风险管理手段中的不同。我国在药品风险管理中主要采取行政手段进行管理.而在新的形势下,一方面在重视行政监管的同时加强对企业的技术性支持;另一方面在保证原有审查方式的同时,应当重视药物流行病学研究结果。     

对药品安全法律保障的思考与建议

频发的药品安全事件,引发了对药品安全法律保障的思考。药品安全事件的“责任认定”和“赔偿问题”存在法律障碍。分析《药品管理法》中对假药、劣药概念的界定,探讨欣带事件、甲氨蝶呤事件的定性。我国目前缺少一部对药品不良事件损害责任有效追究以及对受害者救济帮助的特别法律．分析“齐二药”假药损害案件赔偿判决,提出尽快制定《药品不良事件损害救济条例》保障患者的权益,建议修改完善《药品管理法》中假劣药的界定,在法律责任中补充“民事赔偿优先执行”原则。     

主观无过错经销假劣药品的判定条件

在药品行政执法过程中，行政相对人若违反药品管理相关法律法规实施违法行为，只要具备处罚主体合格、违法事实客观存在、有法律规定责任等要件，药品监管部门就应对行政相对人依法予以行政处罚。但《药品管理法实施条例》第八十一条规定：“药品经营企业、医疗机构未违反《药品管理法》和本条例的规定，并有充分证据证明其不知道所销售或者使用的药品是假药、劣药的，应当没收其销售或者使用的假药、劣药和违法所得，但是，可以免除其他行政处罚”，即主观无过错经营、使用假劣药品可以只承担有限行政责任。     

必须加强药品生产企业GMP认证后的日常监管

今天,当我们回顾实施GMP的历程,不禁有一种“收获”的喜悦,但今年的齐齐哈尔第二制药有限公司(以下简称“齐二药”)假药事件反映出的目前一些药品生产企业在生产管理中对GMP执行不力等突出问题,给我们敲响了警钟。作为一名药品监管人员,深深感到药品生产企业GMP认证后的日常监管任务的艰巨和责任的重大。“齐二药”假药事件教训是惨痛的。药品监管无小事,对GMP认证后企业的日常监督必须适应形势的变化,更重要的是提高监管手段的科学性。"一、实施药品生产企业GMP认证成效显现监督实施GMP以来,我国制药行业变化明显,一大批装备先进的…     

药品包装有防伪号标识提示却无防伪号码该如何论处

案例:某药品生产企业生产的“×××胶囊”,其外包装的醒目位置印有“此产品有防伪号,无防伪号视为假药”的文字。批号为“050101”的药品外包装上防伪号标示处却为空白且已流通上市。患者王某购买该药后,以所买药品为假药为由,于2005年3月21日向当地药品监督管理部门举报。对药品包装上印有“无防伪号视为假药”提示而无防伪号的药品,药品监督管理部门该如何论处,有两种观点:其一,该药品应以假药论处。理由:在该药品的外包装上,印有相关提示:此产品有防伪号,无防伪号视为假药。既然批号为“050101”的药品外包装防伪号标示处为空白,药品监…     

衢州市场非药品冒充药品的现状及监管探索

“非药品冒充药品”在现行的《中华人民共和国药品管理法》中明确判定为假药，但在实际监管工作中并不能简单、明确判定为假药。非药品冒充药品的市场混乱，不仅扰乱了正常的药品市场秩序，而且增加了百姓的用药风险，威胁到群众的身体健康。     

浅谈管理相对人的主观因素与行政处罚

新出台的《药品管理法实施条例》中第八十一条明确规定 :“药品经营企业、医疗机构未违反《药品管理法》和本条例的有关规定 ,并有充分证据证明其不知道所销售或者使用的药品是假药、劣药的 ,应当没收其销售或者使用的假药、劣药和违法所得 ;但是 ,可以免除其他行政处罚”。《实施条例》对药品管理相对人行政法律责任的构成要件作了新的补充 ,处罚的尺度上作了更具体的规定 ,明确提出了药监部门在审理经营、使用假劣药品案件时 ,要考虑管理相对人的主观因素 ,即判定管理相对人是否存在主观过错 ,根据情节决定管理相对人应承担法律责任的程度…     

浅析假药与药品不良反应的法律区别

目的:明确假药与药品不良反应的法律区别。方法:从法律内涵、监管部门、处理措施、法律责任等角度对假药与药品不良反应进行分析对比。结果与结论:假药与药品不良反应存在根本区别,在药品监管和使用过程中对此必须有正确认识。     

我国《药品注册管理办法》拟作重要修改

近年来，随着国内多起假药劣药伤人事件的发生，特别是近期包括原国家食品药品监督管理局局长郑筱萸在内的多位药监局高层领导相继下马，药品安全问题更加引起全社会的广泛关注，药品安全问题也自然成为了今年两会上代表和委员热议的话题。两会代表和委员认为我国现行《药品注册管理办法》存在的漏洞是导致药品管理官员违法、违纪，而造成大量“新药”上市的重要原因。因此，代表委员多次呼吁宜尽快修改《药品注册管理办法》。国家食品药品监管局近日已经对新修订后的《药品注册管理办法（征求意见稿）》在官方网站进行为期两个月的公示，     

Evaluation of Prolonged Versus Continuous Infusions of Piperacillin/Tazobactam During Shortages of Small Volume Parenteral Solutions

Background: In 2017, a national drug shortage of small volume solutions significantly affected the preparation of intravenous antibiotics. In response, a continuous infusion administration protocol for piperacillin/tazobactam (PIP/TAZ) was implemented. Objective: To compare the outcomes of continuous to prolonged infusions of PIP/TAZ in the setting of drug shortages. Methods: This study is a single-center, retrospective cohort study in a community hospital of patients 18 years and older who received intravenous PIP/TAZ through 2 different dosing strategies of intravenous antibiotics from December 2016 to January 2018. Data were collected for 2 months on patients receiving prolonged infusions of PIP/TAZ prior to November 2017 and for 2 months on patients receiving continuous infusions of PIP/TAZ after November 2017. Results: A total of 90 patients who received PIP/TAZ via either prolonged (n = 47) or continuous infusion (n = 43) were evaluated. There were no differences between the groups in mortality (3 vs 2 deaths, P = 1.00), length of therapy (6 ± 4 vs 6 ± 3 days, P = .86), or length of stay (9 ± 7 vs 8 ± 6 days, P = .47). Additionally, no differences were noted between incidences of thrombocytopenia (P = .41), Clostridioides difficile infection (P = .48), acute renal failure (P = 1.00), seizures (P = 1.0), or 30-day readmission rates (P = .27). Conclusions: Administration of continuous infusion PIP/TAZ appears to be a viable mitigation strategy during small volume fluid shortages. Future cost-effectiveness studies may provide information on the financial impact of continuous infusions during costly drug shortages.     

In vitro testing for diagnosis of idiosyncratic adverse drug reactions: Implications for pathophysiology

Idiosyncratic drug reactions (IDRs) represent a major health problem, as they are unpredictable, often severe and can be life threatening. The low incidence of IDRs makes their detection during drug development stages very difficult causing many post-marketing drug withdrawals and black box warnings. The fact that IDRs are always not predictable based on the drug’s known pharmacology and have no clear dose–effect relationship with the culprit drug renders diagnosis of IDRs very challenging, if not impossible, without the aid of a reliable diagnostic test. The drug provocation test (DPT) is considered the gold standard for diagnosis of IDRs but it is not always safe to perform on patients. In vitro tests have the advantage of bearing no potential harm to patients. However, available in vitro tests are not commonly used clinically because of lack of validation and their complex and expensive procedures. This review discusses the current role of in vitro diagnostic testing for diagnosis of IDRs and gives a brief account of their technical and mechanistic aspects. Advantages, disadvantages and major challenges that prevent these tests from becoming mainstream diagnostic tools are also discussed here.     

黄酮类化合物抗卵巢癌化疗耐药的作用进展

摘要：黄酮类化合物是广泛存在于自然界的一类多酚类物质,亦是诸多传统中草药中的有效成分之一,因其高效、低毒,且具有多种生物学活性而得到了广泛的关注。卵巢癌是病死率最高的妇科恶性肿瘤,化疗耐药是导致其预后不良的主要原因之一。研究发现,黄酮类化合物对改善卵巢癌耐药有独特的效果,或将有助于克服卵巢癌耐药。本文就近年来黄酮类化合物改善卵巢癌化疗耐药作用的相关研究进展进行综述。     

Interaction of innovative small molecule drugs used for cancer therapy with drug transporters

Multiple new small molecules such as tyrosine kinase, mammalian target of rapamycin (mTOR) and proteasome inhibitors have been approved in the last decade and are a considerable progress for cancer therapy. Drug transporters are important determinants of drug concentrations in the systemic circulation. Moreover, expression of drug transporters in blood-tissue barriers (e.g. blood-brain barrier) can limit access of small molecules to the tumour (e.g. brain tumour). Finally, transporter expression and (up)regulation in the tumour itself is known to affect local drug concentrations in the tumour tissue contributing to multidrug resistance observed for multiple anticancer agents. This review summarizes the current knowledge on: (i) small molecules as substrates of uptake and efflux transporters; (ii) the impact of transporter deficiency in knockout mouse models on plasma and tissue concentrations; (iii) small molecules as inhibitors of uptake and efflux transporters with possible consequences for drug-drug interactions and the reversal of multidrug resistance; and (iv) on clinical studies investigating the association of polymorphisms in genes encoding drug transporters with pharmacokinetics, outcome and toxicity during treatment with the small molecules.     

合理医疗药品目录网络评审系统的开发和应用

目的：通过建立药品目录网络评审系统,提高药品目录评审程序的科学性、灵活性和效率。方法：通过制定严谨的评审方案,建立Browser/Server（B/S）架构的药品目录网络评审系统,组织专家进行网络评审。结果：共有2042名专家参加药品目录网络评审工作,实现了合理医疗药品目录和基本药物目录的网上评审。结论：合理医疗药品目录网络评审系统能提高评审效率,使评审工作更加规范和科学。     

旋光异构体药物代谢研究的进展

从药效学、药物代谢与血浓度检测方法等三方面,综述了旋光异构体药物代谢研究的近年进展。最后对临床药理学中两个重要领域,即血药浓度监测与新药的研究、开发及审评,结合我国情况进行了讨论。     

Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as carriers for sustained drug delivery

A novel degradable microsphere (MS) for intra-articular drug delivery, composed of a polyethylene glycol (PEG) core containing degradable regions made of short poly-(lactic-co-glycolic acid) (PLGA) sequences – named PEG-hydrogel MS – was injected into the cavity of sheep shoulder joint, and compared to non-degradable MS devoid of hydrolysable crosslinker in terms of location, degradation and inflammation. One week after intra-articular injection both groups of MS were localized beneath the synovial lining of the synovial fringes located at bottom of the shoulder joint, while a fraction of particles remained in synovial fluid. Histological analyses made one and 4 weeks after intra-articular injection showed cell proliferation around the non-degradable MS entrapped within the synovium. By contrast, degradable PEG-hydrogel MS were surrounded by few cells. The degradation of degradable PEG-hydrogel MS within the synovium was slow and was not fully complete after four weeks. Our findings indicate that the tissue entrapment of MS below the synovial lining was independent of the material degradability, while degradable PEG-hydrogel MS are less inflammatory than the non-degradable one. Degradable PEG-hydrogel MS offer several advantages over the non-degradable MS as carriers for a sustained drug delivery in synovial tissue according to the low intensity of inflammatory reaction triggered in synovium.     

住院医嘱不合理药物联用案例分析

目的为临床合理联用药物提供参考。方法随机抽查住院病例医嘱,查找不合理用药问题并进行汇总分析。结果 2406份住院医嘱中,共发现不合理药物联用问题44例。结论临床药师应开展以药物相互作用为主线的药学服务,确保安全有效的药物联用。     

我院2007-2011年抗精神病药应用分析

目的 了解我院抗精神病药使用情况及用药趋势,促进临床合理用药.方法 采用WHO推荐的限定日剂量分析法,对我院2007年1月-2011年12月抗精神病药的销售金额和用药频度(DDDs)进行统计分析.结果 我院使用的12种抗精神病药销售金额和DDDs均呈增长趋势,非典型抗精神病药的销售金额之和占各年度抗精神病药销售总金额的86%～90%,DDDs之和占各年度抗精神病药总DDDs的84%～90%.结论 我院抗精神病药的使用结构比较合理,基本符合我国目前抗精神病药的发展趋势.     

Bcr-Abl酪氨酸激酶抑制剂联合用药治疗慢性粒细胞白血病研究进展

以伊马替尼为代表的酪氨酸激酶抑制剂对慢性粒细胞白血病(CML)的治疗产生了重要影响,但其耐药性已成为CML治疗领域的关键问题。伊马替尼、尼洛替尼、达沙替尼以及普纳替尼等Bcr-Abl酪氨酸激酶抑制剂与其他药物联合使用,可以协同抑制Bcr-Abl及其磷酸化蛋白的表达,显著降低STAT5、CRKL、ERK5等信号通路的磷酸化水平,改善肿瘤微环境,降低肿瘤细胞多药耐药性,已在基础研究和临床Ⅰ期研究中取得阶段性成果,为治疗CML提供新策略。