毒性病理评价的质量保证

毒性病理学评价是一般毒性试验、啮齿类致癌性试验以及一般生殖毒性试验的重要组成部分，在GLP质量管理和质量保证（QA）检查方面有其特殊的要求。现从试验人员、设施资质的确认、实验室质量控制，质量评估措施，病理资料、报告和材料的核查等方面详细介绍了毒性病理学评价QA的程序、要求和重点考虑的问题。     

遗传毒性试验的质量保证与现场检查

遗传毒性试验在毒理学试验中属于短期、小型试验,但因其测试终点的多样性及统计分析的复杂性,在药品非临床研究质量管理规范（GLP）和质量保证（QA）方面有其特殊性。文中从实验室资质的确认、研究过程的核查、原始资料和报告的审核、现场检查等4个方面介绍遗传毒性试验质量保证的程序、要求和注意事项。     

遗传毒性试验的质量保证与现场检查

遗传毒性试验在毒理学试验中属于短期、小型试验,但因其测试终点的多样性及统计分析的复杂性,在药品非临床研究质量管理规范（GLP）和质量保证（QA）方面有其特殊性。文中从实验室资质的确认、研究过程的核查、原始资料和报告的审核、现场检查等4个方面介绍遗传毒性试验质量保证的程序、要求和注意事项。     

遗传毒性试验的质量保证与现场检查

遗传毒性试验在毒理学试验中属于短期、小型试验，但因其测试终点的多样性及统计分析的复杂性，在药品非临床研究质量管理规范（GLP）和质量保证（QA）方面有其特殊性。文中从实验室资质的确认、研究过程的核查、原始资料和报告的审核、现场检查等4个方面介绍遗传毒性试验质量保证的程序、要求和注意事项。     

遗传毒性试验的质量保证与现场检查

遗传毒性试验在毒理学试验中属于短期、小型试验，但因其测试终点的多样性及统计分析的复杂性，在药品非临床研究质量管理规范（GLP）和质量保证（QA）方面有其特殊性。文中从实验室资质的确认、研究过程的核查、原始资料和报告的审核、现场检查等4个方面介绍遗传毒性试验质量保证的程序、要求和注意事项。     

遗传毒性试验的质量保证与现场检查

遗传毒性试验在毒理学试验中属于短期、小型试验，但因其测试终点的多样性及统计分析的复杂性，在药品非临床研究质量管理规范（GLP）和质量保证（QA）方面有其特殊性。文中从实验室资质的确认、研究过程的核查、原始资料和报告的审核、现场检查等4个方面介绍遗传毒性试验质量保证的程序、要求和注意事项。     

新药生殖毒性试验规范性操作介绍

生殖毒性试验是毒理学试验中较为复杂和繁琐、技术要求较高的试验。现从实验技术人员资质要求、试验前准备、试验期观察、试验记录、供试品、对照品的配制和给予、亲本动物的剖杀和检查、与专题负责人沟通确认等方面介绍作为技术人员如何做好安全性评价中的生殖毒性试验工作。     

家兔用于药物生殖发育毒性评价的研究进展

生殖发育毒性评价是药物安全性评价的重要组成部分。家兔属兔科兔形目,是药物生殖发育毒性评价的非啮齿类哺乳动物模型之一,但是其相关研究较啮齿动物少,对不同种属动物模型进行药物生殖发育毒性评价有助于提高风险评估的准确性。从生育力与早期胚胎发育毒性试验、胚胎-胎仔发育毒性试验、围产期发育毒性试验和体外生殖发育毒性评价等方面综述了家兔在药物生殖发育毒性评价中的研究进展,并探讨了家兔在药物生殖发育毒性评价研究中存在的问题及今后的发展方向,以期为今后研究提供参考。     

毒死蜱致雄性生殖毒性及其机制的研究进展

【摘要】毒死蜱（chlorpyrifos,CPF）系有机磷农药（organophosphates,OPs）,广泛应用于农业生产和居住环境。毒死蜱不仅具有急性毒性,其慢性毒性和潜在危害日益引起业界关注。有研究提示CPF为可疑的环境内分泌干扰物（EEDs）,具有生殖发育毒性。CPF的雄性生殖毒性主要表现为组织病理学、精子质量、激素水平和睾丸标志酶活性等发生变化,提示可能机制以脂质过氧化损伤机制研究居多。本文就CPF的雄性生殖毒性及其可能机制进行综述。     

胚胎干细胞试验在生殖毒性替代试验中的研究进展

药物生殖毒性评估是药物安全性评价中必不可少的部分。传统生殖毒性试验周期长,动物使用量大,投入资金多,随着“减少、优化、替代（3R）”原则的实施,胚胎干细胞试验（EST）逐渐成为研究和应用的热点。EST是经欧洲替代方法验证中心验证并推荐的生殖毒性全体外替代试验,可在药物研发早期阶段通过全体外检测和快速高通量检测药物的胚胎毒性类型。近年来,为解决EST在体外替代试验中遇到的问题,研究者们对其进行了优化和改进,包括增加化合物验证数量及种类,代谢体系及体内外浓度的选择,增加除心脏以外的分化检测终点（如神经、成骨和血管内皮等）;增加定量检测方法,从基因和蛋白水平对分化情况进行分析（如流式细胞荧光分选技术等）;增加EST衍生模型（如ReProGlo模型和BeWo运输模型等）以提高EST预测可靠性、模拟代谢活化过程、考虑体内外浓度一致性、对靶器官的毒性、增加定量分析终点。但目前有些检测方法还未明确其判断标准,有待进一步研究。EST更新及优化后,其评价范围不断扩大,风险评估准确性增加,有可能实现自动化、快速且高通量筛选潜在化合物。     

Bioassay Selection, Experimental Design and Quality Control/Assurance for Use in Effluent Assessment and Control

In the UK Direct Toxicity Assessment Programme, carried out in 1998-2000, a series of internationally recognised short-term toxicity test methods for algae, invertebrates and fishes, and rapid methods (ECLOX and Microtox) were used extensively. Abbreviated versions of conventional tests (algal growth inhibition tests, Daphnia magna immobilisation test and the oyster embryo-larval development test) were valuable for toxicity screening of effluent discharges and the identification of causes and sources of toxicity. Rapid methods based on chemiluminescence and bioluminescence were not generally useful in this programme, but may have a role where the rapid test has been shown to be an acceptable surrogate for a standardised test method. A range of quality assurance and control measures were identified. Requirements for quality control/assurance are most stringent when deriving data for characterising the toxic hazards of effluents and monitoring compliance against a toxicity reduction target. Lower quality control/assurance requirements can be applied to discharge screening and the identification of causes and sources of toxicity.     

Drug utilisation research

Drug utilisation research is a multidisciplinary activity which is now seen as a valuable component of quality assurance wherever medicines are used. This article explains what the research involves and outlines its future applications.     

应完善中药毒性药物的质量标准

目的:建议完善中药毒性药物质量标准。方法:以2005年版《中国药典》中收载的72种毒性中药为例,对含量标准及限量标准做扼要阐述。结果:同时具备含量标准及限量标准的药物只占72种毒性中药的11%。结论:应完善中药毒性药物的质量标准,以"低毒高效"来控制其质量,使临床用药安全有效。     

补肾壮阳类中药制剂中非法添加化学药物成分的检测

目的采用液质联用法检测补肾壮阳类中药制剂中非法添加的化学成分西地那非、他达拉非。方法色谱柱为AcquityBEHC18柱（2.1mm×50 mm,1.7μm）,以0.01 mol/L的醋酸铵溶液-乙腈梯度洗脱,流速0.3 mL/min,检测波长254 nm。结果在3批补肾壮阳类中药制剂中检测出西地那非或他达拉非。结论液质联用法灵敏准确,可有于补肾壮阳类中药制剂的质量检验。     

A Proposal for a Quality System for Herbal Products

Today, there is an increasing worldwide demand for botanicals. Developing countries heavily rely on plant-derived medicines for their primary healthcare. One reason amongst many is the relatively inexpensive process economics and the lack of stringent product governance associated with the exploitation of traditional plant medicines compared with modern medicine. Developed countries impose stringent good manufacturing practices and quality control measures on drug products derived from any manufacturing process, regardless of the primary raw material. However, several factors hamper the full-scale application of traditional plant medicines: lack of implementation of effective quality assurance in the manufacturing process; lack of traceability in the supply chain and associated value additions; and inefficient identification of molecular species that affect the therapeutic efficacy of the final product. There lacks an assessable, causative, and prognostic relationship between the raw materials, the manufacturing process and the final product quality. This article suggests some solutions that may be adopted by the phytodrug industry to widen its global reach and retain its credibility. Primarily among them is the implementation of hazards analysis and critical control point in the manufacturing process and employment of process analytical technology for ensuring minimal deviation from the manufacturing process of phytotherapeutics.     

医疗机构中药制剂转化为中药新药的思考

在研究历年来对医疗机构中药制剂监管要求的基础上,提炼出将医疗机构中药制剂转化为中药新药的现存问题,并结合人用经验以及真实世界证据的应用,对来源于医疗机构中药制剂转化为中药新药的有关问题进行思考,建议减免药效学试验,鼓励应用真实世界证据替代Ⅱ期临床试验,视情况决定是否减免单次及重复给药毒性试验;引导业界制定可量化的符合中药特点的诊断标准和疗效评价标准,从而认可中药对症状的治疗优势;推进真实世界证据的应用,特别是针对儿童用药的开发难点进行应用设计,为儿童用药的研发助力。     

对含马兜铃酸类中药被取消药用标准的讨论

目的:探讨马兜铃酸类中药被取消药用标准的有关问题。方法:分析含马兜铃酸类中药引起马兜铃酸肾毒性的原因。结果与结论:对含马兜铃酸药物的肾毒性应予以足够的重视,但应客观、理性对待其肾毒性。     

Responsibility of the pharmaceutical industry in health safety

Under this title will be recalled the responsibilities exerted by the Pharmaceutical Industry in two different fields: in the field of drug production, which has to meet the most rigorous constraints in matter of quality (Good Manufacturing Practices, quality assurance...) under supervision of the pharmaceutical structure; in the field of drug use: after the initial evaluation of the benefit/risk ratio, on which in based the drug registration, it is the responsibility of the Industry to contribute constantly to the good use of medicines and to its optimization (information of health professionals, patient information, pharmacovigilance, and if necessary sanitary safety measures...).