洁净室环境监测在药品生物制品生产控制中的应用及重要性探讨

洁净室环境监测在药品生物制品生产控制中的应用及重要性探讨孙淑滨（卫生部兰州生物制品研究所,兰州７３００４６）分类号Ｒ９５４１前言国家《药品生产质量管理规范》对生产药品生物制品的厂房有严格的要求。笔者就荷兰培训所学结合本所情况做一探讨,以利全所及新建项...     

药品生产质量保证体系的建立

以《药品生产质量管理规范》(GMP)为依据,运用“过程方法”、“管理的系统方法”和“层次分析”理论,以药品生产体系的增值链系统为线索,对药品生产质量管理中的工序控制、信息传递、各子系统间的关联和衔接进行分析,以流程图的形式表示,并将系统要素人、物、信息和程序控制标明,建立起质量保证体系。涵盖了系统的全部关键质量控制点,职责清晰、不易遗漏、便于控制和发现问题。解决了药品生产质量控制及GMP实施中的难点,是药品生产企业行之有效的质量管理的手段。     

浅析数字监控系统

近些年,人们对数字监控技术的需求量越来越大,被广泛的应用于生活与生产的各个领域。数字监控系统主要由摄像头、监控现场主机与远程端主机三部分组成,与模拟系统相比,它具有系统配置简单,录像方式多样,检索方式灵活,可以方便的进行警报系统的设置,访问也会有清楚的记录。本文深入分析了数字监控系统的特点以及关键技术。     

试析药品生产风险管理存在问题归因分析及对策

本文分析了国内药品生产企业应用风险管理的现状,提出了实施质量风险管理的必要性,并指出在加强药品生产风险管理环节中应注意的几个问题,一是强化风险管理意识,二是建立信息反馈机制,三是进行评估与交流。     

生物药品生产过程中污染问题的管控策略

生物药品制药流程严谨,每个步骤都需要达到对应的标准和规范,这是保证生物药品性能发挥的关键所在,也是其不同于其他生产行业的独特之处。文章从这个角度探究,探析生物药品生产过程中强化污染问题管理的必要性,对于生物药品生产过程中污染问题的管控,提出了建设性的意见和建议。     

MeGA-PharM系统和转基因烟草药品

Biotechnology News 2000年20卷4期第4页及Genetic Engineering News 2000 年20卷6期第20页报道:美国烟草重组蛋白生产商Croptech Corp.(Blacksburg, VA)利用烟草生产的重组药用蛋白已经接近临床试验阶段.     

自动感应照像系统在野生动物调查中的应用

自动感应照像系统在野生动物调查中的应用马世来（中国科学院昆明动物研究所保护生物学中心昆明６５０２２３）里查德·何里来（美国纽约野生动物保护协会ＵＳＡ１０４５０－１０９９）关键词自动感应,照像系统,野外应用,云南ＵＳＥＯＦＲＥＭＯＴＥＣＡＭＥＲＡＳＹＳ...     

医疗安全监控系统在卫生监督工作中的作用

医疗安全监督是卫生监督的重要组成部分,发展和完善医疗安全监督模式是卫生监督体系改革的重要任务之一。医疗安全监控系统的建立将医疗安全监督模式由以往事后监管、被动监督转变为事前防范、主动预防的新型监督模式。在实际的医疗安全监督工作中,真正体现了服务、教育、处罚相结合的卫生监督工作理念。     

中央监控系统在护理管理工作中的应用及效果

护理管理是保证、协调、提高护理工作的关键。如何实施更科学、更系统、更全面、更有效的护理管理是护理学面临的新课题之一。我院于2004年启用了现代化数字中央监控系统,通过1年的使用,取得了显著的效果。     

建立洁净区微生物数据库与无菌药品GMP生产过程控制的探讨

目的 建立洁净区微生物数据库,为追溯洁净区微生物污染来源提供依据,为无菌药品生产过程控制提供有力指导.方法 对乙型脑炎减毒活疫苗生产车间洁净区环境和操作人员进行微生物负载检测,并对该车间注射用水、纯化水系统样品进行微生物限度检测,鉴别研究相应分离菌,建立洁净区微生物数据库.同时对乙型脑炎减毒活疫苗中间产品进行无菌检查检测,并对阳性结果分离菌进行鉴别分析.然后根据建立的洁净区微生物数据库对阳性结果举例进行溯源探讨分析.结果 洁净区环境和人员主要存在里拉/藤黄微球菌、人葡萄球菌、表皮葡萄球菌以及科氏葡萄球菌科氏亚种等革兰阳性菌和蜡样芽胞杆菌等,水系统中则主要存在少动鞘氨醇单胞菌和铫子芽胞杆菌等.中间产品无菌阳性结果主要存在里拉/藤黄微球菌、蜡样芽胞杆菌以及奇异变形菌等,经调查分析,分别为操作过程中经环境偶然带入或试验动物操作不慎带入.结论 建立洁净区微生物数据库是追溯产品微生物污染来源的有效方法,能够为无菌药品GMP生产过程制定有效的控制措施提供依据,并使其更有针对性.     

On-line monitoring and controlling system for fermentation processes

A personal computer-based on-line monitoring and controlling system was developed for the fermentation of microorganism. The on-line HPLC system for the analysis of glucose and ethanol in the fermentation broth was connected to the fermenter via an auto-sampling equipment, which could perform the pipetting, filtration and dilution of the sample and final injection onto the HPLC through automation based on a programmed procedure. The A/D and D/A interfaces were equipped in order to process the signals from electrodes and from the detector of HPLC, and to direct the feed pumps, the motor of stirrer and gas flow-rate controller. The software that supervised the control of the stirring speed, gas flow-rate, pH value, feed flow-rate of medium, and the on-line measurement of glucose and ethanol concentration was programmed by using Microsoft Visual Basic under Microsoft Windows. The signal for chromatographic peaks from on-line HPLC was well captured and processed using an RC filter and a smoothing algorithm. This monitoring and control system was demonstrated to be effective in the ethanol fermentation of Zymomonas mobilis operated in both batch and fed-batch modes. In addition to substrate and product concentrations determined by on-line HPLC, the biomass concentration in Z. mobilis fermentation could also be on-line estimated by using the pH control and an implemented software sensor. The substrate concentration profile in the fed-back fermentation followed well the set point profile due to the fed-back action of feed flow-rate control.     

A new semi-determinate tomato hybrid for early production

By using the knowledge of the genetic constitution and the characteristics of the available tomato lines for selection, there were created several dozens of hybrid combinations characterised by semi-determinate habit, with large fruits and early maturing. These hybrids were tested in preliminary and comparative trials with the hybrids Balkan F₁, Balca F₁, Žar F₁, and some others as standard varieties. These tomato hybrids were grown earlier but they are grown even today in the early production, for the market in green houses and in the open field. The hybrid Marco F₁ was the best of all. Its yield was 25 t/ha in the plastic-house (the same as in the standard), up to 32 t/ha in the open field (5 % more than in the standard). This hybrid was a few days later than Balkan, with the fruits weighting 200 grams (fruits were approximately 60 % heavier than in the standard). It possess the genetic V, F and Tm resistance.     

Hair analysis for veterinary drug monitoring in livestock production

This review summarizes the basic information and applications concerning the use of hair analysis for the detection of misuse of therapeutic and anabolic agents in livestock animals. Hair biology, hair-shaft structure and the mechanisms of drug incorporation are described, considering the different factors which can affect the deposition. Sampling and extraction methods are reviewed with special attention to the particularities of this matrix, while the use of different analytical techniques is discussed, taking into account the concentration and the sensitivity required for drug detection. Advantages, drawbacks, promising prospects and possible applications of this technique in the future are also discussed.     

A new culture system for the cultivation of mammalian cells for the production of several biologically active substances

A maximum cell density of 8×10⁶ viable human fibroblast cells/ml was obtained on microcarriers at a perfusion rate of 0.6 mL/min — a rate which maintained a quasi-steady state. The maximum tPA production was approximately 1.2 g/ml and obtained when the cell density was relatively constant during the later periods of cultivation. Specific UTP and tPA production rates had a correlation factor of 0.85, and cell growth to oxygen consumption had an 0.92 correlation factor. ATP generation was strongly correlated to glutamine consumption, with a lower correlation to oxygen utilization.     

A new helicase assay based on graphene oxide for anti-viral drug development

Recently, graphene oxide (GO), one of the carbon nanomaterials, has received much attention due to its unique physical and chemical properties and high potential in many research areas, including applications as a biosensor and drug delivery vehicle. Various GO-based biosensors have been developed, largely based on its surface adsorption properties for detecting biomolecules, such as nucleotides and peptides, and real-time monitoring of enzymatic reactions. In this review, we discuss recent advances in GO-based biosensors focusing on a novel assay platform for helicase activity, which was also employed in high-throughput screening to discover selective helicase inhibitors.     

A new method for monitoring nitric oxide production using Teflon membrane microdialysis

The measurement of nitric oxide (NO) by electron spin resonance (ESR) is complicated by potentially toxic spin-trapping agents, which may affect the NO-producing cells per se and/or cause artifacts and systemic side effects. These problems can be addressed by preventing direct interaction between the agent and the biological system. In the present study, we utilized Teflon as a barrier between the spin trap and the living cell, since the material is permeable to gas only. Our aim was to investigate if NO could diffuse across the membrane in sufficient amounts to be trapped and quantified by ESR. We used standard microdialysis equipment and specially designed dialysis probes, or tubing, with Teflon membranes. Sodium nitroprusside was used as a NO donor and Fe-N-dithiocarboxysarcosine (Fe(DTCS)2) as a spin trap. NO readily diffuses through Teflon and could be quantified in concentrations considerably below 50 nM in a reproducible and accurate manner. In cell cultures of activated murine macrophages, NO synthesis from iNOS could be monitored and we noted a huge increase in NO concentration by superoxide dismutase. We conclude that spin trapping of NO by Fe(DTCS)2 across Teflon membranes is an attractive approach for quantifying and monitoring nitric oxide production without interfering with cell viability.     

A novel method for monitoring monoclonal antibody production during cell culture

We describe a new format for surface-based fluoroimmunoassays that allows detection of biomolecule interactions without separation steps. The bioactive layer was immobilized on the surface of a glass substrate covered with silver islands that provide optical amplification of the distinctive fluorescence signal from bound probes when compared to unbound probes. The technique used was phase-modulation fluorometry that allows sensitive detection of bound probes with a very short lifetime in the presence of excess free probes in solution. The new method was applied to assay monoclonal antibody production during cell culture. Excellent agreement was found between the new method and ELISA analysis of hybridoma cell culture samples. It is predicted that the near real time monitoring of protein products during bioprocessing will be possible with the described technology.     

新一代PEG在修饰抗原和药物缓释中的应用

聚乙二醇及其衍生物是具有许多优良性质的高分子化合物,由于良好的生物相容性、无毒、无免疫原性,广泛用于生物医学领域。本文总结聚乙二醇的发展历史和新一代聚乙二醇的特点,阐述聚乙二醇化修饰的目的,特别是在抗原修饰、血型改造和细胞移植等方面的应用,重点对聚乙二醇在药物缓释方面的应用进行了系统的综述。