Aspects of the Design of Preparative Chromatography for Purification of Antibodies
Aspects of the Design of Preparative Chromatography for Purification of Antibodies
复制标题
抗体纯化制备色谱设计的各个方面
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
David Karlsson
中科院分区：
文献类型：
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作者：
David Karlsson
生物技术产品的开发成本越来越高。抗体是生物制药行业中备受关注的一种蛋白质，在这项工作中也得到了应用。然而，生产抗体的成本很高，主要是由于下游加工，占总成本的50-80%。这项工作描述了基于模型的方法来设计色谱纯化步骤和重要的潜在物理现象。所使用的模型是一般速率模型或反应色散模型，具有两种不同的吸附描述，Langmuir移动相位调制器和空间质量作用。采用电子散斑干涉法、全息干涉法和色谱突破实验等全息方法研究了蛋白质在凝胶中的扩散。采用不同梯度的色谱洗脱实验获得了吸附动力学数据。研究了离子交换模型标定的不同方法。然后使用该模型来优化操作条件并执行基于模型的鲁棒性分析。本文提出的方法是朝着减少下游过程中的开发时间、资本支出和劳动力成本迈出的一步。(少)
The development of biotechnological products is becoming more and more expensive. One type of protein attracting a great deal of attention in the biopharmaceutical industry is antibodies, which was used in this work. The cost of producing antibodies is, however, high, mainly due to the downstream processing, which constitutes 50–80% of the total cost. This work describes model-based methods to design a chromatography purification step and the important underlying physical phenomena. The model used was a general rate model or a reaction dispersive model with two different adsorption descriptions, Langmuir Mobile Phase Modulators and Steric Mass Action. The diffusion of protein in gels was studied using holographic methods as Electronic Speckle Pattern Interferometry and Holographic Interferometry and also by chromatography breakthrough experiments. The adsorption kinetic data was obtained using chromatography elution experiments with different gradients. Different methods to calibrate an ion-exchange model were studied. The model was then used to optimise the operating conditions and to perform a model-based robustness analysis. The methods suggested in this thesis are a step towards reducing time for development, capital expenditure and labour costs in the downstream process. (Less)