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首页> 外文期刊>Chemical Engineering Research & Design: Transactions of the Institution of Chemical Engineers >Modelling of industrial biopharmaceutical multicomponent chromatography
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Modelling of industrial biopharmaceutical multicomponent chromatography

机译:建模的工业生物制药多组分色谱法

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摘要

The development and validation of a chromatography rate model for an industrial multicomponent chromatographic bioseparation is presented. The model is intended for use in a process scenario to allow specific variables critical to product quality to be studied. The chromatography provides impurity clearance whilst producing a complex product composed of six closely related variants of a dimer protein therapeutic (~30 kDa), with their monomer subunits in a specific ratio. Impurity removal is well understood, however, achieving the correct monomer subunit ratio can pose a purification challenge. We utilise a stepwise approach to develop a model for studying the effect of feed material variability on product quality. Scale down experiments are completed to quickly generate data for estimating model parameters, before an iterative procedure is employed where the industrial process is used to refine parameters in a sequential manner, until model predictions exhibit satisfactory agreement with experimental data. Final model predictions were in good agreement with experimental product quality (within 3%). The results demonstrate how good understanding of an industrial process can help facilitate model development when an exhaustive description is not required, despite considering a chromatographic bioseparation with crude feed material and challenging purification objectives.
机译:色谱法的发展和验证一个工业多组分模型色谱bioseparation。模型是用于一个过程的场景允许特定的变量的关键产品质量研究。提供杂质间隙而产生复杂产品组成的六个密切相关变异的二聚体蛋白治疗(~ 30kDa),他们在一个特定的单体单元比率。然而,实现正确的单体单元比率可以构成一个净化的挑战。利用阶梯式方法,开发一个模型对学习的影响饲料的材料在产品质量变化。实验完成快速生成数据估计模型参数,前采用的迭代过程工业过程是用来优化参数以顺序的方式,直到模型预测表现出令人满意的协议与实验数据。协议与实验产品质量(3%以内)。理解一个工业过程可以帮助当一个详尽的促进模型的发展不需要描述,尽管考虑与原油的色谱bioseparation饲料净化材料和具有挑战性的目标。

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