Model-integrated process development demonstrated on the optimization of a robotic cation exchange step

被引：41

作者：

Osberghaus, A. ^{[1
]}

Drechsel, K. ^{[1
]}

Hansen, S. ^{[1
]}

Hepbildikler, S. K. ^{[2
]}

Nath, S. ^{[2
]}

Haindl, M. ^{[2
]}

von Lieres, E. ^{[3
]}

Hubbuch, J. ^{[1
]}

机构：

[1] Karlsruhe Inst Technol, Sect Biomol Separat Engn 4, Inst Proc Engn Life Sci, D-76131 Karlsruhe, Germany

[2] Roche Diagnost GmbH, Pharmaceut Biotech Prod, D-82377 Penzberg, Germany

[3] Forschungszentrum Julich, Inst Bio & Geosci 1, D-52425 Julich, Germany

来源：

CHEMICAL ENGINEERING SCIENCE | 2012年 / 76卷

关键词：

Scale-up; Optimization; Simulation; Mathematical modeling; Chromatography; Downstream processing; MASS-ACTION MODEL; ION-EXCHANGE; CHROMATOGRAPHIC PROCESSES; PROTEIN; ADSORPTION; PREDICTION; DESIGN; PURIFICATION; SIMULATION; DISPLACERS;

D O I：

10.1016/j.ces.2012.04.004

中图分类号：

TQ [化学工业];

学科分类号：

0817 ;

摘要：

A new concept for chromatography process development based on high-through put data and mechanistic modeling will be presented in this paper. The concept is established in close cooperation between experimentation, modeling and model-based experimental design and allows for robustness analyses and upscale predictions. It will be demonstrated based on a case study: the optimization of a multicomponent separation (lysozyme, ribonuclease A and cytochrome c on SP Sepharose FF (TM)), subject to pH conditions and optimal settings for the shape of the elution gradient. Peak resolution and a precise prediction of retention times were chosen as performance variables in the case study to demonstrate the flexibility of the concept. It was shown that the concept of model-integrated process development is simple to perform from miniaturized scale on. The data, derived from model-based optimally designed experiments, provided sufficient information for process development, the model was calibrated and predictions for optimal separation setups as well as for the upscale showed a high precision. Consequently, the accumulation of data from high-throughput screenings can be used profitably for model-based process optimization and upscale predictions. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：129 / 139

页数：11

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