Calibration‐free inverse modeling of ion‐exchange chromatography in industrial antibody purification
Calibration‐free inverse modeling of ion‐exchange chromatography in industrial antibody purification
复制标题
工业抗体纯化中离子交换色谱的免校准逆向建模
DOI：
10.1002/elsc.201400248
复制
发表时间：
2016
影响因子：
2.7
通讯作者：
J. Hubbuch
中科院分区：
文献类型：
--
作者：
Tobias Hahn;Thiemo C Huuk;Anna Osberghaus;Katharina Doninger;S. Nath;Stefan T. Hepbildikler;V. Heuveline;J. Hubbuch
在工业应用中，确定从多组分混合物中分离目标组分的最佳工艺参数尤其具有挑战性。随着上市时间压力的不断增加，筛选大的参数空间是不可行的，实验设计方法可能会因为对小参数变化的动态和非线性反应而失败。一旦模型被校准到特定的工艺步骤，基于模型的优化可以确定最优的操作条件。在这项工作中，只使用不同波长的色谱图和尺寸排除层析的附加组分分析，对目标蛋白和工业抗体阳离子交换纯化步骤中的三种杂质的空间质量作用模型的参数进行了估计。关于饲料中的摩尔浓度或质量浓度的信息不可用。基于模型的优化结果与传统的基于色谱图的优化结果相吻合。
The identification of optimal process parameters for the isolation of a target component from multicomponent mixtures is especially challenging in industrial applications. With constantly increasing time‐to‐market pressure, screening a large parameter space is not feasible and design‐of‐experiment approaches with few experiments might fail due to dynamic and nonlinear reactions to small parameter changes. Model‐based optimization can determine optimal operating conditions, once the model has been calibrated to the specific process step. In this work, parameters for the steric mass action model were estimated for the target protein and three impurities of an industrial antibody cation‐exchange purification step using only chromatograms at different wavelengths and additional fraction analyses with size exclusion chromatography. Information on the molar or mass concentrations in the feed are not available. The model‐based optimization results coincide with conventional chromatogram‐based optimization.