Model based strategies towards protein A resin lifetime optimization and supervision
| Autor: | James Angelo, Fabian Feidl, Alessandro Butté, Zheng Jian Li, Kevin Potter, Xuankuo Xu, Martin F. Luna, Massimo Morbidelli, Sanchayita Ghose, Sebastian Vogg, Matevz Podobnik, Elenore Wiggin |
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| Rok vydání: | 2020 |
| Předmět: |
Work (thermodynamics)
Resin aging Statistics as Topic Protein A chromatography Ligands 010402 general chemistry 01 natural sciences Biochemistry Analytical Chemistry Hybrid modeling Robustness (computer science) Multivariate data analysis Least-Squares Analysis Staphylococcal Protein A Process engineering Chromatography Principal Component Analysis Fouling business.industry Chemistry 010401 analytical chemistry Organic Chemistry Process (computing) General Medicine Function (mathematics) Resin lifetime Models Theoretical 0104 chemical sciences Kinetics Yield (chemistry) Degradation (geology) Performance indicator business Cleaning procedures Algorithms Resins Plant |
| Zdroj: | Journal of Chromatography A. 1625:461261 |
| ISSN: | 0021-9673 |
| DOI: | 10.1016/j.chroma.2020.461261 |
| Popis: | The high cost of protein A resins drives the biopharmaceutical industry to maximize its lifetime, which is limited by several processes, usually referred to as resin aging. In this work, two model based strategies are presented, aiming to control and improve the resin lifetime. The first approach, purely statistical, enables qualitative monitoring of the column state and prediction of column performance indicators (e.g. yield, purity and dynamic binding capacity) from chromatographic on-line data (e.g. UV signal). The second one, referred to as hybrid modeling, is based on a lumped kinetic model, which includes two aging parameters fitted on several resin cycling experimental campaigns with varying cleaning procedures (CP). The first aging parameter accounts for binding capacity deterioration (caused by ligand degradation, leaching, and pore occlusion), while the second accounts for a decreased mass transfer rate (mainly caused by fouling). The hybrid model provides important insights into the prevailing aging mechanism as a function of the different CPs. In addition, it can be applied to model based CP optimization and yield forecasting with the capability of state estimation corrections based on on-line process information. Both approaches show promising results, which could help to significantly extend the resin lifetime. This comes along with increased understanding, reduced experimental effort, decreased cost of goods, and improved process robustness. |
| Databáze: | OpenAIRE |
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