Process development in the Quality by Design paradigm: Modeling of Protein A chromatography resin fouling
| Autor: | Jayati Sakar, Lalita Kanwar Shekhawat, Mili Pathak, Anurag S. Rathore |
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| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
Process development Reuse 01 natural sciences Biochemistry Chromatography Affinity Quality by Design Analytical Chemistry stomatognathic system 010608 biotechnology Mass transfer Statistical analysis Staphylococcal Protein A Chromatography Fouling Chemistry Elution 010401 analytical chemistry Organic Chemistry technology industry and agriculture Antibodies Monoclonal Economic feasibility General Medicine Chromatography Ion Exchange 0104 chemical sciences Resins Synthetic |
| Zdroj: | Journal of Chromatography A. 1570:56-66 |
| ISSN: | 0021-9673 |
| DOI: | 10.1016/j.chroma.2018.07.060 |
| Popis: | Protein A chromatography is quite commonly used for capture of monoclonal antibodies from the clarified cell culture broths. Protein A resins are expensive and economic feasibility demands that the resin be reused for 50-300 cycles. Resin reuse is, however, accompanied by resin fouling, impacting both the binding and mass transfer characteristics of the resin. In the present study, we attempt to model the variations in binding and mass transfer characteristics of a commercially available Protein A resin, mAbSelect SuRe™, as a function of resin's reuse. Simplified linear driving force modeling and kinetic modeling of Protein A chromatography step elution cycling data has been successfully used to predict resin performance up to 100 cycles based on fouling data up to 50 cycles. Fouling factor for Protein A resin has been empirically modeled as a function of binding and mass transfer characteristics of resin and the resin's reuse using a combination of Buckingham's π theorem and statistical analysis. The proposed empirical model enables reliable prediction of performance of Protein A resin as well as offers an improved understanding of the underlying mechanism behind the decline in resin performance during fouling. |
| Databáze: | OpenAIRE |
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