Volume 40, Issue 23-24 p. 3074-3083
Research Article

Analytical tools for monitoring changes in physical and chemical properties of chromatography resin upon reuse

Mili Pathak

Mili Pathak

Department of Chemical Engineering, Indian Institute of Technology, New Delhi, India

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Katherine Lintern

Katherine Lintern

Department of Biochemical Engineering, University College London, London, United Kingdom

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Thomas F. Johnson

Thomas F. Johnson

Department of Biochemical Engineering, University College London, London, United Kingdom

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Aswathy M. Nair

Aswathy M. Nair

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, India

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Soumyo Mukherji

Soumyo Mukherji

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, India

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Daniel G. Bracewell

Daniel G. Bracewell

Department of Biochemical Engineering, University College London, London, United Kingdom

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Anurag S. Rathore

Corresponding Author

Anurag S. Rathore

Department of Chemical Engineering, Indian Institute of Technology, New Delhi, India

Correspondence: Dr. Anurag Rathore, Professor, Department of Chemical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India

E-mail: [email protected]

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First published: 28 September 2019
Citations: 3

Color online: See the article online to view Figs. 1 and 3 in color.

Abstract

Protein A resins are often reused for multiple cycles to improve process economy during mAb purification. Significant reduction in binding capacity and product recovery are typically observed due to the presence of unwanted materials (foulants) deposited on the resin upon reuse. In this paper, we have used a wide spectrum of qualitative and quantitative analytical tools (particle size analysis, HPLC, fluorescence, SEM, MS, and FTIR) to compare the strengths and shortcomings of different analytical tools in terms of their capability to detect the fouling of the resin and relate it to chromatographic cycle performance. While each tool offers an insight into this complex phenomena, fluorescence is the only one that can be used for real-time monitoring of resin fouling. A correlation could be established between fluorescence intensity and the process performance attributes (like yield or binding capacity) impacted upon resin reuse. This demonstration of the application of fluorescence for real-time monitoring correlated empirically with process performance attributes and the results support its use as a PAT tool as part of a process control strategy. While the focus of this paper is on fouling of protein A chromatography resin, the approach and strategy are pertinent to other modes of chromatography as well.