El-Sabbahy, H;
Ward, D;
Ogonah, O;
Deakin, L;
Jellum, GM;
Bracewell, DG;
(2018)
The effect of feed quality due to clarification strategy on the design and performance of protein A periodic counter-current chromatography.
Biotechnology Progress
, 34
(6)
pp. 1380-1392.
10.1002/btpr.2709.
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Abstract
The impact of two different quality feeds, derived using two different harvest clarification processes, on protein A periodic counter-current chromatography (PCC) design and performance is investigated. Data from batch experiments were input into a model to design optimal PCC operating parameters specific to each feed material. The two clarification methods were: depth filtration using a wetlaid matrix which has Q-functionality; and a combination of depth filtration and chromatographic clarification, using a Q-functional nonwoven with a high anion exchange capacity (Emphaze™ AEX Hybrid Purifier) in which key impurities such as host cell DNA (HCDNA) and host cell proteins (HCP) are removed. The model predicted 34% better productivity for the chromatographically clarified cell culture fluid (CCCF) using a 4 column system, and productivity gains of 28% using only 3 columns enabling the option to simplify the protein A PCC strategy. Experimental validation of the predicted optimized PCC operating parameters using industrially relevant monoclonal antibody (mAb) CCCF feedstock over 100 cycles showed productivity gains of 49% for the chromatographically clarified material. HCP concentration was 11-fold lower, and HCDNA concentration was reduced by 4.4 Log Reduction Value (LRV) in the protein A PCC eluates. This work, therefore, demonstrates that the removal of HCDNA and HCP during clarification is an effective strategy for improving protein A PCC performance. This was achieved using the Emphaze™ AEX Hybrid Purifier which can be easily incorporated into a batch or continuous process, in a scalable fashion, without adding additional separate unit operations. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018.
| Type: | Article |
|---|---|
| Title: | The effect of feed quality due to clarification strategy on the design and performance of protein A periodic counter-current chromatography |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/btpr.2709 |
| Publisher version: | http://dx.doi.org/10.1002/btpr.2709 |
| Language: | English |
| Additional information: | © 2018 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Clarification, periodic counter-current chromatography, productivity, protein A, purity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10058794 |
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