A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants
Abstract Downstream processing of mAb charge variants is difficult owing to their similar molecular structures and surface charge properties. This study aimed to apply a novel twin‐column continuous chromatography (called N‐rich mode) to separate and enrich acidic variants of an IgG1 mAb. Besides, a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2021-06-01
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| Series: | Engineering in Life Sciences |
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| Online Access: | https://doi.org/10.1002/elsc.202000094 |
| _version_ | 1818448800049528832 |
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| author | Shu‐Ying Jing Ce Shi Hui Yi Leong Jun‐Jie Yuan Dong Gao Hai‐Bin Wang Shan‐Jing Yao Dong‐Qiang Lin |
| author_facet | Shu‐Ying Jing Ce Shi Hui Yi Leong Jun‐Jie Yuan Dong Gao Hai‐Bin Wang Shan‐Jing Yao Dong‐Qiang Lin |
| author_sort | Shu‐Ying Jing |
| collection | DOAJ |
| description | Abstract Downstream processing of mAb charge variants is difficult owing to their similar molecular structures and surface charge properties. This study aimed to apply a novel twin‐column continuous chromatography (called N‐rich mode) to separate and enrich acidic variants of an IgG1 mAb. Besides, a comparison study with traditional scaled‐up batch‐mode cation exchange (CEX) chromatography was conducted. For the N‐rich process, two 3.93 mL columns were used, and the buffer system, flow rate and elution gradient slope were optimized. The results showed that 1.33 mg acidic variants with nearly 100% purity could be attained after a 22‐cycle accumulation. The yield was 86.21% with the productivity of 7.82 mg/L/h. On the other hand, for the batch CEX process, 4.15 mL column was first used to optimize the separation conditions, and then a scaled‐up column of 88.20 mL was used to separate 1.19 mg acidic variants with the purity of nearly 100%. The yield was 59.18% with the productivity of 7.78 mg/L/h. By comparing between the N‐rich and scaled‐up CEX processes, the results indicated that the N‐rich method displays a remarkable advantage on the product yield, i.e. 1.46‐fold increment without the loss of productivity and purity. Generally, twin‐column N‐rich continuous chromatography displays a high potential to enrich minor compounds with a higher yield, more flexibility and lower resin cost. |
| first_indexed | 2024-12-14T20:25:16Z |
| format | Article |
| id | doaj.art-ab2f3c57d2884fc78ae90d21a747b7e5 |
| institution | Directory Open Access Journal |
| issn | 1618-0240 1618-2863 |
| language | English |
| last_indexed | 2024-12-14T20:25:16Z |
| publishDate | 2021-06-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Engineering in Life Sciences |
| spelling | doaj.art-ab2f3c57d2884fc78ae90d21a747b7e52022-12-21T22:48:39ZengWiley-VCHEngineering in Life Sciences1618-02401618-28632021-06-0121638239110.1002/elsc.202000094A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variantsShu‐Ying Jing0Ce Shi1Hui Yi Leong2Jun‐Jie Yuan3Dong Gao4Hai‐Bin Wang5Shan‐Jing Yao6Dong‐Qiang Lin7Key Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou P. R. ChinaKey Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou P. R. ChinaKey Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou P. R. ChinaBioRay Pharmaceutical Co., Ltd. Taizhou P. R. ChinaBioRay Pharmaceutical Co., Ltd. Taizhou P. R. ChinaBioRay Pharmaceutical Co., Ltd. Taizhou P. R. ChinaKey Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou P. R. ChinaKey Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological Engineering Zhejiang University Hangzhou P. R. ChinaAbstract Downstream processing of mAb charge variants is difficult owing to their similar molecular structures and surface charge properties. This study aimed to apply a novel twin‐column continuous chromatography (called N‐rich mode) to separate and enrich acidic variants of an IgG1 mAb. Besides, a comparison study with traditional scaled‐up batch‐mode cation exchange (CEX) chromatography was conducted. For the N‐rich process, two 3.93 mL columns were used, and the buffer system, flow rate and elution gradient slope were optimized. The results showed that 1.33 mg acidic variants with nearly 100% purity could be attained after a 22‐cycle accumulation. The yield was 86.21% with the productivity of 7.82 mg/L/h. On the other hand, for the batch CEX process, 4.15 mL column was first used to optimize the separation conditions, and then a scaled‐up column of 88.20 mL was used to separate 1.19 mg acidic variants with the purity of nearly 100%. The yield was 59.18% with the productivity of 7.78 mg/L/h. By comparing between the N‐rich and scaled‐up CEX processes, the results indicated that the N‐rich method displays a remarkable advantage on the product yield, i.e. 1.46‐fold increment without the loss of productivity and purity. Generally, twin‐column N‐rich continuous chromatography displays a high potential to enrich minor compounds with a higher yield, more flexibility and lower resin cost.https://doi.org/10.1002/elsc.202000094charge variantcontinuous chromatographyenrichmentmonoclonal antibodyseparation |
| spellingShingle | Shu‐Ying Jing Ce Shi Hui Yi Leong Jun‐Jie Yuan Dong Gao Hai‐Bin Wang Shan‐Jing Yao Dong‐Qiang Lin A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants Engineering in Life Sciences charge variant continuous chromatography enrichment monoclonal antibody separation |
| title | A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants |
| title_full | A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants |
| title_fullStr | A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants |
| title_full_unstemmed | A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants |
| title_short | A novel twin‐column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants |
| title_sort | novel twin column continuous chromatography approach for separation and enrichment of monoclonal antibody charge variants |
| topic | charge variant continuous chromatography enrichment monoclonal antibody separation |
| url | https://doi.org/10.1002/elsc.202000094 |
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