Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers
Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal...
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| Format: | Article |
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MDPI AG
2025-01-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/15/1/34 |
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| author | Solomon Isu Shu-Ting Chen Raheleh Daneshpour Hironobu Shirataki Daniel Strauss Andrew L. Zydney Xianghong Qian Sumith Ranil Wickramasinghe |
| author_facet | Solomon Isu Shu-Ting Chen Raheleh Daneshpour Hironobu Shirataki Daniel Strauss Andrew L. Zydney Xianghong Qian Sumith Ranil Wickramasinghe |
| author_sort | Solomon Isu |
| collection | DOAJ |
| description | Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The formation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hydrophobic interaction membrane adsorber was the most effective in minimizing flux decline during virus filtration. Ion exchange membranes may also be effective if the monoclonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when compared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. These results can help guide the development of more effective virus filtration processes for monoclonal antibody production. |
| format | Article |
| id | doaj-art-eb89107743a44e878fe3c041d2e10d03 |
| institution | Kabale University |
| issn | 2077-0375 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj-art-eb89107743a44e878fe3c041d2e10d032025-01-24T13:41:06ZengMDPI AGMembranes2077-03752025-01-011513410.3390/membranes15010034Enhancing Virus Filter Performance Through Pretreatment by Membrane AdsorbersSolomon Isu0Shu-Ting Chen1Raheleh Daneshpour2Hironobu Shirataki3Daniel Strauss4Andrew L. Zydney5Xianghong Qian6Sumith Ranil Wickramasinghe7Ralph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USARalph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USARalph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USAScientific Affairs Group, Bioprocess Division, Asahi Kasei Medical, Chiyoda, Tokyo 100-0006, JapanResearch and Development, Asahi Kasei Bioprocess America, Glenview, IL 60026, USADepartment of Chemical Engineering, The Pennsylvania State University, University Park, PA 16802, USADepartment of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USARalph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USAVirus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The formation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hydrophobic interaction membrane adsorber was the most effective in minimizing flux decline during virus filtration. Ion exchange membranes may also be effective if the monoclonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when compared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. These results can help guide the development of more effective virus filtration processes for monoclonal antibody production.https://www.mdpi.com/2077-0375/15/1/34aggregationflux declinefoulingmembrane adsorbermonoclonal antibodypH |
| spellingShingle | Solomon Isu Shu-Ting Chen Raheleh Daneshpour Hironobu Shirataki Daniel Strauss Andrew L. Zydney Xianghong Qian Sumith Ranil Wickramasinghe Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers Membranes aggregation flux decline fouling membrane adsorber monoclonal antibody pH |
| title | Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers |
| title_full | Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers |
| title_fullStr | Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers |
| title_full_unstemmed | Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers |
| title_short | Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers |
| title_sort | enhancing virus filter performance through pretreatment by membrane adsorbers |
| topic | aggregation flux decline fouling membrane adsorber monoclonal antibody pH |
| url | https://www.mdpi.com/2077-0375/15/1/34 |
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