Process- and Product-Related Foulants in Virus Filtration
Regulatory authorities place stringent guidelines on the removal of contaminants during the manufacture of biopharmaceutical products. Monoclonal antibodies, Fc-fusion proteins, and other mammalian cell-derived biotherapeutics are heterogeneous molecules that are validated based on the production pr...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
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| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/9/4/155 |
| _version_ | 1797436869053513728 |
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| author | Solomon Isu Xianghong Qian Andrew L. Zydney S. Ranil Wickramasinghe |
| author_facet | Solomon Isu Xianghong Qian Andrew L. Zydney S. Ranil Wickramasinghe |
| author_sort | Solomon Isu |
| collection | DOAJ |
| description | Regulatory authorities place stringent guidelines on the removal of contaminants during the manufacture of biopharmaceutical products. Monoclonal antibodies, Fc-fusion proteins, and other mammalian cell-derived biotherapeutics are heterogeneous molecules that are validated based on the production process and not on molecular homogeneity. Validation of clearance of potential contamination by viruses is a major challenge during the downstream purification of these therapeutics. Virus filtration is a single-use, size-based separation process in which the contaminating virus particles are retained while the therapeutic molecules pass through the membrane pores. Virus filtration is routinely used as part of the overall virus clearance strategy. Compromised performance of virus filters due to membrane fouling, low throughput and reduced viral clearance, is of considerable industrial significance and is frequently a major challenge. This review shows how components generated during cell culture, contaminants, and product variants can affect virus filtration of mammalian cell-derived biologics. Cell culture-derived foulants include host cell proteins, proteases, and endotoxins. We also provide mitigation measures for each potential foulant. |
| first_indexed | 2024-03-09T11:08:49Z |
| format | Article |
| id | doaj.art-28000f057db144919d57c112bf601e03 |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-09T11:08:49Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-28000f057db144919d57c112bf601e032023-12-01T00:49:23ZengMDPI AGBioengineering2306-53542022-04-019415510.3390/bioengineering9040155Process- and Product-Related Foulants in Virus FiltrationSolomon Isu0Xianghong Qian1Andrew L. Zydney2S. Ranil Wickramasinghe3Ralph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USADepartment of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USADepartment of Chemical Engineering, Pennsylvania State University, University Park, PA 16802, USARalph E. Martin Department of Chemical Engineering, University of Arkansas, Fayetteville, AR 72701, USARegulatory authorities place stringent guidelines on the removal of contaminants during the manufacture of biopharmaceutical products. Monoclonal antibodies, Fc-fusion proteins, and other mammalian cell-derived biotherapeutics are heterogeneous molecules that are validated based on the production process and not on molecular homogeneity. Validation of clearance of potential contamination by viruses is a major challenge during the downstream purification of these therapeutics. Virus filtration is a single-use, size-based separation process in which the contaminating virus particles are retained while the therapeutic molecules pass through the membrane pores. Virus filtration is routinely used as part of the overall virus clearance strategy. Compromised performance of virus filters due to membrane fouling, low throughput and reduced viral clearance, is of considerable industrial significance and is frequently a major challenge. This review shows how components generated during cell culture, contaminants, and product variants can affect virus filtration of mammalian cell-derived biologics. Cell culture-derived foulants include host cell proteins, proteases, and endotoxins. We also provide mitigation measures for each potential foulant.https://www.mdpi.com/2306-5354/9/4/155aggregationcharge variantdownstream processingfusion proteinfoulantglycoform |
| spellingShingle | Solomon Isu Xianghong Qian Andrew L. Zydney S. Ranil Wickramasinghe Process- and Product-Related Foulants in Virus Filtration Bioengineering aggregation charge variant downstream processing fusion protein foulant glycoform |
| title | Process- and Product-Related Foulants in Virus Filtration |
| title_full | Process- and Product-Related Foulants in Virus Filtration |
| title_fullStr | Process- and Product-Related Foulants in Virus Filtration |
| title_full_unstemmed | Process- and Product-Related Foulants in Virus Filtration |
| title_short | Process- and Product-Related Foulants in Virus Filtration |
| title_sort | process and product related foulants in virus filtration |
| topic | aggregation charge variant downstream processing fusion protein foulant glycoform |
| url | https://www.mdpi.com/2306-5354/9/4/155 |
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