Document Type
Article
Publication Date
4-2022
Keywords
aggregation; charge variant; downstream processing; fusion protein; foulant; glycoform; prefiltration; process development; monoclonal antibody; virus filtration
Abstract
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.
Citation
Isu, S., Qian, X., Zydney, A. L., & Wickramasinghe, S. (2022). Process- and Product-Related Foulants in Virus Filtration. Bioengineering, 9 (4), 155. https://doi.org/10.3390/bioengineering9040155
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
