Analysis of viral clearance unit operations for monoclonal antibodies
- 13 January 2010
- journal article
- research article
- Published by Wiley in Biotechnology & Bioengineering
- Vol. 106 (2), 238-246
- https://doi.org/10.1002/bit.22662
Abstract
Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log10 were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses. Biotechnol. Bioeng. 2010;106: 238–246. Published 2010 Wiley Periodicals, Inc.Keywords
This publication has 22 references indexed in Scilit:
- Virus Retentive FiltersPublished by Wiley ,2010
- Understanding the mechanism of virus removal by Q sepharose fast flow chromatography during the purification of CHO‐cell derived biotherapeuticsBiotechnology & Bioengineering, 2009
- Phage passage after extended processing in small‐virus‐retentive filtersBiotechnology and Applied Biochemistry, 2007
- Generic/matrix evaluation of SV40 clearance by anion exchange chromatography in flow‐through modeBiotechnology & Bioengineering, 2003
- Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteinsBiotechnology & Bioengineering, 2003
- Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer.The Journal of Experimental Medicine, 1992
- Genomic organization and expression of endogenous retrovirus-like elements in cultured rodent cellsBiologicals, 1991
- The Presence of Viral Particles in Hybridoma Clones Secreting Monoclonal AntibodiesNew England Journal of Medicine, 1982
- M-MuLV-induced leukemogenesis: Integration and structure of recombinant proviruses in tumorsCell, 1981
- Mammalian Cells in Culture Frequently Release Type C VirusesScience, 1973