Characterization and implications of host-cell protein aggregates in biopharmaceutical processing

Author(s)Oh, Young Hoon
Author(s)Becker, Matthew L.
Author(s)Mendola, Kerri M.
Author(s)Choe, Leila H.
Author(s)Min, Lie
Author(s)Lee, Kelvin H.
Author(s)Yigzaw, Yinges
Author(s)Seay, Alexander
Author(s)Bill, Jerome Jr.
Author(s)Li, Xuanwen
Author(s)Roush, David J.
Author(s)Cramer, Steven M.
Author(s)Menegatti, Stefano
Author(s)Lenhoff, Abraham M.
Date Accessioned2023-03-15T20:16:36Z
Date Available2023-03-15T20:16:36Z
Publication Date2023-03-14
DescriptionThis is the peer reviewed version of the following article: Oh, Y. H., Becker, M. L., Mendola, K. M., Choe, L. H., Min, L., Lee, K. H., Yigzaw, Y., Seay, A., Bill, J., Li, X., Roush, D. J., Cramer, S. M., Menegatti, S., & Lenhoff, A. M. (2023). Characterization and implications of host-cell protein aggregates in biopharmaceutical processing. Biotechnology and Bioengineering, 120, 1068– 1080. https://doi.org/10.1002/bit.28325, which has been published in final form at https://doi.org/10.1002/bit.28325. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. This article will be embargoed until 3/14/2024.
AbstractIn the production of biopharmaceuticals such as monoclonal antibodies (mAbs) and vaccines, the residual amounts of host-cell proteins (HCPs) are among the critical quality attributes. In addition to overall HCP levels, individual HCPs may elude purification, potentially causing issues in product stability or patient safety. Such HCP persistence has been attributed mainly to biophysical interactions between individual HCPs and the product, resin media, or residual chromatin particles. Based on measurements on process streams from seven mAb processes, we have found that HCPs in aggregates, not necessarily chromatin-derived, may play a significant role in the persistence of many HCPs. Such aggregates may also hinder accurate detection of HCPs using existing proteomics methods. The findings also highlight that certain HCPs may be difficult to remove because of their functional complementarity to the product; specifically, chaperones and other proteins involved in the unfolded protein response (UPR) are disproportionately present in the aggregates. The methods and findings described here expand our understanding of the origins and potential behavior of HCPs in cell-based biopharmaceutical processes and may be instrumental in improving existing techniques for HCP detection and clearance.
SponsorThis work was performed under a Project Award Agreement from the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and financial assistance award 70NANB21H002 from the US Department of Commerce, National Institute of Standards and Technology.
CitationOh, Y. H., Becker, M. L., Mendola, K. M., Choe, L. H., Min, L., Lee, K. H., Yigzaw, Y., Seay, A., Bill, J., Li, X., Roush, D. J., Cramer, S. M., Menegatti, S., & Lenhoff, A. M. (2023). Characterization and implications of host-cell protein aggregates in biopharmaceutical processing. Biotechnology and Bioengineering, 120, 1068– 1080. https://doi.org/10.1002/bit.28325
ISSN1097-0290
URLhttps://udspace.udel.edu/handle/19716/32451
Languageen_US
PublisherBiotechnology and Bioengineering
Keywordshost-cell proteins
Keywordsmonoclonal antibody
Keywordsprotein aggregation
Keywordsprotein purification
Keywordssize-exclusion chromatography
Keywordsunfolded protein response
TitleCharacterization and implications of host-cell protein aggregates in biopharmaceutical processing
TypeArticle
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