Characterization and implications of host-cell protein aggregates in biopharmaceutical processing
Date
2023-03-14
Journal Title
Journal ISSN
Volume Title
Publisher
Biotechnology and Bioengineering
Abstract
In 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.
Description
This 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.
Keywords
host-cell proteins, monoclonal antibody, protein aggregation, protein purification, size-exclusion chromatography, unfolded protein response
Citation
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