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

Publication ,  Journal Article
Oh, YH; Becker, ML; Mendola, KM; Choe, LH; Min, L; Lee, KH; Yigzaw, Y; Seay, A; Bill, J; Li, X; Roush, DJ; Cramer, SM; Menegatti, S; Lenhoff, AM
Published in: Biotechnology and bioengineering
April 2023

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.

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Published In

Biotechnology and bioengineering

DOI

EISSN

1097-0290

ISSN

0006-3592

Publication Date

April 2023

Volume

120

Issue

4

Start / End Page

1068 / 1080

Related Subject Headings

  • Proteomics
  • Protein Aggregates
  • Humans
  • Cricetulus
  • Cricetinae
  • CHO Cells
  • Biotechnology
  • Biological Products
  • Antibodies, Monoclonal
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Oh, Y. H., Becker, M. L., Mendola, K. M., Choe, L. H., Min, L., Lee, K. H., … Lenhoff, A. M. (2023). Characterization and implications of host-cell protein aggregates in biopharmaceutical processing. Biotechnology and Bioengineering, 120(4), 1068–1080. https://doi.org/10.1002/bit.28325
Oh, Young Hoon, Matthew L. Becker, Kerri M. Mendola, Leila H. Choe, Lie Min, Kelvin H. Lee, Yinges Yigzaw, et al. “Characterization and implications of host-cell protein aggregates in biopharmaceutical processing.Biotechnology and Bioengineering 120, no. 4 (April 2023): 1068–80. https://doi.org/10.1002/bit.28325.
Oh YH, Becker ML, Mendola KM, Choe LH, Min L, Lee KH, et al. Characterization and implications of host-cell protein aggregates in biopharmaceutical processing. Biotechnology and bioengineering. 2023 Apr;120(4):1068–80.
Oh, Young Hoon, et al. “Characterization and implications of host-cell protein aggregates in biopharmaceutical processing.Biotechnology and Bioengineering, vol. 120, no. 4, Apr. 2023, pp. 1068–80. Epmc, doi:10.1002/bit.28325.
Oh YH, Becker ML, Mendola KM, Choe LH, Min L, Lee KH, Yigzaw Y, Seay A, Bill J, Li X, Roush DJ, Cramer SM, Menegatti S, Lenhoff AM. Characterization and implications of host-cell protein aggregates in biopharmaceutical processing. Biotechnology and bioengineering. 2023 Apr;120(4):1068–1080.
Journal cover image

Published In

Biotechnology and bioengineering

DOI

EISSN

1097-0290

ISSN

0006-3592

Publication Date

April 2023

Volume

120

Issue

4

Start / End Page

1068 / 1080

Related Subject Headings

  • Proteomics
  • Protein Aggregates
  • Humans
  • Cricetulus
  • Cricetinae
  • CHO Cells
  • Biotechnology
  • Biological Products
  • Antibodies, Monoclonal
  • Animals