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Application of ER Stress Biomarkers to Predict Formulated Monoclonal Antibody Stability

Talbot, Natalie E., Mead, Emma J, Davies, Stephanie Ann, Uddin, Shahid, Smales, Christopher Mark (2019) Application of ER Stress Biomarkers to Predict Formulated Monoclonal Antibody Stability. Biotechnology Journal, 14 (10). Article Number 1900024. ISSN 1860-6768. (doi:10.1002/biot.201900024) (KAR id:74133)


For a therapeutic mAb to reach the clinic, the molecule must be produced at an appropriate yield and quality, then formulated to maintain efficacy and stability. The formation of sub‐visible particles (SVPs) can impact on product stability and is monitored during formulation development however, the potential of a mAb to form such species can be influenced throughout the whole bioprocess. We investigate levels of intracellular ER stress perceived by cells, day of mAb harvest and the relationship to subsequent product stability of two mAbs (denoted A and B), produced in CHO cell lines, as determined by SVP content after accelerated stability studies. We show the propensity of mAb A to form SVPs can be predicted by transcript expression of biomarkers of cellular ER stress, heavy/light chain transcript and polypeptide amounts, and harvest day. Further, mAb A material harvested on day 9 of culture was more stable, in terms of SVP formation, than material harvested on day 13. These data suggest that ER stress perceived by CHO cells during culture can reflect the stability of a mAb, and that biomarkers of such stress could help define culture harvest time as a tool to control or reduce SVP formation in formulated mAbs.

Item Type: Article
DOI/Identification number: 10.1002/biot.201900024
Uncontrolled keywords: Biomarkers Bioprocess, linking, Monoclonal, Antibody Stability, Sub‐visible particles
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Smales
Date Deposited: 28 May 2019 09:39 UTC
Last Modified: 04 Mar 2024 19:19 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Mead, Emma J.

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Davies, Stephanie Ann.

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Smales, Christopher Mark.

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