Adaptive Process Control and Advanced Sensing for Robust mAb Glycan Quality

The goal of this project is to implement enhanced glycan sensors with control algorithms to produce consistent, desirable glycosylation patterns to improve product quality of biotherapeutics.

Project status

100% Completed

Solution

Performance Period: 5/1/2018 to 10/31/2020

This work focuses on key post-translation modification impacting product quality of biotherapeutics, specifically the carbohydrate groups (glycans) that affect antibody function, stability, immunogenicity, and plasma half-life.

The goal of this multidisciplinary, multi-institute initiative is to implement enhanced glycan sensors with control algorithms to produce consistent, desirable glycosylation patterns. Lectin arrays generating quantitative electrical and fluorescence signals will be tested against antibody standards and samples from bioreactors and then integrated with nested glycan and nutrient control during fed-batch culture.

A bioprocess performance platform producing near real-time control of critical glycan attributes will be ready for pilot scale implementation by completion of the 18-month project.

Impacts

Improved process efficiency and reduced batch-to-batch variability

Publications

Motabar, D., Li, J., Wang, S., Tsao, C., Tong, X., Wang, L., Payne, G. F., & Bentley, W. E. (2021). Simple, rapidly electroassembled thiolated PEG-based sensor interfaces enable rapid interrogation of antibody titer and glycosylation. Biotechnology and Bioengineering, 118(7), 2744-2758. https://doi.org/10.1002/bit.27793

Luo, Y., Lovelett, R. J., Price, J. V., Radhakrishnan, D., Barnthouse, K., Hu, P., Schaefer, E., Cunningham, J., Lee, K. H., Shivappa, R. B., & Ogunnaike, B. A. (2020). Modeling the Effect of Amino Acids and Copper on Monoclonal Antibody Productivity and Glycosylation: A Modular Approach. Biotechnology Journal, 16(2). https://doi.org/10.1002/biot.202000261

Wells, E., Song, L., Greer, M., Luo, Y., Kurian, V., Ogunnaike, B., & Robinson, A. S. (2020). Media supplementation for targeted manipulation of monoclonal antibody galactosylation and fucosylation. Biotechnology and Bioengineering, 117(11), 3310-3321. https://doi.org/10.1002/bit.27496

Li, J., Maniar, D., Qu, X., Liu, H., Tsao, C., Kim, E., Bentley, W. E., Liu, C., & Payne, G. F. (2019). Coupling Self-Assembly Mechanisms to Fabricate Molecularly and Electrically Responsive Films. Biomacromolecules, 20(2), 969-978. https://doi.org/10.1021/acs.biomac.8b01592

Mao, L., Schneider, J. W., & Robinson, A. S. (2023). Use of single analytic tool to quantify both absolute N-glycosylation and glycan distribution in monoclonal antibodies. Biotechnology Progress, 39(5). https://doi.org/10.1002/btpr.3365