A novel approach to residence time distribution characterization in a mAb continuous process

• Published in: Biotechnology and bioengineering Vol. 118; no. 9; pp. 3486 - 3498
• Main Authors: Brantley, Tim, Bogue, Jon, Denny, Kurtis, Elouafiq, Sanaa, Madren, Seth, Nakhle, Bassam, Khattak, Sarwat
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2021
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - biosynthesis; ATF perfusion; Bioreactors; Cell size; Chinese hamster ovary (CHO); CHO Cells; Continuously stirred tank reactors; Cricetulus; Fouling; Glycan; Glycosylation; Inhibitors; Monoclonal antibodies; Perfusion; product sieving; Residence time distribution; product sieving; Chinese hamster ovary (CHO); residence time distribution; ATF perfusion
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.27775

Residence time distribution modeling of integrated perfusion to capture process can elucidate the impact of product quality excursions and filter fouling on monoclonal antibody production. In this case study, a glycosylation inhibitor and fluorescently labeled antibody are applied to the continuous process to study protein quality modulation, perfusion filter fouling, and unit operation hold times. The unit operations were modeled as continuous‐stirred tank reactors and the residence time distribution of a small molecule glycan inhibitor and impact on glycosylation were characterized. A fluorescently labeled antibody was applied as a tracer molecule and confirmed the impact of packed cell volume and filter fouling. This study demonstrates how a biologics continuous process can be modeled and characterized through residence time distribution to ensure a robust, well‐understood process. Residence time distribution modeling of integrated perfusion to capture process can elucidate the impact of product quality excursions and filter fouling on monoclonal antibody production. The model can enable traceability for a continuous biologics process.