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. 2021 Sep;118(9):3486-3498.
doi: 10.1002/bit.27775. Epub 2021 May 11.

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

Tim Brantley  1 , Jon Bogue  2 , Kurtis Denny  1 , Sanaa Elouafiq  1 , Seth Madren  2 , Bassam Nakhle  2 , Sarwat Khattak  1
Affiliations

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

Tim Brantley et al. Biotechnol Bioeng. 2021 Sep.

Abstract

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.

Keywords: ATF perfusion; Chinese hamster ovary (CHO); product sieving; residence time distribution.

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References

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