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

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.

A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing

“…Advantages of the FBC operation are the fast and complete media exchanged at specified times. Common filter-based retention devices utilize a continuous exchange creating a intermixture of fresh and spend media in the reactor ( Brantley et al, 2021 ). This intermixture leads to partial loss of fresh media into the following downstream operation.…”

Residence time distribution of continuous capture of recombinant antibody by precipitation and two stage tangential flow filtration

“…[2][3][4][5] RTD determination of continuous processes is much more advanced in continuous manufacturing of small molecule pharmaceuticals [5][6][7][8][9] compared to therapeutic proteins. 2,[10][11][12] Commonly, the RTD function is measured experimentally by addition of a tracer pulse or step at the inlet of a unit operation or process and the tracer concentration or another measurable attribute, such as absorbance or fluorescence, is measured at the outlet either on-line or off-line. 5,13 The tracer should behave identically to the material being traced and not alter the flow properties of the bulk material (i.e.…”

“…Its determination is particularly useful for understanding process performance during steady‐state operation, but also for understanding the effects of transient events such as start‐up and shut‐down phases, process pauses or disturbances that could lead to product rejection 2‐5 . RTD determination of continuous processes is much more advanced in continuous manufacturing of small molecule pharmaceuticals 5‐9 compared to therapeutic proteins 2,10‐12 …”