Integration of a perfusion reactor and continuous precipitation in an entirely membrane-based process for antibody capture.

Continuous precipitation coupled with continuous tangential flow filtration is a cost-effective alternative for the capture of recombinant antibodies from crude cell culture supernatant. The removal of surge tanks between unit operations, by the adoption of tubular reactors, maintains a continuous harvest and mass flow of product with the advantage of a narrow residence time distribution (RTD). We developed a continuous process implementing two orthogonal precipitation methods, CaCl precipitation for removal of host-cell DNA and polyethylene glycol (PEG) for capturing the recombinant antibody, with no influence on the glycosylation profile.

Model predictive control for steady-state performance in integrated continuous bioprocesses.

Perfusion bioreactors are commonly used for the continuous production of monoclonal antibodies (mAb). One potential benefit of continuous bioprocessing is the ability to operate under steady-state conditions for an extended process time. However, the process performance is often limited by the feedback control of feed, harvest, and bleed flow rates.

Oxygen Uptake Rate Soft-Sensing via Dynamic Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses.

In aerobic cell cultivation processes, dissolved oxygen is a key process parameter, and an optimal oxygen supply has to be ensured for proper process performance. To achieve optimal growth and/or product formation, the rate of oxygen transfer has to be in right balance with the consumption by cells. In this study, a 15 L mammalian cell culture bioreactor was characterized with respect to under varying process conditions.