Comparisons of optically monitored small-scale stirred tank vessels to optically controlled disposable bag bioreactors

Abstract

Background: Upstream bioprocesses are extremely complex since living organisms are used to generate active pharmaceutical ingredients (APIs). Cells in culture behave uniquely in response to their environment, thus culture conditions must be precisely defined and controlled in order for productivity and product quality to be reproducible. Thus, development culturing platforms are needed where many experiments can be carried out at once and pertinent scale-up information can be obtained.

Results: Here we have tested a High Throughput Bioreactor (HTBR) as a scale-down model for a lab-scale wave-type bioreactor (CultiBag). Mass transfer was characterized in both systems and scaling based on volumetric oxygen mass transfer coefficient (kLa) was sufficient to give similar DO trends. HTBR and CultiBag cell growth and mAb production were highly comparable in the first experiment where DO and pH were allowed to vary freely. In the second experiment, growth and mAb production rates were lower in the HTBR as compared to the CultiBag, where pH was controlled. The differences in magnitude were not considered significant for biological systems.

Conclusion: Similar oxygen delivery rates were achieved in both systems, leading to comparable culture performance (growth and mAb production) across scales and mode of mixing. HTBR model was most fitting when neither system was pH-controlled, providing an information-rich alternative to typically non-monitored mL-scale platforms.

Figure 1

k_La in HTBR and CultiBag. k_La in HTBR and CultiBag at various agitation speeds and rocking rates and angles. (A) HTBR – 35 mL, CultiBag – 2 L. (B) HTBR – 35 mL, CultiBag – 3.5 L.

Figure 2

DO and pH profiles: Bioreactor Comparison 1. DO (A) and pH (B) profiles during Bioreactor Comparison 1.

Figure 3

DO and pH profiles: Bioreactor Comparison 2. DO (A) and pH (B) profiles during Bioreactor Comparison 2.