Two scale-down models, a 0.5-L shake flask and a 5-L lab-scale bioreactor, were developed and refined to simulate monoclonal antibody production in a 5000-L bioreactor. For the 0.5-L shake flask model development, one-factor at a time (OFAT) studies were conducted to investigate the influence of CO2 setpoint shifts and flask type on process performance. A custom designed DOE was conducted to establish the design space in terms of process performance and product quality, and the final parameter setpoints were verified in a separate study to support model qualification. For the 5-L bioreactor model, process equipment including sparger type and impeller type were evaluated using OFAT studies. Engineering principles including power per. unit volume, oxygen mass transfer coefficient, and gas flow rate scaling approaches were used to refine and set the scale-dependent parameters. Both scale-down models were developed using materials, solutions, and axenic cell culture broth obtained from a 5000-L bioreactor production run to reduce potential sources of variability. A bioreactor scale-down case study is presented for the production of a monoclonal antibody using a CHO cell line. The results of both the 0.5-L shake flask and 5-L bioreactor runs demonstrate comparable cell culture performance (product titer) and product quality to the 5000-L production bioreactor for most attributes and process trends. Additionally, the results indicate that the 0.5-L shake flask model is appropriate to use in place of lab-scale bioreactors, thus potentially increasing throughput and reducing the required lab resources.

Scale-down model development for a 5000-L production bioreactor process using 0.5-L shake flask and 5-L bioreactor systems

251st National Meeting (2016)

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