By Michael Brown
Adoption of single-use bioreactor platforms across all scales, ranging from benchtop to production, are becoming increasingly popular due to their ease of use and operational flexibility. Knowledge of the performance characteristics at small-scale allows predictable and easy scale-up across the platforms from 3 L to 2000 L bioreactors.
We have developed and characterized the Mobius® family of single-use bioreactors for mammalian cell culture and recombinant protein production ranging from bench scale (3 L) to small scale (50 L), pilot scale/early clinical (200 L) and late clinical/commercial scale (1000 L and 2000 L) (Figure 1).
Bioreactor processes are generally developed andcharacterized at small scale prior to scale-up. This detailed understanding of the dynamic performance capabilities of each system across the platform allows selection of process parameters to achieve scalable performance with a high degree of confidence.
Bioreactor processes have scale independent parameters such as pH setpoint, DO setpoint, temperature, feed volume ratios, inoculation density, nutrient concentrations, as well as scale dependent parameters that can be adjusted to maintain process similarity with increasing bioreactor scale. The performance design space of the entire Mobius® bioreactor platform was characterized using several key engineering parameters including oxygen mass transfer coefficient (kLa), power per unit volume (P/V), mixing time and tip speed.
The successful scale-up of an upstream biomanufacturing process must consider the effects of critical process parameters, such as gas flow rates and impeller agitation speed, on the cell culture environment across the multi-volumetric bioreactor systems. Based on a detailed understanding of the dynamic performance capabilities of each bioreactor system across the platform, appropriate process parameters can be selected to achieve scalable performance.