High‐throughput miniaturized bioreactors for cell culture process development: Reproducibility, scalability, and control

TLDR

Accelerating biopharmaceutical development requires shortening cell culture process development time, which involves complex feed formulations, perturbations, and strict process control aligned with commercial manufacturing. The study compares the ambr™ system to conventional bioreactors for monoclonal antibody production in CHO cells. The ambr™ system uses automated 10–15 mL single‑use bioreactors controlled by a workstation to produce monoclonal antibody in CHO cells, and its performance was compared to conventional bioreactors. The ambr™ system reproduced cell culture profiles, growth, viability, titer, temperature, DO, and pH responses across scales (3 L, 15 L, 200 L) and responded predictably to perturbations, demonstrating its utility as a high‑throughput platform.

Abstract

Decreasing the timeframe for cell culture process development has been a key goal toward accelerating biopharmaceutical development. Advanced Microscale Bioreactors (ambr™) is an automated micro-bioreactor system with miniature single-use bioreactors with a 10-15 mL working volume controlled by an automated workstation. This system was compared to conventional bioreactor systems in terms of its performance for the production of a monoclonal antibody in a recombinant Chinese Hamster Ovary cell line. The miniaturized bioreactor system was found to produce cell culture profiles that matched across scales to 3 L, 15 L, and 200 L stirred tank bioreactors. The processes used in this article involve complex feed formulations, perturbations, and strict process control within the design space, which are in-line with processes used for commercial scale manufacturing of biopharmaceuticals. Changes to important process parameters in ambr™ resulted in predictable cell growth, viability and titer changes, which were in good agreement to data from the conventional larger scale bioreactors. ambr™ was found to successfully reproduce variations in temperature, dissolved oxygen (DO), and pH conditions similar to the larger bioreactor systems. Additionally, the miniature bioreactors were found to react well to perturbations in pH and DO through adjustments to the Proportional and Integral control loop. The data presented here demonstrates the utility of the ambr™ system as a high throughput system for cell culture process development.