White Paper: Scale-Up and Agitation Scale-Up - Tip Speed vs. Power per Volume

Introduction

Ai bottom of bioreactor with a propeller — Scale-up in industrial processes refers to the process of increasing production material from small-scale development to large-scale manufacturing. It involves meticulous attention to factors like agitation, which plays a crucial role in various industries such as pharmaceuticals, chemical processing, and food production.

This white paper delves into the significance of agitation scale-up, best practices, common challenges, emerging trends, and potential areas for future research and development in this critical aspect of industrial production.

The Significance of Agitation Scale-Up

Agitation is vital in the production of bioprocesses, particularly in promoting the mass transfer of gases like oxygen that are essential for optimal cell growth and health. In industries like pharmaceuticals, maintaining optimal agitation ensures consistent product quality and yield across different scale sizes.

As an upstream specialist at Eli Lilly and Cytovance, understanding agitation's relevance was paramount in achieving desired product specifications without compromising cell viability or health.

Best Practices for Scaling Up Agitation Processes

Several strategies exist for scaling up agitation processes while maintaining optimal tip speed and power per volume (P/V) ratios. Constant P/V, Constant Tip Speed, and Constant kLa are commonly used approaches.

Constant P/V, in particular, is widely adopted as it ensures the necessary power for appropriate mixing without causing excessive sheer stress on cultures. Calculating P/V involves factors like fluid density, agitation speed, impeller diameter, working volume, and impeller power number, which is determined during process development.

Challenges and Limitations

Agitation scale-up isn't without challenges. Incorrect scaling can lead to decreased cell viability and health, necessitating process optimization at each scale and potentially causing timeline disruptions. In cell therapies like autologous cell therapy, where each batch serves one patient, scale-up complexities arise from variability in starting materials (patient cells) and production volumes, highlighting the need for precision in scale-up methodologies.

Emerging Trends and Technologies

Advancements in mixing equipment and computational modeling are shaping the future of agitation scale-up. Micro spargers are preferred over macro spargers to minimize shear stress, while redesigned impeller blades enhance aeration and mixing efficiency.

Innovative bioreactor designs like those from Thermo Fisher Scientific offer scalable solutions with advanced mixing technology. Controller software enhancements facilitate seamless scale-up transitions across equipment and production scales.

Future Research and Development

Future research aims to further improve scale-up methodologies and efficiency, particularly in Cell and Gene Therapy.

Automated cell culture platforms and integrated frameworks combining cellular kinetics with computational fluid dynamics show promise in enhancing reproducibility, minimizing product loss, and expediting scale-up processes.

In conclusion, scale-up and agitation scale-up are pivotal aspects of industrial production, requiring a nuanced understanding, strategic approaches, and continuous innovation to meet evolving industry demands and ensure consistent product quality.