Academic Paper

Modeling Mass Transfer in Stirred Microbioreactors

Modeling Mass Transfer in Stirred Microbioreactors

Chemical Engineering Science (2022)

Hooman Farsani, Johannes Wutz, Brian DeVincentis, John A Thomas, Seyed Pouria Motevalian

Microbioreactors play a pivotal role in making biologic medicines. In fact, 10 of the top 15 selling drugs worldwide were made in a bioreactor. In this paper, M-Star and Pfizer present a generalized framework for modeling mass transfer in two-stage, stirred tank bioreactors to aid the scale-up process.

While performing development and quality characterization studies at small-scale is a cost-effective approach compared to testing at pilot scales, scientists still have to conduct a large set of experiments due to the extensive range of operating parameters. Then, once a manufacturer identifies an appropriate set of operating conditions, they must reproduce the fluid mechanical environment at larger scales.

This scale-up process is complicated—stemming from the fact that not all system parameters can be harmonized across all system scales. But there is a pressing demand for the rapid scale-up of biologic antibody production processes due to the rise in emerging COVID variants.

So, this paper seeks to predict fluid flow and transport inside two-phase bioreactors during scale-up. The researchers theorize that predictive tools for understanding the behavior of the microbioreactor can reduce the number of required experiments while streamlining the scale-up process. A physics-based, in-silico modeling approach can provide a roadmap for process scale-up. The approach is tested by studying an Ambr® 15 microbioreactor over a range of operating conditions.

The model can be used as a digital scale-up and tech-transfer strategy for bioreactors used in the pharmaceutical industry. This approach is a key reason why drug products come to market faster now—especially pertinent today. 

The full paper:

  • presents a systematic and mechanistic modeling approach for predicting fluid flow and transport inside two-phase bioreactors.
  • applies this approach to study an Ambr® 15 microbioreactor over a range of operating conditions.
  • provides a roadmap for process scale-up and reducing the number of experiments needed to predict fluid flow in microscale bioreactors.

Read the full paper in Chemical Engineering Science