Scale-up methodologies for Escherichia coli and yeast fermentation processes

Area of Science:

• Biotechnology
• Chemical Engineering
• Process Development

Background:

• Established fermentation pilot plant with vessels from 100 L to 19,000 L.
• Literature review of scale-up techniques for Escherichia coli and yeast.
• Analysis of 10 years of fermentation data focusing on peak oxygen uptake rates.

Purpose of the Study:

• To compile and review scale-up techniques for Escherichia coli and yeast.
• To establish consistency of design and operating parameters for pilot scale vessels.
• To identify key scale-up issues for efficient process development and manufacturing transfer.

Main Methods:

• Comparison of pilot scale vessel parameters with literature approaches.
• Analysis of historical fermentation data at peak oxygen uptake rates.
• Scale-up estimations using geometric similarity, agitator tip speed, power input, and mixing time.

Main Results:

• Scale-up from the 280 L scale showed the most similarity to installed equipment parameters.
• Scale-up from the 30 L laboratory scale typically underpredicted parameters.
• The 19,000 L fermentor's geometric similarity differed due to accommodating wide operating volumes.

Conclusions:

• The 280 L scale is the most appropriate for scale-up predictions in this pilot plant.
• Understanding scale-up differences is critical for process development and manufacturing transfer.
• Geometric similarity and operating volume accommodation impact scale-up effectiveness.