Optimizing capacity utilization by large scale 3000 L perfusion in seed train bioreactors

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Cell Culture Technology

Background:

• Pharmaceutical companies face pressure to increase capacity utilization and reduce manufacturing costs.
• Optimizing cell lines, media, and operational strategies are key to improving yields and competitiveness.
• Next-generation technologies are crucial for enhancing bioprocess efficiency.

Purpose of the Study:

• To describe a large-scale perfusion strategy for the N-1 seed train bioreactor.
• To achieve higher inoculation cell densities in the production culture.
• To improve capacity utilization and reduce manufacturing costs in a cGMP facility.

Main Methods:

• Implementation of a 3,000-L scale N-1 perfusion bioreactor.
• Utilizing an inclined settler for cell retention.
• Achieving high cell densities and perfusion rates with high retention efficiency.

Main Results:

• Attained cell densities of up to 158 × 10(5) cells/mL in the N-1 bioreactor.
• Achieved perfusion rates of 2950 L/day with >85% cell retention efficiency.
• Reduced cultivation times by approximately 20% in a CHO-based fed-batch antibody process.

Conclusions:

• The N-1 perfusion strategy successfully increased inoculation cell densities and decreased cultivation times.
• The approach led to significant increases in capacity utilization and cost improvements.
• Comparable culture performance, productivity, and product quality were maintained.