Perfusion-Based Antibody Production in the Ambr^® 250 Modular

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Cell Culture Technology

Background:

• Perfusion mode is crucial for biopharmaceutical production, especially for monoclonal antibodies (mAbs).
• The Sartorius Ambr 250 Modular system, widely used for mAb process development, was not initially designed for perfusion.
• Existing perfusion capabilities for the Ambr 250 were limited to its high-throughput version.

Purpose of the Study:

• To establish perfusion processes in the Ambr 250 Modular system for Chinese Hamster Ovary (CHO) cell culture.
• To develop an N-1 perfusion process for achieving ultra-high cell densities.
• To demonstrate continuous mAb production using perfusion in a bench-scale bioreactor.

Main Methods:

• Utilized the Ambr 250 Modular system combined with Repligen's ATF 1 single-use device.
• Developed and tested semi-perfusion and N-1 perfusion strategies.
• Conducted a 23-day continuous perfusion experiment for mAb production.

Main Results:

• Achieved ultra-high cell densities exceeding 150 x 10^6 cells/mL in the N-1 perfusion process.
• Successfully demonstrated continuous mAb production over 23 days.
• Attained a volumetric productivity of 0.65 g/L/day, comparable to larger bioreactor systems.

Conclusions:

• The Ambr 250 Modular system, with the ATF 1 device, can be effectively used for perfusion processes.
• This approach enables the production of high cell densities for subsequent mAb production.
• The study validates the feasibility of continuous perfusion for efficient mAb manufacturing at the bench scale.