Triple Space-Time Yield in Discontinuous Antibody Biomanufacturing by Combination of Synergetic Process...

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Process Intensification

Background:

• Monoclonal antibodies are crucial therapeutics requiring efficient and scalable production.
• The COVID-19 pandemic highlighted the need for more flexible and productive biomanufacturing processes.
• Current production methods face challenges in meeting rapidly increasing global demand for therapeutic molecules.

Purpose of the Study:

• To design and evaluate a novel discontinuous biomanufacturing process for therapeutic molecules.
• To combine process intensification strategies, specifically increased inoculation density and media exchange using a fluidized bed centrifuge.
• To assess the impact of these strategies on process duration, product formation, space-time yield, and product quality.

Main Methods:

• A novel discontinuous process was designed by integrating increased inoculation density and media exchange via a fluidized bed centrifuge.
• Small-scale experiments were conducted to verify synergistic effects between the intensification strategies.
• The process was scaled up to proof-of-concept scale to validate performance.

Main Results:

• The combined intensification strategies resulted in a 37% decrease in process duration.
• Product formation was significantly enhanced by 116% compared to standard operations.
• A threefold increase in space-time yield was achieved with negligible impact on product quality.

Conclusions:

• The novel discontinuous process offers a flexible and highly productive alternative for therapeutic molecule manufacturing.
• This intensified process demonstrates significant improvements over standard fed-batch operations.
• The process enhances biomanufacturing capacity, crucial for responding to increased demand and emergency situations.