Perfusion Process Intensification for Lentivirus Production Using a Novel Scale-Down Model.

Area of Science:

• Biotechnology
• Process Engineering
• Virology

Background:

• Process intensification is crucial for reducing biopharmaceutical production costs and increasing capacity.
• Perfusion processes are key for lentivirus (LV) production but require high medium consumption.
• Developing cost-effective small-scale models is essential for optimizing perfusion processes.

Purpose of the Study:

• To develop an intensified perfusion process for lentivirus production using acoustic wave separation technology.
• To evaluate the use of the Ambr 250 high throughput bioreactor system for this application.
• To reduce development costs associated with perfusion process optimization.

Main Methods:

• Utilized acoustic wave separation technology integrated with the Ambr 250 high throughput bioreactor system.
• Employed stable LV producer cells in a perfusion culture model.
• Optimized bioreactor setup and harvest rates for intensified production.

Main Results:

• The intensified perfusion process in the Ambr 250 model achieved a 1.4-fold higher cell-specific functional virus yield and a 2.8-fold higher volumetric virus yield at 3 VVD compared to a 1 VVD control.
• Bench-scale verification confirmed these improvements, showing a 1.4-fold higher cell-specific functional virus yield and a 3.1-fold higher volumetric virus yield.

Conclusions:

• Acoustic wave separation combined with the Ambr 250 system enables intensified perfusion processes for efficient lentivirus production.
• This approach significantly enhances both cell-specific and volumetric virus yields.
• The developed model effectively reduces development costs while meeting the increasing demand for cell and gene therapy vectors.