Semi-continuous scale-down models for clone and operating parameter screening in perfusion bioreactors.

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Cell Culture Technology

Background:

• Perfusion cell culture is increasingly vital for therapeutic protein biomanufacturing.
• Developing these processes is hindered by a lack of suitable scale-down models for continuous operation.
• Optimizing perfusion and bleed rates typically requires time-consuming experiments in scale-down bioreactors.

Purpose of the Study:

• To develop and validate novel, high-throughput scale-down models for perfusion cell culture optimization.
• To reduce the time and workload associated with determining optimal perfusion parameters.
• To enable efficient screening of cell lines and media for biomanufacturing.

Main Methods:

• A semi-continuous VCDmax (viable cell density) approach was developed using shake tubes (ST) and 96-deepwell plates (96-DWP).
• Effectiveness was tested across 12 CHO-K1-SV cell lines producing IgG1.
• Results were compared against traditional lab-scale perfusion bioreactor runs.

Main Results:

• The VCDmax approach using ST and 96-DWP models accurately predicted volumetric productivity and minimum cell specific perfusion rates (CSPRmin).
• Findings were consistent with lab-scale bioreactor results, often within experimental error.
• Successful scale-up was demonstrated from milliliter to liter scales.

Conclusions:

• Shake tubes and 96-deepwell plates serve as reliable and efficient scale-down models for perfusion cell culture.
• These models significantly aid in designing and scaling up bioreactor conditions.
• They facilitate rapid screening of media and cell lines for enhanced therapeutic protein production.