Scale-up issues for commercial depth filters in bioprocessing

Area of Science:

• Bioprocessing and Pharmaceutical Manufacturing
• Chemical Engineering and Fluid Dynamics
• Filtration Technology

Background:

• Depth filtration is crucial for clarifying cell culture fluid in antibody production.
• Filter performance depends on internal pressure and velocity, which are challenging to measure experimentally.
• Scale-up of depth filtration processes faces challenges due to complex flow dynamics.

Purpose of the Study:

• To investigate the impact of flow distribution on depth filter performance during antibody production.
• To compare the hydrodynamics and performance of lab-scale and pilot-scale depth filter modules.
• To utilize computational fluid dynamics (CFD) to explain and predict filter behavior and facilitate scale-up.

Main Methods:

• Employed a combination of experimental studies and CFD simulations.
• Analyzed dual-layer lenticular PDH4 media depth filters in Supracap™ 50 (lab-scale) and Stax™ (pilot-scale) modules.
• Validated CFD predictions using residence time distribution and dye binding measurements.

Main Results:

• Observed more rapid transmembrane pressure increase and DNA breakthrough in the Supracap™ 50 module.
• CFD calculations revealed distinct flow distributions within the lab-scale and pilot-scale modules, explaining the experimental observations.
• Experimental validation confirmed the accuracy of CFD predictions for flow dynamics.

Conclusions:

• Flow distribution significantly impacts depth filter performance and scale-up in antibody production.
• CFD modeling provides valuable insights into filter hydrodynamics, aiding process design and optimization.
• The developed framework can enhance the design of future depth filters and filtration processes.