Critical considerations in small-scale model selection for filter flush determination: A case study on...

Area of Science:

• Pharmaceutical Manufacturing
• Filtration Technology
• Bioprocessing

Background:

• Sterile filtration is essential for parenteral drug product manufacturing.
• Filter membranes can adsorb proteins/surfactants and release leachables.
• Pleated filter capsules maximize membrane surface area for filtration.

Purpose of the Study:

• To investigate a secondary polysorbate 80 adsorption peak observed in pleated filters.
• To compare the performance of pleated versus non-pleated polyethersulfone (PES) filters.
• To evaluate the effect of filter configuration and flux on adsorption characteristics.

Main Methods:

• Conducted filter flush studies using high-concentration monoclonal antibody formulation.
• Compared pleated and non-pleated PES filter membranes.
• Analyzed polysorbate 80 adsorption, maintaining consistent volume-to-surface area ratios.

Main Results:

• A secondary polysorbate 80 adsorption peak was detected exclusively in the pleated PES filter.
• Filter flux did not significantly impact the secondary peak's occurrence.
• Flattening the pleated membrane eliminated the secondary peak, suggesting a configuration-dependent effect.

Conclusions:

• Pleated filter configurations exhibit different performance characteristics compared to non-pleated ones.
• Non-pleated PES filters may not accurately model the behavior of pleated capsule filters in flush studies.
• Understanding filter configuration effects is crucial for accurate process development and risk assessment.