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

Sterile filtration is a critical step in the fill finish process of parenteral drug products. Filter membranes used in sterile filtration are prone to adsorb protein and surfactants, as well as release potential leachables during filtration. They come in different configurations, most commonly a pleated capsule shape that maximizes surface area of membrane filter. In this work, a secondary peak was detected during polysorbate 80 adsorption analysis in a filter flush study comparing non-pleated vs pleated filters using a high concentration monoclonal antibody formulation and polyethersulfone (PES) filter membranes where this peak was observed in the pleated filter. During the study, volume-to-surface area ratio was kept consistent between the two configurations and effect of filter flux and filter membrane configuration was evaluated. Counterintuitively, no effect of filter flux was observed on the secondary peak. Changing the configuration from pleated to flattened, using a membrane extracted from pleated filter, however, led to the absence of secondary peak. Results from this study show that performance of a pleated filter configuration can differ from non-pleated configuration. Correspondingly, PES non-pleated filter may not be a suitable small-scale model for pleated membrane capsule filters with respect to filter flush studies.