Understanding adsorption behavior of Polysorbate-20 to sterile filters in therapeutic proteins final filtration process.

Abstract

Surfactants are commonly used in the therapeutic protein manufacturing process as stabilizer. Polysorbate-20 (PS-20) is one of the most commonly used surfactants to mitigate protein aggregation in the therapeutic protein formulation. It has been observed that polysorbate can be adsorbed by sterile filters during the final filtration process, which poses risk of uneven distribution and potentially reduced polysorbate concentration in final products. In this study, we evaluated the PS-20 adsorption behavior using commonly used sterilizing-grade microfiltration (MF) membranes via a customized filtration set-up. The effect of membrane properties, including the membrane materials, modification, and layer configuration were studied. In addition, the effect of PS-20 concentration was evaluated and the PS-20 adsorption amount by each type of membranes was determined quantitatively and showed good agreement with the in-process adsorption results. Finally, the selection of sterile filters and strategy of pre-flush are discussed for ensuring accurate PS-20 content in the final therapeutic protein drug product.