Modified intermediate pore blockage model describes fouling behavior during sterile filtration of glycoconjugate vaccines

Sterile filtration using 0.2 μm pore size membranes is used to insure sterility of almost all biopharmaceuticals. Sterile filtration can be particularly challenging with large complex molecules such as glycoconjugate vaccines that are nearly 200 nm in size, leading to low yield and capacity. The objective of this study was to develop a fundamental understanding of the fouling behavior during sterile filtration of a glycoconjugate vaccine through the Durapore® PVDF sterile filtration membrane. Confocal microscopy with a fluorescently-labeled glycoconjugate demonstrated that fouling was limited to a thin region near the entrance of the homogeneous membrane. A modified intermediate pore blockage model was developed to describe the rate of flux decline accounting for the fouling at the pore entrance and the highly interconnected pore structure of the Durapore® membrane. Model calculations were in very good agreement with the fouling data during both constant pressure and constant flux filtration. These results provide important insights into the fouling behavior during sterile filtration of glycoconjugate vaccines that are used to provide immunization against significant bacterial infections.