In the past decades, there has been significant interest in the development of glycoconjugates for novel vaccines. Protein-polysaccharide conjugates have been developed for protection against diseases like meningitis, pneumonia, and otitis media. One of the challenges in the manufacture of these large biotherapeutics is in the sterile filtration step, with the high degree of membrane fouling leading to low capacity and potential yield lost. The overall objective of this study was to evaluate the fundamental phenomena governing transmission and fouling during sterile filtration of novel glycoconjugate vaccines.<br/>Experiments were performed using several glycoconjugates provided by Pfizer, Inc. Sterile filtration data were obtained during both constant flux and constant pressure operation using sterile filters with different pore morphologies and chemistries including asymmetric polyethersulfone (PES) and homogeneous polyvinylidene fluoride (PVDF) membranes. The location of fouling within the different filters was examined by confocal microscopy using fluorescently labeled glycoconjugates.<br/>Pressure data obtained during constant flux filtration showed a gradual increase in the transmembrane pressure (TMP) during the initial stage of filtration followed by a sharp rise in TMP as the membrane became more heavily fouled. A noticeable decline in transmission was observed for some of the glycoconjugates, typically corresponding to the time at which the sharp increase in TMP was observed. Confocal microscopy images showed that the glycoconjugates were captured primarily near the filter entrance, typically in a band penetrating several microns into the depth of the membrane. The volumetric capacity for most glycoconjugates was greater for the asymmetric PES membrane compared to that of the PVDF membrane, although the glyco-conjugate with the smallest hydrodynamic radius showed greater capacity with the PVDF membrane. The capacity during constant flux operation was also a function of the filtrate flux, with greater capacity typically achieved when operating at higher filtrate flux. These results provide important insights into the fouling phenomena observed during sterile filtration of glycoconjugate vaccines.

Fouling phenomena during sterile filtration of glycoconjugates

ACS Fall 2020 Virtual Meeting

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