Scale-up issues during sterile filtration of glycoconjugate vaccines

Several recent studies have provided important insights into the factors controlling the sterile filtration of glycoconjugate vaccines; however, this work has been limited to small-scale disk filters with very uniform flow distribution. The objective of this study was to examine the scale-up of the sterile filtration step using a glycoconjugate drug substance made from a single polysaccharide serotype. Experimental data were obtained during constant flux filtration through 0.22 μm Durapore® polyvinylidene difluoride (PVDF) membranes, both with small discs and with the Opticap® XL2 pleated cartridge. The transmembrane pressure increased rapidly during the glycoconjugate filtration due to membrane fouling, with the rate of pressure increase being more pronounced in the pleated cartridge. Additional insights into the fouling behavior were obtained using confocal microscopy by in situ labeling of the glycoconjugate captured within the filter media using an Alexa Fluor fluorescent dye. Glycoconjugate deposition occurred only within the first 5–15 μm of the 0.22 μm Durapore® membrane at both scales, with more variability in the deposition pattern observed for the pleated filter due to the non-uniform flow distribution in the Opticap® XL2 cartridge. These results provide important insights into the underlying fouling behavior during sterile filtration of glycoconjugate vaccines as well as a framework for the scale-up of the sterile filter step in glycoconjugate biomanufacturing.

This is the peer reviewed version of the following article: [Scale‐up issues during sterile filtration of glycoconjugate vaccines. Biotechnology Progress 38, 4 (2022)], which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions:



Work Title Scale-up issues during sterile filtration of glycoconjugate vaccines
Open Access
  1. Zhuoshi Du
  2. Seyed Pouria Motevalian
  3. Brenda Carrillo Conde
  4. Kelvin Reilly
  5. Andrew L. Zydney
  1. Glycoconjugate
  2. Vaccine
  3. Sterile filtration
  4. Scale-up
  5. Fouling
License In Copyright (Rights Reserved)
Work Type Article
  1. Biotechnology Progress
Publication Date April 12, 2022
Publisher Identifier (DOI)
Deposited January 23, 2023




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Work History

Version 1

  • Created
  • Added Scale-up_issues_during_sterile_filtration.pdf
  • Added Creator Zhuoshi Du
  • Added Creator Seyed Pouria Motevalian
  • Added Creator Brenda Carrillo Conde
  • Added Creator Kelvin Reilly
  • Added Creator Andrew L. Zydney
  • Published
  • Updated Keyword, Publication Date Show Changes
    • Glycoconjugate, Vaccine, Sterile filtration, Scale-up, Fouling
    Publication Date
    • 2022-07-01
    • 2022-04-12
  • Updated