Membrane-Based Approach for the Downstream Processing of Influenza Virus-Like Particles

Sofia B. Carvalho, Ricardo J.S. Silva, Mafalda G. Moleirinho, Bárbara Cunha, Ana S. Moreira, Alex Xenopoulos, Paula M. Alves, Manuel J.T. Carrondo, Cristina Peixoto

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Currently, marketed influenza vaccines are only efficient against homologous viruses, thus requiring a seasonal update based on circulating subtypes. This constant reformulation adds several challenges to manufacturing, particularly in purification due to the variation of the physicochemical properties of the vaccine product. A universal platform approach capable of handling such variation is therefore of utmost importance. In this work, a filtration-based approach is explored to purify influenza virus-like particles. Switching from adsorptive separation to size-based purification allows overcoming the differences in retention observed for different influenza strains. The proposed process employs a cascade of ultrafiltration and diafiltration steps, followed by a sterile filtration step. Different process parameters are assessed in terms of product recovery and impurities’ removal. Membrane chemistry, pore size, operation modes, critical flux, transmembrane pressure, and permeate control strategies are evaluated. After membrane selection and parameter optimization, concentration factors and diafiltration volumes are also defined. By optimizing the filtration mode of operation, it is possible to achieve product recoveries of approximately 80%. Overall, the process time is decreased by 30%, its scalability is improved, and the costs are reduced due to the removal of chromatography and associated buffer consumptions, cleaning, and its validation steps.

Original languageEnglish
Article number1800570
JournalBiotechnology Journal
Issue number8
Publication statusPublished - 1 Aug 2019


  • filtration
  • influenza
  • tangential flow filtration
  • vaccines
  • virus-like particles


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