Scale-up for bulk production of vaccine against meningococcal disease

G.J.E. Baart, G. de Jong, M. Philippi, K. van 't Riet, L.A. van der Pol, E.C. Beuvery, J. Tramper, D.E. Martens

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)


At the Netherlands Vaccine Institute (NVI) a vaccine against Neisseria meningitidis serogroup B organisms based on different porA subtypes contained in outer membrane vesicles (OMVs) is in advanced stage of development and will be evaluated in clinical trial studies in the near future. In order to meet the expected demand for product, the current biopharmaceutical production process is being scaled-up. This study describes the scale-up approach for the upstream process and the resulting bioreactor design and operation strategy leading towards a feasible solution for bulk production of a vaccine against meningococcal disease. The technically realized 1.2 m(3) bioreactor, equipped with a turbine impeller for gas dispersion, was complemented with an upward pumping impeller and a rotary plate foam breaker to contain foam inside the bioreactor. Aeration and ventilation in the culture broth were controlled by increasing the stirrer speed and gas flow rate simultaneously at increasing oxygen demand. The scale-up was successful and comparable growth curves and nutrient consumption profiles were reached on 0.06 and 1.2 m(3).
Original languageEnglish
Pages (from-to)6399-6408
Issue number34
Publication statusPublished - 2007


  • fermentation processes
  • vesicle vaccine
  • growth
  • inhibition
  • antibodies
  • turbines
  • vessels
  • regime
  • pora


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