Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller

• Published in: Bioprocess and biosystems engineering 2009-04, Vol.32 (3), p.289-299
• Main Authors: Soons, Z.I.T.A, IJssel, J. van den, Pol, L.A. van der, Straten, G. van, Boxtel, A.J.B. van
• Format: Article
• Language: English
• Subjects: adaptive-control; Algorithms; Bioengineering; Biological and medical sciences; Biomass; Bioreactors; Bioreactors - microbiology; Biotechnology; Bordetella pertussis - cytology; Bordetella pertussis - physiology; bordetella-pertussis; Cell Culture Techniques - methods; Cell Proliferation; Chemistry; Chemistry and Materials Science; Computer Simulation; Control systems; design; Environmental Engineering/Biotechnology; fed-batch cultivation; Feedback - physiology; fermentation processes; Food Science; Fundamental and applied biological sciences. Psychology; Humans; Industrial and Production Engineering; Industrial Chemistry/Chemical Engineering; Models, Biological; online; Original Paper; Oxygen; Oxygen - metabolism; Oxygen consumption; Oxygen uptake; Pertussis Vaccine - biosynthesis; Pertussis Vaccine - isolation & purification; state; Studies; Vaccines; Whooping Cough - prevention & control
• ISSN: 1615-7591; 1615-7605
• DOI: 10.1007/s00449-008-0248-y

This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch production.