Skip to main content

Monitoring and control of large — scale vaccine production via dynamic oxygen uptake rate measurement

  • Chapter

Abstract

For large — scale production of BVD (Bovine Viral Diarrhea) antigen on adherent MDBK target cells we have established a 300 L airlift reactor with stainless steel wire springs as carrier material.

To improve economy, reliability and reproducibility of large-scale virus production, relevant information on cell number and physiological status of the cells is essential. Since direct growth monitoring of adherent cells in bioreactors by sampling is impossible, effective and simple indirect methods such as enzymatic assays were tested. Although they showed good results in small scale experiments, the applicability on 300 L scale was limited.

Dynamic measurement of the Oxygen Uptake Rate (OUR) has several advantages: it is simple, reliable and inexpensive. The method proved feasible for small scale cultivation of MDBK target cells: hemocytometer counts correlated very closely with calculated cell numbers. Thus, OUR measurement is an helpful tool for growth monitoring of adherent cells on 300 L scale. Moreover, characterizing the increased oxygen demand and metabolic activity during the virus phase of the production process should be possible.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Yoon, S.; Konstantinov, K.B. (1994) Continuous, real-time monitoring of the oxygen uptake rate (OUR) in animal cell bioreactors. Biotech. & Bioeng. 44 983–990.

    Article  CAS  Google Scholar 

  2. Oeggerli, A.; Eyer, K.; Heinzle, E. (1995) On-line gas analysis in animal cell cultivation: I. Control of dissolved oxygen and pH. Biotech. & Bioeng. 45 42–53.

    Article  CAS  Google Scholar 

  3. Bergmeyer, H.U. (1974) Methoden der enzymatischen Analyse” Band 13.Auflage, Verlag Chemie Weinheim.

    Google Scholar 

  4. Renner, W.A.; Jordan, M.; Eppenberger, H.M.; Leist, C. (1993) Cell-cell adhesion and aggregation: influence on the growth behaviour of CHO cells. Biotechnol. & Bioeng. 41 188–193.

    Article  CAS  Google Scholar 

  5. Wagner, A.; Marc, A.; Engasser, J.M.; Einsele, A. (1991) The use of Lactate Dehydrogenase (LDH) release kinetics for the evaluation of death and growth of mammalian cells in perfusion reactors. Biotechnol. & Bioeng. 39 320–326.

    Article  Google Scholar 

  6. Bonarius, H.P.J.; Gooijer, C.D. de; Tramper, J.; Schmid, G. (1995) Determination of the respiration quotient in mammalian cell culture in bicarbonate buffered media. Biotech. & Bioeng. 45 524–535.

    Article  CAS  Google Scholar 

  7. Behrendt, U.; Koch, S.; Gooch, D.; Steegmans, U.; Comer, M. (1994) Mass spectrometry: A tool for on-line monitoring of animal cell cultures. Cytotechnology 14 157–165.

    Article  CAS  PubMed  Google Scholar 

  8. Lovrecz, G.; Gray, P. (1994) Use of on-line gas analysis to monitor recombinant mammalian cell cultures. Cytotechnology 14 167–175.

    Article  CAS  PubMed  Google Scholar 

  9. Eyer, K.; Oeggerli, A.; Heinzle, E. (1995) On-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake rate estimation and its application to controlled feeding of glutamine. Biotech. & Bioeng. 45 54–62.

    Article  CAS  Google Scholar 

  10. Miller, W.M.; Wilke, CR.; Blanch, H.W. (1987) Effects of dissolved oxygen concentration on Hybridoma growth and metabolism in continuous culture. J. of cellular physiology 132 524–530.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Preissmann, A., Werner, R.G., Noé, W. (1997). Monitoring and control of large — scale vaccine production via dynamic oxygen uptake rate measurement. In: Carrondo, M.J.T., Griffiths, B., Moreira, J.L.P. (eds) Animal Cell Technology. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5404-8_28

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-5404-8_28

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6273-2

  • Online ISBN: 978-94-011-5404-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics