Disposable Bioreactors pp 1-31

Part of the Advances in Biochemical Engineering / Biotechnology book series (ABE, volume 115)

Disposable Bioreactors: Maturation into Pharmaceutical Glycoprotein Manufacturing


Modern biopharmaceutical development is characterised by deep understanding of the structure activity relationship of biological drugs. Therefore, the production process has to be tailored more to the product requirements than to the existing equipment in a certain facility. In addition, the major challenges for the industry are to lower the high production costs of biologics and to shorten the overall development time. The flexibility for providing different modes of operation using disposable bioreactors in the same facility can fulfil these demands and support tailor-made processes.

Over the last 10 years, a huge and still increasing number of disposable bioreactors have entered the market. Bioreactor volumes of up to 2,000 L can be handled by using disposable bag systems. Each individual technology has been made available for different purposes up to the GMP compliant production of therapeutic drugs, even for market supply. This chapter summarises disposable technology development over the last decade by comparing the different technologies and showing trends and concepts for the future.


Disposable Bioreactor Technologies Wave Bioreactors Disposable Stirred Bag Bioreactors Hollow Fibre Bioreactors Extractables Leachables GMP Production Pilot Plant Commercial Facility 



Antibody derived cytotoxicity


American society for testing and materials


Bioprocess container


Capacity annual growth rate


Capital expenditures


Chinese hamster ovary




Contract manufacturing organisation


Cost of goods


Dissolved oxygen


European pharmacopeia








Food and drug administration


Good manufacturing practice


International conference on harmonisation


Investigational medicinal product


International organisation of standardisation


International safe transit association


Japanese pharmacopeia


Monoclonal antibody


Master cell bank


Minimum essential medium


Process analytical technology




Single use bioreactor


Summary basis of approval


bubble bioreactor




United states pharmacopeia


Working cell bank


Water for injection


  1. 1.
    Market study (2007) Biomanufacturing strategies: market drivers, build-vs-buy decisions and opportunities in contract relationship management. Business Insights, SeptemberGoogle Scholar
  2. 2.
    Jain E, Kumar A (2008) Biotechnol Adv 26:46CrossRefGoogle Scholar
  3. 3.
    Kanda Y, Yamada T, Mori K, Okazaki A, Inoue M, Kitajima-Miyama K, Kuni-Kamochi R, Nakano R, Yano K, Kakita S, Shitara K, Satoh M (2007) Glycobiology 17:104CrossRefGoogle Scholar
  4. 4.
    Mori K, Iida S, Yamane-Ohnuki N, Kanda Y, Kuni-Kamochi R, Nakano R, Imai-Nishiya H, Okazaki A, Shinkawa T, Natsume A, Niwa R, Shitara K, Satoh M (2007) Cytotechnology 55:109CrossRefGoogle Scholar
  5. 5.
    Knazek RA, Gullino PM, Kohler PO, Dedrick RL (1972) Science 178:65CrossRefGoogle Scholar
  6. 6.
    Eibl R, Eibl D (2007) PROCESS special edition, ACHEMA World Wide News 2:8Google Scholar
  7. 7.
    Terrier B, Courtois D, Hénault N, Cuvier A, Bastin M, Aknin A, Dubreuil J, Pétiard V (2007) Biotechnol Bioeng 96:914CrossRefGoogle Scholar
  8. 8.
    Kybal J, Sikyta B (1985) Biotechnol Lett 7:467CrossRefGoogle Scholar
  9. 9.
    Singh V (1999) Cytotechnology 30:149CrossRefGoogle Scholar
  10. 10.
    Marjanovic D, Greller G (2007) Supplement, BioPharm Int 20:38Google Scholar
  11. 11.
    The Wave bioreactor story. www.wavebiotech.com/about_us/about_us.phpAccessed on the 11th of July 2008
  12. 12.
    Houtzager E, van der Linden R, de Roo G, Huurman S, Priem P, Sijmons P (2005) BioProcess Int June:3, pp 60–66Google Scholar
  13. 13.
    Tang YJ, Ohashi R, Hamel JF (2007) Biotechnol Prog 23:255CrossRefGoogle Scholar
  14. 14.
    Pierce LN, Shabram PW (2004) BioProcess J 4:51Google Scholar
  15. 15.
    Ohashi R, Singh V, Hamel JF Presented at ESACT conference 2001 in SwedenGoogle Scholar
  16. 16.
    Kadwell SH, Hardwicke PI (2007) Methods Mol Biol 388:247CrossRefGoogle Scholar
  17. 17.
    Negrete A, Kotin RM (2007) J Virol Methods 145:155CrossRefGoogle Scholar
  18. 18.
    Genzel Y, Olmer RM, Schäfer B, Reichl U (2006) Vaccine 24:6074CrossRefGoogle Scholar
  19. 19.
    Wolpers F (2006) Biological Europe, conference presentation, Amsterdam, The Netherlands, 19–22 June 2006Google Scholar
  20. 20.
    Galliher PM (2007) BioProduction, conference presentation, Berlin, Germany October 30–31Google Scholar
  21. 21.
    Chu L, Robinson DK (2001) Curr Opin Biotechnol 12:180CrossRefGoogle Scholar
  22. 22.
    Sandig V, Rose T, Winkler K and Brecht R (2005) In: Gellissen G (ed) Production of recombinant proteins: novel microbial and eukaryotic expression. Wiley, Weinheim, p 233Google Scholar
  23. 23.
    Gardner TA, Ko SC, Yang L, Cadwell JJ, Chung LW, Kao C (2001) Biotechniques 30:422Google Scholar
  24. 24.
    Cadwell JJ (2004) Am Biotechnol Lab July:14. vol. 22Google Scholar
  25. 25.
    Langhammer S, Brecht R, Marx U (2007) Genet Eng News 27:34Google Scholar
  26. 26.
    Kranjac D (2004) BioProcess Int 2:86Google Scholar
  27. 27.
    Monge M, Sinclair A (2005) In: Godia F, Fussenegger M (eds) Animal cell technology meets genomics: Proceedings of the 18th ESACT Meeting Granada, Spain, May 11–14, 2003. Springer, Netherlands, p 667Google Scholar
  28. 28.
    Kundu S (2007) Future Pharmaceuticals, Q4. vol. 100Google Scholar
  29. 29.
    Fox S (2005) Contract Pharma June:62. vol. 7Google Scholar
  30. 30.
    Wrankmore M (2005) Biologicals Manufacturing Summit, conference presentation, London, UK, February 23–24Google Scholar
  31. 31.
    Jenke DR, Story J, Lalani R (2006) Int J Pharm 315:75CrossRefGoogle Scholar
  32. 32.
    Markovic I (2007) AAPS National Biotechnology Conference. San Diego, June 24–27, 2007Google Scholar
  33. 33.
    Jenke D (2007) PDA J Pharm Sci Technol 61:17Google Scholar
  34. 34.
    Vega H, Schultz TJ (2007) Future Pharmaceuticals Q3 2007:96Google Scholar
  35. 35.
    HyClone (2004) Technical papers series: Disposable Flexible Container Systems for Cell Culture Media and Other Sterile Liquids’; Revision 2, August 2004; Compiled and Edited by the HyClone Technical StaffGoogle Scholar
  36. 36.
    Press Release Fresenius, 22.03.2007, http://www.fresenius.de/internet/fag/com/faginpub.nsf/Content/Press+Releases+2007 Accessed on the 11th of July 2008
  37. 37.
    Harris R (2006) Comparability for Biologics, conference presentation, Zürich, Switzerland, June 27–28Google Scholar
  38. 38.
    Charles I, Lee J, Dasarathy Y (2007) BioPharm Int Suppl Nov. 2:31. vol. 20Google Scholar
  39. 39.
    Miyake T, Kung CK, Goldwasser E (1977) J Biol Chem 252:5558Google Scholar
  40. 40.
    Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC, Chen KK, Fox GM, Martin F, Stabinsky Z (1985) Proc Natl Acad Sci U S A 82:7580CrossRefGoogle Scholar
  41. 41.
    Yuen CT, Storring PL, Tiplady RJ, Izquierdo M, Wait R, Gee CK, Gerson P, Lloyd P, Cremata JA (2003) Br J Haematol 121:511CrossRefGoogle Scholar
  42. 42.
    Rader RA (2005) Biopharmaceutical products in the U.S. and European Markets, 4th edn. Bioplan Associates, Rockville, USA, p 121Google Scholar
  43. 43.
    Rader RA (2005) Biopharmaceutical products in the U.S. and European Markets, 4th edn. Bioplan Associates, Rockville, USA, p 337Google Scholar
  44. 44.
    Brecht R, Koch S, Riedel M, Sandig V, Marx U (2005) BioPharm Int July:22. vol. 18Google Scholar
  45. 45.
    High Tech Business Decisions (2007): Biopharmaceutical Contract Manufacturing 2007: Quality, Capacity and Emerging Technologies’; Industry ReportGoogle Scholar
  46. 46.
    Sinclair A, Monge M (2005) Biopharm Int, Supplement, October:26.vol. 18Google Scholar
  47. 47.
    Sinclair A, Monge M (2002) Pharma Eng 22:20Google Scholar
  48. 48.
    Terryberry JW, Thor G (2006) Biodisposables utility and technological advances. D&MDNew York, USAGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.ProBioGen AGBerlinGermany

Personalised recommendations