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  Establishment of a mink enteritis vaccine production process in stirred-tank reactor and Wave Bioreactor microcarrier culture in 1-10 L scale

Hundt, B., Best, C., Schlawin, N., Kassner, H., Genzel, Y., & Reichl, U. (2007). Establishment of a mink enteritis vaccine production process in stirred-tank reactor and Wave Bioreactor microcarrier culture in 1-10 L scale. Vaccine, 25(20), 3987-3995. doi:10.1016/j.vaccine.2007.02.061.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-9808-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-A1F6-6
Genre: Journal Article

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 Creators:
Hundt, B.1, Author              
Best, C.2, Author
Schlawin, N.1, Author              
Kassner, H.2, Author
Genzel, Y.1, Author              
Reichl, U.1, 3, Author              
Affiliations:
1Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738140              
2IDT, Rosslau, Germany and Otto-von-Guericke University Magdeburg, Bioprocess Engineering, ou_persistent22              
3Otto-von-Guericke-Universität Magdeburg, ou_1738156              

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 Abstract: A scale-up and process optimization scheme for the growth of adherent embryonic feline lung fibroblasts (E-FL) on microcarriers and the propagation of a mink enteritis virus (MEV) strain for the production of an inactivated vaccine is shown. Stirred-tank cultivations are compared with results obtained from Wave Bioreactors. Transfer from a roller bottle-based production process into large-scale microcarrier culture with starting concentrations of 2g/L Cytodex 1 microcarriers and 2.0 x 10(5)cells/mL was successful. A maximum cell yield of 1.2 x 10(6)cells/mL was obtained in stirred-tank microcarrier batch culture while cell numbers in the Wave Bioreactor could not be determined accurately due to the fast sedimentation of microcarriers under non-rocking conditions required for sampling. Detailed off-line analysis was carried out to understand the behaviour of the virus-host cell system in both cultivation systems. Metabolic profiles for glucose, lactate, glutamine, and ammonium showed slight differences for both systems. E-FL cell growth was on the same level in stirred-tank and Wave Bioreactor with a higher volumetric cell yield compared to roller bottles. Propagation of MEV, which can only replicate efficiently in mitotic cells, was characterized in the Wave Bioreactor using a multiple harvest strategy. Maximum virus titres of 10(6.6) to 10(6.8) TCID(50)/mL were obtained, which corresponds to an increase in virus yield by a factor of about 10 compared to cultivations in roller bottles. As a consequence, a single Wave Bioreactor cultivation of appropriate scale can replace hundreds of roller bottles. Thus, the Wave Bioreactor proved to be a suitable system for large-scale production of an inactivated MEV vaccine. © 2006 Elsevier Ltd. All rights reserved [accessed 2013 November 14th]

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Language(s): eng - English
 Dates: 2007
 Publication Status: Published in print
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 Rev. Method: -
 Identifiers: eDoc: 322131
DOI: 10.1016/j.vaccine.2007.02.061
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Title: Vaccine
Source Genre: Journal
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Publ. Info: Guildford, Surrey, UK : Elsevier
Pages: - Volume / Issue: 25 (20) Sequence Number: - Start / End Page: 3987 - 3995 Identifier: ISSN: 0264-410X
CoNE: /journals/resource/954925498091