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          Institute: MPI für Dynamik komplexer technischer Systeme     Collection: Bioprocess Engineering     Display Documents



  history
ID: 322131.0, MPI für Dynamik komplexer technischer Systeme / Bioprocess Engineering
Establishment of a mink enteritis vaccine production process in stirred-tank reactor and Wave Bioreactor microcarrier culture in 1-10 L scale
Authors:Hundt, B.; Best, C.; Schlawin, N.; Kassner, H.; Genzel, Y.; Reichl, U.
Language:English
Date of Publication (YYYY-MM-DD):2007-05
Title of Journal:Vaccine
Volume:25
Issue / Number:20
Start Page:3987
End Page:3995
Review Status:not specified
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:Udo Reichl
Affiliations:MPI für Dynamik komplexer technischer Systeme/Bioprocess Engineering
External Affiliations:IDT, Rosslau, Germany and Otto-von-Guericke University Magdeburg, Bioprocess Engineering
Identifiers:URL:http://dx.doi.org/10.1016/j.vaccine.2007.02.061
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