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  • 1
    Electronic Resource
    Electronic Resource
    Modified microbial fermenter performance in animal cell culture and its implications for flexible fermenter design (1994)
    Springer
    Bioprocess and biosystems engineering 11 (1994), S. 57-63 
    Details
    ISSN: 1432-0797
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Modified microbial fermenters were adapted for use in animal cell cultivations within an active microbial pilot plant rapidly and inexpensively. Multiple batches of Jurkat cells (human T-lymphoma) and Spodoptera frugiperda (using a baculovirus expression vector) were conducted in modified 75 L Chemap fermenters and a 280 L pilot plant seed vessel. These retrofitted reactors were evaluated for suitable temperature control, local hot spots, surface aeration capability, open-pipe sparging, impeller type and impeller speed. Influences of these operating factors on cell growth rate, cell density, glucose uptake and protein yield were quantified. Implications for the flexible design of fermenters for operation in multiuse campaign facilities are discussed. Adaption of existing microbial fermenters was found to be an attractive route for initial implementation of cell culture capacity in a research organization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00389561
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Studies of Baby Hamster Kidney Natural Cell Aggregation in Suspended Batch Cultures (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 745 (1994), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1994.tb44368.x
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  • 3
    Electronic Resource
    Electronic Resource
    Investigation of NS0 Cell Metabolic Behavior in Monoclonal Antibody Producing Clones (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 745 (1994), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1994.tb44382.x
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  • 4
    Electronic Resource
    Electronic Resource
    Changes in animal cell natural aggregates in suspended batch cultures (1994)
    Springer
    Applied microbiology and biotechnology 41 (1994), S. 203-209 
    Details
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Some anchorage-dependent animal cells can form natural aggregates in stirred tanks. Baby hamster kidney (BHK) natural aggregates are described and characterized. Total cell concentration and viability could be obtained after aggregate mechanical aissociation, with negligible cell lysis and no change in cell membrane permeability. During a normal batch run, aggregates were formed immediately after inoculation, a few spherical aggregates increasing size during the initial growth phase. At the end of the growth phase, an increase in aggregate concentration was observed, without a considerable increase in aggregate diameter. At the end of the batch run, 160 h after inoculation, aggregates disintegrated into smaller, non-spherical units, following a sharp viability decrease. Cell concentrations of 1. 2 · 106 cells/ml were obtained, with 60% of the total cells being in aggregates; the cell concentration in aggregates achieved 5 · 108 cells/ml, with a porosity of 55%. Viability was consistently in the range 85–90%, both for aggregate and suspended cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00186960
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  • 5
    Electronic Resource
    Electronic Resource
    Changes in animal cell natural aggregates in suspended batch cultures (1994)
    Springer
    Applied microbiology and biotechnology 41 (1994), S. 203-209 
    Details
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Some anchorage-dependent animal cells can form natural aggregates in stirred tanks. Baby hamster kidney (BHK) natural aggregates are described and characterized. Total cell concentration and viability could be obtained after aggregate mechanical dissociation, with negligible cell lysis and no change in cell membrane permeability. During a normal batch run, aggregates were formed immediately after inoculation, a few spherical aggregates increasing in size during the initial growth phase. At the end of the growth phase, an increase in aggregate concentration was observed, without a considerable increase in aggregate diameter. At the end of the batch run, 160 h after inoculation, aggregates disintegrated into smaller, non-spherical units, following a sharp viability decrease. Cell concentrations of 1.2⋅106 cells/ml were obtained, with 60% of the total cells being in aggregates; the cell concentration in aggregates achieved 5⋅108 cells/ml, with a porosity of 55%. Viability was consistently in the range 85–90%, both for aggregate and suspended cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002530050131
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  • 6
    Electronic Resource
    Electronic Resource
    Two-dimensional versus three-dimensional culture systems: Effects on growth and productivity of BHK cells (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 52 (1996), S. 429-432 
    Details
    ISSN: 0006-3592
    Keywords: BHK ; aggregates ; porous microcarriers ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The influence of surface growth (two-dimensional microcarriers) and three-dimensional growth (aggregates and macroporous supports) in agitated, suspended batch culture systems upon growth and productivity of BHK was compared. Cultures using three porous microcarriers (CultiSpher G, Cellsnow EX, and Cytocell), one nonporous microcarrier (Cytodex 3) and natural aggregates were performed in stirred tanks using two different agitation rates (60 and 100 RPM). With the exception of Cytocell, cell growth, viability, and productivity were similar when three-dimensional structures (porous microcarriers and aggregates) were used. Nonporous microcarriers only compared well at 60 RPM as growth ceased under overagitation. These results suggest that cultures less susceptible to fluid shear are advantageous for scale-up. © 1996 John Wiley & Sons, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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    Paper (German National Licenses)
  • 7
    Electronic Resource
    Electronic Resource
    Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor (1994)
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 44 (1994), S. 1315-1324 
    Details
    ISSN: 0006-3592
    Keywords: static mixer ; MRC-5 ; anchorage dependent ; hepatitis A ; animal cell culture ; bioreactor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The titanium static mixer reactor, demonstrated for a variety of vaccine processes during the late 197s, was investigated for the production of attenuated hepatitis A virus antigen from anchorage-dependent MRC-5 cells. This reactor system used Charles River Biotechnological Services cabinets for monitoring and process control. Cell inoculation protocols, using 6000-10,000 cells/cm2, resulted on over 95% attachment at both the laboratory and pilot scales. Indirect monitoring techniques using oxygen, glucose, L-serine, and L-glutamine uptake rates were indicative of cell growth prior to virus inoculation as well as environmental and/or nutrient limitations. Seven laboratory-scale (3900 cm2) runs and one pilotscale (265,000 cm2) run were conducted to investigate refeeding regiments, parallel versus perpendicular element orientation, increased element surface area per unit volume, and scale-up performance. In general, lysate antigen yields achieved were similar to those of parallel T-flasks cultivated under similar conditions. © 1994 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bit.260441107
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  • 8
    Electronic Resource
    Electronic Resource
    Development, preparation, and testing of VAQTA®, a highly purified hepatitis A vaccine (2000)
    Springer
    Bioprocess engineering 23 (2000), S. 439-449 
    Details
    ISSN: 0178-515X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Manufacture of VAQTA®, an inactivated hepatitis A vaccine, uses state-of-the-art technologies in cell culture and bioprocessing science, which have made it possible to routinely produce the vaccine at manufacturing scale. VAQTA® consists of an attenuated strain of hepatitis A virus that is highly purified and formaldehyde-inactivated, then formulated with an aluminum hydroxide adjuvant. Process development and scale-up have resulted in a well-characterized vaccine manufacturing process with appropriate in-process controls to assure consistent performance, and a reproducible, well-defined product. Results are presented from a series of manufacturing demonstration lots to show consistency, as well as comparability to clinical lots prepared at an earlier stage in development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004499900157
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  • 9
    Electronic Resource
    Electronic Resource
    Repeated-batch cultures of Baby Hamster Kidney cell aggregates in stirred vessels (1994)
    Springer
    Cytotechnology 15 (1994), S. 337-349 
    Details
    ISSN: 1573-0778
    Keywords: BHK ; hydrodynamic size control ; natural aggregates ; cell retention ; repeated-batch culture ; stirred vessels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Natural aggregates of Baby Hamster Kidney cells were grown in stirred vessels operated as repeated-batch cultures during more than 600 hours. Different protocols were applied to passaging different fractions of the initial culture: single cells, large size distributed aggregates and large aggregates. When single cells or aggregates with the same size distribution found in culture are used as inoculum, it is possible to maintain semi-continuous cultures during more than 600 hours while keeping cell growth and viability. These results suggest that aggregate culture in large scale might be feasible, since a small scale culture can easily be used as inoculum for larger vessels without noticeable modification of the aggregate chacteristics. However, when only the large aggregates are used as inoculum, it was shown that much lower cell concentrations are obtained, cell viability in aggregates dropping to less than 60%. Under this ‘selection’ procedure, aggregates maintain a constant size, larger than under batch experiments, up to approximately 400 hours; after this time, aggregate size increases to almost twice the size expected from batch cultures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00762409
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