Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor |
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Authors: | Junker B H Seamans T C Ramasubramanyan K Aunins J Paul E Buckland B C |
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Affiliation: | Merck Research Laboratories, Rahway, New Jersey 07065, West Point, Pennsylvania. |
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Abstract: | 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/cm(2), 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 cm(2)) runs and one pilotscale (265,000 cm(2)) 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. (c) 1994 John Wiley & Sons, Inc. |
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Keywords: | static mixer MRC-5 anchorage dependent hepatitis A animal cell culture bioreactor |
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