Biotechnology and Bioengineering, Vol.44, No.11, 1315-1324, 1994
Cultivation of Attenuated Hepatitis-A Virus-Antigen in a Titanium Static Mixer Reactor
The titanium static mixer reactor, demonstrated for a variety of vaccine processes during the late 1970s, 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 in 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 pilot-scale (265,000 cm(2)) run were conducted to investigate refeeding regimens, 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.