Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor

• Published in: Biotechnology and bioengineering Vol. 44; no. 11; p. 1315
• Main Authors: Junker, B H, Seamans, T C, Ramasubramanyan, K, Aunins, J, Paul, E, Buckland, B C
• Format: Journal Article
• Language: English
• Published: United States 01.12.1994
• ISSN: 0006-3592
• DOI: 10.1002/bit.260441107

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.