title: Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor.
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.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Junker
authors.forename: T C
authors.initials: TC
authors.lastname: Seamans
authors.forename: K
authors.initials: K
authors.lastname: Ramasubramanyan
authors.forename: J
authors.initials: J
authors.lastname: Aunins
authors.forename: E
authors.initials: E
authors.lastname: Paul
authors.forename: B C
authors.initials: BC
authors.lastname: Buckland