Abstract: A microcarrier based process to produce viral vaccines, of which one example is hepatitis A virus (HAV), is composed of an aggregated microcarrier system of glass coated polystyrene microcarriers and MRC-5 cells which creates a stable environment for the propagation of the virus over even extended infection periods. The microcarrier aggregates formed according to this process eliminate the sloughing of cells from the beads during long cultivations seen in other systems, allowing high virus productivity in microcarrier culture. The methodology is applicable where virus production can be enhanced by creating a stable culture during an extended infection period. Scalable stirred bioreactors are used instead of multiple parallel stationary surface bioreactors.

Abstract: A novel method of disrupting cells which do not have a cell wall comprises passing suspended cells through a low pressure impinging jet device. This method disrupts the cells, but does not harm the cell products which are liberated.

Abstract: Bioactive cells are immobilized by suspending bioactive cells in an aqueous solution of a salt-free osmolarity adjuster, alginate and polyethylene glycol, dividing the suspension into bead-sized globules, contacting the globules with a solution of divalent cations to gel the alginate to form beads containing polyethylene glycol-filled areas and removing the polyethylene glycol to form voids in the beads entrapping the bioactive cells. By perfusing the beads with a nutrient medium, the cells can proliferate in the voids to produce high cell densities and produce a product which can be separated from the medium.