Abstract: The instant invention discloses a closed-system, serum-free, microcarrier-based up-stream process to produce dengue virus. The process comprises a closed-system cell expansion comprising cell passages taking place in closed-system containers. These cell expansions represent a closed process, with replacement media, a cell-detachment agent, and quench medium added though sterile, weldable tubing (a closed-system environment) to eliminate all open aseptic processing following the initial vial thaw of the adherent cells. The viral production takes place in a closed-system bioreactor in adherent cell culture grown on microcarriers providing sufficient cell mass to support the production of dengue virus.