engleski

Optimization of Mumps Virus Production Process Using DoE

Background: Traditional virus vaccine production process involves several steps ; virus replication on appropriate cell substrate, harvesting, clarification, virus purification by chromatography, stabilization, formulation and vaccine filling. In order to optimize entire production process with regards to productivity, critical process operations should be identified first. Objective: Optimization of mumps virus production process using process simulation tools, performing sensitivity analysis of process operation to global process productivity. Methods: For mumps virus vaccine production process we have identified virus replication step as the most contributing to overall process productivity. Based on preliminary studies on lab-scale production system, 25 cm2 T-flask, important process factors for optimization studies were found ; X1 – chicken fibroblast primary cell suspension preparation protocol (P-production scale “-“or L-lab-scale “+”) X2 – infection method (A-in cell monolayer “-“or B-in suspension “+”) X3 – harvest interval time (24 hours “-“or 48 hours “+”) Experiments were designed as full factorial experiment with two replicate runs (16 experiments in total). Five virus harvests were collected from each T-flask and virus titer was determined in each sample. Based on individual virus titers in harvests, cumulative virus titer and productivity were estimated as process responses. Main effects of selected factors on estimated process responses were calculated by STATISTICA 6.1 software. Conclusions: It was found that factors X1 and X2 have high positive effect on virus productivity as response variable. The effect of factor X3 is statistically not significant.

mumps ; optimization ; design of experiments

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