Scale-Down Approach for Animal-Free Polio Vaccine Production

The industrial scale inactivated polio vaccine production process, based on micro-carrier technology and Vero cells, was evaluated. A large and unique dataset, comprising multiple tags from more than 60 production runs at two different bioreactor scales (350-L and 750-L), has been analyzed by using multivariate data analysis. While variation in the data was large, this method allowed to detect deviations from the average and to set specifications for critical variables like cell densities and product yield. From scale-down experiments these critical variables were shown to be in good agreement with that at the 350-L production scale. When using animal-component free medium for growth of Vero cells and virus replication comparable results were obtained at the lab-scale (3-L and 10-L). In contrast, the 750-L scale was found to operate differently. It was seen that higher product yields per cell were obtained at this larger scale, probably due to a higher growth rate of the Vero cells at the moment of virus inoculation. Therefore, scale-down experiments have to be adapted to approximate both production scales.