A first step toward commercial antigen bulk manufacturing in flexible production units

Flexible production units for bulk antigen manufacturing require the extensive implementation of single-use equipment for both upstream and downstream processes. For combination vaccines the majority of antigens are derived from bacterial pathogenic strains; among them, several are strictly aerobic. The recent launches of single-use fermenters to grow aerobic microbial strains fill a major gap in the design of flexible production lines. The aim of the work presented here was to transpose the Haemophylus influenzae type b fermentation process from a 1000L stainless steel fermenter to a GE Xcellerex XDR-500 MO single-use fermenter. This was done by a constant k_La approach. Therefore, the first step of the study was a complete characterization of the gas/liquid transfer at various stirring and aeration rates in the GE Xcellerex XDR-500 MO. Then, based on process knowledge from the 1000L stainless steel fermenter, appropriate agitation and gas flow settings were defined. It allowed reproduction of the same growth dynamics and capsular polysaccharide production in the single-use fermenter, from the first run