A methodological approach to scaling up fermentation and primary recovery processes to the manufacturing scale for vaccine production

As the fermentation process is scaled up, the mass-transfer and nutritional requirements are to be maintained in improving antigen yields upon scale-up. A methodology is adopted to scale-down the processes at the laboratory level in order to further optimize the hydrodynamic and nutritional requirements of the bacteria prior to scaling up. For recovery of bacterial proteins, several micro-filtration techniques are discussed. An optimized process consisting of cross-flow micro-filtration, homogenization and batch clarification using ion-exchange resins is used.