A high containment polymodal pilot-plant fermenter--design concepts

A 225 dm3 pilot-plant bioreactor system has been designed and constructed that is suitable for biohazardous fermentations. The design enables operation at containment levels above the requirements of good industrial large-scale practice (GILSP) without secondary containment of the whole plant. The main biosafety features of the systems include the use of steam barriers on O-ring seals, supply lines and stirrer seals, multiple O-ring seals, piping of condensate lines and pressure relief systems to a 'kill tank', double filtration of inlet and off gases and a mobile isolation unit that allows localised containment of sample valve and probe entry ports. The fermenter can, with minor modifications, be operated as a bottom-or top-stirred reactor for the culture of microbial or animal cells, or as an airlift reactor. The design offers considerable flexibility that could prove cost-effective for process development and production. The relevance of the various design features to enable bioreactor operations at pilot-plant scale to be carried out in compliance with current guidelines for large-scale culture of recombinant microorganisms and microbial pathogens is discussed.