Pilot-and production-scale containment of cytotoxic and oncogenic fermentation processes

Proper design of fermentation facilities and equipment modification can control the risks associated with largescale production and purification of microbially produced cytotoxic agents and oncogenic viruses. The primary biohazard risks to operators and the environment are generation of aerosols and accidental spills. Fermentation and recovery facilities can be constructed to contain these agents by installing fermentation equipment within a HEPA-filter-exhausted biological barrier. Within this barrier system, large-scale processing that generates potentially hazaradous areosols (filtration, centrifugation of transformed cells or crystal slurries, and banding of viruses) should be isolated from other operations. Isolation of equipment is often required, with provision for both chemical and biological decontamination of process wastes. Failsafe fermentor over-pressure sensors, parallel exhaust gas filtration, welded transfer lines, and modified sampling systems for elimination of aerosols can be installed on most fermentation equipment. Aerosol and spill containment by proper equipment design, coupled with appropriate personnel protective equipment and medical monitoring, make possible safe production of experimental growth factors and viruses from large-scale culture of transformed mammalian cells and production of cytotoxic antitumor antibiotics.