Mammalian cell cultures. Part III: Safety and future aspects

Long standing experience with mammalian cell cultures demonstrates that they per se do not constitute any hazard to healthy man. However, permanent cell lines may cause transplantable tumors in immune-suppressed animals and man but not in healthy species. A potential hazard associated with mammalian cell cultures might be caused by endogenous viruses which can be harboured in the mammalian cells or adventitious agents associated with mammalian cells. Especially a corresponding validation for removal of viruses has to be established in the manufacturing process. Free nucleic acids or recombinant nucleic acid sequences are regarded as not being biologically active and therefore do not cause any hazard. Because mammalian cell cultures which are ranking lowest in terms of safety measures are able to synthesize reliably complex glycoprotein structures, the economy of mammalian cell culture processes has to be approved for future prospects on the background of the competitive situation with microorganisms and the overall cost limitation of the health insurance systems. High yielding expressing systems are required including detoxification genes for cytotoxic metabolites. Shorter doubling times of the host cell, higher productivity and higher cell densities would be further goals. Also new aspects of mammalian cell cultures, not only their use as factories for protein synthesis, but also in gene therapy as carrier for the desired genetic information or in enhancing the wound healing process, will gain future importance.