Medical Device Link . Pathogen-free human serum protein production using a hollow-fiber bioreactor system

Used in a wide variety of applications, human serum proteins are critical raw materials for the diagnostics industry. Measurements of specific members of this group of proteins comprise some of the most common clinical chemistry tests. An obvious example is the test for alphafetoprotein (AFP), used universally in prenatal diagnosis. Albumin is an essential component of the serum-free cell culture media used to grow hybridomas for monoclonal antibody production and is also used as a stabilizer in their formulation. Other human serum proteins with applications in IVDs include transferrin (used in hybridoma culture), the blood coagulation factors (measured to detect bleeding disorders), proteases, antiproteases, and other serum factors. Traditionally, these proteins have been purified from pooled human plasma for use as antigens or manufacturing components. This source, however, is coming under heavier scrutiny by FDA because of the possibility of contamination by viruses and other infectious agents. Testing can lessen or eliminate the risk from known infectious agents, such as hepatitis B, but cannot detect the new agents that are continually entering the blood supply. Newly discovered strains of human immunodeficiency virus and the agent or agents responsible for the transmissible spongiform encephalopathies, such as Creutzfeldt-Jacob disease and mad cow disease, exemplify this problem. A solution to it is to divorce production of human serum proteins and other commercially important proteins from dependence on the blood supply. We have developed methods using a human liver cell line cultured in hollow-fiber bioreactors to produce human serum proteins in a controlled, closed system. There the risks of contamination by infectious agents can be virtually eliminated. This method can serve as a model for the manufacture of many other reagents, such as viral antigens, which expose the operator and user to unknown risks. The major impediment to the use of cell culture systems for