Cell Lines: Applications and Biosafety

Abstract

The early use of continuous cell lines (CCLs) for the manufacture of biological products is represented by the manufacture of foot-and-mouth disease vaccine in the Syrian hamster cell line baby hamster kidney (BHK), the production of interferon from the B-lymphoblastoid cell line Namalwa, and the introduction of monoclonal antibodies from hybridoma cells. Long-standing experience has shown that contamination with pathogenic agents is the most important hazard and merits careful assessment of safety precautions. The culture types, in order of decreasing risk, are primary cell cultures; CCLs; and intensively characterized cells, including human diploid fibro-blasts. Most national guidelines recommend that human and other primate cells be handled using biosafety level 2 practices and containment and that all work be performed in a biosafety cabinet (BSC). For airfreight, cell cultures have been classified as ‘’diagnostic specimens’’ under the International Air Transport Association (IATA) regulations. In many cases gene therapy concepts are based on viral vectors (e.g., adenoviruses and retroviruses). This chapter describes safety measures for large-scale production of biologicals, and focuses on characterization of cell lines. PCR is now commonly used to identify cell lines and to detect both cross contamination by other cell lines and contamination by adventitious agents or in combination with other methods. Safety testing of cells used in the manufacture of biologicals is usually performed with procedures accredited to good laboratory practice.