ABSTRACT
Regulatory considerations related to the use of cell substrates for the manufacture of human therapeutics were first expressed in the early 1950s in regard to adenovirus vaccine production in HeLa cells (7). At this time, the decision was made that transformed cells, i.e., continuous cell lines, should not be used and that only primary cells derived from normal tissue of normal animals, such as monkey kidney cells, were suitable for use. Over the next several years it became evident that these primary simian cells were often contaminated with indigenous simian adeno and picorna viruses (8, 9), and appropriate safety testing
was devised and carried out. The discovery that the polyoma virus, SV40 (10), was a contaminant of both inactivated and live attenuated poliovirus and other viral vaccines was of special concern as this virus was shown to transform cells in vitro and to be tumorigenic in newborn hamsters.
