Manufacture and Safety of Interferons in Clinical Research

Abstract

Leukocyte interferon for clinical trials became available in the early 1970s, the bulk of which was provided from Finland by Cantell et al. (1974) and Strander and CAntell (1966). Fresh buffy coat cells from human blood were stimulated to produce interferon by induction with Newcastle disease or Sendai viruses. Since the production process involved fresh, primary human cells suspended in serum-containing tissue culture medium and infected with an inducing virus, many of the tests used in examining live and inactivated tissue culture-derived vaccines were considered appropriate for application to leukocyte interferon. At first, these included only sterility, general safety, pyrogenicity, and potency. Also, the manufacturer was asked to provide data which identified the product as interferon, e.g., low pH stability, sedimentation characteristics, and biologic activity. As procedures became available for hepatitis B surface antigen (HB_sAg) testing, it was reasonable to require that buffy coats used in production should be derived only from blood shown to be negative for the presence of HB_sAg. It is quite likely that as tests for hepatitis virus A and for the agents of non-A and non-B hepatitis are developed, these would also be required for source leukocytes used in interferon production. With the refinement of interferon production procedures, experimental materials were also tested for protein and moisture content.