THE BIOLOGICAL PROPERTIES, ASSAY, AND STANDARDIZATION OF INTERFERON-ALPHA - A NEED FOR A WHO COLLABORATIVE STUDY

Interferon-alpha (IFN-alpha) exists as a range of closely related, bio logically active proteins and has been the subject of extensive resear ch and clinical investigation, Standardization of IFN-alpha and the un iform reporting of IFN-alpha activity in International Units (IU) is c ritical to preclinical research and the clinical development of IFN-al pha products as therapeutic agents, Currently, several different IFN-a lpha-containing reference preparations, established as World Health Or ganization (WHO) International Standards (IS) for particular IFN-alpha proteins (mixtures or single molecular species) are available for ass ay calibration, Nevertheless, the heterogeneous nature of IFN-alpha ha s raised standardization issues relating to the activity of individual IFN-alpha proteins, henceforth termed subtypes, in the various biolog ic assays used for determining IFN-alpha levels, These issues include the question of parallelism of dose-response curves among particular I FN-alpha subtypes and different, naturally produced IFN-alpha subtype mixtures, for example, leukocyte IFN-alpha, and the applicablity of IU of IFN-alpha activity defined by antiviral assays to alternative biol ogic assays, for example, antiproliferative assays, To address such is sues, a WHO Consultative Group on Cytokine Standardization requested t hat the National Institute for Biological Standards and Control (NIBSC ) and the Centre for Biologics Evaluation and Research (CBER) organize an international collaborative study to compare the activities and re lative potencies of the several available IFN-alpha preparations, incl uding those derived from human cells containing mixtures of IFN-alpha subtypes and those derived by rDNA methods containing single IFN-alpha subtypes, in different assays, To date, 111 participants in 32 countr ies have been recruited to the study and have agreed to assay a total of 17 different natural and recombinant IFN-alpha preparations or a de fined subset thereof in specific in-house assays, The assay results ge nerated will be statistically analyzed and evaluated to address the st ated issues and to assess whether any individual IFN-alpha preparation is suitable to serve as an IS for all IFN-alpha preparations or wheth er more than one IS will be needed for this purpose.