WHO CYTOKINE STANDARDIZATION - FACILITATING THE DEVELOPMENT OF CYTOKINES IN RESEARCH, DIAGNOSIS AND AS THERAPEUTIC AGENTS

The development and widespread application of recombinant DNA technolo gy has dramatically increased the number of cytokines available for cl inical evaluation. New and novel cytokines are being discovered, clone d and entered into clinical trials at such a rate that it is often the case that the biological activities of these proteins are poorly unde rstood during their development as therapeutic agents. In addition, ma nufacturers of any one cytokine can produce the protein from different cellular sources resulting in materials that exhibit markedly differe nt specific activities. When estimating the amount of biological activ ity of different preparations with different specific activities by bi oassay, mass units cannot be used and biological activity is therefore expressed as 'biological potency units'. The biological unit requires definition by a standard that is assay-independent (especially when m easuring a particular type of biological activity). In many cases, a v ariety of assay methods will be available and the material chosen for a standard should ideally be suitable for use with as many of them as possible. Once the unit is defined, this can be used in any laboratory , thus providing a means of ensuring uniformity throughout the world i n the designation of potency of different biological preparations. The World Health Organisation (WHO) standardization programme involves th e production of biologically stable, well characterised potency and im munoassay standards that are available world-wide using a single inter national unitage. Over the years, WHO international standards have bee n used to dramatically reduce the variation in estimates of cytokine p reparations within and between laboratories for immunoassays and bioas says. WHO international standards are primary reference preparations a gainst which secondary, or working standards (including regional stand ards, national standards, pharmacopoeial standards and in-house workin g standards) can be calibrated. (C) 1998 Elsevier Science B.V. All rig hts reserved.