WHO/BS/2014.2237 WHO International Collaborative Study of the proposed 1st IS for human Proinsulin

Overview

The World Health Organization (WHO) Expert Committee on Biological Standardization (ECBS) has recognized (2010) the need for a replacement for the International Reference Reagent (IRR) for human proinsulin, coded 84/611. We report here the characterization of a candidate standard for human proinsulin in an international collaborative study carried out by seventeen laboratories in nine countries. Phase I of the study confirmed by amino acid analysis and UV spectroscopy that the primary calibrant contained 220 micrograms per vial. The candidate standard, in ampoules coded 09/296, was then calibrated by HPLC analysis in terms of the primary calibrant (phase II) and further characterized by immunoassay in comparison to 84/611 (phase III). Estimates from the HPLC calibration indicated the content of 09/296 to be 7.0 micrograms per ampoule. The results of this study also indicate that the candidate standard shows appropriate immunological activity and appears sufficiently stable on the basis of a thermally accelerated degradation study, and is thus suitable to serve as an International Standard for immunoassays of human proinsulin.