WHO/BS/2015.2256 WHO International Collaborative Study of the Proposed 1st IS for human C-peptide

Overview

The World Health Organisation (WHO) Expert Committee on Biological Standardisation (ECBS) has recognised (2010) the need for a replacement for the International Reference Reagent (IRR) for human C-peptide, coded 84/510. We report here the preparation of a candidate for the 1st International Standard for human C-peptide and its characterisation in an international collaborative study carried out by 24 laboratories in 10 countries. Phase I of the study confirmed by amino acid analysis that the primary calibrant contained 209 µg per vial. The candidate standard, in ampoules coded 13/146, was then calibrated by HPLC analysis in terms of the primary calibrant (Phase II) and further characterised by immunoassay in comparison to 84/510 (Phase III). Estimates from the HPLC calibration from all laboratories were in good agreement, and indicated the content of 13/146 to be 8.64 µg per ampoule. The results of this study also indicate that the candidate standard showed 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 C-peptide. In addition, the results of an assessment of the commutability of the candidate standard with a small cohort of patient samples, indicates that the candidate standard 13/146 is likely to be commutable with serum and urine patient samples as measured by current immunoassays. It is therefore proposed that the candidate standard 13/146 be established as the 1st WHO International Standard for human C-peptide, with an assigned potency of 8.64 µg/ampoule with expanded uncertainty of 8.21-9.07 (95% confidence; k=2.45).