Commutability of widely adopted reference material CRM 470 is still an issue for ceruloplasmin assays

Background. The purpose of measurement standardisation is to achieve closer comparability of results obtained using different commercial systems. Regarding serum protein immunoassays, a reference preparation (CRM 470) was released in 1993 and adopted by manufacturers across the world as working calibrator for routine methods to reduce method-dependent variation. Methods. Moving from nephelometric (Beckman Immage) to turbidimetric determination (Roche Cobas 6000) of 7 serum proteins, we preliminarily checked the comparability of results between the two systems. The study was performed according the CLSI EP9-A protocol on 30 fresh sera, tested on each system in duplicate, subdivided on two different days, without recalibration and using manufacturers’ control materials to validate the runs. Both manufacturers’ package inserts provide statements that kit calibrators are traceable to CRM 470. Suggested reference intervals are also the same. Results. Although good correlation was observed (r=0.943), the comparison of ceruloplasmin methods produced evidence of a highly significant proportional bias (regression slope, 0.571, P <0.0001). Absolute and percentage mean differences were -0.11 g/L (95%CI: -0.128 to -0.093 g/L) and -38.1% (95%CI: -43.1 to -33.0%), respectively. No other evaluated proteins showed similar problems. Conclusions. Lacking a ceruloplasmin reference method, it is impossible to demonstrate that one of the two assays produces true ceruloplasmin values. The problem is, however, that results coming from the two assays are clearly not comparable. Even if different handling of the reference material by the two manufacturers cannot be excluded, apparently a major issue includes commutability of the material with biological samples in the evaluated assays.