Trueness verification and traceability assessment of results from commercial systems for measurement of six enzyme activities in serum: an international study in the EC4 framework of the Calibration 2000 project.

Background: The in vitro diagnostics directive of the European Union requires traceability to higher order reference measurement procedures and materials for analytes in assuring the result trueness and comparability of laboratory measurements. Manufacturers must ensure that the systems they market are calibrated against available reference systems. Validation of metrologically traceable calibrations is, however, required. Methods: A commutable serum-based material was analyzed in three reference laboratories and target values for six enzymes (ALT, AST, CK, GGT, LD, amylase) were assigned using IFCC reference measurement procedures. 70 laboratories in Germany, Italy, and The Netherlands measured the same enzymes in the material using procedures from six commercial companies. A system for maximum allowable error was developed from the biological variation model and the results of the various procedures were tested on their compliance to trueness and between-laboratory and within-laboratory variations relative to the maximum allowable. Results: For ALT results were relatively good. >95% of laboratories using systems from Dade, Olympus, Ortho and Roche are expected to comply traceability within the biologically derived limits, and 94% respectively 89% from Abbott and Beckman. For AST and GGT only Dade respectively Olympus fully complied. For CK all companies showed significant bias. Nevertheless >95% of laboratories applying Abbott, Beckman and Roche systems will comply. Finally, LD and amylase measurements require significant improvement. Some manufacturers continue to sell on the European market assays giving results which are not traceable to the internationally accepted reference systems.