Impact of the manufacturing process on the commutability of erythropoietin control materials for external quality assessment schemes

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Introduction: Erythropoietin (EPO) is a measurand that has not yet been sufficiently standardized in laboratory medicine. This is why quality control within the framework of external quality assessment (EQA) schemes is of great importance. Therefore, the INSTAND e.V. EPO EQA was introduced to support quality assurance of medical laboratories for this measurand. The use of commutable control material (CM) enables the comparison of various measurement systems with one another and allows to assess the level of harmonization between laboratory measurements. This study assessed the suitability of different EPO CMs for use in EPO EQA schemes and the impact of sample preparation, such as dilution, spiking and lyophilization. Methods: Eleven candidate CMs in both frozen and lyophilized forms were analyzed and compared to 80 clinical samples (CS) using a chemiluminescence immunoassay (CLIA) and two different enzyme-linked immunosorbent assay (ELISA) test kits. The commercially available CMs were based on a serum pool that was either diluted with human serum albumin or enriched with various recombinant EPO (rhEPO) preparations. Commutability was assessed oriented towards the principles of difference in bias analysis based on the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group on Commutability. Results: Most CMs remained within the range of the CS bias distribution across all paired method correlations. However, CMs exceeding the limits were also observed in some cases, even the native frozen pooled serum. Dilution and lyophilization affected the inter-method bias to varying degrees. Bias values for CMs enriched with different rhEPO preparations were mostly within the same range, though for CMs containing darbepoetin alfa in some cases higher inter-method bias was observed. Apparent differences in non-selectivity between the assays limited the ability to reliably assess commutability. Conclusion: The findings highlight current methodological challenges regarding the manufacturing of suitable materials and commutability assessment. Further investigations are needed regarding the standardization and harmonization of EPO measurements. Until further data is available, the evaluation within the EPO EQA should remain within method-specific sub-collectives.