Analytical Characterization and Validation of a Novel Automated Amino-Terminal proB-Type Natriuretic Peptide Assay

Abstract Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement has class 1, level of evidence A recommendations in heart failure (HF) guidelines for diagnosis and prognosis. Analytical characterization of a novel automated NT-proBNP assay is necessary to examine its fitness for validation in pivotal clinical trials. Methods The Access NT-proBNP assay is an immunoenzymatic assay using monoclonal capture and detection reagents on the DxI 9000 Immunoassay Analyzer. Clinical and Laboratory Standards Institute guidelines directed limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity, imprecision, interference, and method comparison studies. Age-specific 97.5th percentile upper reference limits (URLs) were established with 675 healthy US adults that are 54.7% female, 79% White, 15% Black, and 8% Latinx. Results LoB = 1.1 ng/L; LoD = 4.8 ng/L; LoQ = 4.8 ng/L, linearity = 25 000 ng/L; and no interfering/cross-reacting substances were identified. Repeatability and reproducibility CVs were 1.5% to 3.5% and 2.7% to 7.9%, respectively, at NT-proBNP concentrations from 38 ng/L to 23 848 ng/L. The Passing-Bablock regression equation for method comparison is Beckman Access = 0.92 * Elecsys-1.20 ng/L, r = 0.99. Age-specific 97.5th percentile URLs for the Access NT-proBNP assay are <50 years, 162 ng/L; 50 to 75 years, 311 ng/L; and >75 years, 457 ng/L. Conclusions A method comparison showed good harmony with an established assay, and analytic parameters demonstrated satisfactory overall performance. Imprecision across the measurement range is <8%. The Access NT-proBNP assay yielded age-specific 97.5th percentile URLs in harmony with the Elecsys reference method. The Access NT-proBNP assay demonstrated robust analytical performance that is fit for the purpose of supporting an NT-proBNP clinical trial for HF diagnosis and prognosis.