title: Clinically relevant lot-to-lot reagent difference in a commercial immunoturbidimetric assay for glycated hemoglobin A1c.
abstract: OBJECTIVE
  Hemoglobin A1c (HbA1c) is employed for diagnosis and therapy monitoring of diabetes mellitus. The effect of a change of reagent lot on the measured values of a commercial immunoturbidimetric HbA1c assay (A1C3) was investigated.
  
  
  METHODS
  Comparison measurements of A1C3 and an automated affinity chromatography method (VIIT) were performed in 15 samples for the initial and in 20 samples for the subsequent A1C3 lot. The results of 27 and 19 measurements of a normal and of 28 and 20 of a pathological control (before and after the switch of the A1C3 reagent lot, respectively) were evaluated. Finally, the results of 6463 patient samples that had been measured with the initial and 434 that had been measured with the subsequent A1C3 lot were investigated.
  
  
  RESULTS
  VIIT yielded significantly higher results than the initial A1C3 lot (bias: 0.41% HbA1c, 4.5mmol/mol) but agreed well with the subsequent lot (bias: -0.01% HbA1c, -0.1mmol/mol). Changing to the subsequent reagent lot resulted in significant increases of the mean of the normal control of 0.316% HbA1c (3.5mmol/mol) and of the pathological control of 0.749% HbA1c (8.2mmol/mol). The median of patient samples measured with the subsequent lot was significantly higher by 0.40% HbA1c (4.4mmol/mol).
  
  
  CONCLUSIONS
  The subsequent A1C3 reagent lot yields significantly higher measurement results than the initial by approximately 0.5% HbA1c (5.5mmol/mol). This difference is considered as clinically relevant. A combined effort of manufacturers and notified bodies is necessary to minimize lot-to-lot variation.
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Thaler
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Iakoubov
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bietenbeck
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany. Electronic address: luppa@klinchem.med.tum.de.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Luppa
mesh_terms: D001681:Biological Assay / Q000379:methods*; D006442:Glycated Hemoglobin / Q000737:chemistry*; D006403:Hematologic Tests / Q000379:methods; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry*; D015203:Reproducibility of Results
chemical_list: D006442:Glycated Hemoglobin; D007202:Indicators and Reagents
keywords: HbA1c; Immunoassay; Lot variability