IFCC Standardization of HbA1c

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The IFCC Reference System

IFCC Working Group: To achieve a uniform international standardization, the IFCC established a working group on HbA1c standardization in 1995.  The list of current IFCC WG members can be found at http://www.ifcchba1c.net/ .

Definition of the Analyte: The IFCC working group has defined HbA1c as Hb that is irreversibly glycated at one or both N-terminal valines of the beta chains. This does not exclude hemoglobin that is additionally glycated at other sites on the alpha or beta chains.

Primary Reference Material: For the calibration of the reference method, mixtures were made of pure HbA1c and pure HbA0. These fractions were isolated using cation exchange and affinity chromatography, and characterized using capillary isoelectric focusing, and electrospray ionization mass spectrometry.

Reference: Finke A., Kobold U, Hoelzel W, Weycamp C, Jeppsson JO, Miedema K. Preparation of a candidate primary reference material for the international standardisation of HbA1c determinations. Clin Chem Lab Med 1998; 36: 299-308

Reference Method: Two reference methods have been developed which specifically measure the glycated N-terminal residue of the beta-chain. The principle is that in a first step hemoglobin is cleaved into peptides by a proteolytic enzyme and thereafter the specific glycated and non-glycated N-terminal peptides of the beta-chain are measured by HPLC and either mass spectrometry or capillary electrophoresis.  These reference methods were approved by the IFCC in July 2001.

Reference: Jeppsson J-O, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, Miedema K, Mauri P, Mosca A, Paroni R, Thienpont L, Umemoto M, Weykamp CW. Approved IFCC reference method for the  measurement of HbA1c in human blood. Clin Chem Lab Med 2002; 40: 78-89

Implementation: An IFCC Laboratory Network has been established.  The lists of current approved and candidate IFCC Network Laboratories can be found at: http://www.ifcchba1c.net/ .

Network laboratories participate in two intercomparison studies each year in order to renew their approval status according to the criteria of the network (CV<2.5%, deviation > 2.5% from mean of all labs). These studies will also be used to evaluate the stability of calibrators and controls and to assess new batches of calibrator and control materials.

Once each year 8 whole blood pools are prepared and shipped to network laboratories and participating manufacturers.  The IFCC network assigns values to each level and manufacturers use them to calibrate their assay methods.  Manufacturers can also subscribe to a monitoring program in which the IFCC provides samples on an ongoing basis (24 samples/year).


Weykamp C, John WG, Mosca A, Hoshino T, Little R, Jeppsson J-O, Goodall I, Miedema K, Myers G, Reinauer H, Sacks DB, Slingerland R, and Siebelder C. The IFCC Reference Measurement System for HbA1c: A 6-Year Progress Report. Clin Chem 2008; 54(2): 240-48

Konnert A, Berding C, Arends S, Parvin C, Rohlfing CL, Wiedmeyer H, Little R, Siebelder C, and Weykamp C. Statistical Rules for Laboratory Networks. J Testing & Evaluation 2006; 34(2): 1-7

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