A nationwide adjustment in medical service prices! Recently, the National Healthcare Security Administration of China issued the “Notice on Carrying Out Price Standardization and Governance of Medical Services (First Batch)” (Medical Insurance Price Purchase Letter [2024] No. 217).

The notice focuses on four tests with significant regional differences in equipment procurement and reagent costs: thromboelastography, HbA1c measurement, BNP measurement, and NT-proBNP measurement. These items were included in the first batch of governance projects for price adjustments.

According to the table, compared to the target price, the highest reductions in fees for the four tests are around 50%. HbA1c testing shows the highest decrease, with a reduction of up to 70%!

Where is the path for HbA1c testing?

From a methodological perspective, the HbA1c measurement governance target is unified at 30 RMB. The liquid chromatography method fees have dropped by around 50% on average across provinces, while the immunoassay fees have decreased by about 33%. The pricing issue for chromatographic HbA1c testing is especially prominent. Currently, in 25 provinces (including Guangdong, Sichuan, Shandong, Jiangsu, Hubei, etc.), the charges for chromatographic testing significantly exceed the target price. With a nationwide trend toward price standardization and large reductions in chromatographic HbA1c testing, will alternative methods such as immunoassay or enzymatic methods, which are cost-effective and easy to operate, gain broader adoption? Who will be the ultimate winner, domestic or imported products?

HbA1c is a stable compound formed when glucose in the blood binds to the N-terminal valine of the hemoglobin β chain through a slow, continuous, and irreversible non-enzymatic reaction. As a major indicator of long-term blood glucose control in diabetes patients over 2-3 months, HbA1c is widely used in diabetes management and monitoring since it is unaffected by short-term blood glucose fluctuations, exercise, or food intake. Since 2010, HbA1c ≥ 6.5% has been recommended as a diagnostic criterion.

Currently, HPLC (high-performance liquid chromatography), immunoassay, and enzymatic methods are the main methods for HbA1c testing. According to the 2023 national external quality assessment results, about 70% of users utilize the HPLC method, and 15% use immunoassays.

The American Association for Clinical Chemistry (AACC) and the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine) recommend HPLC as the gold standard for HbA1c measurement due to its high sensitivity, reproducibility, and specificity. However, enzymatic and immunoassay methods also offer advantages, particularly in cost, and hold a market share.

Comparison of different HbA1c testing methods


New Enzyme Solutions by HZYMES

As the first domestic company to develop HbA1c reagents independently, HZYMES offers various enzymatic HbA1c solutions, meeting different laboratory needs while ensuring accuracy.

The enzymatic HbA1c method is mainly divided into two stages. The first uses a protease to cleave the glycated dipeptide from the N-terminal of the β chain of HbA1c, measuring the absorbance at a specific wavelength to calculate Hb concentration. In the second stage, fructosyl peptide oxidase (FPOX) acts on the glycated dipeptide, producing hydrogen peroxide in the presence of peroxidase, which reacts with 10-(carboxymethylaminocarbonyl)-3,7-bis(dimethylamino)phenothiazine sodium (DA-67), resulting in a color change measurable by absorbance, thus calculating HbA1c%.


Technical Challenges in HbA1c Reagent Development The development of enzymatic HbA1c reagents faces three key challenges:

1.Protease selection: Ensuring specific amino acid segment cleavage.
2.Stable fructosyl peptide oxidase development: As the core enzyme, FPOX stability and sensitivity are crucial.
3.Color system choice: Minimizing interference from co-existing substances.
Hzymes, leveraging its R&D and fine chemical platforms, is dedicated to creating a comprehensive glycated hemoglobin (HbA1c) solution by developing core enzyme materials and precise detection reagents.

Through semi-rational design, we constructed a saturated mutation library of specific sites in fructosyl peptide oxidase (FPOX) and performed high-throughput screening. Seven stability-enhancing sites were identified among 25 mutated sites, resulting in four positive mutation types after exploring the molecular mechanism structure. The top mutant exhibited a thermal stability increase of over 4000-fold.


Using the mutated FPOX in the preparation of HbA1c reagents, stability improved tenfold compared to the wild type.


DA-67, a novel chromogen with an absorbance peak at 666 nm, enhances sensitivity and specificity in HbA1c detection by reducing interference from other substances, thus improving accuracy. As a chromogen previously monopolized by foreign brands, Hzymes broke this monopoly to ensure high-quality control. By modifying the chemical structure, replacing chloride with sulfur ions, and through subsequent acylation, Hzymes’ fine chemical team successfully synthesized DA-67 with high purity and solubility, exceeding imported alternatives in interference resistance.

In the future, Hzymes biotech will always

Accurate, Stable, and Interference-Resistant HbA1c Reagents with Dual Tracing

1.Precision and Accuracy: Meeting international standards, Hzymes’ dual-channel enzyme-based HbA1c reagent correlates well with HPLC and latex methods, showing a high correlation coefficient (r > 0.99) with both methods and international products.

2.Enhanced Stability: With an open-bottle stability of over 30 days and an extended shelf life of up to 18 months at 2°C–8°C, this reagent meets the storage needs of global customers.


3.Strong Interference Resistance: It reduces interference from lipids, bilirubin, vitamin C, glucose, and uric acid while minimizing modified hemoglobin impacts on testing.

4.IFCC and NGSP Dual Tracing: The HbA1c standardization programs by IFCC and NGSP are critical for global HbA1c testing standardization. Hzymes’ dual-channel enzyme-based method aligns with the IFCC reference system, detecting only glycated and non-glycated β chains, ensuring reliability even with hemoglobin variants.


5.Patent Protection and Safe Animal-Based Calibration: Unlike human blood-based HbA1c calibrators, which pose biosafety risks and variability in sample concentrations, Hzymes has innovated animal-derived calibrators. These are low-cost, easy to obtain, suitable for mass production, and circumvent biosafety issues and import-export regulations.


Hzymes offers a complete HbA1c solution, from selective enzyme raw materials and custom OEM reagents to in-depth formulation collaboration, designed to meet your high standards for quality reagents. Contact us today to embark on your journey towards a customized HbA1c reagent solution.

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