(269 days)
Medconn Glycated Hemoglobin Test System is intended for the quantitative determination of hemoglobin A1c (IFCC mmol/mol and NGSP %) in human whole blood or hemolysate with ion-exchange high performance liquid chromatography (HPLC) using the Medconn HbA1c Assay Kit (HPLC) on the Medconn Glycated Hemoglobin Analyzer, models MQ3000 and MQ3000PT.
Hemoglobin A1c measurements are used as an aid in diagnosis of diabetes, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus.
The Medconn Glycated Hemoglobin Test System is intended for the quantitative determination of hemoglobin A1c (IFCC mmol/mol and NGSP %) in human venous blood or hemolysate using ion-exchange high performance liquid chromatography (HPLC) on the Medconn Glycated Hemoglobin analyzer, models MQ-3000 and MQ-3000PT.
A high-pressure pumping system delivers a buffer solution to an analytical cartridge and detector. Whole blood samples undergo an automatic hemolysis and dilution process before being introduced into the analytical flow path. Manually hemolyzed and prediluted samples loaded in sample cups at designated location are directly introduced for analysis. A programmed buffer gradient of increasing ionic strength delivers the sample to the analytical cartridge where the hemoglobin species are separated based upon their ionic interactions with the cartridge material and the buffer gradient. The separated hemoglobin species then pass through the flow cell where changes in the absorbance are measured at 415nm and recorded as a digital chromatogram. The software performs an analysis of the hemoglobin peaks in the chromatogram, recording information including retention time, peak area, and relative peak area of the detected substance over the total peak area of all substances. Peaks identified as target analytes are calibrated to generate a report and a chromatogram for each sample.
Medconn Glycated Hemoglobin Test system contains the following components:
- Medconn Glycated Hemoglobin analyzer
- Medconn HbA1c Assay Kit (HPLC)
- Medconn Hemoglobin A1c Calibrator
- Medconn Hemoglobin A1c Control
- Medconn HbA1c Column Kit (HPLC)
- Medconn HbA1c Haemolyser
The Medconn Glycated Hemoglobin Test System is an in vitro diagnostic device intended for the quantitative determination of hemoglobin A1c (HbA1c) in human whole blood or hemolysate. It uses ion-exchange high-performance liquid chromatography (HPLC) on the Medconn Glycated Hemoglobin Analyzer (models MQ3000 and MQ3000PT). HbA1c measurements are used as an aid in the diagnosis of diabetes, to identify patients at risk for developing diabetes mellitus, and for monitoring long-term blood glucose control in individuals with diabetes mellitus.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Medconn Glycated Hemoglobin Test System's performance are embedded within the "Summary of Performance Data" section of the 510(k) submission, specifically through demonstrating acceptable precision, linearity, analytical specificity (interference), and method comparison against a standardized reference method. The performance criteria as stipulated by the Special Controls requirements for HbA1c systems that diagnose diabetes have clearly been met.
Here's a table summarizing the acceptance criteria and the reported device performance, derived from the provided text:
| Performance Characteristic | Acceptance Criteria (Implied by study design and FDA clearance) | Reported Device Performance (Summary) |
|---|---|---|
| Precision/Reproducibility | Based on CLSI EP05-A3. Acceptable CV% across different levels and sources of variation. | Whole Blood Mode: Total Precision (CV%) for 4 samples (5.11% to 12.25% NGSP): 0.86% to 1.59%. |
| Dilution Mode: Total Precision (CV%) for 4 samples (5.20% to 12.15% NGSP): 0.87% to 1.43%. All CV% values are considered acceptable and within expected ranges for this type of test. | ||
| Linearity | Based on CLSI EP06-A2. Regression parameters (slope, intercept, R2) demonstrating linearity across the claimed measuring range (3.0% to 15.0% NGSP / 9.3-140.5 mmol/mol IFCC). Maximum Bias (mean) between observed and theoretical values should be minimal. | Whole Blood Mode: Slope 0.9967, Intercept 0.0318, R2 0.9999 (NGSP). |
| Dilution Mode: Slope 0.9971, Intercept 0.0352, R2 0.9999 (NGSP). | ||
| Maximum Bias (mean) observed: ± 0.1 (NGSP %) and ±1 (IFCC mmol/mol). Results support the claimed measuring range of 3.0% to 15.0% HbA1c. | ||
| Analytical Specificity (Interference) | Based on CLSI EP07-A3. Significant interference defined as a ± 6% change in %HbA1c value from the control. No significant interference by common endogenous substances, drugs, or common hemoglobin derivatives/variants at specified concentrations. | Endogenous Interference: No significant interference observed for Unconjugated Bilirubin (21.3 mg/dL), Conjugated Bilirubin (19.2 mg/dL), Lipemia (Triglycerides) (6000 mg/dL), RF (750 IU/mL), TP (21.0 g/dL). |
| Drug Interference: No significant interference observed for a wide range of drugs (e.g., Ascorbic acid 100 mg/dL, Acetaminophen 200 mg/dL, Ibuprofen 500 mg/dL, etc.). | ||
| Cross Reactivity with Hemoglobin Derivatives: No interference from Acetylated Hb, Carbamylated Hb, or Labile A1c at tested concentrations. | ||
| Hemoglobin Variant Interference: No significant interference observed for HbC (≤ 40%), HbD (≤ 43%), HbS (≤ 42%), HbE (≤ 30%), HbA2 (≤ 6.2%) and HbF (≤33%) at concentrations tested. | ||
| Method Comparison (Accuracy vs. NGSP Reference) | Based on CLSI EP09c 3rd Edition. Acceptable regression analysis (Deming, Passing-Bablok) and Total Error (TE) values near clinical decision points, showing good agreement with a standardized reference method. | Whole Blood Mode: |
| Deming Regression: y-Intercept 0.0004, Slope 1.0074 (95% CI for slope includes 1). | ||
| Passing-Bablok Regression: y-Intercept 0.0500, Slope 1.0000 (95% CI for slope includes 1). | ||
| Total Error (TE) at key HbA1c levels for Whole Blood Mode: 2.44% to 4.15% (depending on method and level). | ||
| Dilution mode data: | ||
| Deming Regression: y-Intercept 0.1940, Slope 0.9894. | ||
| Passing-Bablok Regression: y-Intercept 0.1000, Slope 1.0000. | ||
| Total Error (TE) at key HbA1c levels for Dilution Mode: 2.27% to 5.70% (depending on method and level). | ||
| Correlates well with current cleared methods and NGSP standardized testing. | ||
| Traceability | To international and national standardization programs (IFCC, NGSP, DCCT). | Device standardization is traceable to IFCC reference calibrators and certified via NGSP Program. Results are provided in both NGSP (%) and IFCC (mmol/mol) units using the Master Equation. |
| Measuring Interval/Reportable Range | The device should accurately measure within its claimed range. | Claimed: 3.0% to 15.0% (NGSP) and 9.3-140.5 mmol/mol (IFCC). Linearity study results support this claimed measuring range. |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Precision/Reproducibility:
- Four K2-EDTA whole blood samples (at concentrations near 5%, 6.5%, 8%, and 12% HbA1c) and two-level quality control products were used.
- For each sample, there were 720 measurements (analyzed in duplicate, twice a day, with three lots of reagents, over 20 non-consecutive days, on three analyzers).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the study design follows laboratory testing standards (CLSI guidelines), suggesting well-controlled, likely prospective, laboratory-based experiments.
-
Linearity:
- Eleven test samples (high, low, and 9 intermediate levels) were used. These were altered patient samples collected using K2-EDTA.
- Each was run three times with 3 lots of reagents on one instrument.
- Data Provenance: Not explicitly stated. Likely laboratory-prepared and tested.
-
Analytical Specificity (Interference):
- Endogenous Interference: Two EDTA whole blood sample pools (low (~6.5% HbA1c) and high (~8.0% HbA1c)). Ten replicates of each pool prepared with test and control samples were analyzed.
- Drug Interference: Two EDTA whole blood sample pools (low (~6.5% HbA1c) and high (~8.0% HbA1c)). Ten replicates of each drug prepared with test and control samples were analyzed.
- Hemoglobin Derivatives: Low (~6.5% HbA1c) and high (~8.0% HbA1c) whole blood EDTA samples. Each sample was analyzed using ten replicates.
- Hemoglobin Variant Interference:
- Study #1: 67 variant samples (HbS=11, HbC=10, HbD=13, HbE=12, HbA2=10, HbF=11).
- Study #2: 143 variant samples (HbS=25, HbC=25, HbD=25, HbE=25, HbA2=20, HbF=23).
- Samples were whole blood EDTA patient variant samples.
- Data Provenance: Not explicitly stated for endogenous/drug/derivative interference. For hemoglobin variants, they were "patient variant samples." It is implied these were collected and tested specifically for the study, likely in a controlled laboratory setting.
-
Method Comparison:
- 124 variant-free whole blood K2-EDTA samples.
- The distribution of samples spanned around clinical decision points (e.g., 25% of samples between 6-6.5%, 24.19% between 6.5-7%).
- Data Provenance: Not explicitly stated. The samples were patient samples. Given the nature of an FDA 510(k) submission, these would typically be from a well-defined cohort, likely retrospective collections or prospectively collected samples in a controlled clinical laboratory or research setting. The comparison was made against a "NGSP Secondary Reference Laboratory," implying adherence to established quality and calibration standards.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not provided in the given text. For an in vitro diagnostic device for HbA1c, the "ground truth" for the test set is established by the reference methods themselves (e.g., NGSP Secondary Reference Laboratory using a previously cleared HPLC HbAlc assay method - BIO-RAD D-100 analyzer, and other reference methods like Trinity Biotech Premier Hb9210, Bio-Rad VARIANT II Hemoglobin Testing System, and Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 for variant studies). The accuracy of these reference methods is inherent in their standardization and certification, rather than requiring expert adjudication of individual results as one might see in imaging studies.
4. Adjudication Method for the Test Set
Since the ground truth is established by well-defined and certified reference laboratory methods (e.g., NGSP Secondary Reference Laboratory using HPLC), there is no human adjudication method described or typically required for this type of quantitative diagnostic device. The comparison is purely analytical, comparing the numerical output of the candidate device to the numerical output of the reference method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study was done. MRMC studies are typically performed for devices where human interpretation is a critical part of the diagnostic process, such as medical imaging AI algorithms (e.g., radiologists reading images with and without AI assistance). This device is a quantitative in vitro diagnostic test, meaning the output is a numerical value directly from the instrument, not an interpretation by a human reader. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
This entire submission describes a standalone performance study of the device. The "Medconn Glycated Hemoglobin Test System" is an automated analytical system (analyzer plus reagents) that provides a quantitative result. Its performance evaluation (precision, linearity, interference, method comparison) is based on the result produced by the device itself, without human intervention in the interpretation of the final HbA1c value.
7. The Type of Ground Truth Used
The ground truth used for performance evaluation is established through:
- Certified/Standardized Reference Laboratory Methods: For the method comparison study, the samples were compared to results obtained by a "NGSP Secondary Reference Laboratory using a previously cleared HPLC HbAlc assay method (BIO-RAD D-100 analyzer)." For hemoglobin variant interference studies, comparison was made to reference methods "demonstrated to be free from interference with the hemoglobin variant being tested (Trinity Biotech Premier Hb9210, Bio-Rad VARIANT II Hemoglobin Testing System and Tosoh Automated Glycohemoglobin Analyzer HLC-723G8)."
- A Priori Known Values/Controlled Samples: For precision, linearity, and interference studies, ground truth is established by the careful preparation of samples with known or targeted concentrations (e.g., spiked samples, diluted samples, or control materials with assigned values).
This is a quantitative analytical ground truth established by established and validated laboratory methodologies, not expert consensus (as in clinical diagnosis from imaging), pathology (as in histopathology), or long-term outcomes data.
8. The Sample Size for the Training Set
The concept of a "training set" is not explicitly applicable in the context of this 510(k) submission for a traditional in vitro diagnostic device like an HbA1c assay. This device is based on a chemical/physical separation principle (HPLC) and established analytical methodologies, not machine learning or artificial intelligence algorithms that inherently require training data sets. The performance data presented (precision, linearity, interference, method comparison) constitutes analytical validation, not the evaluation of a "trained" model.
9. How the Ground Truth for the Training Set Was Established
As noted above, there isn't a "training set" in the machine learning sense for this device. The underlying principles and calibration of the HPLC system and assay kits are established through standard chemical and metrological practices, traceable to international reference materials and methods (IFCC, NGSP, DCCT). This traceability and analytical validation inherently serve the purpose equivalent to ensuring the "accuracy" or "correctness" of the system's measurements.
§ 862.1373 Hemoglobin A1c test system.
(a)
Identification. A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA.
(2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following:
(i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable.
(ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method.
(iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent.
(iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
(3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.