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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:

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.

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The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, 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. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood.

The Hipro® Glycosylated hemoglobin (HbA1c) test system is intended for quantitative determination of % hemoglobin A 1c (DCCT/NGSP) in venous whole blood. It is composed of Glycosylated hemoglobin (HbA1c) test kit and automatic immunoassay analyzer. Glycosylated hemoglobin (HbA1c) test kit consists of two reagents R1 and R2, which are liquid and ready to use. Reagent R1 contains glycine buffer and latex, and reagent R2 contains glycine buffer and two types of antibodies, Goat anti-mouse IgG, mouse anti-human HbAlc monoclonal antibody.

HP-AFS/1 Automatic Immunoassay Analyzer is made up of light absorption test module, scattered light test module, fluorescence test module, press components, data transmission interface and printer. And the absorption test module is made up of absorption light path unit, and lightabsorption sensor part. The scattered light test module is made up of scattered light path unit and scattered light sensor part.

Here's a breakdown of the acceptance criteria and the study details for the Hipro® Glycosylated Hemoglobin (HbA1c) Test System:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for most tests. Instead, it describes performing studies and concluding whether "All acceptance criteria were met" or providing summary statistics. For the purpose of this table, I will infer relevant criteria based on common industry standards for diagnostic devices and the structure of the reported results. For Method Comparison, Total Error, and Linearity, the reported results are directly in line with typical performance metrics. For Interference and Hemoglobin Variants, "met acceptance criteria" and specific thresholds are mentioned.

2. Sample Size Used for the Test Set and Data Provenance

• Precision: Four EDTA K2 whole blood samples with targeted HbA1c concentrations (5.2%, 6.4%, 8.0% and 12.3%) and two controls (6% and 11%). Each sample was analyzed in duplicate per run, two runs per day for 20 days on three analyzers (total of 240 measurements per sample/control).
• Method Comparison: One hundred and twenty (120) samples.
• Linearity: One dilution series consisting of 9 levels. Each level measured in triplicate.
• Endogenous Interference: Pooled whole blood samples with two HbA1c levels, spiked with 5 interferents (10 spiked samples), and one unspiked pool. A 10-level dilution series was created for each. Tested ten-fold.
• Drug Interference: Native patient samples at 2 different HbA1c levels, spiked with 16 drugs at two defined concentrations. Measured ten-fold.
• Hemoglobin Variants: 20 samples for each variant (HbC, HbD, HbE, HbF, HbS, HbA2) for a total of 120 samples. Each sample was tested twice.

Data Provenance:

• Method Comparison: The 120 samples were obtained from the NGSP reference laboratory.
• General: The document does not explicitly state the country of origin or whether samples were retrospective or prospective, but the reliance on the NGSP reference laboratory suggests a standardized, potentially retrospective, approach for the method comparison component. The use of "native patient samples" for drug interference suggests clinical sources.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The establishment of ground truth is primarily through a traceable reference method and a standardization program.

• Method Comparison: The test system was compared against the Bio-Rad Hemoglobin Testing System which was certified by the National Glycohemoglobin Standardization Program (NGSP). The NGSP is a program that standardizes HbA1c results to align with the results of the Diabetes Control and Complications Trial (DCCT). This implies that the 'ground truth' is established by the NGSP's reference methods and processes, rather than individual experts adjudicating each case. The document specifies that the NGSP reference laboratory measured the "X axis" samples.

The document does not specify a number of "experts" in the traditional sense of clinicians or radiologists adjudicating individual cases.

4. Adjudication Method for the Test Set

Not applicable. This is not a study requiring human adjudication of imaging or clinical cases. The "ground truth" is established by a reference laboratory measurement (NGSP Bio-Rad Hemoglobin Testing System) for chemical analysis.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test system for quantitative determination of HbA1c, not a diagnostic imaging or AI-assisted interpretation device that involves human readers.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies described are standalone performance evaluations of the Hipro® Glycosylated Hemoglobin (HbA1c) Test System (the automatic immunoassay analyzer and test kit) without human intervention in the measurement process. The system quantifies HbA1c levels directly.

7. The Type of Ground Truth Used

• Reference Method: For method comparison, the ground truth was established by the NGSP (National Glycohemoglobin Standardization Program) Bio-Rad Hemoglobin Testing System. The device is certified with NGSP.
• Reference Materials: For precision, linearity, interference, and hemoglobin variant studies, the ground truth for HbA1c concentrations was established using characterized samples (e.g., targeted HbA1c concentrations, spiked samples, varying hemoglobin variant concentrations) which would derive their values from established reference methods or known preparations.

8. The Sample Size for the Training Set

The document does not mention a separate "training set" in the context of an AI/ML algorithm that is trained. This device is a chemical assay system, not an AI/ML-based diagnostic. The described studies are all for performance evaluation (test set) of the final device.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no specific "training set" for an AI/ML algorithm mentioned for this device.

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The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c) (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in venous whole blood specimens using ion-exchange high-performance liquid chromatography (HPLC). This test is an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes, and for monitoring of long-term blood glucose control in individuals with diabetes mellitus.

The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is an automated High-Performance Liguid Chromatography (HPLC) system that separates and reports stable hemoglobin A1c (sA1c) percentage in venous whole blood. The operational portion of the G8 is composed of a sampling unit, liquid pump, degasser, column, detector, microprocessors, sample loader, smart media card, operation panel, and a printer. The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 uses ion-exchange HPLC for rapid, accurate, and precise separation of the stable form of HbA1c (sA1c) from other hemoglobin fractions. The G8 uses a non-porous cation exchange column and separates the hemoglobin components in the blood. Separation is achieved by utilizing differences in ionic interactions between the cation and exchange group on the column resin surface and the hemoglobin components in a step gradient elution. The hemoglobin fractions (designated as A1a. A1b. F. LA1c+, SA1c, A0, and, if present, H-V0, H-V2, H-V2 and H-V3) are subsequently removed from the column by performing a step-wise elution gradient using the varied salt concentrations in the Variant Elution Buffers HSi 1, 2 and 3. The peaks, H-V0, H-V1, H-V2 and H-V3 are typically presumptive HbAD, HbAS, HbAC and HbAE respectively. The software compares the retention times of hemoglobin fractions in a sample to the expected "windows of retention" and labels each fraction that correctly elutes within a defined expected window of retention. The software designates a hemoglobin fraction as POX (where X is the order of the peak as it elutes from the column) if it does not match a defined window of retention. All automated processes in the G8 are controlled by internal microprocessors, using software downloaded via a smart media card. The result report is printed and can be stored on the instrument. The data can be transmitted to a host computer through a bi-directional interface. The result report includes the sample ID, date, percentage and retention time of each fraction of hemoglobin, sA1c percentage and total A1 percentage, along with a chromatogram of the elution pattern of the hemoglobin fractions. If a sample contains a hemoglobin variant, the column elutes the fraction depending upon its charge.

The provided text describes the non-clinical performance testing of the Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 (subject device) to support its substantial equivalence to a predicate device. This document focuses on the analytical performance of a diagnostic device rather than an AI/ML powered device, so some of the specific questions regarding AI/ML study design (e.g., number of experts, adjudication methods, MRMC studies) are not applicable.

Here's the information extracted from the document:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the statement "All performance testing results met their pre-determined acceptance criteria." While explicit numerical acceptance criteria for each test are not listed in a consolidated table, the discussion throughout the "Summary of Non-Clinical Performance Testing" implicitly defines them through the methodology and results. For example, for precision/repeatability, the claim of "imprecision at ≤ 2%" was a pre-established criterion. Similarly, for hemoglobin variant interference, "Non-clinically significant interference was defined as

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The ADVIA® Chemistry Enzymatic Hemoglobin A1c (A1c E) assay is an in vitro diagnostic assay for the quantitative determination of mmol/mol HbA1c (IFCC) and % HbA1c (DCCT/NGSP) in human anticoagulated venous whole blood and hemolysate for use on the ADVIA® Chemistry Systems. Measurement of Hemoglobin A1c is used as an aid in the diagnosis and monitoring of long-term blood glucose control in patients with diabetes mellitus, and as an aid in the identification of patients at risk for developing diabetes mellitus.

The ADVIA® Chemistry Enzymatic Hemoglobin A1c (A1c E) assay measures hemoglobin A1c in human anticoagulated whole blood and hemolysate. The assay consists of three reagents (R1, R2, and Pretreatment Solution), which are liquid and ready to use.

The assay offers both an automated and a manual application. The automated application (A1c_E) lyses the anticoagulated whole blood specimen on the system for the automated application (A1c E). Samples may also be lysed manually using the ADVIA® Chemistry A1c_E Pretreatment Solution to obtain hemolysate for the manual application (A1c_EM). The two applications yield the same results.

The provided document is a 510(k) Summary for a medical device called the ADVIA® Chemistry Enzymatic Hemoglobin A1c (A1c E) Assay. This document describes a submission seeking FDA clearance for a modification to an existing device, specifically to extend the low end of the analytical measuring range of total hemoglobin (tHb).

However, the document does not contain the detailed study results, acceptance criteria tables with performance data, information on sample sizes for test and training sets, expert qualifications, or adjudication methods that would be typically found in a comprehensive study report proving a device meets acceptance criteria.

The 510(k) Summary states that "Performance data were needed to evaluate the change" and "The verification study of linearity was done in accordance with the CLSI standard recognized by the FDA. This study along with other verification activities demonstrate equivalent performance to the predicate and effective risk mitigations. The studies met pre-determined acceptance criteria." and "Testing verified all acceptance criteria were met."

While these statements confirm that studies were conducted and met acceptance criteria, the specific details requested in your prompt (e.g., the actual table of acceptance criteria vs. performance, sample sizes, expert involvement, etc.) are not present in this summary document.

Therefore, I cannot provide the requested information from this document. To answer your prompt, I would need a more detailed study report or clinical trial summary that includes the actual performance data and study design specifics.

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The Tina-quant Hemoglobin A1cDx Gen.3 assay is intended for use as an aid in diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes. It is an in vitro diagnostics reagent system intended for quantitative determination of mmol/mol hemoglobin A1c (IFCC) and % hemoglobin A1c (DCCT/NGSP) in hemolysate or venous whole blood on the cobas c 503 clinical chemistry analyzer. HbA1c determinations are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.

Tina-quant Hemoglobin A1cDx Gen.3 assay is an in vitro diagnostics reagent system intended for quantitative determination of mmol/mol hemoglobin A1c (IFCC) and % hemoglobin A1c (DCCT/NGSP) in hemolysate or whole blood on the cobas c 503 clinical chemistry analyzer. The assay offers separate applications that are specific to the sample types whole blood and hemolysate. The Whole Blood Application differs from the Hemolysate Application in the hemolyzing step. For the Whole Blood Application, whole blood samples are placed on the analyzer and hemolysis occurs onboard the analyzer. For the Hemolysate Application, hemolyzed samples are placed on the analyzer and hemolysis occurs manually before placing the samples onboard the analyzer. The two applications yield the same results. Hemolyzing reagent is part of the test system and is either placed on board the analyzer for the Whole Blood Application or used manually for the Hemolysate Application. Anticoagulated whole blood is hemolyzed either manually or automatically prior to determination of HbAlc by a turbidimetric inhibition immunoassay. Liberated hemoglobin (Hb) in the hemolyzed sample is converted to a derivative having a characteristic absorption spectrum and measured bichromatically. The instrument calculates the % HbAlc from the HbAlc/Hb ratio according to a user selected protocol, either IFCC or NGSP protocols.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary for the Tina-quant Hemoglobin A1cDx Gen.3:

1. A table of acceptance criteria and the reported device performance

The document doesn't explicitly state "acceptance criteria" as a single, consolidated table with pass/fail thresholds. Instead, it presents various performance studies and their results. The implicit acceptance criteria are that the device's performance metrics are acceptable for its intended use and comparable to or better than the predicate device.

Here’s a table summarizing the reported device performance for key metrics:

• Reproducibility (total CV%): Most samples/controls show CV% between 1.0% and 1.9%.
• Repeatability (CV%): Most samples/controls show CV% between 0.4% and 0.6%.
  Whole Blood Application:
• Reproducibility (total CV%): Most samples/controls show CV% between 1.2% and 1.6%.
• Repeatability (CV%): Most samples/controls show CV% between 0.4% and 0.8%. |
  | Limit of Blank (LoB) | Detection limit sensitive enough for clinical application. | Hb LoB: 0.0530 mmol/L (0.085 g/dL)
  HbA1c LoB: 0.0220 mmol/L (0.035 g/dL)
  This corresponds to 15 mmol/mol (IFCC) and 3.5% HbA1c (DCCT/NGSP) at 13.2 g/dL Hb. |
  | Limit of Detection (LoD) | Detection limit sensitive enough for clinical application. | Hb LoD: 0.119 mmol/L (0.192 g/dL)
  HbA1c LoD: 0.0437 mmol/L (0.07 g/dL)
  This corresponds to 22 mmol/mol (IFCC) and 4.2% HbA1c (DCCT/NGSP) at 13.2 g/dL Hb. |
  | Linearity/Reportable Range | Linear response across the claimed measuring range. | Hemoglobin (Hb): 4 – 40 g/dL (2.48 – 24.8 mmol/L)
  HbA1c: 0.3 – 2.6 g/dL (0.186 – 1.61 mmol/L)
  This corresponds to a measuring range of 23-196 mmol/mol HbA1c (IFCC) and 4.2-20.1% HbA1c (DCCT/NGSP).
  Empirical First Order Regression: Pearson's r for Hb = 0.9999, HbA1c = 0.9990. |
  | Endogenous Interferences | No significant interference from common endogenous substances at specified concentrations. | Demonstrated claimed maximum concentrations without interference for: Bilirubin (60 mg/dL), Ditaurobilirubin (60 mg/dL), Lipemia (400 mg/dL), Rheumatoid Factors (750 IU/mL), Total Protein (21 g/dL), Albumin (60 g/L), Immunoglobulin (IgG) (60 g/L), Glucose (1000 mg/dL), Triglycerides (1584 mg/dL). A percent deviation criteria was used (not explicitly stated but implied to be within acceptable limits). |
  | Cross-Reactivity | No significant cross-reactivity with specified hemoglobin fractions and glycated albumin. | Max Whole Blood Cross-Reactant Concentration with no Interference: HbA0 (120 g/dL), HbA1(a+b) (0.96 g/dL for Level 1, 1.6 g/dL for Level 2), Carbamylated Hb (2.0 g/dL), Acetylated Hb (2.0 g/dL), Glycated Albumin (10 g/dL), Labile HbA1c (1000 mg/dL).
  Note: Specimens with >7% HbF may yield lower than expected HbA1c values. |
  | Hemoglobin Variants | Accurate results for common hemoglobin variants (HbS, HbC, HbE, HbD, HbA2) within acceptable bias. | Relative % Bias from Reference Method at Low (around 6.5%) and High (around 9%) HbA1c:
• HbS: -2.5% (Low), -4.0% (High)
• HbC: -3.9% (Low), -6.0% (High)
• HbE: -0.1% (Low), -1.2% (High)
• HbD: -1.8% (Low), -2.6% (High)
• HbA2: -1.0% (Low), 0.4% (High)
  Note: Specimens with >7% HbF may yield lower than expected HbA1c values. |
  | Exogenous Interferences (Drugs) | No significant interference from a list of commonly used drugs at specified concentrations. | No significant interference reported for 18 listed drugs (N-Acetylcysteine, Acetylsalicylic acid, Ampicillin-Na, Ascorbic acid, Cefoxitin, Heparin, Levodopa, Methyldopa + 1.5, Metronidazole, Doxycyclin, Rifampicin, Gammagard, Cyclosporine, Phenylbutazone, Acetaminophen, Ibuprofen, Theophylline, Tolbutamide) at tested concentrations. |
  | Sample Matrix Comparison | Acceptable agreement across different anticoagulants and fill levels. | Mean Difference for K2-EDTA, K3-EDTA, Na Heparin, Li Heparin, NaF/Potassium oxalate, EDTA/Fluoride at full and half-full tubes indicate close agreement (e.g., -0.026 to 0.019). Upper and Lower 95% CIs are provided (e.g., -0.181 to 0.172). |
  | Method Comparison | Good agreement with the NGSP reference method (Tosoh Automated Glycohemoglobin Analyzer HLC-723G8). | Whole Blood Application: Mean bias vs. NGSP TOSOH = -0.046%.
  Hemolysate Application: Mean bias vs. NGSP TOSOH = 0.046%.
  Bias at concentrations: (e.g., 5% HbA1c: WB -2.4%, Hemolysate 0.6%; 12% HbA1c: WB 0.7%, Hemolysate 1.2%). |
  | Total Error (TE) | Total Error within clinical requirements, considering both bias and precision. | Hemolysate Application: TE ranging from 3.0% to 4.4% across HbA1c levels.
  Whole Blood Application: TE ranging from 3.1% to 5.2% across HbA1c levels. |

2. Sample size used for the test set and the data provenance

• Precision (Repeatability and Intermediate Precision):

  • Sample Size: 10 samples (2 controls, 8 human samples) for each application (Hemolysate and Whole Blood). Measured for 21 days.
  • Data Provenance: Human samples and controls mentioned. No specific country of origin is stated, but implied to be laboratory-based testing. Prospective study design.

• Analytical Sensitivity (LoB, LoD):

  • Sample Size:
    • LoB: One analyte-free sample. 60 measurements per lot across 3 lots.
    • LoD: Five unique human samples with low-analyte concentrations. 60 measurements per lot across 3 lots.
  • Data Provenance: Human samples mentioned. Laboratory-based testing. Prospective study design.

• Linearity/Assay Reportable Range:

  • Sample Size: Separate dilution series (at least eleven levels) prepared from human hemolysate sample pools.
  • Data Provenance: Human hemolysate samples. Laboratory-based testing. Prospective study design.

• Endogenous Interferences:

  • Sample Size: Pooled whole blood samples at two HbA1c levels, spiked with 9 different interferents. 18 spiked samples + interferent-free pools. Each tested in ten-fold.
  • Data Provenance: Pooled whole blood samples. Laboratory-based testing. Prospective study design.

• Cross-Reactivity:

  • Sample Size: Not explicitly stated as a number of unique samples, but rather a "series of experiments" with specific cross-reactants. Ten replicates of each sample were analyzed for each dilution level.
  • Data Provenance: Laboratory-based testing using prepared samples to introduce cross-reactants. Prospective study design.

• Hemoglobin Variants:

  • Sample Size: 30 HbS, 30 HbC, 30 HbE, 29 HbD, 15 HbA2, 19 Elevated HbF. Total = 153 samples.
  • Data Provenance: Not specified, but implied to be characterized patient samples containing the variants. Laboratory-based testing. Prospective.

• Exogenous Interferences (Drugs):

  • Sample Size: Hemolysate samples at two HbA1c levels, spiked with 18 common drugs at two concentrations. Each drug/concentration combination tested in ten-fold.
  • Data Provenance: Hemolysate samples and spiked drugs. Laboratory-based testing. Prospective study design.

• Sample Matrix Comparison:

  • Sample Size: At least 40 samples of each anticoagulant type (e.g., K2-EDTA, K3-EDTA, Na Heparin, Li Heparin, NaF/Potassium oxalate, EDTA/Fluoride) at full and half-filled tubes. Samples from one donor for full/half-filled comparisons.
  • Data Provenance: Human donor samples. Laboratory-based testing. Prospective study design.

• Method Comparison:

  • Sample Size: 171 whole blood samples and 173 hemolysate samples.
  • Data Provenance: Samples from a "secondary NGSP reference laboratory." This suggests these are clinical samples that have been previously characterized by a gold standard (NGSP certified) method. The nature (retrospective/prospective clinical samples) is not explicitly stated but is consistent with a clinical validation using real patient samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not describe the use of human experts to establish ground truth in the way one would for image-based diagnostic AI. This device is an in vitro diagnostic (IVD) reagent system for quantifying a biomarker (HbA1c).

• Ground truth for the performance studies (e.g., precision, linearity, interferences) is established through:
  • Reference materials (e.g., controls like PreciControl HbA1c norm/path).
  • Dilution series from characterized sample pools.
  • Spiking experiments with known concentrations of interferents or cross-reactants.
• For Hemoglobin Variants and Method Comparison:
  • The "ground truth" or reference method is the NGSP Tosoh HPLC system. This system undergoes certification by the National Glycohemoglobin Standardization Program (NGSP) and is considered a highly accurate laboratory assay method, not dependent on human expert interpretation of a result. No individual human expert counts or qualifications are reported for establishing these reference values.

4. Adjudication method for the test set

Not applicable. This is an IVD device, not an AI or imaging diagnostic device that typically requires expert adjudication for ground truth establishment. The performance is assessed by comparing results to established reference methods, spiked concentrations, or statistical analysis of replicates.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. The Tina-quant Hemoglobin A1cDx Gen.3 assay is an in vitro diagnostic (IVD) device for quantitative determination of HbA1c. It does not involve human readers interpreting images or data with or without AI assistance. It provides a numerical result.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the studies described are all standalone (algorithm only) performance evaluations. The device autonomously measures HbA1c and Hb concentrations, calculates the ratio, and reports the final HbA1c result. There is no human intervention in the result generation process once the sample is loaded onto the analyzer.

7. The type of ground truth used

The ground truth used in various parts of the study consists of:

• Reference Methods: The NGSP Tosoh HPLC system for method comparison, which is a recognized standardized method for HbA1c determination.
• Certified Reference Materials/Controls: PreciControl HbA1c norm and path with assigned values.
• Known Concentrations: For linearity, LoB, LoD studies, the "truth" is derived from preparing samples with known concentrations or by statistical analysis of repeat measurements of low/negative samples.
• Spiked Samples: For interference and cross-reactivity studies, the "truth" is the un-spiked sample value, and the effect is measured by deviation after adding a known amount of interferent.
• Characterized Patient Samples: For hemoglobin variant testing, samples from patients known to carry specific hemoglobin variants were used.

8. The sample size for the training set

This document does not describe a "training set" in the context of machine learning or AI. The Tina-quant Hemoglobin A1cDx Gen.3 is a reagent system for a well-established immunoassay technique. Its development involved chemical and assay optimization, not machine learning model training.

9. How the ground truth for the training set was established

Not applicable, as there is no mention or indication of a machine learning "training set" for this IVD device. The assay's analytical principles are based on turbidimetric inhibition immunoassay (TINIA) and bichromatic photometric determination, which are traditional chemical analysis methods, not AI-driven algorithms requiring training data.

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The HbA 1c (Hemoglobin A 1c) Advanced assay on the Beckman Coulter DxC700 AU Clinical Chemistry Analyzer, is intended for the quantitative determination of mmol/mol HbA1c (DCCT/NGSP) concentration in human venous whole blood. The determination of HbA1c is used as an aid in the diagnosis of diabetes mellitus, for the monitoring of long-term glucose control in individuals with diabetes mellitus and identifying patients who may be at risk for developing diabetes mellitus. For in vitro diagnostic use only.

The HbA1c Advanced reagent kit is in a liquid format and is ready to use. It contains four reagents HbA1c R1 and HbA1c R2, Total Hemoglobin R1 and Hemolyzing reagent R1. The HbA1c calibrator is supplied with the reagent, in a liquid, ready to use format and contains 5 x 2mL calibrator levels. The sample hemolysis is automated on the DxC700 AU Clinical Chemistry analyzer. Sample handling is performed as follows: 200 uL of hemolyzing reagent is aspirated from the Hemolyzing Reagent R1and dispensed into a cuvette. Tetradecyltrimethylammonium bromide (TTAB) in the hemolyzing reagent eliminates interference from leukocytes. 2 µL of whole blood sample is then aspirated from the patient sample and added to the hemolyzing reagent in the cuvette. This hemolyzed whole blood is then added to the THb assay cuvette and HbA1c assay cuvette as per the assay parameters. The concentrations of both HbA1c and Total Hemoglobin are determined. The HbA1c/Total Hemoglobin ratio is expressed either as mmol/mol (IFCC) or %HbA1c (DCCT/NGSP). Total Hemoglobin Reagent is used to measure total hemoglobin concentration by a colorimetric method. Change in absorbance is measured at 570/660 nm. HbA1c reagent is used to measure hemoglobin A1c concentration by a turbidimetric immunoinhibition method. In the reaction, hemoglobin A1c antibodies combine with HbA1c from the sample to form soluble antigen-antibody complexes. Polyhaptens from the reagent then bind with the excess antibodies and the resulting agglutinated complex is measured turbidimetrically. Change in absorbance is measured at 340/700 nm.

Here's an analysis of the acceptance criteria and study details for the HbA1c Advanced device, based on the provided document:

Acceptance Criteria and Device Performance

Study Details

1. Sample size used for the test set and the data provenance:

   • Precision (EP05-A3): Four levels of HbA1c K2 EDTA human venous whole blood patient samples (approx. 5.0%, 6.5%, 8.0%, 12%, and 14%) and two whole blood controls. Samples were analyzed in duplicate, twice daily, over 20 working days on 3 different instrument lots. (n=2 for each sample/control, 2x daily, 20 days: 80 measurements per sample/control per instrument, total for all samples/controls/instruments: 8073 = 1680 individual measurements for precision)
   • Linearity (EP06-A): High and low pools of human whole blood were used to create a linearity series to span the analytical range. The exact number of samples in the linearity series is implied to be at least 9 (N: ≥ 9 for regression parameters).
   • Method Comparison (EP09-A3): 138 venous human frozen whole blood specimens (K2 EDTA anticoagulant type). These were patient samples. The provenance is not explicitly stated as country of origin, but they are referred to as "venous human frozen whole blood specimens." The study design is prospective in the sense that the samples were collected and then tested for the study; it is not explicitly called out as retrospective/prospective.
   • Analytical Specificity (Interference - EP07): Two % HbA1c concentrations (approx. 6.5% and 8.0% HbA1c) using low and high pools prepared from human whole blood. Interfering substances were tested at a minimum of 5 levels each, with 10 replicates per level. The interference assessment was done on human venous whole blood K2 EDTA samples.
   • Hemoglobin Variants: A minimum of 20 samples were tested for each variant (HbC, HbD, HbE, HbF, HbS, HbA2), totaling at least 120 samples. These are patient samples with identified hemoglobin variants.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • For the Method Comparison study, the ground truth was established by an "NGSP Secondary Reference Laboratory (SRL) using a test system (method X - HA8180V HPLC)." The specific number and qualifications of experts at the SRL are not detailed in this document.
   • For Hemoglobin Variants, the reference methods used to establish the ground truth were "Trinity Biotech Hb9210 and Ultra2, Menarini HA8181V and TOSOH G8," which are demonstrated to be free from hemoglobin interference. Again, the number and qualifications of the operators of these reference methods are not specified.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • The document does not describe an adjudication method involving multiple human readers for establishing ground truth. The ground truth for method comparison and hemoglobin variant studies relies on reference methods/laboratories.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No MRMC comparative effectiveness study involving human readers or AI assistance was conducted or described, as this device is an in-vitro diagnostic (IVD) test system (HbA1c assay) and not an imaging AI device that would typically involve human reader interpretation.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, the performance characteristics described are for the "HbA1c Advanced reagent on the DxC 700 AU Clinical Chemistry Analyzer" as a standalone device (algorithm only performance, in a laboratory setting). The entire submission details the analytical performance of the device itself.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Precision: Internal validation against the device's own specifications.
   • Linearity: Internal validation for demonstrating accurate measurement across specific concentration ranges.
   • Method Comparison: Comparison to an NGSP Secondary Reference Laboratory (SRL) standardized method (HA8180V HPLC).
   • Analytical Specificity (Interference): Comparison to baseline measurements of samples without interferents, assessed against a 7% recovery criteria.
   • Hemoglobin Variants: Comparison to reference methods demonstrated to be free from hemoglobin interference (Trinity Biotech Hb9210 and Ultra2, Menarini HA8181V and TOSOH G8).

7. The sample size for the training set:

   • This document describes the analytical validation of a biochemical assay on an automated analyzer. There is no "training set" in the context of machine learning, as the device is a reagent and instrument system, not an AI/ML algorithm that is trained on data. The device's performance is rigorously tested as described above.

8. How the ground truth for the training set was established:

   • Not applicable, as this is not an AI/ML device with a training set. The assay's analytical parameters are established through chemical and immunochemical principles and optimized during development.

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Afinion™ HbA1c Dx is an in vitro diagnostic test for quantitative determination of glycated hemoglobin (% homoglobin Alc, HbAlc) in human venous and capillary whole blood.

This test is to be used as an aid in the diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes.

The measurement of % HbA1c is recommended as a marker of long-term metabolic control in persons with diabetes mellitus.

The Afinion™ 2 System consisting of the Afinion™ 2 Analyser and the Afinion™ Test Cartridges is for in vitro diagnostic use only. The Afinion™ 2 Analyzer is a compact multi-of-care testing and is designed to analyze the Afinion™ Test Cartridges.

The Afinion™ HbA1c Dx test system is a CLIA moderate complexity test for diagnosing diabetes and identifying patients who may be at risk for developing diabetes, as a marker of long-term metabolic control in persons with diabetes mellitus.

The Afinion 2 is a multi-assay analyzer for point-of-care testing, designed for use with Afinion assay test cartridges and Afinion controls. It has the same functionality as the Afinion AS100 analyzer performing identical assay processing.

The provided text describes the 510(k) premarket notification for the Afinion™ HbA1c Dx on Afinion™ 2 device. It focuses on demonstrating substantial equivalence to a predicate device (Afinion™ HbA1c Dx on Alere Afinion™ AS100 Analyzer) rather than explicitly outlining a standalone clinical study for new acceptance criteria.

However, the document states: "Verification and validation studies were performed as required by risk analysis and all acceptance criteria were met." It implies that acceptance criteria were established and subsequently met through these studies. The core of the submission is to show that the modified Afinion 2 analyzer performs equivalently to the previous AS100 analyzer when running the same Afinion HbA1c Dx test.

Based on the provided text, here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document does not explicitly list specific numerical acceptance criteria (e.g., specific accuracy, precision targets) and their corresponding reported device performance values in a table format. Instead, it broadly states that "all acceptance criteria were met" and that the analytical performance was not adversely affected.

However, by comparing the candidate device (Afinion™ HbA1c Dx with Afinion™ 2 analyzer) to the predicate device, we can infer that the acceptance criterion for the new analyzer is to maintain the same performance characteristics as the predicate. The "reported device performance" is the demonstration that its performance is equivalent.

2. Sample Size Used for the Test Set and Data Provenance:

The document mentions "in-house analytical performance verification studies" but does not specify the sample size for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It refers to these as part of "design control activities" to address risk analysis.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:

This information is not provided in the document. The nature of the device (an HbA1c test system) suggests that "ground truth" would likely be based on established reference methods or certified values, rather than expert consensus on images or interpretations.

4. Adjudication Method for the Test Set:

This information is not provided in the document. Given the type of diagnostic test (quantitative determination of glycated hemoglobin), clinical adjudication by experts is unlikely to be the primary method for determining ground truth.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

A MRMC study is typically for evaluating human reader performance, often in image-based diagnostics. This device is an automated in vitro diagnostic test system. Therefore, an MRMC comparative effectiveness study involving human readers is not applicable and was not performed.

6. Standalone (Algorithm Only) Performance:

The entire submission focuses on the performance of the "Afinion™ HbA1c Dx on Afinion™ 2" as a complete system, which is an automated diagnostic test. Therefore, the "standalone" performance is the algorithm's performance integrated into the device, using the specified test cartridges. There is no human-in-the-loop component for the measurement itself. The study details, though not fully disclosed, would pertain to the device operating in this standalone manner.

7. Type of Ground Truth Used:

The document states that the Afinion HbA1c Dx is "traceable to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Reference Method for Measurement of HbA1c" and "certified by NGSP (National Glycohemoglobin Standardization Program)." This indicates that the ground truth for performance evaluation (e.g., accuracy, bias) is established by reference methods and standardization programs rather than expert consensus, pathology, or direct outcomes data.

8. Sample Size for the Training Set:

The document does not provide details on a "training set" or its sample size. This type of device is likely developed and validated using a more traditional analytical validation approach based on measurement science, rather than a machine learning paradigm that typically involves distinct training and test sets. It implies a process of design, calibration, and verification/validation.

9. How Ground Truth for the Training Set Was Established:

As there is no mention of a traditional "training set" in the context of machine learning, this information is not applicable and a method for establishing its ground truth is not provided. The development and calibration of the test would rely on rigorous analytical methods and established reference materials, as indicated by its traceability to IFCC and NGSP certification.

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The Dimension® Hemoglobin A1c assay is an in vitro diagnostic assay for the quantitative determination of %HbA 1c (DCCT/NGSP) and mmol/mol HbA1c (IFCC) in human anticoagulated venous whole blood for use on the Dimension® clinical chemistry system. Measurement of Hemoglobin A1c is used as an aid in diagnosis and monitoring of long-term blood glucose control in patients with diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.

The Dimension® Hemoglobin A1C assay is an in vitro diagnostic device intended to measure the concentration of hemoglobin A1c in venous human anticoagulated whole blood. The assay consists of three reagents packaged in Dimension® Flex® cartridges. The reagents are liquid and ready to use.

The provided text describes the Siemens Healthcare Diagnostics Inc.'s Dimension® Hemoglobin A1c Assay, a Class II medical device for quantitative determination of %HbA1c and mmol/mol HbA1c in human anticoagulated venous whole blood. The document details studies undertaken to demonstrate the device's performance, primarily for a 510(k) premarket notification to show substantial equivalence to a predicate device.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" with numerical targets for each performance characteristic. Instead, it presents study results and, for some criteria, qualitative conclusions (e.g., "No significant interference," "No deviations from linearity"). The assessment of "substantial equivalence" to the predicate device implies that the reported performance meets acceptable clinical standards for HbA1c measurement.

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The SEKURE HbA1c assay is used to measure the percent concentration of hemoglobin A1c (NGSP) or the HbA1c fraction mmol/mol (IFCC) in human venous whole blood and hemolysate on the SK500 Clinical Chemistry System. Measurement of HbA 1c is used as an aid in the diagnosis of diabetes mellitus, as an aid in the identification of patients at risk for development of diabetes mellitus, and for the monitoring of long-term blood glucose with diabetes mellitus. For In Vitro Diagnostic Use Only.

The SEKURE HbA1c assay is an enzymatic assay for the measurement of the percent hemoglobin A1c concentration. The assay consists of a pre-treatment hemolyzing buffer solution and two working reagents. Testing is performed on the SK500 K103531in conjunction with calibrators and controls which will be provided separately.

The SEKURE HbA1c Assay is an in vitro diagnostic device used to measure the percentage concentration of hemoglobin A1c (HbA1c) in human venous whole blood and hemolysate. It's intended to aid in the diagnosis and monitoring of diabetes mellitus. The device's performance was evaluated through various non-clinical studies to demonstrate its substantial equivalence to a predicate device.

1. Acceptance Criteria and Reported Device Performance

Precision (NGSP Units, Whole Blood)

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Afinion™ HbA1c Dx is an in vitro diagnostic test for quantitative determination of glycated hemoglobin (% hemoglobin A1c, HbA1c) in human venous and capillary whole blood.

This test is to be used as an aid in the diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes.

The measurement of % HbA1c is recommended as a marker of long-term metabolic control in persons with diabetes mellitus.

The Afinion™ HbA1c Dx is a fully automated boronate affinity assay for the determination of the percentage of hemoglobin A1c in human whole blood. The Afinion™ HbA1c Dx is a modification of the existing device, Alere Afinion™ HbA1c for use with the Alere Afinion™ AS100 Analyzer, with the addition of a diagnostic intended use.

The test begins with a blood sample collected with the integrated sampling device before the test cartridge is placed in the cartridge chamber of the Alere Afinion™ AS100 Analyzer. The sample is then automatically diluted and mixed with a solution that releases hemoglobin from the erythrocytes. After the hemoglobin is precipitated, the sample mixture is transferred to a blue boronic acid conjugate which binds to the cis-diols of glycated hemoglobin. This reaction mixture is soaked through a filter membrane and all precipitated hemoglobin, conjugate-bound and unbound (i.e. glycated and non-glycated hemoglobin) remains on the membrane. Excess conjugate is removed with a washing reagent. The analyzer measures the reflectance of the precipitate on the membrane as blue (glycated hemoglobin) and red (total hemoglobin) color intensities. The analyzer calculates a ratio proportional to the percentage of HbA1c in the sample and displays as the % HbA1c (NGSP).

The medical device is the Afinion™ HbA1c Dx, a fully automated boronate affinity assay for the determination of the percentage of hemoglobin A1c in human whole blood. It is an in vitro diagnostic test for the quantitative determination of glycated hemoglobin (% hemoglobin A1c, HbA1c) in human venous and capillary whole blood. Its intended use is as an aid in the diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes. It is also used as a marker of long-term metabolic control in persons with diabetes mellitus.

1. Table of Acceptance Criteria and Reported Device Performance

All reported TE values are ≤ 6.0%. |
| Precision/Reproducibility | Not explicitly stated as a single numerical acceptance criteria in terms of SD or CV, but assessed through detailed studies. | Internal (Venous Whole Blood): Total %CV ranged from 1.32% to 1.74% across HbA1c levels and analyzers.
External (Venous Whole Blood): Total %CV ranged from 1.22% to 1.78% across HbA1c levels.
Fingerstick Samples (Combined Studies): Total %CV ranged from 1.30% to 2.03% across HbA1c levels. |
| Linearity/Reportable Range | No specific numerical acceptance criterion stated, but implicitly expected to cover the medical decision range. | Reportable range: 4.00-15.00 % HbA1c (DCCT/NGSP). Previously established in K050574. |
| Endogenous Interference | Significant interference defined as exceeding a 7% change in %HbA1c value from control. | No significant interference observed for tested substances (Bilirubin, Glucose, Intralipid, Rheumatoid factor, Total protein) at specified concentrations. |
| Hemolysis Interference | Significant interference defined as exceeding a 7% change in %HbA1c value from control. | No significant interference observed up to 24% hemolysis. Information codes related to hemolysis may occur above 14% hemolysis. |
| Drug Interference | Significant interference defined as exceeding a 7% change in %HbA1c value from control. | No significant interference observed for 20 tested drugs at specified concentrations. |
| Cross-reactivity with Hemoglobin Derivatives | Significant interference defined as exceeding a 7% change in %HbA1c value from control. | No significant interference observed for Acetylated hemoglobin, Carbamylated hemoglobin, Labile HbA1c, and Glycated albumin at specified concentrations. |
| Hemoglobin Variants Interference | Significant interference defined as exceeding a 7% change in %HbA1c value from reference method. | No significant interference for HbA2, HbS, HbC, HbE, HbD. Significant negative interference with HbF (highest concentration with no significant interference at 10.4% HbF). Device includes a prominent boxed warning for HbF. |

2. Sample Sizes Used for the Test Set and Data Provenance

• Accuracy/Method Comparison Study (Test Set):
  • Sample Size: 120 subjects.
  • Data Provenance: Samples from each study subject were tested with both fingerstick samples and fresh venous EDTA samples. Divided across three study sites. Retrospective or prospective is not explicitly stated, but the collection of fresh venous and fingerstick samples suggests it was prospective. The country of origin of the data is not specified.
• Precision (Internal, Venous Whole Blood): 4 levels of HbA1c patient samples. Each level tested with 2 replicates, twice a day for 20 days with 3 lots on 3 analyzers. (240 measurements per analyzer, 720 combined).
• Precision (External, Venous Whole Blood): 4 levels of HbA1c patient samples. 4 replicates analyzed twice a day for 10 days with 3 lots at each of 3 sites, using 3 analyzers.
• Precision (Fingerstick Samples):
  • Study A (Accuracy study - within-run): 172 subjects (fingerstick samples in duplicate).
  • Study C (Between-instrument and between-operator): 15-16 subjects per HbA1c level (total of 4 levels) across 3 sites. Each subject gave 6 fingerstick samples. Total of 90-96 fingerstick measurements per level.
• Between-Instrument Precision: 4 venous whole blood samples measured in 6 replicates on each of 14 analyzers with 1 test cartridge lot (total of 84 replicates per sample).
• Lot-to-Lot Variation: 18 EDTA venous whole blood samples spanning the reportable range. Each sample analyzed in 1 replicate with each of 3 test cartridge lots on the same analyzer.
• Endogenous/Hemolysis/Drug Interference, Hemoglobin Derivatives Cross-reactivity: Whole blood sample pools. Specific number of samples not given, but tested with 10 replicates for each condition/substance.
• Hemoglobin Variants Interference: 234 fresh EDTA whole blood samples containing 6 common hemoglobin variants. Also, 100 samples for HbA0, HbA1a, HbA1b components.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

• For the Method Comparison study, the ground truth was established by an NGSP secondary reference laboratory method (Tosoh Glycohemoglobin test on the G8 HPLC analyzer). This method itself serves as the "expert" or gold standard. The document does not specify the number or qualifications of human experts involved in operating or verifying this reference method.

4. Adjudication Method for the Test Set

• The document implies that the reference method (Tosoh G8 HPLC) was considered the definitive ground truth for the method comparison study. There is no mention of a human adjudication method (like 2+1 or 3+1 consensus) for the test set results against the reference method. The comparison was statistical, using Deming and Passing-Bablok regressions.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

• This device is an automated in vitro diagnostic test (HbA1c assay). It does not appear to involve "human readers" in the sense of image interpretation or other judgmental tasks where AI assistance might improve their performance. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance is not applicable to this device.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done

• Yes, the performance studies described are for the "algorithm only" (device only) performance. The Afinion™ HbA1c Dx is a fully automated system for determining HbA1c. The performance metrics (precision, accuracy, interference, etc.) reflect the standalone operation of the device.

7. The Type of Ground Truth Used

• The ground truth used for the method comparison and hemoglobin variant interference studies was a reference method, specifically an NGSP secondary reference laboratory method (Tosoh Glycohemoglobin test on the G8 HPLC analyzer). For interference studies, the ground truth was derived from non-spiked control samples or reference samples without the interfering substance.

8. The Sample Size for the Training Set

• The document describes performance characteristics for the Afinion™ HbA1c Dx. It does not provide information on a separate "training set" for an algorithm, as this typically applies to machine learning models. Instead, the device is a chemical assay with established analytical principles. Therefore, a distinct "training set" size in the context of an AI/ML algorithm is not applicable as presented in this document. The "training" or development would refer more to the optimization and validation of the analytical method itself.

9. How the Ground Truth for the Training Set Was Established

• As a chemical assay rather than an AI/ML algorithm, the concept of a "training set" with established ground truth is not applicable in the same way. The device's analytical method (boronate affinity assay) is based on scientific principles and validated through extensive performance testing as detailed in the document, against established reference methods.

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