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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 <= 6% relative difference in the results from a comparative method."

It's important to note that the provided text is a 510(k) summary, which often summarizes detailed study reports. The full reports would contain explicit acceptance criteria thresholds.

Table of Acceptance Criteria (Implied) and Reported Device Performance:

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

• Precision/Repeatability Study:
  • Sample Size: Four concentrations of HbA1c% in K2EDTA venous whole blood. A total of 720 measurements per concentration were performed (three analyzers, over 20 non-consecutive days, with three reagent lots, samples run in duplicate, two times per day).
  • Data Provenance: The study was implicitly conducted retrospectively on collected samples. The country of origin is not explicitly stated, but the testing was performed at "Tosoh Bioscience, Inc." laboratories, likely in the US (given the South San Francisco address).
• Method Comparison Study:
  • Sample Size: 220 K₂EDTA venous whole blood specimens with HbA1c concentrations spanning the measuring range (4.0-16.9%). Each specimen was tested in duplicate.
  • Data Provenance: The study was conducted at "two separate sites," one a "moderate complexity clinical laboratory" (for the candidate device) and the other an "NGSP SRL" (for the comparator device). The precise country of origin is not explicitly stated. The specimens were collected and likely used retrospectively for the comparison.
• Endogenous Interfering Substances / Hemoglobin Variant Interference Studies:
  • Sample Size:
    • Endogenous interference: Not explicitly stated per substance, but specimens were "spiked with increasing amounts of the interfering substance."
    • Hemoglobin Variant Interference:
      • HbC: 26 samples
      • HbD: 24 samples
      • HbE: 26 samples
      • HbS: 29 samples
      • HbA2: 20 samples
      • HbF: 21 samples
  • Data Provenance: Not explicitly stated, but implies lab-tested, potentially spiked, and clinical samples from unknown origin (likely retrospective).

3. Number of Experts and Qualifications for Ground Truth:

This device is an automated in vitro diagnostic analyzer for quantitative measurement of HbA1c. The "ground truth" for such devices is typically established by:

• Reference methods (e.g., NGSP SRL certified methods).
• Traceability to international standards (DCCT, IFCC).
• Direct analytical measurements and statistical comparisons, rather than expert consensus on image interpretation.

Therefore, the concept of "number of experts used to establish the ground truth" similar to that in an AI imaging study is not applicable here. The ground truth is the chemical measurement itself, validated against recognized reference standards.

4. Adjudication Method for the Test Set:

Not applicable, as this is an analytical device for quantitative measurement, not an interpretative AI/ML system requiring human adjudication of results. The "adjudication" is through statistical agreement with reference methods and assessment against predetermined analytical performance criteria.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done:

No. An MRMC study is relevant for AI/ML systems that assist human readers in tasks like image interpretation. This device performs automated quantitative measurements, and its performance is evaluated against reference methods and analytical standards, not human readers.

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

Yes, the studies described are standalone performance studies of the device (Tosoh Automated Glycohemoglobin Analyzer HLC-723G8) without human intervention in the measurement process itself. The device is an automated HPLC system.

7. The Type of Ground Truth Used:

The ground truth for evaluating the subject device's performance is based on:

• Reference Methods: Specifically, the NGSP SRL (National Glycohemoglobin Standardization Program Secondary Reference Laboratory) using the Trinity Biotech Premier Hb9210™ HbA1c Analyzer (for method comparison) and Primus Model CLC 330 (for some hemoglobin variant interference testing), and the Bio-Rad VARIANT II TURBO HbA1c Kit - 2.0 (for some hemoglobinopathy interference testing).
• Traceability and Standardization: The device's results are traceable to the Diabetes Control and Complications Trial (DCCT) reference method and IFCC, and it is certified by the NGSP.
• Analytical Standards: For precision, linearity, and interference, the "ground truth" reflects the known concentrations of spiked samples or validated concentrations in patient samples, against which the device's measurements are compared.

8. The Sample Size for the Training Set:

The provided document describes non-clinical performance testing to support substantial equivalence after a software modification (v5.24). It does not provide information on the training set used for the development of the device's algorithms or software. This 510(k) summary is focused on verification and validation of the modified device.

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

This information is not provided in the 510(k) summary. Given that the device is an automated HPLC system, its "training" per se would involve optimization of its operational parameters, calibration curves, and potentially peak detection/integration algorithms, likely using well-characterized samples with known HbA1c concentrations established by reference methods. However, the details of such a "training set" and its ground truth establishment are not discussed here.

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