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cobas b 101 system: The cobas b 101 instrument is a multi-assay system designed to quantitatively analyze cobas reagent discs. The system is intended for professional, in vitro diagnostic use in a clinical laboratory setting or point-of-care (PoC) locations.

HbA1c test: The cobas HbA1c Test is an in vitro diagnostic test designed to quantitatively determine glycated hemoglobin (HbA1c) in human capillary and venous whole blood on the cobas b 101 instrument. The system is intended for professional use in a clinical laboratory setting or point-of-care (PoC) locations. Measurement of hemoglobin A1c is used to assess the level of control of a patient's diabetes and to monitor long term blood glucose control. Elevated levels of hemoglobin A1c indicate uncontrolled diabetes in a patient.

The cobas b 101 system is a bench top analyzer which measures HbA1c. The system is fully automated, self-contained and utilizes a single use reagent disc. The system has the ability to measure capillary or venous whole blood samples. Sample is applied directly from the fingerstick or via a pipette when testing venous whole blood. The operator simply applies sample to the disc and places the disc in the instrument. There are no pre-analytics needed as the disc is self-filling by capillary forces. There is no intervention by the operator during measurement. At completion of the test, the instrument displays a quantitative result. No calculations or interpretation are required by the operator.

Calibration of the instrument is completed as part of the manufacturing process. Calibration information is contained on each disc and is read when the disc is loaded on the instrument. No calibration intervention is required by the operator.

An optional barcode scanner can be provided to read barcode information for patient identification. The barcode scanner uses LED as the light source. Results can be printed out by using an optional external printer.

A connection to a Data Management System is possible either via a USB interface to a local PC or via an Ethernet converted to a Laboratory Information Management System (LIMS). The communication protocol is defined according to the CLSI approved POCT1-A2 standard.

HbA1c (glycated hemoglobin) can be determined by using samples from capillary blood directly from the fingertip or from venous whole blood with heparin or EDTA (K2 or K3) anticoagulant. The blood sample is diluted and mixed with TRIS buffer to release hemoglobin from the erythrocytes. A fraction of the sample is conveyed into a reaction chamber where it is mixed with sodium lauryl sulfate (SLS). SLS is used to form the SLS-hemoglobin complex. The concentration of total hemoglobin is calculated by measuring SLS-hemoglobin complex with a wavelength of 525 nm. Hemoglobin A1c (HbA1c) in another fraction of the sample is first denaturated by potassium ferricyanide and sucrose laurate. The denatured HbA1c bonds with HbA1c antibody on the latex particle. Latex agglutination inhibition reaction then occurs by reacting the agglutinator that has synthetic antigen which can bond with HbA1c antibody. The concentration of HbA1c is calculated by measuring the latex agglutination inhibition reaction with a wavelength of 625 nm. The % hemoglobin A1c value is measured using a ratio of concentrations of HbA1c to total hemoglobin.

The provided document describes the cobas b 101 system and cobas HbA1c Test, an in vitro diagnostic device for quantitative determination of glycated hemoglobin (HbA1c).

Here's an analysis of the acceptance criteria and the studies performed to meet them:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state a single table of "acceptance criteria" against which all performance metrics are measured. Instead, it discusses various performance evaluations with implicit acceptance criteria (e.g., "no significant interference," "within acceptance criteria," "met the predefined acceptance criteria," "non-significant interference was defined as ≤ 10% difference").

Based on the provided information, I can construct a summary table and highlight what can be inferred as acceptance criteria for those tests:

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

• Precision (Internal): 8 K2EDTA or K3EDTA venous whole blood samples and 2 control samples. Each sample measured 84 times (duplicate in 2 runs per day for 21 days).
• Precision (External): 4 human sample pools and 3 lots of controls. Each assessed 168 times (duplicate 2x/day for 21 days per site), for a total of 504 measurements per sample/control pool combined across 3 sites.
• Linearity/Assay Reportable Range: 11 dilutions of a low (3.6% HbA1c) and high (12.9% HbA1c) K2EDTA whole blood sample. (Number of replicates per dilution not specified but implied to be sufficient for CLSI EP06-A).
• Hemoglobin Linearity: 4 K2EDTA and Li-Heparin venous whole blood samples. For each, a 10-level dilution series (using NaCl as diluent) was prepared and tested in triplicate.
• Endogenous Interferences: Two HbA1c levels (normal and pathological range) for each interferent. Sample pools were K2EDTA venous whole blood. Varying dilutions mixed to create dilution series. (Number of replicates per dilution not specified but implied to be sufficient for CLSI EP07-A2).
• Exogenous Interferences (Drugs): K2EDTA venous whole blood pools. Each sample tested in 5 replicates.
• Cross-Reactivity (Carbamylated Hb, Acetylated Hb, Labile HbA1c): K2EDTA venous whole blood samples at normal and pathological HbA1c levels. Each dilution level tested in singlicate on 3 instruments.
• Cross-Reactivity (HbA0): Approximately 60 K2EDTA whole blood samples.
• Cross-Reactivity (HbA1a, HbA1b): 11 K2EDTA samples of varying HbA1a+b concentrations. Each measured in triplicate on the cobas b 101 instrument.
• Hemoglobin Variants: 130 samples total, covering HbAS (20), HbAC (20), HbAD (20), HbAE (20), Elevated F (20), Elevated A2 (10). Each sample tested once.
• Method Comparison: Capillary whole blood (N=125, 133, 121 per site), EDTA (K2) whole blood (N=125, 133, 121 per site), Lithium Heparin whole blood (N=125, 130, 117 per site). All from prospective blood sampling. Tested in singlicate.
• Matrix Comparison: 91 samples of EDTA (K2) and EDTA (K3) whole blood. Tested in singlicate.

Data Provenance: Most studies use human blood samples, either K2EDTA/K3EDTA venous whole blood or capillary whole blood. The External Precision and Method Comparison studies were conducted at "3 Point-of-Care sites," implying real-world or near-real-world clinical settings, likely within the country where the studies were conducted (not specified, but often the manufacturer's location or major market). The data appears to be prospective for the clinical performance (Method Comparison) as it mentions "prospective blood sampling" and "No contrived samples were tested." For other non-clinical performance studies (e.g., interferences, linearity), samples were prepared according to CLSI guidelines, which may involve spiking or diluting samples to achieve specific concentrations.

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

The document does not mention the use of "experts" to establish ground truth in the traditional sense of consensus reading for image-based diagnostics. For HbA1c measurements, the ground truth is established by reference methods or predicate devices, which are themselves highly standardized and validated laboratory instruments.

• For Method Comparison vs. Reference, the reference method used was the Tosoh G8 HPLC Analyzer. This is a well-established and validated laboratory instrument for HbA1c measurement.
• For Hemoglobin Variants, reference methods were "selected based on no interference for a particular variant." The specific reference methods for each variant are not listed, but they are implied to be established, accurate methods.
• For Cross-Reactivity (HbA0), the reference system was the cobas c 501.

Therefore, the "ground truth" is analytical, derived from established laboratory methods, not expert consensus on qualitative interpretation.

4. Adjudication Method (for the test set)

Not applicable. This device provides quantitative measurements of HbA1c. "Adjudication method" typically refers to how disagreements among multiple human readers are resolved in qualitative or semi-quantitative assessments (e.g., radiology reads). Here, the comparison is against an objective reference measurement.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is primarily relevant for diagnostic imaging or similar scenarios where human readers interpret cases, and the AI's impact on reader performance (e.g., accuracy, efficiency) is evaluated. The cobas b 101 system and cobas HbA1c Test is an in vitro diagnostic device for quantitative chemical analysis, not a device interpreted by human readers in the same manner.

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

Yes, the entire document describes the standalone performance of the cobas b 101 system and cobas HbA1c Test. All the precision, linearity, interference, cross-reactivity, and method comparison studies were performed on the device itself comparing its quantitative output to established reference methods or accepted criteria. There is no human-in-the-loop component in the direct measurement and reporting of HbA1c values by the device. The "user" interaction involves sample application, but the analytical process is fully automated within the instrument.

7. The Type of Ground Truth Used

The ground truth used is primarily analytical measurements from established reference methods.

• Tosoh G8 HPLC Analyzer: Used as the reference method for the main method comparison studies for capillary, EDTA (K2), and Lithium Heparin whole blood.
• cobas c 501: Used as a reference system for HbA0 cross-reactivity.
• Selected reference methods: Used for hemoglobin variant testing.
• Calculated values: For linearity studies and some cross-reactivity studies, target concentrations were prepared by dilution from known high/low samples.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the cobas b 101 system or the cobas HbA1c Test. This is typical for an IVD device like this, which likely uses a rule-based algorithm and/or pre-calibrated sensor systems rather than a machine learning model that requires a distinct training phase. The "calibration information is contained on each disc and is read when the disc is loaded on the instrument," suggesting an internal calibration process defined by the manufacturer rather than a data-driven training set used by the end-user.

If there were any internal development or calibration data used by the manufacturer during the design of the reagent or instrument, it is not disclosed as a "training set" in this 510(k) summary.

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

As no specific "training set" is identified for a machine learning model, this question is not directly applicable. For the development and calibration of the device (if that's considered analogous to "training"), the ground truth would have been established through a rigorous process of using known standards, calibrators, and reference materials, similar to how the "ground truth" for the test set was established (i.e., against established analytical reference methods and validated materials). The document states the "Calibration of the instrument is completed as part of the manufacturing process," implying this process.

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