(175 days)
The AxSYM HbA1c assay is an immunoassay for the quantitative determination of percent hemoglobin A1c (HbA1c) in whole blood samples on the AxSYM System. Percent HbA1c measurements are used in the clinical management of diabetes to assess the long-term efficacy of diabetic control.
The AxSYM HbA1c Standard Calibrators are for the standard calibration of the AxSYM System when used for the quantitative determination of percent HbA1c in whole blood samples.
The AxSYM HbA1c Controls are for the use in quality control to monitor the accuracy and precision of the AxSYM HbA1c assay when used for the quantitative determination of percent hemoglobin A1c (HbA1c) in whole blood samples on the AxSYM System.
For in vitro diagnostic use.
The AxSYM HbA1c assay is an immunoassay for the quantitative determination of percent hemoglobin A1c (HbA1c) in whole blood samples on the AxSYM System. Percent HbA1c measurements are used in the clinical management of diabetes to assess the long-term efficacy of diabetic control.
In the AxSYM HbA1c assay, whole blood sample is lysed, releasing hemoglobin and HbA1c analyte. Lysed sample is added to the glass fiber matrix that has been coated with Blocking Buffer in a previous step. Hemoglobin and HbA1c analyte are captured on the glass fiber matrix by the binding reaction that occurs between the analyte and the Blocking Buffer. HbA1c is quantified by measuring the amount of HbA1c analyte captured on the matrix cell, using a conjuqate of Anti-HbA1c and Alkaline Phosphatase as the signal-generating molecule, and the substrate, 4-Methylumbelliferyl Phosphate (MUP).
The AxSYM HbA1c reagents and sample are pipetted in the following sequence:
SAMPLING CENTER
- The whole blood samples can be processed from AxSYM sample . cups or from primary blood collection tubes (fluoride oxalate and fluoride EDTA). Potassium EDTA blood collection tubes that have undergone a single freeze-thaw cycle may also be processed from AxSYM sample cups or from the primary blood collection tube. Fresh (non-frozen) potassium EDTA primary whole blood collection tubes may be used if testing is performed in STAT mode and run in groups of eight tubes or less. For further instructions on use of potassium EDTA whole blood samples, refer to the SAMPLE COLLECTION AND PREPARATION FOR ANALYSIS section.
The sample and all AxSYM HbA1c reagents required for one test . are pipetted by the Sampling Probe into various wells of a Reaction Vessel (RV).
The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center by the Processing Probe.
PROCESSING CENTER
- The whole blood sample is combined with the Lysis Buffer and . incubated for 450 seconds.
- . The matrix cell is coated with Blocking Buffer.
The lysed sample is diluted with Sample Diluent and transferred to . the matrix cell. Hemoglobin and the HbA1c analyte are captured on the glass fiber matrix through interactions with the blocking buffer overcoat.
- . The matrix cell is washed to remove unbound materials.
- . The Anti-HbA1c:Alkaline Phosphatase Conjugate is dispensed onto the matrix cell and binds to the analyte, forming an antigen-antibody complex.
- . The matrix cell is washed to remove unbound materials.
- . The substrate, 4-Methylumbelliferyl Phosphate, is added to the matrix cell and the fluorescent product is measured by the MEIA optical assembly.
The concentration of HbA1c in the sample is determined using a previously generated calibration curve
Here's a breakdown of the acceptance criteria and the study details for the AxSYM HbA1c device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a numerical or categorical format for performance metrics. Instead, it demonstrates substantial equivalence to a predicate device ("G7 Automated Glycosylated Hemoglobin HPLC Analyzer") by comparing various performance characteristics. The implied acceptance criterion for the clinical performance, therefore, is substantial equivalence to the predicate device.
| Performance Metric | Implied Acceptance Criteria (via Substantial Equivalence to Predicate) | Reported Device Performance (AxSYM HbA1c) |
|---|---|---|
| Precision | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | Demonstrated substantial equivalence |
| Linearity | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | Demonstrated substantial equivalence |
| Interferences | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | Demonstrated substantial equivalence |
| Stability | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | Demonstrated substantial equivalence |
| Bias (Clinical Performance) | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | -0.26% HbA1c (95% CI: -0.32 to -0.20% HbA1c) against HPLC method |
| Passing-Bablok Linear Regression (Slope) | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | 1.02 (95% CI: 0.97 to 1.06) versus HPLC |
| Passing-Bablok Linear Regression (Intercept) | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | -0.35 (95% CI: -0.63 to -0.07) versus HPLC |
| Correlation Coefficient (Pearson r) | Substantially equivalent to G7 Automated Glycosylated Hemoglobin HPLC Analyzer | 0.96 (95% CI: 0.95 to 0.97) versus HPLC |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Test Set: 300 samples were used for the method comparison study.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts:
This information is not provided in the given text. For a device like this (an immunoassay), the "ground truth" is typically established by the predicate device (the G7 Automated Glycosylated Hemoglobin HPLC Analyzer) rather than human expert interpretation of images or other subjective data. Therefore, the concept of "experts" to establish ground truth in the traditional sense for this type of device is not directly applicable.
4. Adjudication Method for the Test Set:
This information is not applicable as the ground truth is established by a reference method (the HPLC analyzer) and not by human experts whose discrepancies would need adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging devices where human readers interpret outputs, and the AI assists that interpretation. The AxSYM HbA1c is an automated immunoassay, and its performance is evaluated against a reference method directly. Therefore, there's no "human readers improve with AI vs without AI assistance" effect size to report.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:
Yes, the performance reported is a standalone (algorithm only) performance. The AxSYM HbA1c assay is an automated immunoassay system. The study compares its quantitative results directly against a predicate automated method (HPLC), without human involvement in the interpretation of the AxSYM HbA1c's output.
7. The Type of Ground Truth Used:
The ground truth used was the results obtained from the predicate device, the G7 Automated Glycosylated Hemoglobin HPLC Analyzer. This constitutes a "reference method" comparison.
8. The Sample Size for the Training Set:
The document does not specify the sample size for a training set. This is typical for an immunoassay that operates based on established chemical reactions and calibration curves, rather than a machine learning model that requires a dedicated training set. The calibration curve is generated using specific calibrators mentioned (AxSYM HbA1c Standard Calibrators), but the sample size for establishing these is not detailed in the summary.
9. How the Ground Truth for the Training Set Was Established:
This information is not explicitly detailed in the document. For an immunoassay, the "ground truth" for calibration (which is analogous to training in a machine learning context) is established through the known concentrations of the AxSYM HbA1c Standard Calibrators used to create the calibration curve. These calibrators would themselves have been precisely characterized, but the method for their characterization is not described in this summary.
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).