(186 days)
The CAPI 3 Hb A1c kit is designed for separation and quantification of the HbA1c glycated fraction of hemoglobin in venous whole human blood, by capillary electrophoresis in alkaline buffer (pH 9.4) with the CAPILLARYS 3 TERA instrument. Measurement of hemoglobin A1c is effective in monitoring long-term glycemic control in individuals with diabetes mellitus. This test is not for screening or diabetes. The CAPI 3 Hb A1c kit is designed for Professional Use Only.
The Multi-system Hb A1c CAPILLARY Controls (2) are designed for the migration control and quality control of human glycated hemoglobin Alc quantification with SEBIA capillary electrophoresis procedures:
- CAPILLARYS Hb A1c performed with the CAPILLARYS 2 FLEX-PIERCING automated instrument,
- CAPI 3 Hb Alc performed with the CAPILLARYS 3 TERA automated instrument and,
- MINICAP Hb A1c performed with the MINICAP FLEX-PIERCING automated instrument.
The Hb Alc CAPILLARY Controls are designed for Professional Use Only.
For In Vitro Use.
The CAPILLARYS 3 TERA instrument uses the principle of capillary electrophoresis in free solution. With this technique, charged molecules are separated by their electrophoretic mobility in an alkaline buffer with a specific pH. Separation occurs according to the electrolyte pH and electroosmotic flow.
The CAPILLARYS 3 TERA instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses of HbA1c quantification in a whole blood sample. A sample dilution with hemolysing solution is prepared and injected by aspiration at the anodic end of the capillary. A high voltage protein separation is then performed and direct detection of the hemoglobins is made at the cathodic end of the capillary at 415 nm, which is the absorbance wave length specific to hemoglobins. Before each run, the capillaries are washed with a wash solution and prepared for the next analysis with buffer.
Direct detection provides accurate relative quantification of individual hemoglobin A1c fraction. In addition, the high resolution of CAPI 3 Hb A1c procedure allows the quantification of HbA1c even in the presence of labile HbA1c, carbamylated and acetylated hemoglobins, and major hemoglobin variants.
By using an alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: A2/C, E, S/D, F, A0, other Hb (including minor Hb A1) and then A1c.
The provided document describes the Sebia CAPI 3 Hb A1c kit and the MULTI-SYSTEM Hb A1c CAPILLARY Controls (2), which are devices used for the separation and quantification of the HbA1c glycated fraction of hemoglobin. The document presents performance data primarily related to analytical precision and accuracy, rather than a clinical study with human readers or ground truth established by experts in a diagnostic context.
Here's an analysis based on the categories requested:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria mentioned are implicitly derived from the reported performance, as specific quantitative criteria are not explicitly stated for all aspects (e.g., a target CV for precision). However, the study aims to demonstrate that the device performs within acceptable analytical limits for precision and accuracy.
| Performance Characteristic | Acceptance Criteria (Implicit from Industry Standards/Predicate Device) | Reported Device Performance (CAPI 3 Hb A1c) |
|---|---|---|
| Precision | Low coefficient of variation (CV%) for both mmol/mol and % HbA1c across various experimental factors (within-capillary, between-capillary, between-run, between-day, between-lot, between-instrument). | Overall Total Reproducibility CV%: |
- mmol/mol: 0.9% - 2.3%
- Percentage: 0.7% - 1.3%
(Specific CVs are provided across different factors and instruments, demonstrating consistently low variability). |
| Linearity | Linear response across the measuring range. | Linear within the stated measuring range of 21-132 mmol/mol (4.0% - 14.7% HbA1c) and for total hemoglobin concentrations from 2.9 to 30.5 g/dL. |
| Accuracy (Internal Correlation) | High correlation (correlation coefficient close to 1) and a slope close to 1 with a y-intercept close to 0 when compared to a NGSP-standardized method. | Correlation Coefficient: 0.998 for both concentration and percentage.
Y-Intercept: -0.238 (mmol/mol), -0.024 (%).
Slope: 1.000 for both. |
| Accuracy (External Correlation - Study 1) | High correlation (correlation coefficient close to 1) and a slope close to 1 with a y-intercept close to 0 when compared to a NGSP-standardized method. | Correlation Coefficient: 0.998 (mmol/mol), 0.997 (%).
Y-Intercept: 0.249 (mmol/mol), 0.045 (%).
Slope: 0.993 (mmol/mol), 0.992 (%). |
| Accuracy (External Correlation - Study 2) | High correlation (correlation coefficient close to 1) and a slope close to 1 with a y-intercept close to 0 when compared to a NGSP-standardized method. | Correlation Coefficient: 0.998 (mmol/mol), 0.998 (%).
Y-Intercept: 1.417 (mmol/mol), 0.205 (%).
Slope: 0.970 (mmol/mol), 0.968 (%). |
| Interference | No significant interference from common factors. | No interference detected from high concentrations of various substances/factors (Triglycerides, Bilirubin, Ascorbic Acid, Urea, Rheumatoid factor, Glybenclamide, Total Protein, Glucose, Acetylsalicylic acid, Acetaminophen, Ibuprofen, Metformin, Acetylated hemoglobin, Carbamylated hemoglobin, Labile HbA1c, Hb A2, Hb F, Hb S, Hb C, Hb D, Hb E). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set: 8 different blood samples (3 normal HbA1c, 1 near cut-off, 4 elevated HbA1c). These samples were run extensively: each in duplicate on two capillaries per run, two runs per day over six days per lot of CAPI 3 Hb A1c kit, using three lots, yielding a total of 432 results per sample over 18 days. The provenance of these blood samples (e.g., country of origin, retrospective/prospective) is not specified in the provided text.
- Linearity Test Set:
- Mixture of 2 different blood samples (normal and elevated HbA1c) in different proportions, analyzed in triplicate.
- Dilution of 4 different blood samples (1 normal, 1 near cut-off, 2 elevated HbA1c), serially diluted.
Provenance not specified.
- Accuracy (Internal Correlation) Test Set: 100 blood samples (normal and elevated HbA1c levels). Provenance not specified.
- Accuracy (External Correlation - Study 1) Test Set: 175 blood samples (normal and elevated HbA1c levels). Provenance not specified.
- Accuracy (External Correlation - Study 2) Test Set: 117 blood samples (normal and elevated HbA1c levels). Provenance not specified.
- Combined Accuracy Study Set: 392 whole blood samples (100 internal + 175 external study 1 + 117 external study 2). Provenance not specified, but the studies were likely conducted internally or by contract labs in the company's operational regions (e.g., France, USA given the submitter and manufacturer locations). Retrospective vs. prospective is not explicitly stated, but blood samples were used for testing the device's performance retrospectively to their collection.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable in the context of this device. This device is an in vitro diagnostic (IVD) for quantitative measurement of HbA1c. The "ground truth" for the test set is established by a "commercially available capillary electrophoresis technique for HbA1c quantification that is NGSP standardized," which serves as the reference method. There were no human experts adjudicating diagnostic outcomes based on the device's output.
4. Adjudication Method for the Test Set
Not applicable. As this is a quantitative analytical device, the comparison is against a reference measurement method directly, not through expert adjudication of images or clinical cases.
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. This is an in vitro diagnostic device for automated quantitative measurement, not an AI-powered diagnostic imaging or decision support tool that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies reported are standalone performance studies of the CAPI 3 Hb A1c procedure (kit + CAPILLARYS 3 TERA instrument). It measures HbA1c levels automatically without human interpretation of the measurement itself, beyond loading samples and reviewing the quantitative results.
7. The Type of Ground Truth Used
The ground truth for the accuracy studies was established by a "commercially available capillary electrophoresis technique for HbA1c quantification that is NGSP standardized." This is a reference method, not expert consensus, pathology, or outcomes data in the usual sense of clinical diagnostic studies. NGSP (National Glycohemoglobin Standardization Program) standardization indicates traceability to the Diabetes Control and Complications Trial (DCCT) reference method.
8. The Sample Size for the Training Set
The provided document describes performance evaluation studies (precision, linearity, accuracy, interference) for a finished diagnostic device. It does not mention a "training set" in the context of machine learning or AI algorithm development because the device is a laboratory instrument based on an electrokinetic separation technique (capillary electrophoresis), not a machine learning model that requires training data. Therefore, the concept of a training set as typically understood in AI/ML is not applicable here.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of this device's analytical methodology.
§ 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).