(263 days)
The HbA1c (Hemoglobin A1c) reagent, when used in conjunction with Beckman Coulter Systems, HbA1c Calibrators, and SYNCHRON and AU Hemolyzing Reagent, is intended for the quantitative determination of hemoglobin A1c concentration in human whole blood. For In Vitro Diagnostic Use only.
The absolute HbA1c and Total Hemoglobin (THb) values generated as part of the HbA1c assay are intended for use in the calculation of the HbA1c/Total Hemoglobin ratio and must be not used individually for diagnostic purposes.
The HbA1c Calibrators is an in vitro diagnostic product for the calibration of the hemoglobin A1c (HbA1c) method on the AU clinical chemistry systems.
Measurement of hemoglobin A1c is accepted as a method to measure long-term glucose control in patients with diabetes mellitus.
The HbA1c assay (B00389) involves the use of four reagents: Total Hemoglobin R1, HbA1c R1, HbA1c R2, and Hemolyzing Reagent (sold separately as Cat. No. 472137). In a pre-treatment step, whole blood is mixed with the Hemolyzing Reagent in a 1 to 100 dilution and the resultant hemolysate is used. Tetradecyltrimethylammonium bromide (TTAB) in the Hemolyzing Reagent eliminates interference from leukocytes.
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 is 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 provided 510(k) summary for the Beckman Coulter AU® Systems HbA1c (Hemoglobin) Test System, broken down by your requested categories:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are established by demonstrating substantial equivalence to a predicate device (SYNCHRON Systems Hemoglobin A1c (HbA1c) Reagent, K010748), primarily focusing on aspects like precision, analytical measuring range, and method correlation. The summary doesn't explicitly state quantitative "acceptance criteria" separate from the "reported device performance," but rather presents the performance data to show it meets or improves upon the predicate.
| Performance Metric | Acceptance Criteria (Implied by Predicate/Regulatory Expectations) | Reported Device Performance (AU Systems HbA1c Test System) |
|---|---|---|
| Precision (Within Run CV%) | ≤ 5.0% for predicate (Within Run) | Control Pool 1 (5.3% HbA1c): 1.44% |
| Control Pool 2 (7.4% HbA1c): 1.03% | ||
| Control Pool 3 (9.4% HbA1c): 1.03% | ||
| Precision (Total CV%) | ≤ 7.5% for predicate (Total) | Control Pool 1 (5.3% HbA1c): 2.07% |
| Control Pool 2 (7.4% HbA1c): 1.84% | ||
| Control Pool 3 (9.4% HbA1c): 1.68% | ||
| Analytical Measuring Range | 2 - 20% HbA1c (Predicate) | 4 - 15% HbA1c (NGSP) / 20 - 140 mmol/mol (IFCC) |
| Method Comparison (Slope vs. Predicate) | Close to 1.0 | 0.901 |
| Method Comparison (Intercept vs. Predicate) | Close to 0 | 0.3140 |
| Method Comparison (Correlation Coefficient R vs. Predicate) | High (e.g., >0.95 or >0.97) | 0.9941 |
| Interfering Substances | No significant interference (within ± 0.80% HbA1c or 10%) for predicate on tested substances (Bilirubin, Lipemia, RF, Ascorbic acid, Labile glycated hemoglobin) | Bilirubin ≤6% up to 30 mg/dL |
| Lipemia ≤6% up to 400 mg/dL Intralipid® | ||
| RF ≤6% up to 1000 IU/mL | ||
| Ascorbic Acid ≤6% up to 50 mg/dL | ||
| Labile glycated hemoglobin ≤10% up to 2000 mg/dL (5 hours at 37°C) | ||
| Sensitivity (LoB/LoD) | Defined for predicate (e.g., Total Hb 6 g/dL, A1c 0.3 g/dL) | THb: LoB = 0.05 mmol/L (0.09 g/dL); LoD = 0.10 mmol/L (0.16 g/dL) |
| HbA1c: LoB = 0.12 mmol/L (0.19 g/dL); LoD = 0.13 mmol/L (0.22 g/dL) |
Notes on Acceptance Criteria:
- The summary explicitly states: "Performance data within the submission supports improved precision and substantial equivalence of the new test system." This indicates that the new device's precision (Total CV% of ≤4.0% vs. predicate's ≤7.5%) is better than the predicate, thus meeting and exceeding the implicit acceptance criteria inferred from predicate performance.
- For the Analytical Measuring Range, the new device has a slightly different range (4-15% vs 2-20%), but the method comparison and linearity data are reported to support extending the range on the AU HbA1c.
- For Interfering Substances and Sensitivity, the data presented also aims to demonstrate "substantial equivalence and new claim."
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison Study:
- Sample Size: N = 130
- Data Provenance: Not explicitly stated (e.g., country of origin). Typically, clinical samples for such studies are collected prospectively or retrospectively from diverse patient populations within a single country or region where the testing is intended. The document does not specify if the data was retrospective or prospective, though method comparison studies often utilize a mix of patient samples to cover the analytical range.
- Precision Study:
- Sample Size: 80 data points for each of 3 control pools. This implies multiple replicates over several days or runs to calculate within-run and total precision.
- Data Provenance: Not explicitly stated. Control pools are typically manufactured materials, not patient samples, designed to represent different analyte concentrations.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This type of in vitro diagnostic device (IVD) for HbA1c measurement does not typically rely on "experts" to establish ground truth for individual test samples in the same way an imaging AI device would. Instead, the "ground truth" or reference values are established through:
- Reference Methods: The device's traceability is stated as "IFCC HbA1c Reference Method." This refers to standardized, highly accurate laboratory methods used to assign target values to calibrators and control materials. These reference methods themselves are meticulously developed and validated by expert committees (e.g., IFCC working groups).
- Predicate Device Comparison: For the method comparison study, the "ground truth" for the 130 samples would be the results obtained from the predicate device (SYNCHRON Systems Hemoglobin A1c (HbA1c) Reagent). The predicate device itself would have been validated against IFCC or NGSP (National Glycohemoglobin Standardization Program) reference methods.
Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth for a test set of this nature (chemical assay) is not directly applicable in the same way as for subjective interpretation tasks (like radiology images). The ground truth is rooted in established, standardized analytical methods.
4. Adjudication Method for the Test Set
Not applicable for this type of chemical assay. Adjudication methods (like 2+1, 3+1) are used for resolving disagreements in subjective expert interpretations, which is not relevant for quantitative measurements from an automated analyzer.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI vs. Without AI Assistance
Not applicable. This is an in vitro diagnostic assay, not an AI-assisted diagnostic tool designed to augment human reader performance in a subjective task. There is no "human reader" involved in interpreting the results of the HbA1c test in a way that would necessitate an MRMC study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this is essentially a standalone device performance study. The AU® Systems HbA1c Test System is an automated analyzer designed to provide quantitative results directly from a sample without real-time human interpretive input beyond running the test and validating the instrument's performance. The performance data (precision, method comparison, interference) directly reflects the algorithm/assay's output.
7. The Type of Ground Truth Used
The ground truth for this device's performance studies is based on:
- IFCC HbA1c Reference Method: For traceability and calibration of materials.
- Predicate Device Measurements: For the method comparison study (results from the SYNCHRON Systems HbA1c Reagent).
- Assigned Values for Control Materials: For precision studies, control materials have defined target values established through rigorous testing against reference methods.
8. The Sample Size for the Training Set
Not applicable in the conventional sense of AI/machine learning training sets. This is a traditional chemical assay, not an algorithm that learns from a large dataset. The "training" of such a system involves:
- Method Development & Optimization: Where various reagents, protocols, and instrument settings are empirically optimized.
- Calibration: The system is calibrated using a set of calibrators with established values.
The document doesn't specify a "training set" size as it would for an AI model.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, there isn't a "training set" in the AI sense. However, the ground truth for calibration (which could be considered analogous in its role of establishing the system's accuracy) is established through:
- IFCC HbA1c Reference Method: The calibrators for the AU systems HbA1c assay are traceable to the IFCC Reference Method. This means the values assigned to these calibrators are determined using highly accurate, standardized reference procedures.
- NGSP Certification: The device and its calibrators are NGSP certified, which ensures standardization and traceability to the Diabetes Control and Complications Trial (DCCT) reference method. This involves a rigorous process where manufacturers' methods are compared to the NGSP reference network.
§ 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).