(167 days)
ACE® Hemoglobin A1c (HbA1c) Reagent is intended for the quantitative determination of hemoglobin A1c (umol/L) and total hemoglobin (g/dL) in human EDTA whole blood for the calculation of percent hemoglobin A 1 c using the ACE clinical chemistry system. This test is intended for use in clinical laboratories or physician office laboratories to monitor long term blood glucose control in individuals with diabetes mellitus. For in vitro diagnostic use only.
The umol HbA1c and total hemoglobin (THb) values generated are intended for use in the calculation of the HbA1c/THb ratio and cannot be used individually for diagnostic purposes.
Hemoglobin A1c Calibrators are intended for use in the performance of both a multi-point calibration for hemoglobin A1c and a single-point calibration of total hemoglobin on the ACE® clinical chemistry system, for the quantitative determination of percent (%) hemoglobin A1c in whole blood. For in vitro diagnostic use only.
Hemoglobin Alc Controls are intended to reliably monitor the accuracy and precision of quantitative determinations of hemoglobin A1c on the ACE® clinical chemistry system. For in vitro diagnostic use only,
ACE® Hemoglobin A1c (HbA1c) Reagent is provided as a single kit and consists of four bottles containing a hemoglobin denaturant, a total hemoglobin reagent, a HbAlc agglutinator reagent and a HbA1c antibody reagent.
The ACE Hemoglobin Alc Calibrators are provided as a single kit and contain ready-to-use liquid calibrators, one of each of six levels.
The ACE Hemoglobin A1c Controls are provided as a single kit and contain lyophilized controls with normal and elevated levels of HbA1c and a reconstitution fluid. The controls are prepared from human whole blood, which has been tested and found negative for antibody to Human Immunodeficiency Virus (anti-HIV) Types 1 and 2, antibody to Hepatitis C (anti-HCV) and for Hepatitis B Surface Antigen (HBsAg) by FDA recommended (approved/licensed) tests.
The document, K063306, describes the Alfa Wassermann, Inc. ACE® Hemoglobin A1c Reagent, Hemoglobin A1c Calibrators and Hemoglobin A1c Controls device. This device is intended for the quantitative determination of hemoglobin A1c and total hemoglobin in human EDTA whole blood for the calculation of percent hemoglobin A1c using the ACE clinical chemistry system.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a table format with pass/fail thresholds. However, it presents performance data against which the device's efficacy can be judged, particularly in comparison to a predicate device. The implied acceptance is that the device's performance metrics are comparable to or within acceptable limits relative to established methods, as evidenced by successful correlation and precision studies.
| Metric | Implied Acceptance Criteria (Based on Study Design and Predicate Comparison) | Reported Device Performance |
|---|---|---|
| Precision | Within-run CV: Low (e.g., 0.95), slope close to 1, intercept close to 0, and reasonable standard error. | Overall Study (n=unspecified, presumably larger): |
- Regression Equation: y = 1.052x + 0.23
- Correlation Coefficient: 0.975
- Standard Error of the Estimate: 0.49
- Confidence Interval Slope: 1.000 to 1.104
- Confidence Interval Intercept: -0.20 to 0.67
POL Labs (n=20 samples per lab): - Lab A: y = 0.940x + 0.41, R=0.9762, SEE=0.46, CI Slp=0.871-1.009, CI Int=-0.16-0.99
- Lab B: y = 1.102x - 0.04, R=0.9818, SEE=0.47, CI Slp=1.032-1.172, CI Int=-0.63-0.55
- Lab C: y = 1.035x + 0.38, R=0.9844, SEE=0.41, CI Slp=0.974-1.095, CI Int=-0.89-0.13 |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Studies:
- Main Study: For the ACE clinical chemistry system, two patient samples (one normal, one elevated) were used for determining within-run and total CVs. The number of replicates or days for this specific part is not explicitly stated, but it followed CLSI/NCCLS EP5-A2 which outlines such protocols.
- POL Sites: Three EDTA whole blood samples with varying HbA1c levels were run in triplicate on five different days at each of the three POL sites.
- Measuring Range Study: One whole blood sample was used, which was serially diluted.
- Accuracy (Correlation) Studies:
- Main Correlation Study: The document does not specify the exact number of samples for the main correlation study against the Tosoh Bioscience's A1c 2.2 Plus Automated Glycohemoglobin Assay. It refers to "patient samples" but no count.
- POL Labs: Each of the three POL labs ran 20 EDTA whole blood samples in duplicate in four different runs (total of 80 measurements per lab, 240 measurements across all POL labs for accuracy comparison).
- Data Provenance: The document does not explicitly state the country of origin for the data. Given the submitter's address (West Caldwell, NJ, USA) and FDA submission context, it is highly probable the data was gathered in the United States. The studies appear to be prospective in nature, designed specifically for this submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- For this type of in-vitro diagnostic device (quantitative measurement of a biomarker), "experts" in the sense of human readers (like radiologists) are not typically used to establish ground truth.
- The ground truth is established by a predicate device or reference method, which is considered the gold standard. In this case, the Tosoh Bioscience's A1c 2.2 Plus Automated Glycohemoglobin Assay was used as the predicate device against which the accuracy of the ACE Hemoglobin A1c kit was evaluated. The performance characteristics of the predicate device are the "ground truth" here.
- There is no mention of a specific number of human experts or their qualifications for establishing ground truth, as the ground truth itself is an established laboratory method.
4. Adjudication Method for the Test Set
- Adjudication methods (like 2+1, 3+1) are common in studies where human interpretation or subjective assessment plays a role in establishing ground truth (e.g., image-based diagnostics).
- For a quantitative in-vitro diagnostic device like the ACE Hemoglobin A1c kit, which relies on chemical reactions and automated measurement, adjudication by human experts is not applicable or performed. The "adjudication" is inherent in the direct comparison of the device's quantitative output against the quantitative output of the predicate device. Discrepancies are handled through statistical analysis (e.g., linear regression, correlation).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done.
- MRMC studies are typically used to assess the impact of an AI system (or new diagnostic tool) on human reader performance, especially in fields like radiology where human interpretation of images is critical.
- This device is an automated, in-vitro diagnostic assay for a chemical biomarker (HbA1c). Its primary function is to provide a quantitative measurement, not to assist human interpretation in a comparative effectiveness study setting.
6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)
- Yes, this entire study is essentially a standalone performance study.
- The ACE Hemoglobin A1c kit, when used with the ACE clinical chemistry system, operates as an automated system. The performance data presented (precision, measuring range, accuracy against a predicate) represents the performance of the algorithm/reagent system on its own, without human intervention influencing the measurement outcome once the process is initiated. Personnel (even those without formal medical technology education in POL sites) are involved in sample preparation and loading, but the actual analytical measurement and calculation are automated by the device.
7. Type of Ground Truth Used
- The ground truth used for the accuracy studies was the concurrent measurement obtained from a legally marketed and established predicate device: the Tosoh Bioscience's A1c 2.2 Plus Automated Glycohemoglobin Assay. This is a common and accepted method for establishing accuracy for new in-vitro diagnostic devices. It operates as a "reference method" in this context.
8. Sample Size for the Training Set
- The document does not explicitly mention a training set sample size. This device is a reagent/assay kit for a clinical chemistry system, not a machine learning or AI algorithm that typically goes through a distinct "training phase" on a dataset in the same way.
- The methods described (latex agglutination inhibition assay, conversion to alkaline hematin, measurement of absorbance) are biochemical principles. While there might have been internal development/optimization data, it's not described as a formal "training set" in the context of this 510(k) summary. The calibration procedure itself (using calibrators) is a form of "training" the system for accurate measurements, but this is distinct from a dataset used for training an AI model.
9. How the Ground Truth for the Training Set Was Established
- As concluded in point 8, a formal "training set" in the AI sense is not described.
- For the calibration process (which could be considered analogous to a system's "learning" or setting up its operational parameters), the Hemoglobin A1c Calibrators are used. These calibrators are presumably manufactured with known, precise concentrations of HbA1c and total hemoglobin, established through rigorous manufacturing and quality control standards. The ground truth for these calibrators would be established through a combination of gravimetric/volumetric preparation and validation against higher-order reference methods and materials (e.g., IFCC reference methods for HbA1c primary calibration). However, this specific process for the calibrators' ground truth is not detailed in this 510(k) 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).