(34 days)
GlyPro Reagent: For the quantitative determination of glycated proteins. Measurement of glycated serum protein is representative of the mean blood glucose levels over the preceding 2-3 weeks. For In Vitro Diagnostic Use.
GlyPro Calibrator: For calibration of the GlyPro™ assay. For In Vitro Diagnostic Use.
GlyPro Low and High Controls: To monitor the performance of the GlyPro assay. For In Vitro Diagnostic Use.
The Genzyme GlyPro Assay System (consisting of Reagent, Calibrator, Low Control and High Control) is a quantitative method for the detection of glycated proteins in serum and plasma.
Here's a breakdown of the acceptance criteria and study information for the Genzyme GlyPro™ Reagent, Calibrator, and Controls, based on the provided 510(k) summary:
Description of Acceptance Criteria and Study Findings
The Genzyme GlyPro™ Assay System is intended for the quantitative determination of glycated proteins in serum and plasma, serving as a measure of mean blood glucose levels over the preceding 2-3 weeks for diabetes management. The primary study presented is a comparative performance study against a predicate device (Roche Unimate Fructosamine) and Furosine, along with linearity, precision, and interference studies. The overarching acceptance criterion for the premarket notification is demonstrating substantial equivalence to a legally marketed predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria/Tests | Reported Device Performance |
|---|---|---|
| Comparative Performance | Correlation with Predicate (Roche Unimate Fructosamine) | Slope: 1.33 |
| Intercept (µmol/L): -127.45 | ||
| Correlation Coefficient (r): 0.9915 | ||
| Sample Range (µmol/L): 169.0 - 675.5 | ||
| Conclusion: Acceptable correlation. | ||
| Correlation with Furosine Method | Slope: 15.25 | |
| Intercept (µmol/L): 0.41 | ||
| Correlation Coefficient (r): 0.9881 | ||
| Sample Range (peak area x 10^4): 7.40 - 48.58 | ||
| Conclusion: Acceptable correlation. | ||
| Linearity | Demonstrate linearity across the usable range | Linear up to 1734 µmol/L. |
| Precision (Within-Run) | Coefficient of Variation (CV) ≤ 1.0% and SD ≤ 5 µmol/L | Low Level: Mean 180.7 µmol/L, SD 1.34, %CV 0.74 |
| Medium Level: Mean 405.3 µmol/L, SD 1.25, %CV 0.31 | ||
| High Level: Mean 663.6 µmol/L, SD 4.55, %CV 0.69 | ||
| Conclusion: Excellent within-run precision (CVs ≤ 1.0%, SDs ≤ 5 µmol/L). | ||
| Precision (Between-Run) | Coefficient of Variation (CV) ≤ 2.0% and SD ≤ 6 µmol/L | Low Level: Mean 179.6 µmol/L, SD 2.99, %CV 1.66 |
| Medium Level: Mean 402.3 µmol/L, SD 3.17, %CV 0.79 | ||
| High Level: Mean 654.6 µmol/L, SD 5.73, %CV 0.88 | ||
| Conclusion: Excellent between-run precision (CVs ≤ 2.0%, SDs ≤ 6 µmol/L). | ||
| Interference | No significant interference from common substances at specified levels; identify interfering drugs. | No Interference (up to indicated levels): Triglyceride (Avian) 750 mg/dL, Ascorbic Acid 8 mg/dL, Bilirubin 29 mg/dL, Hemoglobin 200 mg/dL, Uric Acid 33 mg/dL, Glucose 1800 mg/dL. |
| Interfering Drugs: Dobesilate (10 mg/L), Gentisic Acid (25 mg/L), Methampyrone (100 mg/L) at concentrations less than therapeutic dose. | ||
| Sample Type Equivalence | Understand differences between serum and plasma | EDTA plasma results are 6% lower than serum results. Recommendation: use the same sample type for comparative analyses of the same patient. |
| Reference Range | Establish a normal reference range | 95% Reference Range: 122 - 238 µmol/L. |
2. Sample Size Used for the Test Set and Data Provenance
- Comparative Performance Studies:
n = 61samples were used for comparison against both the predicate Roche Unimate Fructosamine and the Furosine method. - Linearity, Within-Run, Between-Run, and Interference Studies: Specific sample sizes are given for each:
- Within-Run and Between-Run Precision: 20 replicates for each of 3 serum pools (total 60 measurements per study).
- Interference Studies: "a specimen pool" and "varying levels" of interferents were used; specific 'n' for each interferent not provided but implied to be sufficient for evaluation.
- Serum vs. Plasma: "Matched sets of serum and EDTA plasma specimens" were tested; specific 'n' not provided.
- Reference Range: Calculated using non-parametric analysis (NCCLS C28-A), but the number of individuals/samples used to establish the range is not specified.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it is a 510(k) submission from a US-based manufacturer for a clinical laboratory device, it is highly probable the data was generated in a clinical laboratory setting, likely in the US, and was prospective for the purpose of the submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This device is an in-vitro diagnostic (IVD) assay measuring a quantitative analyte. The "ground truth" for the test set is established by the performance of reference methods (Roche Unimate Fructosamine and Furosine) and the analytical characteristics of the device itself (linearity, precision). It does not involve human expert interpretation of images or other qualitative assessments requiring expert consensus. Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth in the traditional sense for diagnostic imaging AI is not directly applicable here. The "experts" are the validated methodologies and laboratory instrumentation.
4. Adjudication Method for the Test Set
Not applicable. This is an IVD device for quantitative measurement. Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective human interpretation of results, such as reading medical images, where there might be disagreement among readers. For an analytical assay, the "adjudication" is inherent in the analytical method's performance and comparison to a quantitative standard or predicate.
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 relevant for diagnostic devices that involve human interpretation (like radiologists reading images) and aims to measure the improvement in human reader performance with the assistance of the device. The GlyPro™ Assay is an automated quantitative assay, not an assistive AI tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The studies presented are standalone performance evaluations of the GlyPro™ assay system. The device's performance characteristics (correlation, linearity, precision, interference) were assessed directly, without the involvement of a human-in-the-loop for interpretation beyond standard laboratory procedures for running the assay and reporting results. The device itself is an "algorithm only" in the sense that it performs its quantitative measurement automatically.
7. The Type of Ground Truth Used
The ground truth for the comparative performance studies was the results obtained from the predicate device (Roche Unimate Fructosamine) and another established method, Furosine. For other studies like linearity and precision, the ground truth is based on reference materials/serum pools with known or precisely characterized analyte concentrations. The interference studies used controlled additions of potential interferents. For the reference range, it was established using non-parametric analysis of a reference population, which implies direct measurement of a healthy population.
8. The Sample Size for the Training Set
This document describes a premarket notification for an in-vitro diagnostic assay, not a machine learning or AI algorithm in the contemporary sense that requires distinct "training" and "test" sets. The "training" for such an assay typically involves the manufacturer's internal development, optimization, and validation of the reagent formulation, instrument parameters, and assay protocol. This information is not typically detailed in this section of a 510(k) summary. The studies described are validation and verification studies, analogous to what might be considered "test sets" for evaluation of the final product.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, the concept of a separate "training set" with established ground truth as understood for modern AI/ML models is not directly applicable here. The assay's development and optimization ("training") would have involved:
- Analytical chemistry principles: ensuring the reagents react specifically and quantitatively with glycated proteins.
- Calibration: using a calibrator (GlyPro™ Calibrator) with known or assigned values to establish the relationship between instrument signal and analyte concentration.
- Control materials: using GlyPro™ Low and High Controls with known ranges to monitor assay performance and ensure accuracy and precision over time.
The "ground truth" during this development phase would be established through careful analytical measurements, use of certified reference materials (if available for glycated proteins), and comparison to established laboratory methods during the internal R&D process. This information is typically proprietary and not disclosed in the 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).