(26 days)
The VARIANT Express Glycohemoglobin Program is intended for the separation and area percent determination of glycohemoglobin (GHb) in whole blood using boronate affinity high performance liquid chromatography (HPLC).
The Bio-Rad VARIANT Express Glycohemoglobin Program is designed for use on the Bio-Rad VARIANT Express Instrument. The analytical system, consisting of instrument, software and reagent kit, provides an assay for the separation and percent determination of glycohemoglobin in whole blood. The VARIANT Express Glycohemoglobin Program is for use on the fully automated VARIANT Express analyzer. The analytical system of instrument and reagent kit provides a means of measuring a mixture of hemoglobins, each formed by the non-enzymatic attachment of circulating blood glucose to a receptive amino acid site on the hemoglobin molecule (HbAo). Attachment of glucose to hemoglobin is achieved in a two step process: formation of an unstable aldimine (Schiff base) intermediate followed by production of a stable ketoamine linkage. Formation of the Schiff base intermediate is a reversible reaction and is influenced by short-term blood glucose fluctuations. In contrast, conversion of the Schiff base intermediate to the "ketoamine" products (Total GHb) is much slower and irreversible. The percentage of total glycated hemoglobin in whole blood is dependent upon the level of sustained blood glucose and is indicative of mean blood glucose over the lifetime of red blood cells (~120 days). Thus, monitoring of total GHb levels has become a routine test for the long-term management of patients with diabetes mellitus.
The Bio-Rad VARIANT™ Express Glycohemoglobin Program is an in-vitro diagnostic device intended for the separation and area percent determination of glycohemoglobin (GHb) in whole blood using boronate affinity high performance liquid chromatography (HPLC).
Here's an analysis of its acceptance criteria and the study that demonstrates its performance:
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (Bio-Rad VARIANT Express Glycohemoglobin Program) |
|---|---|---|
| Precision | Must meet requirements of the National Glycohemoglobin Standardization Program (NGSP) and be comparable to the predicate (Bio-Rad VARIANT Total GHb Program). | Within-run % CV: Low: 3.54%, Medium: 2.90%, High: 2.30% |
| Between-run % CV: Low: 3.97%, Medium: 4.47%, High: 3.55% | ||
| Total Precision: Low: 5.03%, Medium: 4.70%, High: 3.67% | ||
| The method meets NGSP precision requirements. | ||
| Accuracy | High correlation with the predicate device (Bio-Rad VARIANT Total GHb Program). | Correlation coefficient ("r") = 0.9895 when compared to the Bio-Rad VARIANT Total GHb Program. |
| Intended Use | Same as predicate: Separation and area percent determination of glycohemoglobin (GHb) in whole blood using boronate affinity high performance liquid chromatography (HPLC). | Same as predicate: Separation and area percent determination of glycohemoglobin (GHb) in whole blood using boronate affinity high performance liquid chromatography (HPLC). |
| Underlying Technology | Same as predicate: Boronate affinity gel chromatography, direct dilution of whole blood for sample preparation, visible detection at the same wavelength. | Same as predicate: Boronate affinity gel chromatography, direct dilution of whole blood in aqueous medium for sample prep, visible detection at the same wavelength. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Precision Study: "low, medium and high patient" samples were used. The exact number of individual patient samples for each level or total number of runs is not specified, but it was sufficient to satisfy NCCLS EP5-T2 protocol.
- Accuracy/Correlation Study: Not explicitly stated, but the study "followed NCCLS Document EP9-T," which would typically involve a sufficient number of samples across the measuring range to establish a robust correlation.
- Data Provenance: Not explicitly stated in the provided text. It's likely from an internal Bio-Rad study, but details regarding country of origin or whether the data was retrospective or prospective are not provided. Given it's a 510(k) submission for a diagnostic device, the studies are typically prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable as this device is a diagnostic assay, not an AI or imaging device that relies on human expert interpretation for ground truth. The "ground truth" for this device's performance is established by comparison to a legally marketed predicate device (Bio-Rad VARIANT Total GHb Program) using established laboratory protocols and measurements.
4. Adjudication Method for the Test Set
This information is not applicable for the same reason as point 3. Adjudication methods like 2+1 or 3+1 are used when human expert opinions need to be reconciled for a ground truth label, typically in situations where qualitative assessment or image interpretation is involved.
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
This information is not applicable. The Bio-Rad VARIANT Express Glycohemoglobin Program is an automated laboratory assay for measuring glycohemoglobin. It does not involve human readers interpreting images or data that would be assisted by AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies conducted (precision and accuracy/correlation) were for the standalone performance of the Bio-Rad VARIANT Express Glycohemoglobin Program as an analytical system (instrument, software, and reagent kit). The device itself is "fully automated" and provides quantitative results directly.
7. The Type of Ground Truth Used
The "ground truth" for the performance evaluation was established by:
- Predicate Device Comparison: For accuracy, the Bio-Rad VARIANT Express Glycohemoglobin Program's results were correlated with those obtained from the legally marketed Bio-Rad VARIANT Total GHb Program (K941616). This predicate device served as the reference standard for accuracy.
- Established Analytical Protocols: For precision, the studies followed NCCLS Evaluation protocol, Vol. 12, No 4, EP5-T2. These protocols define how to measure and verify precision in laboratory assays.
- National Standardization Program: The device's precision performance was evaluated against the requirements of the National Glycohemoglobin Standardization Program (NGSP).
8. The Sample Size for the Training Set
This information is not applicable in the context of this device's development as described. The Bio-Rad VARIANT Express Glycohemoglobin Program is an analytical system based on established chemical and physical principles (affinity chromatography and HPLC), not a machine learning or AI model that requires a distinct "training set" in the computational sense. The development of such systems involves extensive analytical validation, calibration, and optimization rather than machine learning training.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable for the same reasons as point 8.
§ 862.3450 Gentamicin test system.
(a)
Identification. A gentamicin test system is a device intended to measure gentamicin, an antibiotic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of gentamicin overdose and in monitoring levels of gentamicin to ensure appropriate therapy.(b)
Classification. Class II.