(422 days)
The Diazyme Fibrinogen Assay is for the quantitative determination of fibrinogen levels in citrated human plasma. For in vitro diagnostic use only.
The Diazyne Fibringen Calibrator Set is intended for use in the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The Diazyme Fibringen Control Set is intended for use as quality controls for the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The performance of this device has not been established in neonate and pediatric patient populations.
Diazyme Fibrinogen Assay System consists of the following items:
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- The Diazyme Fibrinogen Assay: containing reagent R1 and reagent R2. Reagent 1 contains buffer, saline, and sodium azide. Reagent 2 containing anti-human fibrinogen Ig fraction tittered to optimal concentrations dependent on sera lot and sodium azide.
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- Diazyme Fibrinogen Calibrator Set: 3 levels, serum based, intended for use in the calibration of the Diazyme Fibrinogen Assay. The calibrators are in lyophilized form containing purified human fibrinogen antigen, defibrinated human serum and sodium azide
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- Diazyme Fibrinogen Control Set: 2 levels, serum based, intended for use as quality controls for the Diazyme Fibrinogen Assay. The controls are in lyophilized form containing purified human fibrinogen antigen, defibrinated human serum and sodium azide.
The Diazyme Fibrinogen Assay is run on Roche Modular P analyzer (K953239/005). The Diazyme Fibrinogen Assay never comes into direct contact with patient's venous blood sample is first collected by a phlebotomist and then submitted for determination of fibrinogen concentration using Diazyme Fibrinogen Assay by trained professionals.
The Control Unit of the Roche Modular P analyzer uses a graphical interface to control all instrument functions. The computer, keyboard, and touchscreen monitor allows users to navigate through the software, enter assay, calibrator, and control information, and make test selections. The Diazyme Fibrinogen Modular P application parameters provided are programmed into the Modular P analyzers. The reagents, calibrators and controls are loaded into the analyzer. The Roche Modular P stores the Diazyme Fibrinogen Assay reagents in a refrigerated compartment. Reagent and sample pipettes automatically aspirate and dispense specified amounts of reagent or calibrators, controls, and sample into reaction cells. The change in absorbance is measured at specified wavelengths.
After a 4-point calibration, spline-fitting is used to smoothly fit polynomial functions through mean values of the response for calibrators of known concentrations. The Roche Modular P calculates the fibrinogen concentration of a patient sample by interpolation of the obtained signal to a stored 4-point calibration curve.
This document describes the Diazyme Fibrinogen Assay and compares its performance characteristics to a predicate device, the Kamiya K-Assay Fibrinogen (K993482), to demonstrate substantial equivalence.
Here's the breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate, pre-defined set of values that the device met. Instead, it presents performance characteristics and then concludes "Performance data and risk analysis indicates that differences should not affect the safety and effectiveness of the Diazyme Fibrinogen Assay and offers users an in vitro diagnostic device system to measure fibrinogen in human plasma," implicitly suggesting these performance levels are acceptable for substantial equivalence.
Here's a comparison of the Diazyme Fibrinogen Assay's performance against the predicate:
| Performance Characteristic | Predicate (Kamiya K-Assay Fibrinogen) | Subject Device (Diazyme Fibrinogen Assay) | Equivalency Statement |
|---|---|---|---|
| Assay/Linear Range | 100 – 900 mg/dL | 100 – 900 mg/dL | Similar |
| Precision (CV%) | 1.8 – 13.0% | Less than 10% (Specifically, total CVs were 5-7% for samples, 6-8% for calibrators, 2-3% for controls across various studies) | Similar |
| Accuracy (Correlation to Predicate) | Correlation Coefficient (R²) = 0.990 (vs Incstar ITA) | Correlation Coefficient (R²) = 0.9946 (vs. Kamiya K-Assay) | Similar |
| Accuracy (Slope) | 0.967 (vs Incstar ITA) | 0.986 (vs. Kamiya K-Assay) | Similar |
| Accuracy (Y-Intercept) | 33.91 (vs Incstar ITA) | 2.72 (vs. Kamiya K-Assay) | Similar |
| Reagent Composition | R1: Buffer R2: Anti-human fibrinogen goat antiserum Calibrator: Lyophilized | R1: Phosphate buffered saline R2: Goat anti-human Fibrinogen reagent Calibrators: Lyophilized | Same |
| Calibrator Set | 1 x 1.0 mL Single-Level Calibrator | 1 x 1.0 mL Calibrator 1, 1 x 1.0 mL Calibrator 2, 1 x 1.0 mL Calibrator 3 | Different |
| Control Set | 5 x 1.0mL Control 1, 5 x 1.0mL Control 2 (plasma based) | 1 x 1.0mL Control 1, 1 x 1.0mL Control 2 (serum based) | Similar |
2. Sample Size Used for the Test Set and Data Provenance
- Precision (Sample Repeatability): 6 citrated plasma samples. Tested over 10 days, 2 runs/day, 2 replicates/run = 240 measurements per sample type.
- Precision (Calibrator Repeatability): 3 levels of calibrators. Tested over 10 days, 2 runs/day, 2 replicates/run = 360 measurements per calibrator level.
- Precision (Control Repeatability): 2 levels of controls. Tested over 20 days, 2 runs/day, 2 replicates/run = 160 measurements per control level.
- Reproducibility (Multi-site precision): 6 citrated plasma samples, 3 calibrator levels, 2 control levels. Plasma: 60 measurements per sample (implies 3 sites, but not explicitly stated how many measurements per site). Calibrator/Control: 120 measurements per level.
- Linearity: An eleven-level linearity set prepared by mixing a pooled fibrinogen spiked plasma sample and saline at different proportions.
- Method Comparison: A total of 176 human plasma samples.
- Interference: Not specified as a specific "test set" size, but various interferents were tested at specified concentrations.
Data Provenance:
The document does not explicitly state the country of origin of the samples. For precision, linearity, and interference, it implies in-house testing by Diazyme Laboratories. For method comparison, it states "Human plasma samples" from "3 clinical sites," but the location of these sites and whether the data is retrospective or prospective is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. For in vitro diagnostic devices like this, the "ground truth" for method comparison is typically established by results from the predicate device itself, or in some cases, a well-established reference method. There is no mention of experts establishing a ground truth for individual samples.
4. Adjudication Method for the Test Set
This information is not applicable/provided. For analytical performance studies of quantitative IVD assays, an adjudication method (like 2+1 expert consensus) is typically not used in the same way it would be for qualitative image-based diagnostic systems. The reference method (predicate device) provides the comparative "truth."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging interpretation where human readers are involved. The Diazyme Fibrinogen Assay is an in vitro diagnostic assay run on an automated analyzer (Roche Modular P), not a system designed for human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance studies described (Precision, Linearity, Method Comparison, Interference) are all standalone performance evaluations of the Diazyme Fibrinogen Assay device itself, without human-in-the-loop performance measurement. The device runs on an automated analyzer (Roche Modular P), and its performance is assessed against established analytical performance metrics and comparison to a predicate device.
7. The Type of Ground Truth Used
For the method comparison study, the predicate device's results (Kamiya K-Assay Fibrinogen) served as the comparative "ground truth" or reference method. For linearity, it was prepared standards. For precision, the "truth" is the statistical mean of repeated measurements.
8. The Sample Size for the Training Set
This information is not applicable/provided. The Diazyme Fibrinogen Assay is an immunoturbidimetric assay based on chemical reactions and optical measurements, not a machine learning or AI-based device that would typically involve a "training set" in the computational sense. The "training" of the assay involves establishing calibration curves using known calibrator concentrations.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable/provided. As above, the device is not an AI/ML system requiring a training set with "ground truth" labels. Calibration curves are established using the "Diazyme Fibrinogen Calibrator Set," which contains purified human fibrinogen antigen at known concentrations. These known concentrations serve as the basis for the instrument to interpret sample results.
§ 864.7340 Fibrinogen determination system.
(a)
Identification. A fibrinogen determination system is a device that consists of the instruments, reagents, standards, and controls used to determine the fibrinogen levels in disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot).(b)
Classification. Class II (special controls). A control or fibrinogen standard intended for use with a fibrinogen determination system is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.