(172 days)
The RAMP Reader is a general use fluorometer that analyzes results produced by immunoassays that use a fluorophore having an excitation wavelength at 560 nm and an emission wavelength of 610 nm.
The RAMP™ Myoglobin Assay is an immunochromatographic test for the quantitative determination of myoglobin in human EDTA whole blood, using the RAMP Reader.
The RAMP Myoglobin Assay is an immunochromatographic test for the quantitative determination of myoglobin in human EDTA whole blood, using the RAMP Reader.
Diluted EDTA whole blood is applied into the sample well of the Test Cartridge. The red blood cells are retained in the sample pad, and the separated plasma migrates along a strip, through a contact zone where it interacts with fluorescent latex particles. Latex (test) particles, coated with mouse monoclonal anti-myoglobin antibodies bind to myoglobin in the sample.
The sample moves by capillary action towards the end of the strip. As the sample migrates to the detection zone, myoglobin anti-myoglobin particles are immobilized at the detection zone. and additional particles are immobilized at the internal control zone.
The RAMP Reader then measures the amount of fluorescence emitted by the complexes bound at the detection zone and at the internal control zone. Using a ratio between the two fluorescence values, a quantitative reading is calculated.
This document describes the regulatory submission for the RAMP™ Myoglobin Assay and RAMP Reader.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in terms of pass/fail thresholds for clinical performance but are implied by demonstrating substantial equivalence to predicate devices through correlation. The reported device performance is presented as correlation coefficients (r), slopes, and intercepts from method comparison studies, and precision data.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (Intra-assay) | Demonstrated variability consistent with predicate devices for an immunochromatographic assay. | Ranged between 6.5% to 13.0% (%CV) for 50, 100, and 200 ng/mL myoglobin standards. |
| Precision (Inter-assay) | Demonstrated variability consistent with predicate devices for an immunochromatographic assay. | Ranged between 9.1% to 13.8% (%CV) for 50, 100, and 200 ng/mL myoglobin standards. |
| Precision (Total) | Demonstrated variability consistent with predicate devices for an immunochromatographic assay. | Ranged between 10.6% to 14.3% (%CV) for 50, 100, and 200 ng/mL myoglobin standards. |
| Linearity | Strong linear correlation between expected and actual myoglobin concentrations. | R = 0.998, Slope = 1.07, Offset = 1.143 |
| Hook Effect | No significant high-dose hook effect within the expected analytical range. | Not observed up to 8000 ng/mL myoglobin. |
| Analytical Sensitivity (LLD) | Lower limit of detection suitable for clinical application. | 2.36 ng/mL. Levels >400 ng/mL reported as ">400 ng/mL". |
| Analytical Specificity | Minimal interference from common substances and endogenous components. | Samples with rheumatoid factor >1300 Rf IU/mL may interfere; otherwise, no interference from Hb, triglyceride, bilirubin, cholesterol, or coumadin at tested supraphysiological levels. |
| Method Comparison (Patients with suspect AMI) | Strong correlation and agreement with Beckman ACCESS Myoglobin Assay. | n=219, Slope = 1.0059x, Intercept = 29.576, r = 0.928 |
| Method Comparison (Normal Individuals) | Strong correlation and agreement with Beckman ACCESS Myoglobin Assay. | n=196, Slope = 1.3831x, Intercept = 15.609, r = 0.889 |
| Method Comparison (Combined Populations) | Strong overall correlation and agreement with Beckman ACCESS Myoglobin Assay. | n=415, Slope = 1.0309x, Intercept = 25.905, r = 0.932 |
| Method Comparison (Precision Study - Suspect AMI) | Strong correlation and agreement between duplicate measurements. | n=102, Slope = 0.9750x, Intercept = 1.9026, r = 0.986 |
| Method Comparison (Precision Study - Normal Individuals) | Strong correlation and agreement between duplicate measurements. | n=77, Slope = 0.9013x, Intercept = 3.7143, r = 0.967 |
| Method Comparison (Precision Study - Combined) | Strong overall correlation and agreement between duplicate measurements. | n=179, Slope = 0.9702x, Intercept = 0.9349, r = 0.968 |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison Study (vs. Beckman ACCESS Myoglobin Assay):
- Test Set Size: 415 subjects (196 normal individuals, 219 patients suspected of AMI).
- Data Provenance: Not explicitly stated but inferred to be from a clinical setting where samples for patients suspected of AMI were collected and compared with the predicate device. The samples were "EDTA whole blood samples obtained for each of these subjects." The study was likely prospective to obtain samples for direct comparison.
- Precision Study (duplicate testing):
- Test Set Size: 179 subjects (77 normal individuals, 102 patients suspected of AMI).
- Data Provenance: Samples were "selected randomly from those obtained during the Method Comparison Study." These samples were stored refrigerated for up to five days between analyses. This suggests retrospective analysis of samples collected during the method comparison, or a subset of freshly collected samples used specifically for this precision arm.
- Expected Values (Normal Range Study):
- Test Set Size: 196 healthy individuals.
- Data Provenance: Not explicitly stated, but "Whole blood samples from 196 healthy individuals" implies prospective collection from a healthy population.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
There were no experts used to establish ground truth in the traditional sense. The device's performance was evaluated by comparing its quantitative myoglobin measurements to those obtained from an already marketed, legally predicate device (Beckman ACCESS Myoglobin Assay). The "ground truth" here is the measurement provided by the predicate device at the time of the study rather than a consensus of human experts interpreting diagnostic images or clinical scenarios.
4. Adjudication Method for the Test Set
No adjudication method was used, as this was a quantitative measurement comparison study against a predicate device. The comparison involved direct numerical measurements, not subjective interpretations requiring adjudication.
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
No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic (IVD) assay for quantitative measurement, not an AI-assisted diagnostic imaging or interpretation tool. It does not involve human readers interpreting cases with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are standalone performance studies. The RAMP Myoglobin Assay, when used with the RAMP Reader, directly generates a quantitative myoglobin result. The performance data (precision, linearity, analytical sensitivity, and method comparison) evaluate the device's ability to produce accurate and reproducible measurements independently. Human input is limited to sample collection, loading, and reading the final numerical result from the RAMP Reader.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The "ground truth" for the method comparison studies was the quantitative myoglobin concentration determined by the predicate device, the Beckman ACCESS Myoglobin Assay. For analytical performance, the "ground truth" was established by known concentrations of myoglobin antigen (e.g., for linearity and analytical sensitivity).
8. The Sample Size for the Training Set
The document does not provide details about a specific "training set" for the RAMP™ Myoglobin Assay in the context of machine learning or AI models. This device is an immunochromatographic assay; its "training" or calibration would typically involve laboratory procedures to establish standard curves and internal controls during manufacturing and quality control, rather than a data-driven training set in the AI sense.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" and its "ground truth" in the AI sense does not apply directly to this particular device. Calibration and quality control for an immunoassay involve:
- Known Calibrators: Using substances with precisely known concentrations of myoglobin to establish a standard curve for the RAMP Reader to accurately convert fluorescence signals into myoglobin concentrations.
- Controls: Running samples with known myoglobin concentrations (quality controls) to ensure the assay is performing within established limits over time.
§ 866.5680 Myoglobin immunological test system.
(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).