(29 days)
The products encompassed by this request are intended for in-vitro diagnostics use and for use in calibrating the electrodes and flushing the sample flow path of the equivalent Corning 6X4 Series Electrolyte Analyzers. Corning (undergone several owner and name changes incl.: Corning Glass, Ciba-Corning, Chiron, and currently Bayer) is the Original Equipment Manufacturer (OEM) of the analyzers and the predicate reagents. Mission reagents are intended to serve as direct replacements to like named products manufactured by Corning (under the label of current owner, Bayer). The products encompassed are to be handled using normal laboratory precautions.
The Calibrators for the Corning Electrolyte Instruments are aqueous reagents with salts added to obtain desired analyte levels to provide calibration of the electrodes and rinse the sample path. Mission uses a similar composition, description and packaging as that used by Corning in its products.
This medical device submission (K020596) describes the performance of Mission Diagnostic Reagents for Corning 6X4 Electrolyte Analyzers. The submission establishes substantial equivalence to existing Corning calibrators.
Here's an analysis of the provided text to answer your questions:
Acceptance Criteria and Device Performance Study
The study evaluates the performance of Mission Diagnostic reagents (calibrators) as direct replacements for Corning's original calibrators on Corning 6X4 Electrolyte Analyzers. The acceptance criteria are implicitly defined by demonstrating "performance equivalence" through precision data and correlation with Corning reagents. The study aims to show that the Mission reagents produce results comparable to the predicate Corning reagents.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Analyte | Device | Acceptance Criteria (Implicit) | Reported Performance (Mission Reagents) |
|---|---|---|---|---|
| Precision | Na | 614 | CV% within acceptable range for clinical use (not explicitly stated, but inferred from predicate device performance) | QC1: 0.79%, QC2: 0.50%, QC3: 0.50% |
| K | 614 | CV% within acceptable range for clinical use | QC1: 1.67%, QC2: 0.46%, QC3: 0.92% | |
| Na | 644 | CV% within acceptable range for clinical use | QC1: 0.56%, QC2: 0.85%, QC3: 0.72% | |
| K | 644 | CV% within acceptable range for clinical use | QC1: 1.13%, QC2: 0.40%, QC3: 0.68% | |
| Cl | 644 | CV% within acceptable range for clinical use | QC1: 1.40%, QC2: 1.99%, QC3: 1.85% | |
| Na | 654 | CV% within acceptable range for clinical use | QC1: 1.75%, QC2: 1.06%, QC3: 1.32% | |
| K | 654 | CV% within acceptable range for clinical use | QC1: 1.49%, QC2: 0.65%, QC3: 1.14% | |
| Li | 654 | CV% within acceptable range for clinical use | QC1: 8.89%, QC2: 3.27%, QC3: 3.75% | |
| Correlation | Na | All | Slopes of ~1.0 and R² ≥ 0.99 | 614: Slope 1.00, R² 1.00; 644: Slope 1.03, R² 1.00; 654: Slope 0.97, R² 1.00 |
| K | All | Slopes of ~1.0 and R² ≥ 0.99 | 614: Slope 1.01, R² 1.00; 644: Slope 1.04, R² 1.00; 654: Slope 1.07, R² 1.00 | |
| Cl | 644 | Slopes of ~1.0 and R² ≥ 0.99 | Slope 0.97, R² 1.00 | |
| Li | 654 | Slopes of ~1.0 and R² ≥ 0.99 | Slope 0.96, R² 0.99 |
Note: The acceptance criteria for precision are not explicitly stated as numerical cut-offs but are implied by demonstrating performance equivalence with the predicate device, which would typically involve showing CV% values are within clinically acceptable limits for the analytes and the instrument type.
2. Sample Size Used for the Test Set and Data Provenance
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Precision Data (Test Set):
- Sample Size: For each analyte and QC level across the different Corning instruments (614, 644, 654), N typically ranged from 21 to 24 measurements. For example, for Na on Corning 614, N=24 for each of the three QC levels.
- Data Provenance: The data was collected from "QC samples (or control material)" measured over a minimum of 7 days on equivalent Corning analyzers where Mission products were installed. The control materials are standardized solutions, not patient data from a specific country. This is prospective data collection focused on the device's performance.
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Correlation Data (Test Set):
- Sample Size:
- Na: 50 human serum samples per instrument type (614, 644, 654).
- K: 60 human serum samples per instrument type (614, 644, 654).
- Cl: 50 human serum samples on Corning 644.
- Li: 30 human serum samples on Corning 654.
- Data Provenance: The data used "human serum samples." These samples were "spiked with LiCl to obtain a base Li concentration" and then further "spiked to yield varying concentrations of each of the measuring analytes." This setup indicates a controlled laboratory study using prepared samples, not necessarily from a specific country of origin in a retrospective manner. It appears to be prospective data collection for this comparison.
- Sample Size:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of submission for in-vitro diagnostic reagents does not typically involve human experts establishing "ground truth" in the way a diagnostic imaging study (e.g., radiologists interpreting images) would. The "ground truth" for the correlation study is implicitly established by the predicate Corning reagents run on the same analyzer. The study design involves comparing the results from the new Mission reagents against the results from the established Corning reagents, with the latter serving as the reference for equivalence. No information on experts is provided for this type of test.
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
Not applicable to this type of in-vitro diagnostic reagent study. The "adjudication" is a direct numerical comparison of results between the test (Mission) and predicate (Corning) reagents on the same samples and instruments.
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
Not applicable. This is an in-vitro diagnostic device (reagent) and does not involve human readers interpreting cases or AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This is a standalone performance demonstration of the reagents themselves in an automated system, without human intervention needed for interpretation. The instrument (Corning 6X4 Electrolyte Analyzer) operates automatically once calibrated, and the reagents are a component of that automatic system. The study evaluates the performance of the reagents as an algorithm-only component of the analyzer.
7. The Type of Ground Truth Used
- For Precision Data: The ground truth is the expected target concentration of the analyte in the control materials (QC1, QC2, QC3). The "Mean" values in the precision tables likely reflect the observed values relative to these expected targets.
- For Correlation Data: The "ground truth" for comparison is the measurement obtained when the Corning reagents are used to calibrate the analyzer and measure the same human serum samples. This is a comparative ground truth established by the predicate device performance.
8. The Sample Size for the Training Set
There is no explicit mention of a "training set" in the context of machine learning. This submission is for reagents, not an AI/ML algorithm that requires training. The "performance characteristics" and "correlation" data described here are for the validation of the reagents. For the development of the reagents themselves, Mission Diagnostics would have conducted internal R&D, but that is not detailed as a "training set" in this regulatory submission.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an AI/ML algorithm being developed or assessed here. The submission is for chemical reagents.
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.