(286 days)
The CKMB Test is an in vitro diagnostic assay for the quantitative determination of creatine kinase isoform MB in EDTA or lithium heparin whole-blood or plasma specimens on the AQT90 FLEX analyzer in point of care and laboratory settings. It is intended for use as an aid in the diagnosis of myocardial infarction.
The Myo Test is an in vitro diagnostic assay for the quantitative determination of myoglobin in EDTA or lithium heparin whole-blood or plasma specimens on the AQT90 FLEX analyzer in point of care and laboratory settings. It is intended for use as an aid in the rapid diagnosis of heart disease, for example, acute myocardial infarction.
For in vitro diagnostic use. The AQT90 FLEX analyzer is an immunoassay instrument based on the quantitative determination of time-resolved fluorescence to estimate the concentrations of clinically relevant markers on whole-blood and plasma specimens to which a relevant anticoagulant has been added. It is intended for use in point-of-care and laboratory settings.
The AQT90 FLEX is a cartridge-based immunoassay analyzer, based on time-resolved fluorescence using a europium (Eu) chelate as the fluorescent label. The test receptacles for the assay are test cups, which contain the antibodies used for capture of the analyte, and the Eu chelate labeled antibodies used to trace the captured analyte. The sample is added to the test cup together with assay buffer. The cup is then incubated to allow formation of the immuno-complex, and subsequently washed to remove unbound antibodies and sample material. Finally, the cup is exposed to excitation light, and after a delay the emitted light generated by the fluorescent label is measured by single photon counting. The total count is then compared to an assay calibration curve to obtain a quantitative measurement of the analyte's concentration in the sample.
This technology uses dried reagents deposited in the test cups and in the calibration adjustment cups – no liquids other than the sample itself together with the assay buffer are required.
The provided document is a 510(k) premarket notification from Radiometer Medical ApS for their AQT90 FLEX CKMB Test Kit, AQT90 FLEX Myo Test Kit, and the AQT90 FLEX analyzer. The submission is to seek clearance for modifications to the existing AQT90 FLEX system devices.
The document does not describe a study involving an AI model or a human-in-the-loop performance study. Instead, it describes analytical performance studies of in-vitro diagnostic assays (Myoglobin and CKMB) on a laboratory analyzer. Therefore, many of the requested elements pertaining to AI models, human experts, ground truth adjudication, MRMC studies, and training datasets are not applicable to this document.
However, I can extract information related to the acceptance criteria (implicitly, the performance metrics evaluated) and the studies conducted to prove the device meets these criteria in the context of an in-vitro diagnostic device.
Here's a breakdown of the available information:
1. Table of Acceptance Criteria (Performance Metrics) and Reported Device Performance
For an in-vitro diagnostic device, acceptance criteria are typically related to analytical performance characteristics such as linearity, limits of detection/quantitation, method comparison (agreement with a predicate), and precision. The reported device performance is the outcome of the studies conducted for these characteristics.
AQT90 FLEX Myo Test Kit
| Performance Metric (Implicit Acceptance Criteria) | Reported Device Performance |
|---|---|
| Linearity (within 10% non-linearity) | Whole Blood & Plasma: Linear within the reportable range (20 – 900 ng/mL), with non-linearity within 10%. |
| Limit of Blank (LoB) | Myo: 0.5 ng/mL (µg/L) |
| Limit of Detection (LoD) | Myo: 1 ng/mL (µg/L) |
| Limit of Quantitation (LoQ) (at 10% CVWithin-lab) | Myo: 1 ng/mL (µg/L) |
| Method Comparison (vs. predicate) | |
| (Implicitly, good correlation and minimal bias) | Plasma: y = 1.01 x - 0.14 (n=103; r²=1.0) compared to predicate. |
| Matrix Comparison | |
| (Implicitly, interchangeability of matrix types) | Equivalence confirmed: No significant matrix effect differences between whole blood vs. plasma or lithium heparin vs. EDTA. (Regression equations provided for various comparisons, all showing strong correlation (r²=1.0) and slopes close to 1). |
| Precision (Repeatability, Between-Run, Total CVs) | Myo Whole Blood: |
| L1 (57 ng/mL): Total CV 2.3% | |
| L2 (92 ng/mL): Total CV 3.0% | |
| L3 (622 ng/mL): Total CV 2.4% | |
| Myo Plasma: | |
| L1 (53 ng/mL): Total CV 2.1% | |
| L2 (95 ng/mL): Total CV 2.2% | |
| L3 (586 ng/mL): Total CV 2.2% |
AQT90 FLEX CKMB Test Kit
| Performance Metric (Implicit Acceptance Criteria) | Reported Device Performance |
|---|---|
| Linearity (within 10% non-linearity) | Whole Blood & Plasma: Linear within the reportable range (1.5 – 300 ng/mL), with non-linearity within 10%. |
| Limit of Blank (LoB) | CKMB: 0.5 ng/mL (µg/L) |
| Limit of Detection (LoD) | CKMB: 1 ng/mL (µg/L) |
| Limit of Quantitation (LoQ) (at 20% CVWithin-lab) | CKMB: 1 ng/mL (µg/L) |
| Method Comparison (vs. predicate) | |
| (Implicitly, good correlation and minimal bias) | Plasma: y = 0.99 x - 0.18 (n=107; r²=1.0) compared to predicate. |
| Matrix Comparison | |
| (Implicitly, interchangeability of matrix types) | Equivalence confirmed: No significant matrix effect differences between whole blood vs. plasma or lithium heparin vs. EDTA. (Regression equations provided for various comparisons, all showing strong correlation (r²=1.0) and slopes close to 1). |
| Precision (Repeatability, Between-Run, Total CVs) | CKMB Whole Blood: |
| L1 (2.6 ng/mL): Total CV 4.8% | |
| L2 (14 ng/mL): Total CV 4.9% | |
| L3 (204 ng/mL): Total CV 3.4% | |
| CKMB Plasma: | |
| L1 (2.3 ng/mL): Total CV 3.7% | |
| L2 (8.4 ng/mL): Total CV 2.8% | |
| L3 (209 ng/mL): Total CV 2.2% |
2. Sample Size Used for the Test Set and Data Provenance
- Linearity (Myo & CKMB): 11 sample levels for linearity series, measured with 10 replicates each. This is an in vitro analytical study, not patient data.
- LoB/LoD/LoQ (Myo & CKMB):
- LoB: Four blank samples measured with 5 replicates on 3 days, using 2 test kit lots and 2 analyzers. Total 60 measurements per test kit lot.
- LoD/LoQ: 10 samples per matrix (lithium heparin whole blood and plasma).
- Method Comparison (Myo & CKMB):
- Myo: n=103 lithium heparin plasma samples.
- CKMB: n=107 lithium heparin plasma samples.
- Matrix Comparison (Myo & CKMB):
- Myo: n=125 for most comparisons (e.g., Liph/Pl vs Liph/WB), some n=127. Paired lithium heparin and EDTA specimens.
- CKMB: n=106 for Liph/Pl vs Liph/WB, others n=104, 103, 101. Paired lithium heparin and EDTA specimens.
- Precision (Myo & CKMB):
- Whole Blood: 3 lithium heparin whole blood samples, measured 5 times five replicates (total 25 measurements per sample level).
- Plasma: 3 lithium heparin plasma pools, measured across 20 test days, twice a day with 2 replicates (total 80 measurements per sample level).
Data Provenance: The studies were conducted "at one internal test site" for method comparison and "at three hospital laboratory sites" for matrix comparison. This indicates domestic (likely Denmark, where the manufacturer is located) or potentially international clinical laboratory settings. The data are prospective in the sense that they were generated specifically for these validation studies using prepared samples (diluted native specimens, spiked specimens, blank samples). They are not patient-outcome data or retrospective chart reviews.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts:
- Not Applicable. For an in-vitro diagnostic device measuring analytes (myoglobin, CK-MB), the "ground truth" isn't established by human experts in the same way as, for example, image interpretation. The ground truth for these studies is the reference measurement from the original (predicate) device or the known concentration of prepared analytical samples.
4. Adjudication Method for the Test Set:
- Not Applicable. No human interpretation or adjudication is involved in determining the concentration of analytes in a blood sample by an immunoassay method.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This type of study is relevant for AI systems that assist human readers in tasks like image interpretation. This document describes the analytical performance of an in-vitro diagnostic device that quantitatively measures biochemical markers. There are no human readers or AI assistance involved in this context.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance):
- Yes, in the context of an IVD. The performance data presented (linearity, LoD/LoQ, method comparison, precision) are all "standalone" in the sense that they demonstrate the analytical performance of the AQT90 FLEX system (analyzer and test kits) independent of human interpretation or intervention beyond proper sample handling and instrument operation. This isn't an "algorithm only" in the AI sense, but rather the performance of analytical machines.
7. The Type of Ground Truth Used:
- Reference Measurement/Known Concentration:
- For Linearity, LoB/LoD/LoQ, and Precision: The ground truth is established by preparing samples with known or precisely characterized concentrations of the analytes (e.g., diluted native specimens, spiked specimens, blank samples).
- For Method Comparison: The ground truth is the measurement obtained from the predicate device (the previously cleared version of the AQT90 FLEX system devices). The goal is to show agreement between the modified device and the predicate.
8. The Sample Size for the Training Set:
- Not Applicable. This document describes the validation of an in-vitro diagnostic device, not an AI model. Therefore, there's no "training set" in the machine learning sense. The device performs a chemical reaction and optical measurement based on established immunoassay principles, not a learned algorithm trained on data.
9. How the Ground Truth for the Training Set was Established:
- Not Applicable. As there is no training set for an AI model, this question is not relevant.
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.