(55 days)
ELITech Clinical Systems ALP IFCC SL is intended for the quantitative in vitro diagnostic determination of alkaline phosphatase in human serum and plasma on ELITech Clinical Systems Selectra analyzers.
It is not intended for use In Point of Care settings.
Alkaline phosphatase or its isoenzymes measurements are used in the diagnosis and treatment of liver, bone, parathyroid and intestinal diseases.
The device for this submission is available as kit only. It consists of 2 reagents R1 & reagent R2.
Reagent R1 contains: 2-Amino-2-methyl-1-propanol (AMP) buffer (pH 10.45), Magnesium ions, Zinc ions.
Reagent R2 contains: p-Nitrophenylphosphate (p-NPP), sodium azide.
The provided text describes a 510(k) premarket notification for the ELITech Clinical Systems ALP IFCC SL device, which is an in vitro diagnostic for measuring alkaline phosphatase. The document focuses on establishing substantial equivalence to a predicate device (Roche Diagnostics ALP2S).
Here's an analysis of the acceptance criteria and the study data, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets. Instead, the document presents a comparison of performance characteristics between the new device (ELITech Clinical Systems ALP IFCC SL) and the predicate device (Roche Diagnostics ALP2S). The "acceptance criteria" are implicitly demonstrated by showing comparable or superior performance to the predicate.
| Performance Metric | ELITech Clinical Systems ALP IFCC SL | Predicate Device (Roche Diagnostics ALP2S) | Implied Acceptance Criteria (relative to Predicate) |
|---|---|---|---|
| Measuring Range | 20 - 1023 U/L | 3 - 1200 U/L | Comparable range |
| Limit of Detection (LoD) | 6 U/L | 3 U/L | Comparable LoD |
| Limit of Quantification (LoQ) | 20 U/L | Not explicitly stated (implied by LoD and range) | Comparable LoQ |
| Precision (Within Run) | Level 57 U/L: CV=1.3% | ||
| Level 144 U/L: CV=0.9% | |||
| Level 262 U/L: CV=0.6% | Level 87.5 U/L: CV=0.5% | ||
| Level 229 U/L: CV=0.7% | |||
| Level 43.1 U/L: CV=0.6% | |||
| Level 190 U/L: CV=1.2% | Comparable or better CV | ||
| Precision (Total) | Level 57 U/L: CV=4.4% | ||
| Level 144 U/L: CV=3.8% | |||
| Level 262 U/L: CV=2.9% | Level 90.0 U/L: CV=1.0% | ||
| Level 229 U/L: CV=0.8% | |||
| Level 53.2 U/L: CV=0.8% | |||
| Level 195 U/L: CV=0.9% | Comparable or better CV | ||
| Method Comparison | y= 1.025 x - 1 U/L | ||
| r= 0.998 | |||
| Range: 18 to 1005 U/L | y= 1.008 x - 2.207 U/L | ||
| r= 1.000 | |||
| Range: 32 to 828 U/L | Strong correlation (r>0.99) and similar regression equation slope/intercept | ||
| Interferences (Hemoglobin) | No significant interference up to 500 mg/dL | No significant interference up to 250 mg/dL | Comparable or better interference tolerance |
| Interferences (Triglycerides/Lipemia) | No significant interference up to 3141 mg/dL | No significant influence up to an L index of 2000 (poor correlation to triglycerides) | Comparable or better interference tolerance |
| Interferences (Bilirubin) | Unconjugated: No significant interference up to 30.0 mg/dL | ||
| Conjugated: No significant interference up to 29.5 mg/dL | No significant influence up to I Index of 60 (approx. 60 mg/dL total bilirubin) | Comparable or better interference tolerance | |
| Interferences (Ascorbic Acid) | No significant interference up to 20.0 mg/dL | Not explicitly stated | Comparable interference tolerance |
| Interferences (Acetaminophen) | No significant interference up to 30.0 mg/dL | Not explicitly stated | Comparable interference tolerance |
| Interferences (Acetylsalicylic Acid) | No significant interference up to 200.0 mg/dL | Not explicitly stated | Comparable interference tolerance |
| Calibration Frequency | 1 day | 5 days | Acceptable calibration frequency (new device is more frequent, implying sufficient stability for daily calibration) |
| On Board Stability | 1 day | 10 days | Acceptable stability (new device has shorter stability, but within acceptable limits for IVD use) |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size for the test set used for performance validation studies (e.g., precision, method comparison, interference). It only provides the results (CVs, regression equations, interference limits).
The data provenance (country of origin, retrospective/prospective) is not explicitly stated. However, given the manufacturer (SEPPIM S.A.S. in FRANCE) and the submission to the FDA, it's highly probable the studies were conducted by the manufacturer, likely in Europe, with data collected prospectively for the purpose of regulatory submission. The samples used would typically be human serum and plasma, as per the intended use.
3. Number of Experts and Qualifications for Ground Truth
This device is an in vitro diagnostic for measuring a biochemical analyte (alkaline phosphatase). The concept of "ground truth" for such a device is typically established through:
- Reference Methods: Highly accurate and precise laboratory methods.
- Certified Reference Materials: Solutions with known concentrations of the analyte.
- Clinical Samples with Established Values: Values determined by existing, validated diagnostic methods.
The document does not mention the use of human experts (like radiologists) for establishing ground truth, as this is not a device that relies on human interpretation of images or other qualitative data. The ground truth for chemical analytes is quantitative and typically relies on analytical methods.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used for qualitative assessments, especially in image interpretation tasks, where multiple experts review cases and resolve discrepancies. Since this is an in vitro diagnostic for a quantitative measurement, such adjudication methods are not applicable and thus not mentioned.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
An MRMC study was not done. MRMC studies are relevant for devices that involve human readers (e.g., radiologists, pathologists) interpreting data, potentially with AI assistance. This device is an automated biochemical analyzer, and therefore, human-in-the-loop performance or comparison is not relevant to its validation.
6. Standalone (Algorithm Only) Performance
This device is a standalone algorithm/device in the context of its function. It is a reagent kit used on an automated analyzer (ELITech Clinical Systems Selectra analyzers) to quantitatively determine alkaline phosphatase. Its performance metrics (precision, linearity, interference, method comparison) are inherently "standalone" in that they describe the performance of the device itself (reagent + analyzer) in measuring the analyte without human interpretation as part of the primary measurement.
7. Type of Ground Truth Used
The ground truth used for validating this type of device would typically be:
- Reference Standards/Calibrators: Solutions with precisely known concentrations of alkaline phosphatase.
- Comparison to a Predicate Device/Established Method: The "Method comparison" section (y= 1.025 x - 1 U/L, r= 0.998) explicitly indicates that the new device's results were compared against those obtained from an existing, validated method (likely the predicate device or a reference method for the x-axis values). The high correlation coefficient (r=0.998) demonstrates agreement with this established truth.
- Internal Quality Control Materials: Often assayed with known target ranges.
8. Sample Size for the Training Set
The document does not mention a "training set" in the context of machine learning or AI. This device is a traditional chemical assay kit. As such, there isn't a "training set" in the sense it's used for AI models. The development and optimization of the assay would involve various experiments, but not a formally defined "training set" as in AI.
9. How Ground Truth for the Training Set Was Established
Since there is no "training set" in the AI sense, this question is not applicable. The assay's chemical principles, reagent concentrations, and reaction conditions are established through chemical and biological experimentation, aiming to accurately reflect the activity of alkaline phosphatase. Performance characteristics, like those listed in the comparison table, are then verified through rigorous testing with known standards and clinical samples.
§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.