(107 days)
For in vitro diagnostic use in the quantitative determination of alkaline phosphatase (orthophosphoric - monoester phospho-hydrolase, alkaline optimum, EC 3.1.3.1) activity in human serum or plasma on T60 instruments according to the IFCC method.
The Alkaline Phosphatase test system is intended for quantitative in-vitro diagnostic determination of the activity of the enzyme Alkaline Phosphatase in serum and plasma on T60 instrument according to the IFCC method. Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver and bone diseases.
For in vitro diagnostic use on T60 instrument. eCal is used as a calibrator for enzyme tests using methods defined by Thermo Fisher Scientific Oy.
For in vitro diagnostic use for quantitative testing on T60 instrument. Nortrol is a control serum to monitor trueness and precision of the analytes listed in the separate Nortrol value sheet. The given values are valid for T60 Clinical Chemistry Instruments using methods defined by Thermo Fisher Scientific Oy.
For in vitro diagnostic use for quantitative testing on T60 instrument. Abtrol is a control serum to monitor trueness and precision of the analytes listed in the separate Abtrol value sheet. The given values are valid for T60 Clinical Chemistry Instruments using methods defined by Thermo Fisher Scientific Oy.
Alkaline Phosphatase (IFCC) plus, codes 981832 and 981833. Common name: Alkaline Phosphatase (IFCC). Classification: Clinical Chemistry, Class II, Product Code: CJE.
eCal, code 981830. Common Name: Calibrator, Multi-Analyte Mixture. Classification: Clinical Chemistry, Class II, Product Code: JIX.
Nortrol, code 981043. Common Name: Multi-analyte Controls (Assayed and unassayed). Classification: Clinical Chemistry, Class I, Product Code: JJY.
Abtrol, code 981044. Common Name: Multi-analyte Controls (Assayed and unassayed). Classification: Clinical Chemistry, Class I, Product Code: JJY.
The acceptance criteria and device performance for the Alkaline Phosphatase (IFCC) Plus test system are detailed below based on the provided 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
| Attribute | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (New Device #1) |
|---|---|---|
| Measuring Range | 0-1100 U/L | 20 - 1000 U/L |
| Precision (Within run) | ||
| Level 68 U/l | SD= 0.9, CV(%)= 1.3 | Level 91 U/l: SD= 0.7, CV(%)= 0.7 |
| Level 127 U/l: SD=0.9, CV(%)=0.7 | ||
| Level 374 U/l: SD= 2.0, CV(%)=0.5 | ||
| Level 41 U/l: SD= 0.5, CV(%)= 1.1 | ||
| Level 810 U/l: SD= 6.6, CV(%)=0.8 | ||
| Precision (Within run) | ||
| Level 148 U/l | SD=2.1, CV(%)= 1.4 | Level 91 U/l: SD= 0.8, CV(%)=0.9 |
| Level 127 U/l: SD= 1.1, CV(%)=0.9 | ||
| Level 374 U/l: SD= 2.0, CV(%)=0.5 | ||
| Level 41 U/l: SD= 1.4, CV(%)= 3.5 | ||
| Level 810 U/l: SD= 2.5, CV(%)=0.3 | ||
| Precision (Total) | ||
| Level 68 U/l | SD= 2.2, CV(%)= 3.2 | Level 91 U/l: SD= 2.9, CV(%)= 3.2 |
| Level 127 U/l: SD= 2.6, CV(%)= 2.0 | ||
| Level 374 U/l: SD= 8.4, CV(%)=2.3 | ||
| Level 41 U/l: SD= 1.5, CV(%)= 3.7 | ||
| Level 810 U/l: SD= 18.5, CV(%)= 2.3 | ||
| Precision (Total) | ||
| Level 148 U/l | SD= 3.8, CV(%)= 2.6 | (Not directly comparable levels) |
| Method Comparison | y = 1.00x + 1.1, r = 0.998, n = 402 (with Advia 1650) | y = 1.023x - 1.61, R = 0.998, N = 154 |
| y = 1.04x - 14.6, r = 0.998, n = 96 (with reference method) | (Comparison with predicate device) | |
| Limitations (Lipemia) | No significant interference found up to 500 mg/dl | No interference found up to 1000 mg/dL |
| Limitations (Hemolysate) | No significant interference found up to 500 mg/dl | No interference found up to 300 mg/dl |
| Limitations (Bilirubin) | No significant interference found up to 25 mg/dl (unspecified type) | Conjugated: No interference up to 58 mg/dL; Unconjugated: No interference up to 21 mg/dL |
Note: The table above primarily compares the new device's performance against the predicate device's stated performance, which is implicitly treated as the acceptance criteria for determining substantial equivalence.
2. Sample Size and Data Provenance for the Test Set
- Method Comparison (New device vs. Predicate device):
- Sample size (N): 154
- Data Provenance: Not explicitly stated, but given that the submitter is Thermo Fisher Scientific Oy (Finland), it is likely that parts of the study were conducted in Finland or other relevant locations. The data type is prospective, as it involves testing the device against clinical samples.
- Limitations (Interference):
- The sample size for interference studies (Lipemia, Hemolysate, Bilirubin) is not specified.
- Data Provenance: Not explicitly stated, but assumed to be from internal studies conducted by Thermo Fisher Scientific Oy. This would be prospective data generated under controlled conditions.
3. Number of Experts and Qualifications for Ground Truth
This document describes an In Vitro Diagnostic (IVD) assay for measuring alkaline phosphatase activity. For such assays, "ground truth" is typically established by:
- Reference Methods: The document states the new device is "traceable to the molar absorbance coefficient of p-nitrophenol" and the predicate device is "traceable to the IFCC reference method via patient sample correlation."
- Consensus or Clinical Outcomes: For IVD tests, the "ground truth" for patient samples is usually the result obtained from a well-established, often older or gold-standard, clinical laboratory method or a reference laboratory test.
- For this specific document: The "ground truth" for the method comparison study (N=154) was the measurements produced by the identified predicate device (Bayer ADVIA 2400 Chemistry System) or the reference method mentioned for the predicate. The document does not mention the involvement of "experts" in the sense of clinicians or radiologists establishing ground truth by medical review or interpretation. The ground truth here is the quantitative measurement provided by the comparative method.
4. Adjudication Method for the Test Set
Not applicable. This is a quantitative diagnostic assay, not an image-based diagnostic or clinical decision-support system requiring adjudication of interpretations by clinical experts. The comparison is based on numerical results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an IVD device measuring an enzymatic activity directly, not an AI system assisting human readers in interpreting clinical cases. Therefore, there is no "human readers improve with AI vs without AI assistance" effect to measure.
6. Standalone Performance (Algorithm Only without Human-in-the-loop Performance)
Yes, this study is inherently a standalone performance study. The Alkaline Phosphatase (IFCC) Plus test system, as an IVD, operates autonomously to measure the analyte concentration. Its performance (precision, measuring range, method comparison, limitations) is evaluated based on its own output, independent of human interaction or interpretation beyond running the assay and interpreting the numerical result.
7. Type of Ground Truth Used
The ground truth used for the method comparison study was quantitative measurements obtained from the predicate device (Bayer ADVIA 2400 Chemistry System) or a referenced IFCC method. This is a form of comparative measurement data or reference method equivalency. The internal validation "ground truth" for linearity, precision, and interference would be based on known concentrations or controlled interference levels.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its sample size. For an IVD assay like this, method development and optimization (which could be analogous to "training") typically involve numerous experiments with various reagents, concentrations, and conditions. However, the document focuses on the validation or test set used for substantial equivalence demonstration.
9. How the Ground Truth for the Training Set was Established
As no specific "training set" is mentioned in the context of machine learning, this question is not directly applicable. For the development of the assay, the "ground truth" during optimization would be established through standard analytical chemistry techniques, using known concentrations of alkaline phosphatase, reference materials, and established biochemical principles (e.g., spectrophotometry for p-nitrophenol formation) to ensure the assay accurately measures the intended activity.
§ 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.