(91 days)
The Calcium test system is intended for in vitro diagnostic use in the quantitative determination of the calcium concentration in human serum or plasma on T60 instruments. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.
For in vitro diagnostic use on T60 instrument. sCal is used as a multicalibrator for quantitative measurements 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.
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The provided text describes the Thermo Fisher Scientific Calcium Test System (Calcium, sCal, Nortrol, Abtrol) and its substantial equivalence to a predicate device, the Bayer ADVIA Calcium assay. The information largely focuses on comparing performance metrics between the new device and the predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text, structured according to your requested points:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a set of pre-defined thresholds the new device had to meet. Instead, it presents a comparison table (Table 1) of various performance attributes between the new device (Calcium) and the predicate device (Bayer ADVIA Calcium assay). The implicit "acceptance" is that the new device's performance is substantially equivalent to or better than the predicate's.
| Attribute | Acceptance Criteria (Implicit - based on predicate) | New Device Performance (Calcium) | Predicate Device Performance (Bayer ADVIA Calcium assay) |
|---|---|---|---|
| Intended Use | Similar quantitative determination of calcium in human serum/plasma | For quantitative determination of calcium in human serum or plasma on T60 instruments. | For quantitative determination of calcium in human serum, plasma (lithium heparin), and urine on ADVIA Chemistry systems. |
| Indication for Use | Similar diagnostic and treatment uses for parathyroid disease, bone diseases, renal disease, and tetany | Diagnosis and treatment of parathyroid disease, bone diseases, chronic renal disease and tetany. | Same as intended use. |
| Assay Protocol | Comparable method for calcium detection | Calcium ions form a highly coloured complex with Arsenazo III at neutral pH, measured at 660 nm. | Calcium ions form a violet complex with o-cresolphthalein complexone in an alkaline medium, measured at 545/658 nm. |
| Traceability/ Standardization | Traceable to recognized standard | NIST SRM 909b as a primary reference. | Traceable to a NIST atomic absorption reference method, using NIST reference materials via patient sample correlation. |
| Sample Type | Serum, plasma (Li-heparin) | Serum, plasma (Li-heparin) | Serum, plasma (Li-heparin) and urine. |
| Reagent Storage | Stable under specified conditions | 2-25°C until expiration date, away from sunlight. | 15-25°C until expiration date, do not freeze. |
| Expected Values (Serum/plasma) | Comparable range for normal values | 8.6 - 10.3 mg/dl (2.15 - 2.57 mmol/l) | 8.3 - 10.6 mg/dL (2.08 - 2.65 mmol/L) |
| Instrument | Compatible with clinical chemistry analyzers | T60 and DPC T60i, DPC T60i Kusti. | ADVIA® 2400 Chemistry system. |
| Measuring Range (Serum/plasma) | Comparable analytical measurement range | 2.8 - 16.0 mg/dl (0.70 - 4.00 mmol/l) | 1.0 - 15.0 mg/dL (0.25 - 3.75 mmol/L) |
| Precision (Within-run Serum) | Low SD and CV(%) values across levels | Level 4.0 mg/dL: SD=0.04, CV(%)=1.0; Level 8.4 mg/dL: SD=0.07, CV(%)=0.8; Level 11.9 mg/dL: SD=0.08, CV(%)=0.7 | Level 6.2 mg/dL: SD=0.06, CV(%)=1.0; Level 8.5 mg/dL: SD=0.17, CV(%)=2.0; Level 10.9 mg/dL: SD=0.18, CV(%)=1.6 |
| Precision (Total Serum) | Low SD and CV(%) values across levels | Level 4.0 mg/dL: SD=0.06, CV(%)=1.6; Level 8.4 mg/dL: SD=0.12, CV(%)=1.5; Level 11.9 mg/dL: SD=0.18, CV(%)=1.5 | Level 6.2 mg/dL: SD=0.12, CV(%)=2.0; Level 8.5 mg/dL: SD=0.21, CV(%)=2.4; Level 10.9 mg/dL: SD=0.23, CV(%)=2.1 |
| Method Comparison (Serum) | Strong correlation with predicate (R close to 1, slope close to 1, intercept close to 0) | y = 1.04x - 0.002, R = 0.994 | y = 1.01x +0.27, R = 0.988 (vs ADVIA 1650); y = 1.00x - 0.56, R = 0.996 (vs reference method) |
| Limitations (Lipemia) | No significant interference up to a certain concentration | No interference found up to 1000 mg/dL (10 g/l) of Intralipid. | No significant interference found up to 625 mg/dl of Intralipid. |
| Limitations (Hemolysate) | No significant interference up to a certain concentration | No interference found up to 1000 mg/dl (10 g/l) of hemoglobin. | No significant interference found up to 525 mg/dl of hemoglobin. |
| Limitations (Bilirubin, conjugated) | No significant interference up to a certain concentration | No interference found up to 58 mg/dL (1000 µmol/l). | Not specified, but predicate states no significant interference up to 30 mg/dl for general Bilirubin. |
| Limitations (Bilirubin, unconjugated) | No significant interference up to a certain concentration | No interference found up to 58 mg/dL (1000 µmol/l). | Not specified, but predicate states no significant interference up to 30 mg/dl for general Bilirubin. |
2. Sample Size Used for the Test Set and Data Provenance
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Method Comparison (Serum):
- Sample Size: N = 112
- Data Provenance: Not explicitly stated, but it's a comparison to the Bayer ADVIA 2400. Given the submission is from Thermo Fisher Scientific Oy in Finland, and the clinical chemistry context, it's highly likely to be prospective clinical samples, but the country of origin is not specified. It is an in vitro diagnostic device, so the samples used for this study would be human serum/plasma.
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Precision Studies:
- Sample Size: Not explicitly stated as "N" for the precision studies, but rather by "levels" (e.g., Level 4.0 mg/dL). Typically, precision studies involve running a sample multiple times within a run and across multiple runs. The 'SD' and 'CV(%)' values are calculated from these repeated measurements. The exact number of replicates is not provided.
- Data Provenance: Not explicitly stated. Likely laboratory-prepared control samples or spiked patient samples.
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Limitations (Interference):
- Sample Size: Not explicitly stated. Interference studies typically involve spiking samples with known interferents at various concentrations.
- Data Provenance: Not explicitly stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For this type of in vitro diagnostic device (a chemical assay), the "ground truth" is established through analytical reference methods or highly accurate laboratory instruments, not by human experts in the way image analysis or clinical diagnosis might be.
- Method Comparison: The new device was compared to the predicate device (Bayer ADVIA 2400). The predicate device itself would have been validated against a reference method. The text also mentions the Bayer ADVIA Calcium assay's traceability to a NIST atomic absorption reference method.
- Traceability: The new device's value has been assigned by using NIST SRM 909b as a primary reference. This implies that NIST standards and reference methods are the "ground truth" for calibrating and validating the assay.
Therefore, there were no human "experts" establishing ground truth in the sense of clinical reviewers for this device. The ground truth relies on established analytical standards and reference measurement procedures.
4. Adjudication Method for the Test Set
Not applicable. As this is an in vitro diagnostic assay, adjudication methods such as 2+1 or 3+1 (often used in clinical image interpretation) are not relevant. The "adjudication" is inherent in the analytical process, where results are compared against reference methods or statistically analyzed for agreement.
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 not an AI-assisted diagnostic tool or an imaging device requiring human interpretation. It is a chemical reagent and calibrator system for measuring calcium concentration. Therefore, MRMC studies and "human readers improving with AI" are not relevant to this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in a sense, the entire performance evaluation presented is "standalone" for the device itself. The studies on precision, measuring range, and interference demonstrate the performance of the Calcium test system (reagents, calibrators, and the T60 instrument) independently. The method comparison study also assesses the direct output of the new device relative to the predicate without human intervention in result generation.
7. The Type of Ground Truth Used
The ground truth used for establishing the performance and enabling substantial equivalence determination includes:
- NIST Standards: NIST SRM 909b for primary reference, and the predicate's traceability to a NIST atomic absorption reference method. (This is a form of highly certified reference measurement procedure/material).
- Predicate Device Output: The Bayer ADVIA 2400 Chemistry System's Calcium assay served as the comparative "ground truth" for the method comparison study. The predicate itself would have been validated against a reference standard.
- Laboratory Control Materials/Spiked Samples: Likely used for precision and interference studies.
8. The Sample Size for the Training Set
Not applicable. This is not a machine learning or AI-based device that requires a "training set" in the computational sense. It is a chemical reagent-based assay. Its performance is characterized through traditional analytical validation, not by training an algorithm on a dataset.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this chemical assay device.
§ 862.1145 Calcium test system.
(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).(b)
Classification. Class II.