(53 days)
The S TEST Reagent Cartridge Total Protein (TP) is intended for the quantitative determination of TP in serum, lithium heparinized plasma, K3 EDTA plasma and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge TP is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
Total protein measurements are used in the diagnosis and treatment of a variety of diseases involving the liver, kidney, or bone marrow as well as other metabolic or nutritional disorders.
The S TEST Reagent Cartridge Albumin (ALB) is intended for the quantitative determination of ALB in serum, lithium heparinized plasma, K3 EDTA plasma and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge ALB is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.
The Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system intended for use in clinical laboratories or physician office laboratories. The instrument consists of a desktop analyzer unit, an operations screen that prompts the user for operation input and displays data, a printer, and a unit cover. The analyzer unit includes a single probe, an incubation rotor, carousels for sample cups and reagent cartridges, and a multi-wavelength photometer. The single-use reagent cartridges may be placed in any configuration on the carousel, allowing the user to develop any test panel where the reagent cartridges are available.
The S TEST reagent cartridges are made of plastic and include two small reservoirs capable of holding two separate reagents (R1 and R2), separated by a reaction cell/photometric cuvette. The cartridges also include a dot code label that contains all chemistry parameters. calibration factors, and other production-related information, e.g., expiration dating. The dimensions of the reagent cartridges are: 13.5 mm (W) × 28 mm (D) × 20.2 mm (H).
System operation: After the sample cup is placed into the carousel, the analyzer pipettes the sample, pipettes the reagent, and mixes (stirs) the sample and reagent together. After the sample and reagent react in the incubator bath, the analyzer measures the absorbance of the sample, and based on the absorbance of the reactions, it calculates the concentration of analyte in the sample. The test system can measure analytes in serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridges TP and ALB.
Chemistry reactions: (TP) Proteins in samples react with the biuret reagent to form a purplered complex. The concentration of total protein can be determined by measuring the absorbance of the purple-red substance.
(ALB) Albumin in the sample combines with bromcresol green to form a blue-green dye conjugate. The albumin concentration is directly proportional to the color intensity and can be determined photometrically by measuring the absorbance of this resulting blue-green color.
The provided document is a 510(k) summary for the Hitachi S TEST Reagent Cartridge Total Protein (TP) and Albumin (ALB). It details the nonclinical and clinical studies performed to demonstrate the safety and effectiveness of these in-vitro diagnostic devices.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a singular, formal table. Instead, performance characteristics are presented as results from various studies, often implicitly comparing them to the predicate device or general industry standards (e.g., CLSI guidelines). The performance characteristics are reported as the outcome of the tests performed.
Below is a table summarizing the reported device performance for both TP and ALB, drawing from the "Technological Similarities and Differences to the Predicate" section and the "Brief Description of Nonclinical Data" and "Brief Description of Clinical Data" sections. Implicit acceptance is typically shown by these results being deemed "safe and effective for their intended uses."
Hitachi S TEST Reagent Cartridge: Reported Device Performance
| Performance Characteristic | Total Protein (TP) Reported Performance | Albumin (ALB) Reported Performance |
|---|---|---|
| Analytical Sensitivity (Limits of Detection) | 0.2 g/dL | 0.1 g/dL |
| Quantitation Limit | 0.2 g/dL | 0.5 g/dL |
| Linearity/Reportable Range | 0.2 to 11.0 g/dL | 0.1 to 8.0 g/dL (Linearity) / 0.5 to 8.0 g/dL (Reportable Range) |
| In-house Precision (%CV Total) | 1.0% to 2.5% | 1.6% to 4.8% |
| External Site Precision (%CV Total) | 0.7% to 4.4% (across 3 sites) | 0.0% to 4.8% (across 3 sites) |
| Interference (Recovery 90-110%) TP | Unconjugated bilirubin: up to 50 mg/dL | |
| Lipemia: up to 500 mg/dL | ||
| Ascorbic acid: up to 50 mg/dL | ||
| Hemoglobin: up to 1,000 mg/dL | Not applicable | |
| Interference (Recovery 90-110%) ALB | Not applicable | Hemoglobin: up to 250 mg/dL |
| Unconjugated bilirubin: up to 12.5 mg/dL | ||
| Lipemia: up to 500 mg/dL | ||
| Ascorbic acid: up to 50 mg/dL | ||
| Method Comparison (n, r, Slope CI, Y-intercept CI) - Internal | n=115, r=0.989, Slope=1.02 (1.01-1.04), Y-intercept=0.01 (-0.13-0.15) | n=118, r=0.975, Slope=1.01 (0.96-1.06), Y-intercept=0.24 (0.06-0.41) |
| Method Comparison (n, r, Regression Eq.) - External POL Sites | Site 1: n=52, r=0.996, y=0.98x+0.14 | |
| Site 2: n=52, r=0.994, y=1.00x-0.07 | ||
| Site 3: n=53, r=0.996, y=0.96x+0.03 | Site 1: n=87, r=0.982, y=0.99x+0.24 | |
| Site 2: n=81, r=0.979, y=0.95x+0.30 | ||
| Site 3: n=81, r=0.985, y=0.91x+0.35 | ||
| Matrices Comparison (n, r, Slope CI, Y-intercept CI) - TP | Heparinized: n=45, r=0.989, Slope=1.00 (0.96-1.04), Y-int=-0.11 (-0.43-0.21) | |
| EDTA: n=45, r=0.992, Slope=1.00 (0.96-1.04), Y-int=-0.06 (-0.33-0.22) | ||
| Na Citrate: n=45, r=0.987, Slope=0.98 (0.93-1.03), Y-int=-0.09 (-0.45-0.26) | Not applicable | |
| Matrices Comparison (n, r, Slope CI, Y-intercept CI) - ALB | Not applicable | Heparinized: n=41, r=0.992, Slope=0.99 (0.95-1.03), Y-int=-0.01 (-0.20-0.18) |
| EDTA: n=41, r=0.995, Slope=0.95 (0.92-0.98), Y-int=0.22 (0.08-0.36) | ||
| Na Citrate: n=41, r=0.986, Slope=1.00 (0.94-1.05), Y-int=-0.22 (-0.48-0.03) |
2. Sample Size Used for the Test Set and Data Provenance
The document describes test sets for various studies:
- Method Comparison (Internal):
- TP: 115 clinical specimens
- ALB: 118 clinical specimens
- Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Described as "clinical specimens."
- Matrices Comparison:
- TP: 45 matched serum/plasma samples
- ALB: 41 matched serum/plasma samples
- Provenance: Not explicitly stated.
- External Site Precision Study:
- TP: 3 "blinded serum samples" (low, middle, high) at each of 3 sites. Each sample assayed 30 times (6 times/day for 5 days). So, 3 samples * 30 replicates * 3 sites = 270 measurements per analyte for total precision.
- ALB: 3 "blinded serum samples" (low, middle, high) at each of 3 sites. Each sample assayed 30 times (6 times/day for 5 days). So, 3 samples * 30 replicates * 3 sites = 270 measurements per analyte for total precision.
- Provenance: "three external POL-type sites," implying clinical settings, likely within the US given the submission to the FDA. Retrospective/prospective not specified for the samples, but the testing itself was prospective within the study timeframe.
- External Method Comparison Studies (POL Accuracy Data Summary):
- TP: Approximately 50-80 serum specimens per site (n=52, 52, 53). Total around 157.
- ALB: Approximately 50-80 serum specimens per site (n=87, 81, 81). Total around 249.
- Provenance: "three external POL-type sites," implying clinical settings, likely within the US. Retrospective/prospective not specified for samples but the comparative testing was prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
This document describes a diagnostic device for quantitative determination of Total Protein and Albumin. For such devices, "ground truth" is typically established by recognized reference methods, not by expert consensus (e.g., radiologists).
- Method Comparison (Internal and External): The comparison was made against a "standard laboratory system" or "comparative method as the reference method (x)." The specific details of this reference method are not given beyond its use for comparison. No information is provided about human expert involvement in establishing this ground truth.
4. Adjudication Method for the Test Set
Not applicable. Diagnostic devices like this establish their accuracy against a reference method, not through human adjudication of results.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No. This is an in-vitro diagnostic device that provides quantitative measurements. MRMC studies are relevant for imaging devices or those requiring human interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, all studies described (analytical sensitivity, linearity, precision, interference, method comparisons, matrices comparisons) represent the standalone performance of the device (Hitachi Clinical Analyzer E40 with S TEST Reagent Cartridges) in measuring TP and ALB concentrations in samples. These are automated processes without direct human interpretation of results for the purpose of the measurement itself. Human operators are involved in running the analyzer, but the "performance" here refers to the device's analytical capability.
7. The Type of Ground Truth Used
The ground truth for the performance studies was established using:
- Reference Methods/Standard Laboratory Systems: For method comparison studies, the device's results (Y) were compared to a "standard laboratory system" or "comparative method" (X). This is a common approach for establishing accuracy of new in-vitro diagnostic devices.
- CLSI Guidelines: Studies like Analytical Sensitivity, Linearity, and Precision followed CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., EP17-A, EP-6A, EP5-A2). These guidelines define how to determine these performance characteristics, often involving reference materials or established statistical methods for calculation rather than external ground truth.
- Defined Concentrations: For precision and interference studies, samples were used that represented specific (low, middle, high) or known concentrations of the analytes.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. This is a traditional in-vitro diagnostic device based on chemical reactions and photometric measurements. Its "development" would involve optimizing reagents and calibration, not "training" an algorithm in the AI sense. Therefore, the concept of a training set as understood in AI/ML is not applicable here.
9. How the Ground Truth for the Training Set Was Established
As noted in #8, there is no "training set" in the context of AI/ML for this device. The ground truth for developing and calibrating such devices typically relies on:
- Primary Reference Materials: Highly characterized materials with known concentrations of analytes.
- Secondary Reference Materials: Materials traceable to primary reference materials.
- Validated Reference Methods: Established and highly accurate methods, often more complex or expensive, used to assign values to control or calibration materials.
The document implicitly refers to these as part of "assay performance claims were established on the HITACHI Clinical Analyzer."
§ 862.1635 Total protein test system.
(a)
Identification. A total protein test system is a device intended to measure total protein(s) in serum or plasma. Measurements obtained by this device are used in the diagnosis and treatment of a variety of diseases involving the liver, kidney, or bone marrow as well as other metabolic or nutritional disorders.(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 § 862.9.