(59 days)
The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for the quantitative measurement of alkaline phosphatase activity in serum, lithium heparinized plasma, or sodium citrate plasma using the HITACHI Clinical Analyzer. The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
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 Cartridge ALP.
Chemistry reactions: Alkaline phosphatase (ALP) in the sample reacts with its substrate, pnitrophenyl phosphate (p-NPP), in ethylaminoethanol (EAE) buffer, to release p-nitrophenol (yellow). The ALP activity is determined by measuring the rate of p-nitrophenol production.
The provided text describes the performance characteristics and acceptance criteria for the Hitachi S TEST Reagent Cartridge Alkaline Phosphatase (ALP).
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as a separate column for all metrics. However, the performance data provided implies that the reported results met the internal development criteria for each study. Where a specific acceptance range or threshold is mentioned (e.g., for interference testing), it is included.
| Performance Characteristic | Acceptance Criteria (Implied/Stated) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity (Limit of Detection) | Not explicitly stated, but lower is better. | 1.8 U/L |
| Linearity Range | Performance within the specified range (predicate: 5 to 1,200 U/L) | 5 U/L to 1,000 U/L |
| Detection Limit | Match predicate (5 U/L) | 5 U/L |
| Precision (%CVs) | For in-house, %CVs range from 4.4% to 5.8% (predicate). For external, performance is reported. | In-house: 3.1% to 5.3% (Low), 3.8% to 5.8% (Middle), 2.5% to 4.4% (High). External site precision ranged from 3.0% to 9.2%. |
| Interference Testing (Recovery) | Recoveries between 90% and 110% of the neat value. | Hemoglobin: no interference up to 500 mg/dL. Unconjugated bilirubin: no interference up to 50 mg/dL. Lipemia: no interference up to 2,000 mg/dL. Ascorbic acid: no interference up to 50 mg/dL. |
| Method Comparison (Correlation coefficient 'r') | High correlation, likely >0.90 for good agreement. | In-house: 0.996. External sites: 0.99 for all three sites. |
| Method Comparison (Slope, in-house) | Close to 1.0; 95% CI covering 1.0 or very close. | 0.926 (95% CI: 0.909 to 0.943) |
| Method Comparison (y-intercept, in-house) | Close to 0; 95% CI covering 0 or very close. | 4.8 (95% CI: -0.2 to 9.8) |
| Matrices Comparison (Correlation coefficient 'r') | High correlation, likely >0.90 for good agreement. | Sodium Citrate Plasma: 0.999. Heparinized Plasma: 0.999. |
| Matrices Comparison (Slope, plasma types) | Close to 1.0; 95% CI covering 1.0 or very close. | Sodium Citrate Plasma: 1.03 (1.01 to 1.05). Heparinized Plasma: 1.01 (1.00 to 1.02). |
| Matrices Comparison (y-intercept, plasma types) | Close to 0; 95% CI covering 0 or very close. | Sodium Citrate Plasma: -11.2 (-15.5 to -7.0). Heparinized Plasma: -5.4 (-8.3 to -2.6). |
2. Sample Size Used for the Test Set and Data Provenance:
- Analytical Sensitivity (Limits of Detection): Not specified, but likely involved multiple replicates for statistical analysis as per CLSI EP17-A.
- Linearity: Not specified, but involved samples spanning 5 U/L to 1,000 U/L as per CLSI EP-6A.
- 20-day In-house Precision: Three levels of samples, each tested in two runs, twice a day, for 20 days. This means 80 data points per level (2 runs/day * 2 times/run * 20 days). Total around 240 data points across 3 levels.
- Interference Testing: Two serum pools tested.
- Method Comparison (in-house): 97 clinical specimens. Data provenance: Not explicitly stated, but implied to be in-house or from a domestic source. Retrospective.
- Matrices Comparisons: 38 matched serum/plasma samples. Data provenance: Not explicitly stated, but implied to be in-house or from a domestic source. Retrospective.
- External Site Precision: Each site tested three blinded serum samples, six times per day for five days. This means 30 replicates per sample per site. With 3 sites and 3 samples, approximately 270 data points (30 * 3 * 3).
- External Site Method Comparison: Approximately 70 serum specimens per site, for a total of around 210 specimens (3 sites * ~70 samples/site). Data provenance: Not explicitly stated, but typically from within the country where the study is conducted (likely USA, given the FDA submission). Retrospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
This information is not applicable as the device is a quantitative chemical analyzer. The "ground truth" for the test sets (samples used in the studies) is established by the reference methods or known concentrations, not by expert interpretation.
4. Adjudication Method for the Test Set:
This information is not applicable as the device is a quantitative chemical analyzer. Ground truth is determined objectively through reference methods or known concentrations, not through expert adjudication.
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:
This information is not applicable. The device is a diagnostic instrument (chemistry analyzer) and not an AI-based imaging or diagnostic aid that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
The studies described (precision, linearity, method comparison, interference, matrices comparison) represent the standalone performance of the Hitachi Clinical Analyzer with the S TEST Reagent Cartridge ALP. This is the direct measurement by the instrument, without a human interpretation step.
7. The Type of Ground Truth Used:
The ground truth for the performance studies was established using:
- Reference Methods: For method comparison studies, the Hitachi system was compared against a "standard laboratory system" (predicate device or another established method).
- Known Concentrations/Values: For linearity, precision, and interference studies, samples with known or carefully characterized concentrations of ALP and potential interferents were used.
- CLSI Guidelines: Studies followed established Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP17-A for detection limit, EP-6A for linearity, EP5-A2 for precision, EP7-A2 for interference).
8. The Sample Size for the Training Set:
This information is not applicable. This device is a traditional chemical analyzer, not an AI/machine learning system that requires a "training set" in the computational sense. The device's parameters are set during its manufacturing and calibration process, not through a data-driven training phase.
9. How the Ground Truth for the Training Set Was Established:
This information is not applicable for the reason stated in point 8.
§ 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.