(435 days)
The S TEST Reagent Cartridge Alanine Amino Transferase (ALT) is intended for the quantitative measurement of the activity of the enzyme alanine amino transferase (ALT) in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. ALT measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.
The S TEST Reagent Cartridge Aspartate Amino Transferase (AST) is intended for the quantitative measurement of the activity of the enzyme aspartate amino transferase (AST) in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. AST measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart 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 test systems for glucose.
The Hitachi Chemical Diagnostics S TEST Reagent Cartridges for Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) underwent nonclinical and clinical testing to demonstrate their safety and effectiveness.
Here’s a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Characteristic | Acceptance Criteria (Implicit from Predicate/Standard) | S TEST ALT Performance (Reported) | S TEST AST Performance (Reported) |
|---|---|---|---|
| Analytical Sensitivity (LoD) | Comparable to predicate (10 U/L for ALT, 5 U/L for AST) or lower | 2.2 U/L | 1.4 U/L |
| Linearity/Reportable Range | Comparable to predicate (10 to 600 U/L for ALT, 5 to 700 U/L for AST) | 6 to 400 U/L | 4 to 400 U/L |
| Precision | Comparable to predicate (%CVs 2.4-3.6% for ALT, 0.4-3.1% for AST) | 2.3% to 5.6% (%CVs for ALT) | 1.4% to 3.2% (%CVs for AST) |
| Interference | No significant interference from common substances at specified levels | No interference up to: Hemoglobin 250 mg/dL, Unconjugated bilirubin 25 mg/dL, Triglyceride 500 mg/dL, Ascorbic acid 50 mg/dL | No interference up to: Hemoglobin 31-125 mg/dL, Unconjugated bilirubin 50 mg/dL, Triglyceride 500 mg/dL, Ascorbic acid 50 mg/dL |
| Method Comparison (Correlation with Predicate/Reference Method) | High correlation (implied by r > 0.99) and acceptable slope/intercept | Internal: r=0.999, Slope 1.09, y-intercept 2.3 | Internal: r=0.997, Slope 1.09, y-intercept -3.7 |
| External (POL Sites): High correlation and acceptable slope/intercept across sites | Site 1: r=0.998, y=1.09x-0.8 | ||
| Site 2: r=0.997, y=1.05x+0.1 | |||
| Site 3: r=0.997, y=1.11x+0.2 | Site 1: r=0.999, y=1.00x-0.1 | ||
| Site 2: r=0.998, Y=1.04x-0.3 | |||
| Site 3: r=0.999, y=1.05x+0.7 | |||
| Matrices Comparison | Acceptable correlation (r) and slope/intercept when comparing plasma types to serum | Na Citrate Plasma: r=0.998, Slope 0.99 | |
| Heparinized Plasma: r=0.998, Slope 1.02 | |||
| EDTA Plasma: r=0.997, Slope 1.01 | Na Citrate Plasma: r=0.999, Slope 1.02 | ||
| Heparinized Plasma: r=0.999, Slope 1.04 | |||
| EDTA Plasma: r=0.992, Slope 0.98 |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Nonclinical Studies (Internal):
- Analytical Sensitivity (LoD): Sample sizes not explicitly stated for individual calculations beyond "followed CLSI EP17."
- Linearity: Sample sizes not explicitly stated beyond "followed CLSI EP-6A."
- 20-day In-house Precision: 80 replicates per level for AST (ALT not clearly defined due to formatting issues in the document but likely similar).
- Interference Testing: Sample sizes not explicitly stated.
- Method Comparisons: 103 serum samples for ALT, 169 serum samples for AST.
- Matrices Comparisons: Approximately 35 matched serum/plasma samples (28-31 for ALT, 38-39 for AST) per plasma type.
- Clinical Studies (External POL-type sites):
- External Precision Study: 30 replicates per sample per site (6 times a day for 5 days) for 3 sample levels (A, B, C or D, E, F) at each of 3 sites.
- External Method Comparisons: 49-50 blinded serum samples for ALT per site; 62-64 blinded serum samples for AST per site tested at 3 POL sites.
- Data Provenance: The document does not explicitly state the country of origin for the data. The studies were conducted internally ("in-house") and at "three external POL-type sites," suggesting the data is retrospective as it was collected before submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
- For the nonclinical and clinical method comparison studies, the "ground truth" was established by "routine laboratory methods" or "traditional methods at the central laboratory."
- The document does not specify the number or qualifications of experts involved in performing these reference methods. It relies on the established accuracy and widely accepted nature of these "traditional" or "routine" methods.
4. Adjudication Method for the Test Set:
- No explicit adjudication method is described. The "ground truth" was derived from measurements by established laboratory methods, and the Hitachi device's results were compared to these.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No, an MRMC comparative effectiveness study was not done. This submission focuses on the analytical performance of an in vitro diagnostic (IVD) device (reagent cartridges for an analyzer), not a diagnostic imaging or AI-driven decision-support system that typically involves human reader performance. Therefore, there is no mention of human readers, AI assistance, or effect sizes related to human improvement.
6. If a Standalone Study (algorithm only without human-in-the-loop performance) was done:
- Yes, this entire submission is effectively a standalone performance study. The device itself is an automated chemical analyzer with reagent cartridges. The studies evaluate the analytical performance of this automated system directly (e.g., sensitivity, linearity, precision, method comparison to reference methods). There is no "human-in-the-loop" component in the operational use or performance evaluation of the ALT/AST test results themselves, beyond the initial sample loading and result interpretation by laboratory personnel.
7. The Type of Ground Truth Used:
- The ground truth used for method comparison and accuracy studies was established by measurements from "routine laboratory methods" or "traditional methods at the central laboratory." This implies a highly accurate and well-established chemical assay, which serves as the reference standard for the analyte concentration or activity.
8. The Sample Size for the Training Set:
- This submission describes a premarket notification (510(k)) for an IVD device (reagent cartridges). It does not involve a machine learning or AI algorithm that typically requires a distinct "training set." Therefore, no training set sample size is reported or relevant in this context. The "training" of the device is inherent in its chemical design and calibration, not in data-driven machine learning.
9. How the Ground Truth for the Training Set Was Established:
- As stated above, this is an IVD device, not an AI/ML-driven device. Thus, the concept of a "training set" and associated ground truth establishment for such a set does not apply. The device's performance is validated against established laboratory standards and reference methods as described in point 7.
§ 862.1030 Alanine amino transferase (ALT/SGPT) test system.
(a)
Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended to measure the activity of the enzyme alanine amino transferase (ALT) (also known as a serum glutamic pyruvic transaminase or SGPT) in serum and plasma. Alanine amino transferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.