(94 days)
The S TEST reagent cartridge for glucose is intended for the quantitative measurement of glucose in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia.
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.
Chemistry reactions: Glucose is phosphorylated to glucose-6-phosphate by hexokinase (HK) in the presence of ATP. When the glucose-6-phosphate is converted into 6-phosphogluconic acid by glucose-6phosphate dehydrogenase (G6PD), NADP is converted into NADPH with an increase in absorbance at 340 nm. The concentration of glucose can be determined by measuring the amount of change in absorbance of NADPH.
HK Glucose + ATP Glucose-6-phosphate + ADP Mg2+ GRPD
Glucose-6-phosphate + NADP 6-Phosphogluconic acid + NADPH
The provided text describes the 510(k) summary for the Hitachi Clinical Analyzer S TEST Reagent Cartridge for Glucose. It details various performance studies conducted to demonstrate its safety and effectiveness.
Here's an analysis of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" as pass/fail thresholds for each metric. Instead, it presents the results of various performance studies and implies that these results demonstrate substantial equivalence to the predicate devices. The information available allows for a comparison of the Hitachi S TEST and the predicate device's listed performance.
| Performance Metric | Acceptance Criteria (Implied / Predicate) | Reported Hitachi S TEST Performance |
|---|---|---|
| Analytical Sensitivity (Detection Limit) | Predicate: 2 mg/dL | Calculated: 0.3 mg/dL. Limit of Quantitation (LoQ): 5 mg/dL. |
| Linearity (Reportable Range) | Predicate: 2 to 750 mg/dL | 5 to 500 mg/dL |
| Precision (In-house) | Predicate: %CVs range from 0.7% to 1.3% (from product labeling) (Lower %CV is better) | Within-Run %CV: Level 1: 3.9%, Level 2: 1.5%, Level 3: 1.1% |
| Total %CV: Level 1: 3.9%, Level 2: 2.1%, Level 3: 3.0% | ||
| Precision (External POL) | (Not explicitly stated, but clinical acceptability is implied by comparison to predicate) | Site 1: A: 4.6% (Total %CV), B: 3.7% (Total %CV), C: 3.6% (Total %CV) |
| Site 2: A: 1.7% (Total %CV), B: 1.1% (Total %CV), C: 1.9% (Total %CV) | ||
| Site 3: A: 2.3% (Total %CV), B: 1.7% (Total %CV), C: 3.0% (Total %CV) | ||
| Method Comparison (Accuracy) | Implied acceptable correlation (e.g., r > 0.97, slope close to 1, intercept close to 0) | In-house (vs. cobas 6000): n=100. y=0.99x -2.7, r=0.994. 95% CI slope: 0.98 to 1.02, 95% CI y-intercept: -5.5 to 0.8. |
| External POL (vs. cobas 6000): | ||
| Site 1 (n=53): y=1.01x -1.1, r=0.99. CI Slope: 0.99 to 1.02, CI Intercept: -2.7 to 0.6. | ||
| Site 2 (n=52): y=0.97x -0.1, r=0.99. CI Slope: 0.96 to 0.99, CI Intercept: -2.1 to 1.9. | ||
| Site 3 (n=51): y=1.05x -2.5, r=0.99. CI Slope: 1.03 to 1.07, CI Intercept: -5.1 to 0.1. | ||
| Interference | No significant interference at specified levels of common interfering substances. | Not affected by Hemoglobin (up to 1000 mg/dL for ~200 mg/dL glucose, up to 500 mg/dL for ~50 mg/dL glucose), Unconjugated bilirubin (up to 50 mg/dL for ~200 mg/dL glucose, up to 6.25 mg/dL for ~50 mg/dL glucose), Triglyceride (up to 800 mg/dL), Ascorbic acid (up to 50 mg/dL). |
| Matrices Comparison | Acceptable correlation/equivalence between serum and plasma types. | Na Citrate Plasma: Slope: 0.98 (0.96-1.00), y-intercept: -4.6 (-8.2 to -0.8), r=0.998. |
| Heparinized Plasma: Slope: 1.00 (0.98-1.02), y-intercept: -2.1 (-5.8 to 1.6), r=0.998. | ||
| EDTA Plasma: Slope: 1.00 (0.99-1.02), y-intercept: -0.3 (-3.1 to 2.6), r=0.999. |
2. Sample Sizes and Data Provenance
The document does not explicitly state the "test set" in the context of an AI/ML device, as this is a traditional in-vitro diagnostic device. However, studies were performed to validate its performance.
- Analytical Sensitivity (Limits of Detection):
- One experiment: "sensitivity for glucose was calculated to be 0.3 mg/dL." (Exact sample size not specified for this calculation).
- Second experiment: "three low-level samples assayed 6 times a day for 3 days on three separate analyzers" (54 measurements per sample, total 162 measurements).
- Linearity: "The S TEST glucose is linear between 5 and 500 mg/dL." (Exact sample size not specified, but followed CLSI EP-6A which typically uses multiple levels and replicates).
- 20-day In-house Precision: 80 measurements per level (3 levels), total 240 measurements.
- Interference Testing: "not affected by high levels of the following substances at the levels noted" (Number of samples for each interference test not explicitly stated, but followed CLSI EP7-A2).
- Method Comparison (In-house): 100 serum samples.
- Matrices Comparisons: 38 matched serum/plasma samples (sodium citrate, lithium heparin, K3 EDTA).
- External POL Precision Study: Each of the 3 sites received 3 blinded serum samples (A, B, C). Each sample was assayed 6 times per day for 5 days, resulting in 30 results per level per analyte per site (3 sites * 3 levels * 30 results = 270 measurements for precision).
- External POL Method Comparisons Study: Each of the 3 POL sites received approximately 50 blinded serum samples (Total ~150 samples).
Data Provenance: The studies were conducted "in-house" (Hitachi Chemical Diagnostics) and at "three external POL-type sites" (Physician Office Laboratories). The central laboratory for predicate comparisons was likely in the US, but specific country of origin is not mentioned. All studies appear to be prospective as they are designed to evaluate the performance of the device.
3. Number of Experts and Qualifications for Ground Truth
This is an in-vitro diagnostic device (chemistry analyzer) measuring a biological analyte (glucose). The ground truth is established by quantitative measurement methods rather than expert interpretation of images or clinical data.
- Ground Truth for Method Comparison: The "ground truth" or reference method for comparison was primarily the Roche/Hitachi cobas 6000, which is a legally marketed predicate device (K100853). The cobas 6000 itself is a chemistry analyzer, not a human expert.
- Ground Truth for Matrices Comparison: The reference for plasma samples was serum samples.
Therefore, the concept of "number of experts used to establish the ground truth" and "qualifications of those experts" as it might apply to image-based diagnostics or disease diagnosis is not directly applicable here. The ground truth accuracy is against established, validated methods.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used for subjective assessments or when multiple human readers interpret results. This is an automated quantitative measurement device. Therefore, no adjudication method as described would be applicable or necessary. The comparisons are statistical (linear regression, correlation) between two quantitative measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This type of study is relevant for AI systems that assist human readers in tasks like image interpretation to evaluate the impact of AI assistance on human performance (e.g., accuracy, efficiency). The Hitachi Clinical Analyzer is a standalone automated diagnostic device, not an AI-assisted human reading system.
6. Standalone (Algorithm Only) Performance
Yes, a standalone performance study was done. The entire performance evaluation described (analytical sensitivity, linearity, precision, interference, method comparison, matrices comparison) demonstrates the performance of the Hitachi Clinical Analyzer S TEST Reagent Cartridge for Glucose as a standalone automated system, without human-in-the-loop performance modifications or assistance once the samples are loaded and the test initiated.
7. Type of Ground Truth Used
The primary ground truth used for comparison and validation was:
- Comparison to a Legally Marketed Predicate Device: Specifically, the Roche/Hitachi cobas 6000 (a chemistry analyzer with a glucose module), which itself has established performance characteristics. This is a form of reference method comparison.
- Internal reference (e.g., serum for plasma matrices): For the matrices comparison, serum was used as the reference against different plasma types.
- Defined reference standards/controls: For precision, linearity, and sensitivity, the device was tested against samples with known or precisely characterized glucose concentrations, which serves as the "ground truth" for those specific studies.
This is not "expert consensus," "pathology," or "outcomes data" in the typical sense, but rather comparison against established analytical chemical methods and reference materials.
8. Sample Size for the Training Set
The concept of a "training set" is not applicable here. This is a traditional in-vitro diagnostic device (chemistry analyzer) and not an AI/ML algorithm that undergoes a "training" phase with data. The device's calibration, which is somewhat analogous to initial setup/tuning, would be done using calibrator materials provided or specified by the manufacturer, but this is not "data training" in the AI sense.
9. How the Ground Truth for the Training Set was Established
As mentioned above, there is no "training set" in the AI/ML context for this traditional IVD device.
§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.