(345 days)
For in vitro diagnostic use in the quantitative determination of total billrubin in human serum and plasma on the ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of hemolytic, biliary, and liver disorders, including hepatitis and cirrhosis.
The ADVIA Chemistry Total Bilirubin_2 is used for the in vitro quantitative determination of total bilirubin in human serum and plasma on the ADVIA® Chemistry Systems. The proposed labeling indicates the ADVIA Chemistry Total Bilirubin_2 reagents can be used on the ADVIA Chemistry Systems 1650, 1800, 2400, and 1200. The Total Bilirubin_2 assay is based on a chemical oxidation method, utilizing vanadate as the oxidizing agent. Total bilirubin (conjugated and unconjugated) is oxidized by vanadate at about pH 2.9 to produce biliverdin. In the presence of detergent and vanadate, both conjugated and unconjugated bilirubin are oxidized. This oxidation causes a decrease in optical density of the yellow color, which is specific to bilirubin. The decrease in optical density at 451/545 nm is proportional to the total bilirubin concentration in the sample. The concentration is measured as an endpoint reaction.
Here's an analysis of the provided 510(k) summary regarding the ADVIA® Chemistry Total Bilirubin_2 device, focusing on acceptance criteria and supporting studies:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary does not explicitly state formal "acceptance criteria" in terms of pre-defined thresholds for performance metrics. Instead, it demonstrates "substantial equivalence" to a predicate device (ADVIA® IMS Total Bilirubin) by comparing performance characteristics. The implied acceptance criterion is that the new device's performance is comparable to or better than the predicate device's performance, and within generally accepted analytical standards for clinical laboratory assays.
| Performance Characteristic | Stated Acceptance Criteria (Implied) | Reported Device Performance (ADVIA Chemistry Total Bilirubin_2) | Predicate Device Performance (ADVIA IMS Total Bilirubin) |
|---|---|---|---|
| Imprecision (Total CV) | Comparable to predicate and generally acceptable for clinical assays. | ADVIA 1650/1800: 1.1% - 3.2% | ADVIA IMS: 2.1% - 8.2% |
| ADVIA 2400: 1.0% - 4.7% | (comparable levels) | ||
| ADVIA 1200: 1.3% - 3.6% | |||
| Correlation (Method Comparison) | Regression statistics (slope, intercept, r) to indicate strong linear correlation with predicate/comparison methods, and low Syx. | ADVIA 1650 vs ADVIA IMS: $y=0.925x + 0.12$, Syx=0.42, r=0.998 | N/A (predicate itself) |
| ADVIA 2400 vs ADVIA 1650: $y=0.999x - 0.02$, Syx=0.19, r=1.000 | |||
| ADVIA 1200 vs ADVIA 1650: $y=1.036x - 0.05$, Syx=0.21, r=1.000 | |||
| Interfering Substances | Minimal clinically significant interference (e.g., within a predefined percentage change or acceptable clinical limits). | Ascorbic acid (50 mg/dL): -1.16% to 0.00% change | Not explicitly stated in the summary, implied acceptable. |
| Hemoglobin (1000 mg/dL): -2.1% to 7.0% change | |||
| Lipids (Triglycerides, 750 mg/dL): 6.8% to 8.6% change | |||
| Analytical Range | Comparable to predicate and suitable for clinical diagnosis. | ADVIA 1650/1800: 0.1 - 35.0 mg/dL | Not explicitly stated in summary, implied covered. |
| ADVIA 2400: 0.1 - 35.0 mg/dL | |||
| ADVIA 1200: 0.1 - 35.0 mg/dL |
2. Sample Size and Data Provenance for the Test Set
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Imprecision Study (Test Set):
- The sample size for the imprecision study is not explicitly stated as a single "test set" size. Instead, it reports CVs at multiple bilirubin levels. The common practice for imprecision studies involves running samples (controls or patient pools) multiple times over several days. The table shows 3-5 different bilirubin levels tested on each of the four ADVIA Chemistry Systems.
- Data Provenance: Not specified in the summary (e.g., country of origin). The studies appear to be prospective as they were conducted specifically for this 510(k) submission to evaluate the performance of the new device.
-
Correlation (Method Comparison) Study (Test Set):
- Sample Size:
- Serum, ADVIA 1650 vs ADVIA IMS: 118 samples (N=118)
- Serum, ADVIA 2400 vs ADVIA 1650: 119 samples (N=119)
- Serum, ADVIA 1200 vs ADVIA 1650: 119 samples (N=119)
- Data Provenance: Not specified (e.g., country of origin). Appears to be prospective as these studies would have been designed to compare the new device against existing methods.
- Sample Size:
-
Interfering Substances Study (Test Set):
- The sample size for the interfering substances experiment is not explicitly stated. Typically, a small number of samples (e.g., one or two per interference level) are spiked with the interfering substance and tested.
- Data Provenance: Not specified. Appears to be prospective.
-
Analytical Range Study (Test Set):
- The sample size used to establish the analytical range (linearity) is not explicitly stated. These studies typically use a series of diluted/spiked samples to cover the claimed range.
- Data Provenance: Not specified. Appears to be prospective.
3. Number of Experts and Qualifications for Ground Truth
- No external "experts" (e.g., radiologists) were explicitly used to establish ground truth for these analytical performance studies.
- For an in vitro diagnostic (IVD) device like a bilirubin assay, "ground truth" is typically established by:
- Reference Methods: The "AACC Reference Method" is stated as the standardization method for both the new device and the predicate. This is a highly standardized and validated analytical method.
- Predicate Device: The predicate device itself (ADVIA IMS Total Bilirubin) serves as a gold standard or "truth" for comparison in the method correlation studies. Its results are assumed to be accurate.
- Known Concentrations: For studies like imprecision, interfering substances, and analytical range, commercial controls or spiked samples with known, verified concentrations are used.
4. Adjudication Method for the Test Set
- Not applicable. This product is an in vitro diagnostic (IVD) lab assay. Adjudication, particularly multi-reader methods (e.g., 2+1, 3+1), is typically relevant for interpretative devices like imaging diagnostics where human readers make a judgment, and their discrepancies need to be resolved. For a quantitative chemical assay, the measurement itself is the output, and any discrepancies would be resolved through re-testing, calibration checks, or investigation into analytical errors, rather than expert adjudication of a qualitative result.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC study was done. This type of study is for interpretative devices involving human perception (e.g., radiology AI). The ADVIA Chemistry Total Bilirubin_2 is a quantitative analytical device that produces numerical results, not images or qualitative interpretations that a human reads. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply here.
6. Standalone (Algorithm Only) Performance Study
- Yes, this entire submission is a standalone performance study in the context of an IVD. The device is the algorithm/reagent system that performs the measurement without human interpretation of the primary data (other than reading the final numerical output). The performance data (imprecision, correlation, etc.) reflects the algorithm/reagent system's capabilities without human-in-the-loop directly influencing the outputted bilirubin concentration. Human interaction is limited to operating the instrument, loading samples, and interpreting the final numerical result in a clinical context.
7. Type of Ground Truth Used
- Reference Methods and Predicate Device:
- For standardization, the AACC Reference Method is explicitly stated as the ground truth.
- For method comparison/correlation, the ADVIA IMS Total Bilirubin assay (predicate device) served as the comparison method, implicitly representing the accepted "truth" for validating the new device's accuracy.
- For imprecision, analytical range, and interfering substances, the ground truth would have been established using calibrated materials, known-concentration controls, and carefully prepared spiked samples.
8. Sample Size for the Training Set
- Not applicable / Not explicitly stated for algorithm training. This device is a traditional chemical assay, not an AI/ML-based device that undergoes a distinct "training" phase with a large dataset in the sense of machine learning algorithms. The development of such an assay involves chemical formulation, optimization, and extensive analytical validation in a laboratory setting, but not typically "training data" as would be used for neural networks or similar AI.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As explained above, this is not an AI/ML device with a training set in the conventional sense. The "ground truth" for the device's development and optimization would have been established through standard chemical and laboratory practices, utilizing reference methods, standards, and control materials to ensure the reagents and measurement principles were accurate and robust.
§ 862.1110 Bilirubin (total or direct) test system.
(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.