(263 days)
In vitro test for the quantitative determination of the total bilirubin concentration in human serum on COBAS Integra systems. Measurement of the level of bilirubin is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.
The Cobas Integra Bilirubin Total reagent is intended for use with the Cobas Integra systems for the quantitative determination of the total bilirubin concentration in human serum.
The provided text describes the 510(k) summary for the COBAS INTEGRA 400/800 Bilirubin Total device. This document is a premarket notification for an in vitro diagnostic (IVD) device, which are typically assessed for analytical performance characteristics rather than clinical performance based on ground truth established by experts.
Therefore, many of the requested categories (e.g., number of experts, adjudication method, MRMC study, sample size for training set, how ground truth for training set was established) are not applicable to this type of device submission. The study focuses on demonstrating analytical performance metrics like precision, accuracy (method comparison), measuring range, and sensitivity.
Here's the breakdown of the available information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a separate section with pass/fail thresholds. Instead, it presents the performance characteristics of the modified device and compares them to the predicate device, implying that equivalence to the predicate's performance or standard analytical performance is the "acceptance criteria."
| Characteristic | Acceptance Criteria (Implied / Predicate Performance) | Reported Device Performance (Modified COBAS Integra Bilirubin Total) |
|---|---|---|
| Measuring Range | Test range: 0-340 umol/L (0-20 mg/dL) w/ postdilution: 0-1020 umol/L (0-60 mg/dL) Postdilution factor: 3 | 1.7-340 umol/L (0.099-20 mg/dL). Samples with higher concentrations can be determined via rerun function (1:3 dilution), results automatically multiplied by 3. |
| Lower Detection Limit | Sensitivity: 2.9 x 10-3 ΔA per umol/L (5.0 x 10-2 ΔA per mg/dL) total bilirubin | 1.7 umol/L (0.099 mg/dL). Calculated as zero sample + 3 SD (within-run precision, n=30). |
| Precision (Reproducibility) | Level 1: Mean: 24.2 umol/L (1.4 mg/dL); CV w/in run: 0.46%; CV day/day: 0.48%; CV total: 0.78% | |
| Level 2: Mean: 72.5 umol/L (4.2 mg/dL); CV w/in run: 0.45%; CV day/day: 0.53%; CV total: 0.80% | Level 1: Mean: 24.2 umol/L (1.4 mg/dL); CV w/in run: 0.45%; CV total: 0.78% | |
| Level 2: Mean: 72.5 umol/L (4.2 mg/dL); CV w/in run: 0.53%; CV total: 0.80% | ||
| (Note: Table format is slightly different, but values are very similar) | ||
| Accuracy (Method Comparison) | Cobas Mira vs. Predicate: Sample size (n) 208, Values 1.7 to 350.6 umol/L (0.1 to 20.5 mg/dL), Corr Coefficient (r) 0.999, Lin Regression y = 1.00x + 1.2 umol/L, Passing Bablock y = 1.00x + 0.6 umol/L | |
| Alternative System vs. Predicate: Sample size (n) 210, Values 1.7 to 350.6 umol/L (0.1 to 20.5 mg/dL), Corr Coefficient (r) 0.999, Lin Regression y = 0.93x + 0.8 umol/L, Passing Bablock y = 0.93x + 0.4 umol/L | Modified vs. Cobas Integra Total Bilirubin Special (Cobas Integra 800): Sample size (n) = 49, Values 5.49 to 317 umol/L (0.321 to 18.5 mg/dL), Passing/Bablok y = 0.956x + 2.113 umol/L, r = 0.999 | |
| Modified vs. Roche/Hitachi 911 (Cobas Integra 400): Sample size (n) = 104, Values 3.29 to 282 umol/L (0.192 to 16.5 mg/dL), Linear regression y = 0.989x - 0.520 umol/L, Passing/Bablok y = 0.991x + 0.219 umol/L, r = 0.999 | ||
| Limitations – Interference (Hemolysis) | Avoid hemolyzed specimens. Even slight hemolysis interferes with the test. | No significant interference up to an H index of 10 (approximate hemoglobin concentration 6 umol/L or 10 mg/dL). |
| Limitations – Interference (Lipemia) | Avoid lipemic specimens. Even slight lipemia interferes with the test. | No significant interference up to an L index of 9. |
| Limitations – Interference (Drugs) | Propranolol and theophylline cause artificially low total bilirubin values. | No interference found except for Propranolol and theophylline (causing artificially low values). Hydroxocobalamin (Cyanokit) may cause false-high results. In very rare cases, gammopathy (Type IgM / Waldenstrom's macroglobulinemia) may cause unreliable results. |
2. Sample Size Used for the Test Set and Data Provenance:
- Precision (Reproducibility):
- Within-run: n=20
- Between-run: n=20 (These likely refer to replicates per sample/control, not unique patient samples. The NCCLS manual EP5-T2, referenced for the predicate, typically involves multiple days/runs.)
- Accuracy (Method Comparison):
- Cobas Integra 800 Analyzer (comparison against Cobas Integra Total Bilirubin Special): n = 49 human serum samples.
- Cobas Integra 400 Analyzer (comparison against Roche/Hitachi 911 analyzer): n = 104 human serum samples.
- Lower Detection Limit: n=30 (for within-run precision of a zero sample).
Data Provenance: The method comparison studies used "human serum samples." The document does not specify the country of origin. Given Roche Diagnostics is listed with an Indianapolis, IN address, it's reasonable to infer a US-based study, but this is not explicitly stated. The studies appear to be retrospective in the sense that they tested samples to evaluate device performance post-development.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
Not applicable. For IVD devices like this bilirubin assay, "ground truth" is established by reference methods or validated comparative methods (other commercially available or predicate devices), not by expert human interpretation.
4. Adjudication Method for the Test Set:
Not applicable. There is no expert adjudication for chemical assays.
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:
Not applicable. This is an automated analytical device, not an imaging device requiring human readers or AI assistance in interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the studies described (precision, accuracy, sensitivity, linearity, interference) are all standalone performance evaluations of the analytical device. The "algorithm" here is the chemical assay and the instrument's processing of the spectrophotometric readings.
7. The Type of Ground Truth Used:
For analytical devices, "ground truth" is typically established by:
- Reference methods: Highly accurate and precise methods often used in specialized laboratories for validation.
- Comparative methods: Established, legally marketed devices (predicate devices or other commercially available, validated assays) that serve as a comparative standard.
In this submission, the ground truth for the accuracy studies was established by comparison with other established bilirubin measurement systems:
- Cobas Integra Total Bilirubin Special reagent on a Cobas Integra 800 analyzer.
- Commercially available reagents for total bilirubin on a Roche/Hitachi 911 analyzer.
8. The Sample Size for the Training Set:
Not applicable. This is not a machine learning or AI device that undergoes a discrete "training" phase with a specific dataset. Its performance is based on the chemical reactions and optical detection system.
9. How the Ground Truth for the Training Set Was Established:
Not applicable. See point 8.
§ 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.