(168 days)
The ISE module of the Roche/Hitachi cobas c system is intended for the quantitative determination of sodium, potassium and chloride in serum, plasma or urine using ion-selective electrodes.
The cobas 8000 ISE module is a fully automated ion-specific analyzer intended for the in vitro potentiometric determination of chloride, potassium, and sodium in serum, plasma, and urine using ion-selective electrodes. Measurements obtained by this device are used in the diagnosis and treatment of diseases or conditions involving electrolyte imbalance.
The cobas 8000 ISE module is an Ion-Selective Electrode (ISE) system for the determination of sodium, potassium, and chloride in serum, plasma, and urine. The cobas 8000 ISE module and the ISE Gen 2 reagents were previously cleared for serum and plasma sample types under K100853. This premarket notification seeks to obtain FDA review and clearance for the urine sample type for the ISE Gen 2 reagents on the cobas 8000 ISE module.
An ISE makes use of the unique properties of certain membrane materials to develop an electrical potential (electromotive force, EMF) for the measurements of ions in solution. The electrode has a selective membrane in contact with both the test solution and an internal filling solution. The internal filling solution contains the test ion at a fixed concentration. Because of the particular nature of the membrane, the test ions will closely associate with the membrane on each side. The membrane EMF is determined by the difference in concentration of the test ion in the test solution and the internal filling solution. The EMF develops according to the Nernst equation for a specific ion in solution (see package insert for further explanation). Please refer to K100853 for detailed hardware and software information relating to the cobas 8000 modular analyzer series.
Commercially available controls are recommended for the urine sample type. Aqueous ISE standard calibrators (S1, S2, and S3) were cleared under K053165 and ISE Compensator under K052193.
The cobas 8000 ISE Indirect Na, K, Cl for Gen. 2 device is intended for the in vitro potentiometric determination of chloride, potassium, and sodium in serum, plasma, and urine using ion-selective electrodes. This summary outlines the acceptance criteria and the study results demonstrating the device's performance.
1. Acceptance Criteria and Reported Device Performance
The device's performance was evaluated against a predicate device (COBAS INTEGRA ISE cleared under K963627) and, for method comparison, against reference methods (flame photometer for Sodium and Potassium, coulometry for Chloride). While explicit acceptance criteria (e.g., target CV% or correlation coefficients) are not directly stated as numerical thresholds for substantial equivalence, the reported performance metrics are compared to the predicate device and reference methods to demonstrate analytical validity. The tables below summarize the reported performance for the cobas 8000 Urine ISE.
Sodium Performance
| Parameter | Acceptance Criteria (Implied by Predicate/Reference) | cobas 8000 Urine ISE Performance |
|---|---|---|
| Repeatability (CV%) | Comparable to predicate (Low: 1.0%, High: 0.49%) | Low: 0.6%, Med: 0.5%, High: 0.2%, Liq 1: 0.4%, Liq 2: 0.3% |
| Intermediate Precision (CV%) | Comparable to predicate (Low: 3.0%, High: 1.2%) | Low: 1.6%, Med: 0.6%, High: 0.7%, Liq 1: 1.4%, Liq 2: 0.6% |
| Method Comparison to Reference (Flame Photometer) | High Correlation, Slope ~1, Intercept ~0 | N=59, Days=2, Correlation=0.9997, Slope=0.976, Intercept=4.3548 |
| Method Comparison to Predicate | High Correlation, Slope ~1, Intercept ~0 | N=59, Days=2, Correlation=0.9996, Slope=0.930, Intercept=12.0671 |
| Reportable Range | 20-350 mmol/L (Predicate) | 60-350 mmol/L |
Potassium Performance
| Parameter | Acceptance Criteria (Implied by Predicate/Reference) | cobas 8000 Urine ISE Performance |
|---|---|---|
| Repeatability (CV%) | Comparable to predicate (Low: 0.26%, High: 2.0%) | Low: 1.2%, 0.6%, 0.8%, 0.6%, 0.6% (multiple levels) |
| Intermediate Precision (CV%) | Comparable to predicate (Low: 1.4%, High: 2.0%) | Low: 1.7%, 1.3%, 1.6%, 1.2%, 1.7% (multiple levels) |
| Method Comparison to Reference (Flame Photometry) | High Correlation, Slope ~1, Intercept ~0 | N=59, Days=2, Correlation=0.9993, Slope=0.962, Intercept=1.7605 |
| Method Comparison to Predicate | High Correlation, Slope ~1, Intercept ~0 | N=59, Days=2, Correlation=0.9997, Slope=0.920, Intercept=1.4589 |
| Reportable Range | 1-150 mmol/L (Predicate) | 3-100 mmol/L |
Chloride Performance
| Parameter | Acceptance Criteria (Implied by Predicate/Reference) | cobas 8000 Urine ISE Performance |
|---|---|---|
| Repeatability (CV%) | Comparable to predicate (Low: 0.44%, High: 0.30%) | Low: 0.7%, Med: 0.5%, High: 0.3%, Liq 1: 0.5%, Liq 2: 0.3% |
| Intermediate Precision (CV%) | Comparable to predicate (Low: 1.1%, High: 2.1%) | Low: 1.7%, Med: 0.7%, High: 1.0%, Liq 1: 1.2%, Liq 2: 0.9% |
| Method Comparison to Reference (Coulometry) | High Correlation, Slope ~1, Intercept ~0 | N=59, Days=2, Correlation=0.9985, Slope=1.092, Intercept=-11.2893 |
| Method Comparison to Predicate | High Correlation, Slope ~1, Intercept ~0 | N=59, Days=2, Correlation=0.9997, Slope=0.952, Intercept=0.5078 |
| Reportable Range | 20-350 mmol/L (Predicate) | 60-350 mmol/L |
2. Sample Size and Data Provenance for the Test Set
- Sample Size for Test Set:
- Method Comparison (to reference method and predicate): N = 59 unique samples were used for the method comparison studies for Sodium, Potassium, and Chloride. These samples were tested over 2 days.
- Repeatability and Intermediate Precision: The number of unique samples for these studies is not explicitly stated as 'test set' but rather multiple levels of controls/samples were run, e.g., "Low", "Med", "High", "Liq 1", "Liq 2" for the cobas 8000 Urine ISE. The data presented are statistical summaries (mean, SD, CV%) derived from these runs.
- Data Provenance: The document does not explicitly state the country of origin for the data. However, the submitter is Roche Diagnostics (Indianapolis, IN, USA) with establishment registration in Mannheim, Germany, suggesting the studies could have been conducted in either or both locations. The studies appear to be prospective as they detail the evaluation of the new device for urine sample types.
3. Number of Experts and Qualifications for Ground Truth
Not applicable. This is a submission for an in vitro diagnostic device (analyzing electrolytes) where the 'ground truth' is established by established reference methods (e.g., flame photometry, coulometry) or by comparison to a legally marketed predicate device, not by expert human interpretation of medical images or other subjective data.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth is established by objective laboratory methods, not by human interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an IVD device and does not involve human readers for interpretation, thus an MRMC study is not relevant.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire submission details the performance of the cobas 8000 ISE module as an algorithm-only (device-only) without human-in-the-loop performance measurement. The repeatability, intermediate precision, method comparison, detection limits (LOB, LOD, LOQ), and reportable range data reflect the standalone performance of the device.
7. Type of Ground Truth Used
The ground truth used for performance evaluation includes:
- Reference Methods:
- For Sodium and Potassium: Flame Photometer
- For Chloride: Coulometry
- Comparison to a Predicate Device: COBAS INTEGRA ISE (K963627)
8. Sample Size for the Training Set
Not applicable. This device is a diagnostic instrument using ion-selective electrodes, not a machine learning or AI algorithm that requires a "training set" in the context of supervised learning. The device's calibration and controls would be analogous to continuous internal checks, but there isn't a "training set" in the traditional AI sense.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no training set in the context of an AI algorithm. The device's operational parameters and calibration are established through physical and chemical principles of ion-selective electrodes, and validated through the performance studies described.
§ 862.1665 Sodium test system.
(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.