(MODIFIED VERSION) INTEGRA ION SELECTIVE ELECTRODE (ISE) MODULE
Device Facts
| Record ID | K963627 |
|---|---|
| Device Name | (MODIFIED VERSION) INTEGRA ION SELECTIVE ELECTRODE (ISE) MODULE |
| Applicant | Roche Diagnostic Systems, Inc. |
| Product Code | JGS · Clinical Chemistry |
| Decision Date | Oct 24, 1996 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1665 |
| Device Class | Class 2 |
Intended Use
The COBAS INTEGRA ISE module applications are intended for use for the quantitative determination of sodium, potassium, chloride, and lithium concentrations using ion-selective electrodes: the direct application is intended for undiluted serum and plasma; the indirect application is intended for diluted serum and plasma (does not include lithium); the urine application is intended for diluted urine (does not include lithium).
Device Story
The COBAS INTEGRA ISE Module is an automated diagnostic system component for the COBAS INTEGRA Analyzer. It utilizes ion-selective electrodes (ISE) to measure electrolyte concentrations in serum, plasma, or urine. The system processes samples via robotics and a user interface, with reagent cassettes stored on-board at 2-8°C. Barcode readers identify samples, reagents, and calibration data. The device transforms electrochemical signals from the ISE into quantitative concentration values. It is used in clinical laboratory settings by trained personnel. The output is provided to healthcare providers to assist in clinical decision-making regarding electrolyte balance and patient monitoring. The system streamlines workflow through random sample access and high throughput (up to 600 tests/hour).
Clinical Evidence
Bench testing only. Precision evaluated per NCCLS EP5-T2 guidelines using two levels of controls. Correlation studies performed comparing subject device applications against predicate analyzers (Hitachi 911, Kodak Ectachem 250) using >200 specimens per application. Results analyzed via linear regression; correlation coefficients (r) ranged from 0.964 to 0.999 across all analytes (Sodium, Potassium, Chloride, Lithium).
Technological Characteristics
Ion-selective electrode (ISE) sensing principle. System utilizes reagent cassettes with on-board storage at 2-8°C. Connectivity includes barcode readers for sample and reagent identification. Throughput up to 600 tests/hour. Automated system with robotics and user interface for workflow management.
Indications for Use
Indicated for quantitative determination of sodium, potassium, chloride, and lithium in serum, plasma, or urine samples for diagnostic testing.
Regulatory Classification
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.
Predicate Devices
- BM / Hitachi 911 Sodium (Indirect) (K912648)
- BM / Hitachi 911 Potassium (Indirect) (K912649)
- BM / Hitachi 911 Chloride (Indirect) (K912647)
- Kodak Ectachem Lithium (K924488)
- ISE Solution 1 (K951595)
- ISE Solution 2 (K951595)
- ISE Solution 3 (K951595)
Related Devices
- K123726 — COBAS 8000 ISE INDIRECT NA, K, CI FOR GEN. 2 · Roche Diagnostics · May 21, 2013
- K053165 — ISE INDIRECT NA, K, CL FOR GEN.2 · Roche Diagnostics Corp. · Dec 14, 2005
- K140373 — ISE INDIRECT NA, K, C1 FOR GEN 2 · Roche Diagnostics · May 22, 2014
- K230890 — ISE Electrodes · Randox Laboratories, Ltd. · Sep 8, 2023
Submission Summary (Full Text)
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OCT 24 1996
K963627
Roche Diagnostic Systems
A Member of the Roche Group
Roche Diagnostic Systems, Inc.
Branchburg Township
1080 U.S. Highway 202
Somerville, New Jersey 08876-3771
Direct Dial
Fax
# 510(k) Summary
Roche COBAS INTEGRA ISE Module Modification
In accordance with the Safe Medical Devices Act of 1990, a 510(k) summary as outlined in 21 CFR 807.92 is provided herewith.
## I. Identification of 510(k) Sponsor:
Roche Diagnostic Systems, Inc.
a subsidiary of Hoffmann-La Roched, Inc.
Branchburg Township
1080 US Highway 202
Somerville, NJ 08876-3771
510(k) Submission dated September 10, 1996
## II. Description of the Device/Statement of Intended Use:
The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for *in vitro* diagnostic testing. The COBAS INTEGRA Analyzer along with 79 COBAS INTEGRA Reagent Cassettes were cleared on September 8, 1995 (K951595), January 25, 1996 (K954992) and July 23, 1996 (K961824). The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8°C. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with
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the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents.
Through this submission, it is the intention of Roche Diagnostic Systems to gain clearance of a modified ISE Module which includes modified versions of the Direct Sodium, Direct Potassium, and Direct Chloride applications. These applications were previously cleared on September 8, 1995 (K951595). This premarket notification also includes new ISE applications for Direct Lithium, Indirect Sodium, Indirect Potassium, Indirect Chloride, Urine Sodium, Urine Potassium, and Urine Chloride.
The COBAS INTEGRA ISE module applications are intended for use for the quantitative determination of sodium, potassium, chloride, and lithium concentrations using ion-selective electrodes:
- the direct application is intended for undiluted serum and plasma
- the indirect application is intended for diluted serum and plasma (does not include lithium)
- the urine application is intended for diluted urine (does not include lithium)
## III. Identification of the legally marketed device to which the 510(k) sponsor claims equivalence:
The COBAS INTEGRA ISE Module applications are substantially equivalent to the corresponding applications for the Boehringer Mannheim / Hitachi 911 analyzer or the Kodak Ectachem 250 analyzer.
The ancillary reagents for the COBAS INTEGRA ISE Module were previously cleared in the original 510(k) for the ISE Module (K951595). However, ISE Solution 1 is now intended to be sold in two new packages with different names, "Calibrator Direct" and in a diluted form as "Calibrator Indirect/Urine". The new containers are larger and are stored on board the instrument, instead of using multiple vials of ISE Solution 1 in the ISE reagent rack.
The following table lists each ISE application and ancillary reagents with the corresponding predicate device or previously cleared device name.
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Table of Predicate Devices
| Product Name | Predicate Product Name | K number | date of substantial equivalence |
| --- | --- | --- | --- |
| Roche COBAS INTEGRA ISE Module Tests: | | | |
| Direct Sodium | BM / Hitachi 911 Sodium (Indirect) | K912648 | 07/17/91 |
| Direct Potassium | BM / Hitachi 911 Potassium (Indirect) | K912649 | 07/15/91 |
| Direct Chloride | BM / Hitachi 911 Chloride (Indirect) | K912647 | 07/17/91 |
| Direct Lithium | Kodak Ectachem Lithium | K924488 | 01/26/93 |
| Indirect Sodium | BM / Hitachi 911 Sodium (Indirect) | K912648 | 07/17/91 |
| Indirect Potassium | BM / Hitachi 911 Potassium (Indirect) | K912649 | 07/15/91 |
| Indirect Chloride | BM / Hitachi 911 Chloride (Indirect) | K912647 | 07/17/91 |
| Urine Sodium | BM / Hitachi 911 Sodium (Urine) | K912648 | 07/17/91 |
| Urine Potassium | BM / Hitachi 911 (Urine) | K912649 | 07/15/91 |
| Urine Chloride | BM / Hitachi 911 (Urine) | K912647 | 07/17/91 |
| Roche COBAS INTEGRA ISE Module Ancillary Reagents | Previously approved Product Name | K Number | date of substantial equivalence |
| ISE Solution 1 | ISE Solution 1 | K951595 | 09/08/95 |
| ISE Solution 2 | ISE Solution 2 | K951595 | 09/08/95 |
| ISE Solution 3 | ISE Solution 3 | K951595 | 09/08/95 |
| ISE Calibrator Direct | ISE Solution 1 | K951595 | 09/08/95 |
| ISE Calibrator Indirect / Urine | ISE Solution 1 (diluted) | K951595 | 09/08/95 |
IV. Summary of the technological characteristics of the new device in comparison to those of the predicate.
A summary of the similarities, differences and performance characteristics between the COBAS INTEGRA ISE Module applications and the corresponding Boehringer Mannheim / Hitachi 911 or Kodak Ectachem 250 applications are listed in the following tables.
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Comparison Table - Direct Sodium
| | COBAS INTEGRA
Current ISE Direct
Sodium Application | COBAS INTEGRA
Modified ISE Direct
Sodium Application | Boehringer
Mannheim/Hitachi 911
Sodium |
| --- | --- | --- | --- |
| Intended Use | quantitative
determination of sodium | quantitative determination
of sodium | quantitative determination of
sodium |
| Sample type | serum and plasma | serum and plasma | serum, plasma and urine |
| Methodology | Ion Selective Electrode -
Direct | Ion Selective Electrode -
Direct | Ion Selective Electrode -
Indirect |
| Standards | ISE Sol'n 1: 150 mmol/L
ISE Sol'n 2: 110 mmol/L | ISE Sol'n 1: 150 mmol/L
ISE Sol'n 2: 110 mmol/L | STD 1: 120.0 mmol/L
STD 2: 160.0 mmol/L |
| Performance Characteristics: | | | |
| Test Range | 20 - 250 mmol/L | 20 - 250 mmol/L | 80 - 180 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
135.7 153.7
0.40 0.17
1.1 1.6 | Level 1 Level 2
116 146
0.32 0.25
1.0 0.69 | Level 1 Level 2 Level 3
128.9 137.5 148.5
0.3 0.2 0.2
0.5 0.4 0.6 |
| Accuracy | y= 1.06x - 5.1 mmol/L
r= 0.998 n=100
vs. BM / Hitachi 911 | y= 0.99x + 5.3 mmol/L
r= 0.989 n= 208
vs. BM / Hitachi 911 | y= 1.018x - 2.35 mmol/L
r= 0.999 n= 45
vs. flame photometry |
Comparison Table - Direct Potassium
| | COBAS INTEGRA
Current ISE Direct
Potassium Application | COBAS INTEGRA
Modified ISE Direct
Potassium Application | Boehringer
Mannheim/Hitachi 911
Potassium |
| --- | --- | --- | --- |
| Intended Use | quantitative determination
of potassium | quantitative determination
of potassium | quantitative determination
of potassium |
| Sample type | serum and plasma | serum and plasma | serum and plasma |
| Methodology | Ion Selective Electrode -
Direct | Ion Selective Electrode -
Direct | Ion Selective Electrode -
Indirect |
| Standards | ISE Sol'n 1: 5 mmol/L
ISE Sol'n 2: 1.8 mmol/L | ISE Sol'n 1: 5 mmol/L
ISE Sol'n 2: 1.8 mmol/L | STD 1: 3.00 mmol/L
STD 2: 7.00 mmol/L |
| Performance Characteristics: | | | |
| Test Range | 0.2 - 30 mmol/L | 0.2 - 30 mmol/L | 1.5 - 10.0 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
3.18 7.25
0.30 0.42
1.5 1.8 | Level 1 Level 2
4.3 7.2
0.24 0.29
0.75 0.89 | Level 1 Level 2 Level 3
3.41 5.69 6.40
0.3 0.2 0.3
0.7 0.5 0.7 |
| Accuracy | y= 1.07x - 0.22 mmol/L
r= 0.999 n=100
vs. BM / Hitachi 911 | y= 1.03x + 0.02 mmol/L
r= 0.998 n= 208
vs. BM / Hitachi 911 | y= 1.041x - 0.177 mmol/L
r= 0.999 n= 52
vs. flame photometry |
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Comparison Table - Direct Chloride
| | COBAS INTEGRA
Current ISE Direct
Chloride Application | COBAS INTEGRA
Modified ISE Direct
Chloride Application | Boehringer
Mannheim/Hitachi 911
Chloride |
| --- | --- | --- | --- |
| Intended Use | quantitative determination
of chloride | quantitative determination
of chloride | quantitative determination of
chloride |
| Sample type | serum and plasma | serum and plasma | serum, and urine |
| Methodology | Ion Selective Electrode -
Direct | Ion Selective Electrode -
Direct | Ion Selective Electrode -
Indirect |
| Standards | ISE Sol'n 1: 115 mmol/L
ISE Sol'n 2: 72 mmol/L | ISE Sol'n 1: 115 mmol/L
ISE Sol'n 2: 72 mmol/L | STD 1: 80.0 mmol/L
STD 2: 120.0 mmol/L |
| Performance Characteristics: | | | |
| Test Range | 20 - 250 mmol/L | 20 - 250 mmol/L | 60 - 140 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
135.7 153.7
0.40 0.17
1.1 1.6 | Level 1 Level 2
92 106
0.39 0.37
1.3 0.85 | Level 1 Level 2 Level 3
89.2 102.2 113.7
0.4 0.3 0.3
0.7 0.5 0.8 |
| Accuracy | y= 1.19x - 17.9 mmol/L
r= 0.996 n=100
vs. BM / Hitachi 911 | y= 0.91x + 12.8 mmol/L
r= 0.969 n= 208
vs. BM / Hitachi 911 | y= 1.073x - 8.80 mmol/L
r= 0.999 n= 42
vs. chloridometer |
Comparison Table - Direct Lithium
| | COBAS INTEGRA ISE Direct
Lithium Application | Kodak Ectachem Lithium |
| --- | --- | --- |
| Intended Use | quantitative determination of lithium | quantitative determination of lithium |
| Sample type | serum and plasma | serum and plasma |
| Methodology | Ion Selective Electrode - Direct | Colorimetric |
| Standards | ISE Sol'n 1: 0.3 mmol/L
ISE Sol'n 2: 0.3 mmol/L
ISE Sol'n 3: 1.4 mmol/L | information not available |
| Performance Characteristics: | | |
| Test Range | 0.1 - 4 mmol/L | 0.20 - 4.00 mmol/L |
| Precision:
Mean (mmol/L)
%CV (total) | Level 1 Level 2
0.44 1.9
3.4 2.9 | Level 1 Level 2 Level 3 Level 4
0.47 0.96 1.17 2.14
6.93 4.76 3.86 3.12 |
| Accuracy | y= 0.98x - 0.10 mmol/L
r= 0.964 n= 244
vs. Kodak Ectachem | y= 1.00x - 0.03 mmol/L
r= 0.991 n= 200
vs. ion-selective electrode |
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# Comparison Table - Indirect Sodium
| | COBAS INTEGRA Modified ISE Indirect Sodium Application | Boehringer Mannheim/Hitachi 911 Sodium |
| --- | --- | --- |
| Intended Use | quantitative determination of sodium | quantitative determination of sodium |
| Sample type | serum and plasma | serum, plasma and urine |
| Methodology | Ion Selective Electrode - Indirect | Ion Selective Electrode - Indirect |
| Standards | ISE Sol'n 1: 150 mmol/L
ISE Sol'n 2: 110 mmol/L | STD 1: 120.0 mmol/L
STD 2: 160.0 mmol/L |
| Performance Characteristics: | | |
| Test Range | 20 - 250 mmol/L | 80 - 180 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
112 138
0.26 0.24
1.0 0.59 | Level 1 Level 2 Level 3
128.9 137.5 148.5
0.3 0.2 0.2
0.5 0.4 0.6 |
| Accuracy | y= 0.96x - 1.2 mmol/L
r= 0.994 n= 208
vs. BM / Hitachi 911 | y= 1.018x - 2.35 mmol/L
r= 0.999 n= 45
vs. flame photometry |
# Comparison Table - Indirect Potassium
| | COBAS INTEGRA ISE Indirect Potassium Application | Boehringer Mannheim/Hitachi 911 Potassium |
| --- | --- | --- |
| Intended Use | quantitative determination of potassium | quantitative determination of potassium |
| Sample type | serum and plasma | serum, plasma and urine |
| Methodology | Ion Selective Electrode - Indirect | Ion Selective Electrode - Indirect |
| Standards | ISE Sol'n 1: 5 mmol/L
ISE Sol'n 2: 1.8 mmol/L | STD 1: 3.00 mmol/L
STD 2: 7.00 mmol/L |
| Performance Characteristics: | | |
| Test Range | 0.2 - 30 mmol/L | 1.5 - 10.0 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
4.3 6.9
0.44 0.31
0.75 0.83 | Level 1 Level 2 Level 3
3.41 5.69 6.40
0.3 0.2 0.3
0.7 0.5 0.7 |
| Accuracy | y= 1.00x - 0.09 mmol/L
r= 0.999 n= 208
vs. BM / Hitachi 911 | y= 1.041x - 0.177 mmol/L
r= 0.999 n= 52
vs. flame photometry |
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Comparison Table - Indirect Chloride
| | COBAS INTEGRA ISE Indirect Chloride Application | Boehringer Mannheim/Hitachi 911 Chloride |
| --- | --- | --- |
| Intended Use | quantitative determination of chloride | quantitative determination of chloride |
| Sample type | serum and plasma | serum, plasma and urine |
| Methodology | Ion Selective Electrode - Indirect | Ion Selective Electrode - Indirect |
| Standards | ISE Sol'n 1: 115 mmol/L
ISE Sol'n 2: 72 mmol/L | STD 1: 80.0 mmol/L
STD 2: 120.0 mmol/L |
| Performance Characteristics: | | |
| Test Range | 20 - 250 mmol/L | 60 - 140 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
92 107
0.36 0.26
1.1 0.83 | Level 1 Level 2 Level 3
89.2 102.2 113.7
0.4 0.3 0.3
0.7 0.5 0.8 |
| Accuracy | y= 0.90x + 11.1 mmol/L
r= 0.980 n= 208
vs. BM / Hitachi 911 | y= 1.073x - 8.80 mmol/L
r= 0.999 n= 42
vs. chloridometer |
Comparison Table - Urine Sodium
| | COBAS INTEGRA ISE Urine Sodium Application | Boehringer Mannheim/Hitachi 911 Sodium |
| --- | --- | --- |
| Intended Use | quantitative determination of sodium | quantitative determination of sodium |
| Sample type | urine | serum, plasma and urine |
| Methodology | Ion Selective Electrode - Indirect | Ion Selective Electrode - Indirect |
| Standards | ISE Sol'n 1: 150 mmol/L
ISE Sol'n 2: 110 mmol/L | STD 1: 120.0 mmol/L
STD 2: 160.0 mmol/L |
| Performance Characteristics: | | |
| Test Range | 20 - 350 mmol/L | 10 - 250 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
56 259
1.0 0.49
3.0 1.2 | Level 1 Level 2 Level 3
58.3 107.2 177.4
0.4 0.3 0.3
1.0 0.6 0.6 |
| Accuracy | y= 0.95x + 3.4 mmol/L
r= 0.996 n= 174
vs. BM / Hitachi 911 | y= 0.963x + 3.06
r= 1.000 n= 49
vs. flame photometry |
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Comparison Table - Urine Potassium
| | COBAS INTEGRA ISE Urine Potassium Application | Boehringer Mannheim/Hitachi 911 Potassium |
| --- | --- | --- |
| Intended Use | quantitative determination of potassium | quantitative determination of potassium |
| Sample type | urine | serum, plasma and urine |
| Methodology | Ion Selective Electrode - Indirect | Ion Selective Electrode - Indirect |
| Standards | ISE Sol'n 1: 5 mmol/L
ISE Sol'n 2: 1.8 mmol/L | STD 1: 3.00 mmol/L
STD 2: 7.00 mmol/L |
| Performance Characteristics: | | |
| Test Range | 1 - 150 mmol/L | 1.5 - 80 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
33 125
0.26 0.67
1.4 2.0 | Level 1 Level 2 Level 3
22.9 44.1 69.5
0.4 0.7 0.9
0.8 1.1 1.6 |
| Accuracy | y= 1.04x - 0.7 mmol/L
r= 0.999 n= 162
vs. BM / Hitachi 911 | y= 1.035x + 1.45
r= 0.999 n= 42
vs. flame photometry |
Comparison Table - Urine Chloride
| | COBAS INTEGRA ISE Urine Chloride Application | Boehringer Mannheim/Hitachi 911 Chloride |
| --- | --- | --- |
| Intended Use | quantitative determination of chloride | quantitative determination of chloride |
| Sample type | urine | serum, plasma and urine |
| Methodology | Ion Selective Electrode - Indirect | Ion Selective Electrode - Indirect |
| Standards | ISE Sol'n 1: 115 mmol/L
ISE Sol'n 2: 72 mmol/L | STD 1: 80.0 mmol/L
STD 2: 120.0 mmol/L |
| Performance Characteristics: | | |
| Test Range | 20 - 350 mmol/L | 1.5 - 80 mmol/L |
| Precision:
Mean (mmol/L)
%CV (within run)
%CV (total) | Level 1 Level 2
147 274
0.44 0.30
1.1 2.1 | Level 1 Level 2 Level 3
50.3 122.5 202.0
0.7 0.7 0.6
1.6 0.9 1.2 |
| Accuracy | y= 0.95x + 11.0 mmol/L
r= 0.981 n= 164
vs. BM / Hitachi 911 | y= 1.033x - 3.08
r= 0.996 n= 41
vs. flame photometry |
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V. Breif discussion of the clinical and nonclinical tests relied on for a determination of substantial equivalence:
To demonstrate equivalence in performance characteristics, the COBAS INTEGRA ISE Module applications were tested for precision and accuracy. See tables in previous section for results.
**Precision Study**
Precision was evaluated using two levels of controls following the guidelines from NCCLS EP5-T2.
**Correlation Study**
Correlation studies were done comparing the Sodium, Potassium, Chloride, and Lithium applications with the corresponding applications on the Boehringer Mannheim / Hitachi 911 analyzer and Lithium with the Kodak Ectachem 250 application. Greater than 200 specimens were tested on both systems for each application. The results were evaluated using linear regression analysis.
