Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on the principles of ion-selective electrodes and a modification to the calibration procedure, with no mention of AI or ML technologies.

Therapeutic

No.
This device is an in-vitro diagnostic (IVD) device used for the quantitative determination of sodium, potassium, and chloride in patient samples. It provides diagnostic information but does not directly deliver therapy or treat a condition.

Diagnostic

Yes

The device quantifies sodium, potassium, and chloride in bodily fluids, and these measurements are explicitly stated to be used in the "diagnosis and treatment" of various diseases and conditions involving electrolyte imbalances, such as aldosteronism, diabetes insipidus, Addison's disease, cystic fibrosis, and diabetic acidosis. This direct link to diagnosis and treatment classifies it as a diagnostic device.

SaMD (Software as a Medical Device)

No

The device description clearly states it is an "Ion-Selective Electrode (ISE) system" and describes the physical components and principles of operation involving electrodes and membranes, indicating it is a hardware-based system with associated software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states the quantitative determination of sodium, potassium, and chloride in serum, plasma, or urine. These are biological specimens taken from the human body.
Purpose: The measurements are used in the diagnosis and treatment of various diseases and conditions involving electrolyte imbalance, such as aldosteronism, diabetes insipidus, adrenal hypertension, Addison's disease, dehydration, inappropriate antidiuretic hormone secretion, cystic fibrosis, and diabetic acidosis. This directly aligns with the definition of an IVD, which is used to examine specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
Device Description: The device is an Ion-Selective Electrode (ISE) system designed to measure ions in solution, specifically in serum, plasma, and urine. This is a common technology used in clinical laboratories for in vitro testing.
Regulatory Context: The document mentions a "premarket notification" and seeking "FDA review and clearance," which are processes specific to medical devices, including IVDs, regulated by the FDA. It also references previous clearances (K060373 and K053165), further indicating its status as a regulated medical device.

Therefore, based on the intended use, the type of specimens analyzed, the purpose of the measurements, and the regulatory context, this device clearly falls under the definition of an In Vitro Diagnostic.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The ISE module of the Roche / Hitachi systems is intended for the quantitative determination of sodium, potassium, and chloride in serum, plasma, or urine using ion-selective electrodes.

Sodium measurements 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.

Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.

Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.

Product codes (comma separated list FDA assigned to the subject device)

JGS, CEM, CGZ

Device Description

The cobas 6000 analyzer series with an ISE module is an Ion-Selective Electrode (ISE) system for the determination of sodium, potassium, and chloride in serum, plasma, and urine. The cobas 6000 analyzer series, including the cobas c 501 with ISE for Serum, Plasma and Urine sample types was previously cleared in K060373. This premarket notification seeks to obtain FDA review and clearance for the cobas c 501 ISE, Modified Calibration for Serum, Plasma and Urine sample types.

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).

Aqueous ISE Standards Low and High were cleared in K053165. The modified calibration in this submission included the use of ISE Standards Low (S1) and High (S2) for 2-point calibration and the Standard High for compensation (S3). Previously, a serum-based ISE compensator was used for S3 compensation. The modification is switching from serum-based ISE compensator for S3 to ISE Standard High. In the new calibration scheme, the ISE Standard High will be used for both S2 and S3.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

The submission includes various performance comparisons against predicate devices and reference methods for Sodium, Potassium, and Chloride assays in serum, plasma, and urine.

Sodium - Serum/Plasma:

Repeatability:
- Predicate: Low (124.8 mmol/L, SD 0.36, CV 0.3%), High (144.9 mmol/L, SD 0.43, CV 0.3%)
- New Device: Low (84.8 mmol/L, SD 0.2, CV 0.3%), High (176.7 mmol/L, SD 0.3, CV 0.2%)
Intermediate precision (CLSI):
- Predicate: Low (124.9 mmol/L, SD 0.75, CV 0.6%), High (144.9 mmol/L, SD 0.77, CV 0.5%)
- New Device: Low (84.8 mmol/L, SD 1.0, CV 1.1%), High (176.7 mmol/L, SD 0.6, CV 0.4%)
Method Comparison to reference (Flame Photometer):
- Predicate: N = 51 (Plasma), Correlation = 0.993, Slope = 0.976, Intercept = +2.041
- New Device: N = 52 (Plasma), Correlation = 0.999, Slope = 1.000, Intercept = 0.200; N = 51 (Serum), Correlation = 0.998, Slope = 0.992, Intercept = 1.633
Method comparison to predicate:
- N = 51 (Plasma), Correlation = 0.998, Slope = 1.000, Intercept = -0.100 (for predicate vs. new)
- New Device: N = 52 (Plasma), Correlation = 1.000, Slope = 1.016, Intercept = -1.456; N = 51 (Serum), Correlation = 0.999, Slope = 1.009, Intercept = -0.515
Detection Limit: Predicate: Not determined, New Device: LoB = 3.9 mmol/L, LoD = 5.7 mmol/L, LoQ = 11.1 mmol/L
Reportable range: Predicate: 80-180 mmol/L, New Device: 80-180 mmol/L

Sodium - Urine:

Repeatability:
- Predicate: Low (16.7 mmol/L, SD 0.27, CV 1.6%), High (166.8 mmol/L, SD 0.63, CV 0.4%)
- New Device: Low (30.6 mmol/L, SD 0.1, CV 0.2%), High (236.7 mmol/L, SD 0.4, CV 0.2%)
Intermediate precision (CLSI):
- Predicate: Low (15.5 mmol/L, SD 0.62, CV 4.0%), High (166.7 mmol/L, SD 0.87, CV 0.5%)
- New Device: Low (30.6 mmol/L, SD 0.9, CV 3.0%), High (236.7 mmol/L, SD 1.3, CV 0.6%)
Method Comparison to reference (flame photometer):
- Predicate: N = 51, Correlation = 1.000, Slope = 1.001, Intercept = -1.263
- New Device: N = 100, Correlation = 1.000, Slope = 0.964, Intercept = 4.032
Method comparison to predicate:
- N = 51, Correlation = 1.000, Slope = 1.011, Intercept = -0.247
- New Device: N = 100, Correlation = 1.000, Slope = 0.995, Intercept = 0.687
Detection Limit: Predicate: Not determined, New Device: LoB = 3.9 mmol/L, LoD = 5.7 mmol/L, LoQ = 11.1 mmol/L
Reportable range: Predicate: 10-250 mmol/L, New Device: 20-250 mmol/L
Extended Range: Predicate: 250-375 mmol/L, New Device: 250-375 mmol/L

Potassium - Serum/Plasma:

Repeatability:
- Predicate: Low (4.68 mmol/L, SD 0.03, CV 0.5%), High (8.62 mmol/L, SD 0.04, CV 0.5%)
- New Device: Low (1.62 mmol/L, SD 0.01, CV 0.7%), High (9.46 mmol/L, SD 0.06, CV 0.6%)
Intermediate precision (CLSI):
- Predicate: Low (4.72 mmol/L, SD 0.03, CV 0.7%), High (8.63 mmol/L, SD 0.04, CV 0.5%)
- New Device: Low (1.62 mmol/L, SD 0.03, CV 1.6%), High (9.46 mmol/L, SD 0.07, CV 0.7%)
Method Comparison to reference (Flame Photometry):
- Predicate: N = 51 (Plasma), Correlation = 0.998, Slope = 0.983, Intercept = -0.026
- New Device: N = 52 (Plasma), Correlation = 1.000, Slope = 1.010, Intercept = -0.022; N = 54 (Serum), Correlation = 1.000, Slope = 1.005, Intercept = -0.020
Method comparison to predicate:
- N = 51 (Plasma), Correlation = 0.998, Slope = 0.988, Intercept = 0.052
- New Device: N = 52 (Plasma), Correlation = 1.000, Slope = 1.008, Intercept = 0.018; N = 54 (Serum), Correlation = 1.000, Slope = 1.004, Intercept = 0.302
Detection Limit: Predicate: Not determined, New Device: LoB = 0.17 mmol/L, LoD = 0.24 mmol/L, LoQ = 0.41 mmol/L
Reportable range: Predicate: 1.5-10.0 mmol/L, New Device: 1.5-10.0 mmol/L

Potassium - Urine:

Repeatability:
- Predicate: Low (8.79 mmol/L, SD 0.04, CV 0.4%), High (72.04 mmol/L, SD 0.53, CV 0.7%)
- New Device: Low (5.15 mmol/L, SD 0.03, CV 0.6%), High (90.34 mmol/L, SD 0.67, CV 0.7%)
Intermediate precision (CLSI):
- Predicate: Low (8.99 mmol/L, SD 0.04, CV 0.4%), High (72.04 mmol/L, SD 0.53, CV 0.7%)
- New Device: Low (5.15 mmol/L, SD 0.04, CV 0.7%), High (90.34 mmol/L, SD 1.38, CV 1.5%)
Method Comparison to reference (Flame Photometry):
- Predicate: N = 51, Correlation = 1.000, Slope = 1.033, Intercept = -0.023
- New Device: N = 105, Correlation = 1.000, Slope = 1.018, Intercept = 0.397
Method comparison to predicate:
- N = 51, Correlation = 0.999, Slope = 0.982, Intercept = 0.323
- New Device: N = 105, Correlation = 0.999, Slope = 0.997, Intercept = 0.062
Detection Limit: Predicate: Not determined, New Device: LoB = 0.17 mmol/L, LoD = 0.24 mmol/L, LoQ = 0.41 mmol/L
Reportable range: Predicate: 1-100 mmol/L, New Device: 3-100 mmol/L
Extended Range: Predicate: 100-150 mmol/L, New Device: 100-150 mmol/L

Chloride - Serum/Plasma:

Repeatability:
- Predicate: Low (86.6 mmol/L, SD 0.30, CV 0.3%), High (118.4 mmol/L, SD 0.38, CV 0.3%)
- New Device: Low (68.5 mmol/L, SD 0.2, CV 0.3%), High (139.0 mmol/L, SD 0.3, CV 0.2%)
Intermediate precision (CLSI):
- Predicate: Low (88.2 mmol/L, SD 0.55, CV 0.6%), High (118.4 mmol/L, SD 0.61, CV 0.5%)
- New Device: Low (68.5 mmol/L, SD 0.6, CV 0.8%), High (139.0 mmol/L, SD 0.6, CV 0.4%)
Method Comparison to reference (Coulometry):
- Predicate: N = 51 (Plasma), Correlation = 0.995, Slope = 0.954, Intercept = +1.438
- New Device: N = 52 (Plasma), Correlation = 0.998, Slope = 1.023, Intercept = -0.769; N = 53 (Serum), Correlation = 0.999, Slope = 1.043, Intercept = -2.843
Method comparison to predicate:
- N = 51 (Plasma), Correlation = 0.999, Slope = 0.978, Intercept = +1.744
- New Device: N = 52 (Plasma), Correlation = 0.999, Slope = 1.006, Intercept = -0.118; N = 53 (Serum), Correlation = 1.000, Slope = 0.997, Intercept = 0.872
Detection Limit: Predicate: Not determined, New Device: LoB = 3.40 mmol/L, LoD = 4.7 mmol/L, LoQ = 5.5 mmol/L
Reportable range: Predicate: 60-140 mmol/L, New Device: 60-140 mmol/L

Chloride - Urine:

Repeatability:
- Predicate: Low (20.4 mmol/L, SD 0.29, CV 1.4%), High (165.0 mmol/L, SD 0.81, CV 0.5%)
- New Device: Low (25.8 mmol/L, SD 0.1, CV 0.2%), High (243.4 mmol/L, SD 0.6, CV 0.2%)
Intermediate precision (CLSI):
- Predicate: Low (100 mmol/L, SD 0.55, CV 2.8%), High (165.4 mmol/L, SD 1.17, CV 0.7%)
- New Device: Low (25.8 mmol/L, SD 0.6, CV 2.3%), High (243.4 mmol/L, SD 1.8, CV 0.7%)
Method Comparison to reference (Coulometry):
- Predicate: N = 51, Correlation = 1.000, Slope = 1.002, Intercept = -2.739
- New Device: N = 105, Correlation = 0.998, Slope = 1.020, Intercept = -1.700
Method comparison to predicate:
- N = 51, Correlation = 1.000, Slope = 1.009, Intercept = -1.715
- New Device: N = 105, Correlation = 1.000, Slope = 0.989, Intercept = 0.669
Detection Limit: Predicate: Not determined, New Device: LoB = 3.4 mmol/L, LoD = 4.7 mmol/L, LoQ = 5.5 mmol/L
Reportable range: Predicate: 10-250 mmol/L, New Device: 20-250 mmol/L
Extended Range: Predicate: 250-375 mmol/L, New Device: 250-375 mmol/L

Conclusion: The data presented demonstrates cobas c 501 ISE Gen. 2 assay with the modified calibration performs substantially equivalent to the predicate device.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Key metrics include repeatability (Mean, SD, CV), intermediate precision (Mean, SD, CV), correlation, slope, and intercept from method comparisons, and detection limits (LoB, LoD, LoQ) for the new device. Specific sensitivity, specificity, PPV, or NPV metrics are not explicitly provided.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K053165

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 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.

Summary

0

510(k) Summary: 510(k) for the cobas c 501 ISE, Modified Calibration

DEC 1 8 2013

Introduction

The information in this 510(k) summary is being submitted in accordance with requirements of 21 CFR 807.92.

cobas c 501 ISE Indirect Na, K, Cl for Gen. 2.

K053165

Submitter name, address, and contact

Contact Person: Khoa Tran Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250

Phone: (317) -521-3409 Fax: (317) -521-2324 Email: khoa.tran@roche.com

Proprietary name:

Date Prepared: October 17, 2013

ISE Indirect Na, K, Cl for Gen.2

Device name

Common name: Sodium Test System Potassium Test System Chloride Test System Classification: Ion-Specific Electrode Sodium Ion-Specific Electrode Potassium Ion-Specific Electrode Chloride

Predicate Device

Establishment registration

For the cobas c 501 ISE module, the establishment registration number for Roche Diagnostics GmbH in Mannheim, Germany is 9610126. The establishment registration number for Roche Diagnostics, United States is 1823260.

1

Classification

The FDA has classified the Sodium, Potassium, and Chloride Test Systems as Class II devices.

| Panel | Product
Code | Classification Name | Regulation |
|----------------------------|-----------------|--------------------------------------|--------------------|
| Clinical
Chemistry (75) | JGS | Ion Specific Electrode, Sodium | 21 CFR
862.1665 |
| Clinical
Chemistry (75) | CEM | Ion Specific Electrode,
Potassium | 21 CFR
862.1600 |
| Clinical
Chemistry (75) | CGZ | Ion Specific Electrode, Chloride | 21 CFR
862.1170 |

Proposed labeling

· :

Draft labeling sufficient to describe the device, its intended use, and the directions for use on the cobas c 501 analyzer module is included in the submission. .

2

The ISE Gen 2 reagent was cleared in K053165 for application to the Roche/Hitachi family of analyzers.

Device description

The cobas 6000 analyzer series with an ISE module is an Ion-Selective Electrode (ISE) system for the determination of sodium, potassium, and chloride in serum, plasma, and urine. The cobas 6000 analyzer series, including the cobas c 501 with ISE for Serum, Plasma and Urine sample types was previously cleared in K060373. This premarket notification seeks to obtain FDA review and clearance for the cobas c 501 ISE, Modified Calibration for Serum, Plasma and Urine sample types.

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).

Aqueous ISE Standards Low and High were cleared in K053165. The modified calibration in this submission included the use of ISE Standards Low (S1) and High (S2) for 2-point calibration and the Standard High for compensation (S3). Previously, a serum-based ISE compensator was used for S3 compensation. The modification is switching from serum-based ISE compensator for S3 to ISE Standard High. In the new calibration scheme, the ISE Standard High will be used for both S2 and S3.

Intended use

The ISE module of the Roche/Hitachi cobas c systems is intended for the quantitative determination of sodium, potassium and chloride in serum. plasma or urine using ion-selective electrodes.

3

Indications for use

The ISE module of the Roche / Hitachi systems is intended for the quantitative determination of sodium, potassium, and chloride in serum, plasma, or urine using ion-selective electrodes.

Sodium measurements 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.

Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels.

Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.

Substantial equivalence comparison

The following table compares the cobas c 501 ISE Gen. 2, Modified Calibration for Serum, Plasma and Urine sample types to its predicate device, the cobas c 501 analyzer module with ISE Gen.2 reagent, originally cleared in K053165.

4

Comparison of Systems – similarities and differences

:

100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

| | Parameter | Predicate: cobas.c 501 ISE
Gen: 2 with serum-based
ISE Compensator
K053165 | cobas c 501 ISE Gen. 2,
Modified Calibration,
with ISE Standard High-
(S3) |
|--|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| | Intended
use | 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. | Same |
| | Measurement
principle | ISE Potentiometry | Same |
| | Reagent
container | Plastic bottles closed via
screw caps | Same |
| | Onboard
storage
temperature | 5-12 °C | Same |
| | ISE Module | Integrated into cobas c 501
analyzer | Same |
| | Ion
Selective
electrodes
(ISES) | Potentiometric chloride,
potassium, sodium and
reference electrodes | Same |

.

11.11

:

5

Comparison of

assays –
similarities and differences

(Sodium)

Parameter	Predicate: cobas c 501-ISE Gen. 2 with serum-based ISE Compensator			cobas c 501 ISE Gen. 2, Modified Calibration, with ISE Standard High
Repeatability		Mean [mmol/L]	SD [mmol/L]	CV [%]		Mean [mmol/L]	SD [mmol/L]	CV [%]
	Low	124.8	0.36	0.3	Low	84.8	0.2	0.3
	High	144.9	0.43	0.3	Med	121.4	0.3	0.3
	PNU	124.9	0.38	0.3	MDL	131.6	0.3	0.2
	PPU	149.2	0.35	0.3	High	176.7	0.3	0.2
					PNU	126.0	0.2	0.2
					PPU	148.2	0.3	0.2
Intermediate
precision
(CLSI)		Mean [mmol/L]	SD [mmol/L]	CV [%]		Mean [mmol/L]	SD [mmol/L]	CV [%]
	Low	124.9	0.75	0.6	Low	84.8	1.0	1.1
	High	144.9	0.77	0.5	Med	121.4	0.8	0.6
	PNU	124.7	0.75	0.6	MDL	131.6	0.7	0.5
	PPU	149.9	0.80	0.5	High	176.7	0.6	0.4
					PNU	126.0	0.7	0.6
					PPU	148.2	0.5	0.4
Method Comparison
to reference
(Flame Photometer)	N = 51 (Plasma)
Days = 3
Correlation = 0.993
Slope (Bablok) = 0.976
Intercept (Bablok) = +2.041
Range (X) = 132.7-164.1				N = 52 (Plasma)
Days = 2
Correlation = 0.999
Slope (Bablok) = 1.000
Intercept (Bablok) = 0.200
Range (X) = 86.7-172
					N = 51 (Serum)
Days = 2
Correlation = 0.998
Slope (Bablok) = 0.992
Intercept (Bablok) = 1.633
Range (X) = 97.6-178
Method
comparison
to predicate	N = 51 (Plasma)
Days = 3
Correlation = 0.998
Slope (Bablok) = 1.000
Intercept (Bablok) = -0.100
Range (X) = 131.2-162.3				N = 52 (Plasma)
Days = 2
Correlation = 1.000
Slope (Bablok) = 1.016
Intercept (Bablok) = -1.456
Range (X) = 87.6-170
					N = 51 (Serum)
Days = 2
Correlation = 0.999
Slope (Bablok) = 1.009
Intercept (Bablok) = -0.515
Range (X) = 97.3-176
LoB = 3.9 mmol/L
Detection
Limit	Not determined				LoD = 5.7 mmol/L
LoQ = 11.1 mmol/L
Reportable
range	80-180 mmol/L				80-180 mmol/L

:

·

6

Comparison of assays –

similarities
and
differences

(Sodium)

| | Assay Comparison
Sodium - Urine | | | | | | | |
|---------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------|------------------|----------------|-----------|------------------------------------------------------------------------------------------------------------------------------|------------------|----------------|-----------|
| Parameter | Predicate: cobas c 501 ISE
Gen. 2 with serum-based
ISE Compensator | | | | cobas c 501 ISE Gen. 2,
Modified Calibration,
with ISE Standard High | | | |
| | | Mean
[mmol/L] | SD
[mmol/L] | CV
[%] | | Mean
[mmol/L] | SD
[mmol/L] | CV
[%] |
| Repeatability | Low | 16.7 | 0.27 | 1.6 | Low | 30.6 | 0.1 | 0.2 |
| | High | 166.8 | 0.63 | 0.4 | Med | 131.7 | 0.2 | 0.2 |
| | Liq 1 | 76.3 | 0.31 | 0.4 | MDL | 23.3 | 0.1 | 0.3 |
| | Liq 2 | 175.5 | 0.47 | 0.3 | High | 236.7 | 0.4 | 0.2 |
| | | | | | Liq 1 | 81.6 | 0.2 | 0.2 |
| | | | | | Liq 2 | 172.3 | 0.2 | 0.1 |
| | | Mean
[mmol/L] | SD
[mmol/L] | CV
[%] | | Mean
[mmol/L] | SD
[mmol/L] | CV
[%] |
| Intermediate
precision
(CLSI) | Low | 15.5 | 0.62 | 4.0 | Low | 30.6 | 0.9 | 3.0 |
| | High | 166.7 | 0.87 | 0.5 | Med | 131.7 | 0.6 | 0.5 |
| | Liq 1 | 75.7 | 0.75 | 1.0 | MDL | 23.3 | 0.9 | 3.8 |
| | Liq 2 | 176.6 | 1.07 | 0.6 | High | 236.7 | 1.3 | 0.6 |
| | | | | | Liq 1 | 81.6 | 1.3 | 1.6 |
| | | | | | Liq 2 | 172.3 | 2.6 | 1.5 |
| Method
Comparison
to reference
(flame
photometer) | N = 51
Days = 3
Correlation = 1.000
Slope (Bablok) = 1.001
Intercept (Bablok) = -1.263
Range (X) = 19.9-257.4 | | | | N = 100
Days = 2
Correlation = 1.000
Slope (Bablok) = 0.964
Intercept (Bablok) = 4.032
Range (X) = 23.5-249.8 | | | |
| Method
comparison
to predicate | N = 51
Days = 3
Correlation = 1.000
Slope (Bablok) = 1.011
Intercept (Bablok) = -0.247
Range (X) = 17.9 -253.0 | | | | N = 100
Days = 2
Correlation = 1.000
Slope (Bablok) = 0.995
Intercept (Bablok) = 0.687
Range (X) = 25.1-245.4 | | | |
| Detection
Limit | Not determined | | | | LoB = 3.9 mmol/L
LoD = 5.7 mmol/L
LoQ = 11.1 mmol/L | | | |
| Reportable
range | 10-250 mmol/L | | | | 20 - 250 mmol/L | | | |
| Extended
Range | 250-375 mmol/L
(samples diluted via rerun
function) | | | | 250 - 375 mmol/L
(samples diluted via rerun function) | | | |

7

Comparison of

assays –
similarities and differences,
(Potassium)

.

·

.

Parameter	Predicate: cobas c 501 ISE Gen. 2, with serum-based ISE Compensator			cobas c 501 ISE Gen. 2, Modified Calibration, with ISE Standard High
	Mean [mmol/L]	SD [mmol/L]	CV [%]	Mean [mmol/L]	SD [mmol/L]	CV [%]
Repeatability	Low 4.68	0.03	0.5	Low 1.62	0.01	0.7
	High 8.62	0.04	0.5	Med 4.97	0.04	0.7
	PNU 3.37	0.02	0.5	MDL 2.63	0.02	0.6
	PPU 6.06	0.03	0.5	High 9.46	0.06	0.6
				PNU 3.57	0.03	0.8
				PPU 6.59	0.04	0.6
Intermediate precision (CLSI)	Mean [mmol/L]	SD [mmol/L]	CV [%]	Mean [mmol/L]	SD [mmol/L]	CV [%]
	Low 4.72	0.03	0.7	Low 1.62	0.03	1.6
	High 8.63	0.04	0.5	Med 4.97	0.04	0.8
	PNU 3.39	0.02	0.5	MDL 2.63	0.03	1.0
	PPU 6.08	0.03	0.6	High 9.46	0.07	0.7
				PNU 3.57	0.04	1.0
				PPU 6.59	0.05	0.7
Method Comparison to reference (Flame Photometry)	N = 51 (Plasma)
Days = 3
Correlation = 0.998
Slope (Bablok) = 0.983
Intercept (Bablok) = -0.026
Range (X) = 3.23-6.35			N = 52 (Plasma)
Days = 2
Correlation = 1.000
Slope (Bablok) = 1.010
Intercept (Bablok) = - 0.022
Range (X) = 2.1-9.19

N = 54 (Serum)
Days = 2
Correlation = 1.000
Slope (Bablok) = 1.005
Intercept (Bablok) = -0.020
Range (X) = 1.59-9.56 | | |
| Method comparison to predicate | N = 51 (Plasma)
Days = 3
Correlation = 0.998
Slope (Bablok) = 0.988
Intercept (Bablok) = 0.052
Range (X) = 3.14-6.26 | | | N = 52 (Plasma)
Days = 2
Correlation = 1.000
Slope (Bablok) = 1.008
Intercept (Bablok) = 0.018
Range (X) = 2.02-9.13

8

Comparison of assays –

similarities and differences, (Potassium)

Assay Comparison
Potassium - Urine
Parameter	Predicate: cobas c 501 ISE
Gen. 2 with serum-based
ISE Compensator				cobas c 501 ISE Gen. 2,
Modified Calibration,
with ISE Standard High
	Mean
[mmol/L]	SD
[mmol/L]	CV
[%]		Mean
[mmol/L]	SD
[mmol/L]	CV
[%]
Repeatability	Low
8.79	0.04	0.4	Low
5.15	0.03	0.6
	High
72.04	0.53	0.7	Med
52.08	0.32	0.6
	Liq 1
31.13	0.21	0.7	MDL
15.39	0.09	0.6
	Liq 2
68.76	0.36	0.5	High
90.34	0.67	0.7
				Liq 1
31.48	0.19	0.6
				Liq 2
70.56	0.43	0.6
Intermediate
precision
(CLSI)	Mean
[mmol/L]
8.99	SD
[mmol/L]
0.04	CV
[%]
0.4	Mean
[mmol/L]
5.15	SD
[mmol/L]
0.04	CV
[%]
0.7
	High
72.04	0.53	0.7	Med
52.08	0.67	1.3
	Liq 1
31.13	0.21	0.7	MDL
15.39	0.14	0.9
	Liq 2
68.76	0.36	0.5	High
90.34	1.38	1.5
				Liq 1
31.48	0.53	1.7
				Liq 2
70.56	1.17	1.7
Method
Comparison
to reference
(Flame
Photometry)	N = 51
Days = 3
Correlation = 1.000
Slope (Bablok) = 1.033
Intercept (Bablok) = -0.023
Range (X) = 9.20-95.10			N = 105
Days = 2
Correlation = 1.000
Slope (Bablok) = 1.018
Intercept (Bablok) = 0.397
Range (X) = 4.00-97.20
Method
comparison
to predicate	N = 51
Days = 3
Correlation = 0.999
Slope (Bablok) = 0.982
Intercept (Bablok) = 0.323
Range (X) = 9.68-98.55			N = 105
Days = 2
Correlation = 0.999
Slope (Bablok) = 0.997
Intercept (Bablok) = 0.062
Range (X) = 4.05-97.35
Detection
Limit	Not determined			LoB = 0.17 mmol/L
LoD = 0.24 mmol/L
LoQ = 0.41 mmol/L
Reportable
range	1 -100 mmol/L			3 - 100 mmol/L
Extended
Range	100-150 mmol/L
(samples diluted via rerun
function)			100 -150 mmol/L
(samples diluted via rerun function)

:

9

Comparison of assays –

similarities and differences,
(Chloride)

.

Assay Comparison
Chloride
Parameter	Predicate: cobas c 501 ISE Gen. 2 with serum-based ISE Compensator	cobas c 501 ISE Gen. 2, Modified Calibration, with ISE Standard High
Repeatability	Mean [mmol/L] SD [mmol/L] CV [%] Low 86.6 0.30 0.3 High 118.4 0.38 0.3 PNU 82.1 0.41 0.5 PPU 114.7 0.31 0.3		Mean [mmol/L] SD [mmol/L] CV [%] Low 68.5 0.2 0.3 Med 129.0 0.4 0.3 MDL 92.3 0.2 0.3 High 139.0 0.3 0.2 PNU 86.2 0.2 0.3 PPU 119.2 0.3 0.2
Intermediate precision (CLSI)	Mean [mmol/L] SD [mmol/L] CV [%] Low 88.2 0.55 0.6 High 118.4 0.61 0.5 PNU 81.9 0.36 0.4 PPU 115.4 0.62 0.5		Mean [mmol/L] SD [mmol/L] CV [%] Low 68.5 0.6 0.8 Med 129.0 0.6 0.5 MDL 92.3 0.5 0.6 High 139.0 0.6 0.4 PNU 86.2 0.5 0.6 PPU 119.2 0.5 0.4
Method Comparison to reference (Coulometry)	N = 51 (Plasma)
Days = 3
Correlation = 0.995
Slope (Bablok) = 0.954
Intercept (Bablok) = +1.438
Range (X) = 92.0 - 132.0	N = 52 (Plasma)
Days = 2
Correlation = 0.998
Slope (Bablok) = 1.023
Intercept (Bablok) = -0.769
Range (X) = 69.0 - 133
N = 53 (Serum)
Days = 2
Correlation = 0.999
Method comparison to predicate	N = 51 (Plasma)
Days = 3
Correlation = 0.999
Slope (Bablok) = 0.978
Intercept (Bablok) = +1.744
Range (X) = 90.7-128.9	Slope (Bablok) = 1.043
Intercept (Bablok) = -2.843
Range (X) = 62.0 - 136
N = 52 (Plasma)
Days = 2
Correlation = 0.999
Slope (Bablok) = 1.006
Intercept (Bablok) = -0.118
Range (X) = 69.4-134
N = 53 (Serum)
Days = 2
Correlation = 1.000
Slope (Bablok) = 0.997
Intercept (Bablok) = 0.872
Range (X) = 61.4 - 138
Detection Limit	Not determined	LoB = 3.40 mmol/L
LoD = 4.7 mmol/L
LoQ = 5.5 mmol/L
Reportable range	60-140 mmol/L	60-140 mmol/L

10

Comparison of assays similarities and differences, (Chloride)

Assay Comparison
Chloride - Urine
arameter		Predicate: cobas c 501 ISE cobas c 501 ISE Gen. 2			视频中国网站

					Gen. 2 with serum-based - - - Modified Calibration,
					ISE.Compensator --------------------------------------------------------------------------------------------------------------------------------------------------------------
		Mean	SD	CV		Mean	SD	CV
Repeatability		[mmol/L]	[mmol/L]	[%]		[mmol/L]	[mmol/L]	[%]
	Low	20.4	0.29	1.4	Low	25.8	0.1	0.2
	High	165.0	0.81	0.5	Med	131.4	0.3	0.2
	Lig 1	101.9	0.43	0.4	MDL	24.3	0.1	0.3
	Liq 2	203.0	0.54	0.3	High	243.4	0.6	0.2
					Liq 1	97.5	0.2	0.2
					Lig 2	198.2	0.4	0.2
		Mean	SD	CV		Mean	SD	CV
Intermediate		[mmol/L]	[mmol/L]	1%]		[mmol/L]	[mmol/L]	[%]
precision	Low	1 0 0	0.55	2.8	Low	-25.8	0.6	2.3
(CLSI)	High	165.4	1.17	0.7	Med	131.4	0.7	0.5
	Liq 1	101.5	0.34	0.3	MDL	24.3	0.6	2.4
	Liq 2	206.1	1.26	0.6	High	243.4	1.8	0.7
					Lig 1	97.5	1 Q	1.6
					Lig 2	198.2	2.3	1.2
Method	N = 51				N = 105
Comparison	Days = 3				Days = 2
to reference		Correlation = 1.000				Correlation = 0.998
(Coulometry)	Slope (Bablok) = 1.002
Intercept (Bablok) = - 2.739				Slope (Bablok) = 1.020
		Range (X) = 21.0-274.0			Intercept (Bablok) = - 1.700
Range (X) = 22.0 - 248.0
					N = 105
Method
comparison	N = 51				Days = 2
to predicate		Days = 3
Correlation = 1.000				Correlation = 1.000
		Slope (Bablok) = 1.009				Slope (Bablok) = 0.989
		Intercept (Bablok) = - 1.715				Intercept (Bablok) = 0.669
		Range (X) = 18.5-269.0				Range (X) = 21.2-249.9
Detection						LoB = 3.4 mmol/L
Limit	Not determined				LoD = 4.7 mmol/L
					LoQ=5.5 mmol/L
Reportable	10 -250 mmol/L				20 - 250 mmol/L
range
Extended	250 - 375 mmol/L				250 - 375 mmol/L
Range	(samples diluted via rerun .
function)				(samples diluted via rerun function)

Conclusion:

The data presented in this premarket notification demonstrates cobas c 501 ISE Gen. 2 assay with the modified calibration performs substantially equivalent to the predicate device, the cobas c 501 ISE Gen. 2 with the original calibration (K053165).

11

Image /page/11/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white and appears to be a scanned image.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 18, 2013

ROCHE DIAGNOSTICS KHOA TRAN REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250

Re: K132418

Trade/Device Name: cobas c 501 ISE Indirect Na, K, Cl for Gen. 2 Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium test system Regulatory Class: II Product Code: JGS, CEM, CGZ Dated: December 12, 2013 Received: December 13, 2013

Dear Mr. Tran:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

12

Page 2-Mr. Tran

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21.CFR Part 807.97). For questions regarding of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industrv/default.htm.

Sincerely yours.

Carol Benson -S for

Courtney H. Lias. Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

13

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

510(k) Number (if known)

K132418

Device Name

cobas c 501 ISE Indirect Na, K, Cl for Gen. 2 Indications for Use (Describe)

The ISE module of the Roche / Hitachi systems is intended for the quantitative determination of sodium. potassium. and chloride in serum, plasma, or urine using ion-selective electrodes.

Sodium measurements 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. Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.

Type of Use (Select one or both, as applicable)

X |Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

FORM FDA 3881 (9/13)