COBAS C 501 ISE INDIRECT NA, K, CL FOR GEN. 2

• K Number: K132418
• Device Name: COBAS C 501 ISE INDIRECT NA, K, CL FOR GEN. 2
• Manufacturer: Roche Diagnostics
• Date Cleared: 2013-12-18 ( 138 days)
• Product Code: JGS , CEM , CGZ
• Regulation Number: 862.1665
• Type: Traditional
• Panel: Clinical Chemistry
• Reference & Predicate Devices: k060373 , k053165
• Predicate For: N/A

Intended 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.

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.

AI/ML Overview

The provided text describes a 510(k) summary for the cobas c 501 ISE, Modified Calibration for Sodium, Potassium, and Chloride assays. It focuses on demonstrating substantial equivalence to a predicate device rather than presenting a study for meeting acceptance criteria in the typical AI/ML context. However, I can extract and structure the information into the requested format by interpreting "acceptance criteria" as the performance parameters considered for substantial equivalence and "reported device performance" as the data provided for the modified device.

Here's the breakdown:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the performance of the predicate device and the new device showing comparable or improved performance for various metrics. The study aims to demonstrate that the modified calibration maintains or improves performance.

Parameter	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (Modified Calibration)
Sodium (Serum/Plasma)
Repeatability CV (%) (Low)	0.3	0.3
Repeatability CV (%) (High)	0.3	0.2
Intermediate Precision CV (%) (Low)	0.6	1.1
Intermediate Precision CV (%) (High)	0.5	0.4
Method Comparison (Reference) Correlation	0.993 (Plasma)	0.999 (Plasma), 0.998 (Serum)
Method Comparison (Predicate) Correlation	0.998 (Plasma)	1.000 (Plasma), 0.999 (Serum)
Reportable Range	80-180 mmol/L	80-180 mmol/L
Sodium (Urine)
Repeatability CV (%) (Low)	1.6	0.2
Repeatability CV (%) (High)	0.4	0.2
Intermediate Precision CV (%) (Low)	4.0	3.0
Intermediate Precision CV (%) (High)	0.5	0.6
Method Comparison (Reference) Correlation	1.000	1.000
Method Comparison (Predicate) Correlation	1.000	1.000
Reportable Range	10-250 mmol/L	20-250 mmol/L
Potassium (Serum/Plasma)
Repeatability CV (%) (Low)	0.5	0.7
Repeatability CV (%) (High)	0.5	0.6
Intermediate Precision CV (%) (Low)	0.7	1.6
Intermediate Precision CV (%) (High)	0.5	0.7
Method Comparison (Reference) Correlation	0.998 (Plasma)	1.000 (Plasma), 1.000 (Serum)
Method Comparison (Predicate) Correlation	0.998 (Plasma)	1.000 (Plasma), 1.000 (Serum)
Reportable Range	1.5-10.0 mmol/L	1.5-10.0 mmol/L
Potassium (Urine)
Repeatability CV (%) (Low)	0.4	0.6
Repeatability CV (%) (High)	0.7	0.7
Intermediate Precision CV (%) (Low)	0.4	0.7
Intermediate Precision CV (%) (High)	0.7	1.5
Method Comparison (Reference) Correlation	1.000	1.000
Method Comparison (Predicate) Correlation	0.999	0.999
Reportable Range	1-100 mmol/L	3-100 mmol/L
Chloride (Serum/Plasma)
Repeatability CV (%) (Low)	0.3	0.3
Repeatability CV (%) (High)	0.3	0.2
Intermediate Precision CV (%) (Low)	0.6	0.8
Intermediate Precision CV (%) (High)	0.5	0.4
Method Comparison (Reference) Correlation	0.995 (Plasma)	0.998 (Plasma), 0.999 (Serum)
Method Comparison (Predicate) Correlation	0.999 (Plasma)	0.999 (Plasma), 1.000 (Serum)
Reportable Range	60-140 mmol/L	60-140 mmol/L
Chloride (Urine)
Repeatability CV (%) (Low)	1.4	0.2
Repeatability CV (%) (High)	0.5	0.2
Intermediate Precision CV (%) (Low)	2.8	2.3
Intermediate Precision CV (%) (High)	0.7	0.7
Method Comparison (Reference) Correlation	1.000	0.998
Method Comparison (Predicate) Correlation	1.000	1.000
Reportable Range	10-250 mmol/L	20-250 mmol/L

2. Sample Size Used for the Test Set and Data Provenance

The "test set" here refers to the samples used for method comparison studies.

• Sodium (Serum/Plasma): N = 52 (Plasma, Modified), N = 51 (Serum, Modified). N = 51 (Plasma, Predicate).
• Sodium (Urine): N = 100 (Modified). N = 51 (Predicate).
• Potassium (Serum/Plasma): N = 52 (Plasma, Modified), N = 54 (Serum, Modified). N = 51 (Plasma, Predicate).
• Potassium (Urine): N = 105 (Modified). N = 51 (Predicate).
• Chloride (Serum/Plasma): N = 52 (Plasma, Modified), N = 53 (Serum, Modified). N = 51 (Plasma, Predicate).
• Chloride (Urine): N = 105 (Modified). N = 51 (Predicate).

Data Provenance: The document does not specify the country of origin of the data. The studies appear to be prospective, laboratory-based analytical studies designed to test the performance of the modified device against a reference method and the predicate device. They are not clinical studies necessarily involving patient outcomes.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of information is not applicable to this submission. This is a submission for an in vitro diagnostic (IVD) device (a measurement instrument and reagents) used to quantify specific analytes (sodium, potassium, chloride) in biological samples. The "ground truth" for the test set is established by recognized reference methods (e.g., Flame Photometry, Coulometry) which are laboratory instruments, not human experts making diagnostic decisions. There were no experts involved in establishing ground truth for these analytical performance studies.

4. Adjudication Method for the Test Set

This is not applicable. As stated above, this is an analytical performance study using objective reference standard measurements, not human interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

This is not applicable. MRMC studies are typically performed for AI/ML diagnostic interpretation algorithms where human readers' performance is evaluated and compared with and without AI assistance. This submission is for an IVD device where measurements are performed by an automated analyzer, not human "readers" interpreting cases.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

The study described is inherently a "standalone" or "algorithm only" performance evaluation relative to the context of AI/ML. The device (cobas c 501 ISE with modified calibration) performs the measurement and produces results without human interpretation of raw data in the same way an AI algorithm would. The study directly evaluates the analytical performance of this automated system.

7. The Type of Ground Truth Used

The ground truth for the analytical performance studies was established using:

• Reference Methods:
  • Flame Photometry for Sodium (Plasma, Urine) and Potassium (Plasma, Urine).
  • Coulometry for Chloride (Plasma, Urine).
• Predicate Device Performance: The original cobas c 501 ISE Gen. 2 with serum-based ISE Compensator (K053165) served as a benchmark for comparison to demonstrate substantial equivalence, rather than a "ground truth" per se.

8. The Sample Size for the Training Set

This is not applicable in the context of AI/ML. This device is a chemistry analyzer with a modified calibration process, not a machine learning algorithm that requires a "training set" in the conventional sense. The "training" of the device involves the 2-point calibration and compensation using ISE Standards Low (S1) and High (S2, S3), as described in the submission.

9. How the Ground Truth for the Training Set was Established

This is not applicable in the context of AI/ML. The "ground truth" for the calibration process is established by the known concentrations of the ISE Standards Low (S1) and High (S2, S3). These are manufactured with highly controlled, known concentrations, serving as the basis for the instrument's calibration.

Summary

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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: [e-mail]

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.

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Classification

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

Panel	ProductCode	Classification Name	Regulation
ClinicalChemistry (75)	JGS	Ion Specific Electrode, Sodium	21 CFR862.1665
ClinicalChemistry (75)	CEM	Ion Specific Electrode,Potassium	21 CFR862.1600
ClinicalChemistry (75)	CGZ	Ion Specific Electrode, Chloride	21 CFR862.1170

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. .

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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.

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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.

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Comparison of Systems – similarities and differences

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	Parameter	Predicate: cobas.c 501 ISEGen: 2 with serum-basedISE CompensatorK053165	cobas c 501 ISE Gen. 2,Modified Calibration,with ISE Standard High-(S3)
	Intendeduse	The ISE module of theRoche/Hitachi cobas csystem is intended for thequantitative determination ofsodium, potassium andchloride in serum, plasma orurine using ion-selectiveelectrodes.	Same
	Measurementprinciple	ISE Potentiometry	Same
	Reagentcontainer	Plastic bottles closed viascrew caps	Same
	Onboardstoragetemperature	5-12 °C	Same
	ISE Module	Integrated into cobas c 501analyzer	Same
	IonSelectiveelectrodes(ISES)	Potentiometric chloride,potassium, sodium andreference electrodes	Same

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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
Intermediateprecision(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 Comparisonto reference(Flame Photometer)	N = 51 (Plasma)Days = 3Correlation = 0.993Slope (Bablok) = 0.976Intercept (Bablok) = +2.041Range (X) = 132.7-164.1				N = 52 (Plasma)Days = 2Correlation = 0.999Slope (Bablok) = 1.000Intercept (Bablok) = 0.200Range (X) = 86.7-172
					N = 51 (Serum)Days = 2Correlation = 0.998Slope (Bablok) = 0.992Intercept (Bablok) = 1.633Range (X) = 97.6-178
Methodcomparisonto predicate	N = 51 (Plasma)Days = 3Correlation = 0.998Slope (Bablok) = 1.000Intercept (Bablok) = -0.100Range (X) = 131.2-162.3				N = 52 (Plasma)Days = 2Correlation = 1.000Slope (Bablok) = 1.016Intercept (Bablok) = -1.456Range (X) = 87.6-170
					N = 51 (Serum)Days = 2Correlation = 0.999Slope (Bablok) = 1.009Intercept (Bablok) = -0.515Range (X) = 97.3-176LoB = 3.9 mmol/L
DetectionLimit	Not determined				LoD = 5.7 mmol/LLoQ = 11.1 mmol/L
Reportablerange	80-180 mmol/L				80-180 mmol/L

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·

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Comparison of assays –

similarities
and
differences

(Sodium)

	Assay ComparisonSodium - Urine
Parameter	Predicate: cobas c 501 ISEGen. 2 with serum-basedISE 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[%]
Intermediateprecision(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
MethodComparisonto reference(flamephotometer)	N = 51Days = 3Correlation = 1.000Slope (Bablok) = 1.001Intercept (Bablok) = -1.263Range (X) = 19.9-257.4				N = 100Days = 2Correlation = 1.000Slope (Bablok) = 0.964Intercept (Bablok) = 4.032Range (X) = 23.5-249.8
Methodcomparisonto predicate	N = 51Days = 3Correlation = 1.000Slope (Bablok) = 1.011Intercept (Bablok) = -0.247Range (X) = 17.9 -253.0				N = 100Days = 2Correlation = 1.000Slope (Bablok) = 0.995Intercept (Bablok) = 0.687Range (X) = 25.1-245.4
DetectionLimit	Not determined				LoB = 3.9 mmol/LLoD = 5.7 mmol/LLoQ = 11.1 mmol/L
Reportablerange	10-250 mmol/L				20 - 250 mmol/L
ExtendedRange	250-375 mmol/L(samples diluted via rerunfunction)				250 - 375 mmol/L(samples diluted via rerun function)

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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 = 3Correlation = 0.998Slope (Bablok) = 0.983Intercept (Bablok) = -0.026Range (X) = 3.23-6.35			N = 52 (Plasma)Days = 2Correlation = 1.000Slope (Bablok) = 1.010Intercept (Bablok) = - 0.022Range (X) = 2.1-9.19N = 54 (Serum)Days = 2Correlation = 1.000Slope (Bablok) = 1.005Intercept (Bablok) = -0.020Range (X) = 1.59-9.56
Method comparison to predicate	N = 51 (Plasma)Days = 3Correlation = 0.998Slope (Bablok) = 0.988Intercept (Bablok) = 0.052Range (X) = 3.14-6.26			N = 52 (Plasma)Days = 2Correlation = 1.000Slope (Bablok) = 1.008Intercept (Bablok) = 0.018Range (X) = 2.02-9.13N = 54 (Serum)Days = 2Correlation = 1.000Slope (Bablok) = 1.004Intercept (Bablok) = 0.302Range (X) = 1.52-9.45.
Detection Limit	Not determined			LoB = 0.17 mmol/LLoD = 0.24 mmol/LLoQ = 0.41 mmol/L
Reportable range	1.5-10.0 mmol/L			1.5 - 10.0 mmol/L

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Comparison of assays –

similarities and differences, (Potassium)

Assay Comparison
Potassium - Urine
Parameter	Predicate: cobas c 501 ISEGen. 2 with serum-basedISE 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	Low8.79	0.04	0.4	Low5.15	0.03	0.6
	High72.04	0.53	0.7	Med52.08	0.32	0.6
	Liq 131.13	0.21	0.7	MDL15.39	0.09	0.6
	Liq 268.76	0.36	0.5	High90.34	0.67	0.7
				Liq 131.48	0.19	0.6
				Liq 270.56	0.43	0.6
Intermediateprecision(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
	High72.04	0.53	0.7	Med52.08	0.67	1.3
	Liq 131.13	0.21	0.7	MDL15.39	0.14	0.9
	Liq 268.76	0.36	0.5	High90.34	1.38	1.5
				Liq 131.48	0.53	1.7
				Liq 270.56	1.17	1.7
MethodComparisonto reference(FlamePhotometry)	N = 51Days = 3Correlation = 1.000Slope (Bablok) = 1.033Intercept (Bablok) = -0.023Range (X) = 9.20-95.10			N = 105Days = 2Correlation = 1.000Slope (Bablok) = 1.018Intercept (Bablok) = 0.397Range (X) = 4.00-97.20
Methodcomparisonto predicate	N = 51Days = 3Correlation = 0.999Slope (Bablok) = 0.982Intercept (Bablok) = 0.323Range (X) = 9.68-98.55			N = 105Days = 2Correlation = 0.999Slope (Bablok) = 0.997Intercept (Bablok) = 0.062Range (X) = 4.05-97.35
DetectionLimit	Not determined			LoB = 0.17 mmol/LLoD = 0.24 mmol/LLoQ = 0.41 mmol/L
Reportablerange	1 -100 mmol/L			3 - 100 mmol/L
ExtendedRange	100-150 mmol/L(samples diluted via rerunfunction)			100 -150 mmol/L(samples diluted via rerun function)

:

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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 = 3Correlation = 0.995Slope (Bablok) = 0.954Intercept (Bablok) = +1.438Range (X) = 92.0 - 132.0	N = 52 (Plasma)Days = 2Correlation = 0.998Slope (Bablok) = 1.023Intercept (Bablok) = -0.769Range (X) = 69.0 - 133N = 53 (Serum)Days = 2Correlation = 0.999
Method comparison to predicate	N = 51 (Plasma)Days = 3Correlation = 0.999Slope (Bablok) = 0.978Intercept (Bablok) = +1.744Range (X) = 90.7-128.9	Slope (Bablok) = 1.043Intercept (Bablok) = -2.843Range (X) = 62.0 - 136N = 52 (Plasma)Days = 2Correlation = 0.999Slope (Bablok) = 1.006Intercept (Bablok) = -0.118Range (X) = 69.4-134N = 53 (Serum)Days = 2Correlation = 1.000Slope (Bablok) = 0.997Intercept (Bablok) = 0.872Range (X) = 61.4 - 138
Detection Limit	Not determined	LoB = 3.40 mmol/LLoD = 4.7 mmol/LLoQ = 5.5 mmol/L
Reportable range	60-140 mmol/L	60-140 mmol/L

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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) = 1.002Intercept (Bablok) = - 2.739				Slope (Bablok) = 1.020
		Range (X) = 21.0-274.0			Intercept (Bablok) = - 1.700Range (X) = 22.0 - 248.0
					N = 105
Methodcomparison	N = 51				Days = 2
to predicate		Days = 3Correlation = 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).

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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.

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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 [phone] or [phone] 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 [phone] or [phone] 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

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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)

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.