ISE Reagent, Glucose, CRP Latex, DxC 700 AU Clinical Chemistry Analyzer

K161837 · Beckman Coulter, Inc. · JGS · Dec 16, 2016 · Clinical Chemistry

Device Facts

• Record ID: K161837
• Device Name: ISE Reagent, Glucose, CRP Latex, DxC 700 AU Clinical Chemistry Analyzer
• Applicant: Beckman Coulter, Inc.
• Product Code: JGS · Clinical Chemistry
• Decision Date: Dec 16, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1665
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

The Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer is an automated chemistry analyzer that measures analytes in samples, in combination with appropriate reagents, calibrators, quality control (QC) material and other accessories. This system is for in vitro diagnostic use only. Applications include colorimetric, latex agglutination, and ion selective electrode. The Glucose test system is for the quantitative measurement of glucose in human serum, plasma, urine and cerebrospinal fluid on Beckman Coulter AU analyzers. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemnia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma. System reagent for the quantitative determination of C-Reactive Protein in human serum and plasma on Beckman Coulter AU Analyzers. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. Measurements may also be useful as an aid in the identification of individuals at risk for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes. Reagents for the quantitative determination of Sodium, Potassium and Chloride concentrations in human serum, plasma and urine on the Beckman Coulter ISE modules. The sodium test system is intended for the quantitative measurement 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. The potassium test system is intended for the quantitative measurement of potassium in serum, plasma, and urine. Measurements obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. The chloride test system is intended for the quantitative measurement of the level of chloride in plasma, serum, and urine. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.

Device Story

DxC 700 AU Clinical Chemistry Analyzer is a fully automated, random-access system for in vitro diagnostic testing. It processes serum, plasma, urine, and CSF samples. The system utilizes ion-selective electrodes (ISE) for electrolytes (Na+, K+, Cl-), colorimetric enzymatic assays for glucose, and latex agglutination for hs-CRP. Samples are loaded via racks or STAT table; the analyzer aspirates samples and reagents, performs automated mixing and incubation, and measures absorbance or electrical potential. The system uses a halogen lamp (340-800 nm) for photometric detection. Results are displayed to clinicians to aid in diagnosing metabolic disorders, electrolyte imbalances, and cardiovascular risk. The device is intended for clinical laboratory use by trained personnel. It supports barcode-based sample identification and automated reagent management. The system provides quantitative data to support clinical decision-making regarding patient treatment and monitoring.

Clinical Evidence

Bench testing only. Performance evaluated per CLSI guidelines (EP05-A3, EP06-A, EP07-A2, EP09-A3, EP17-A2, EP28-A3c). Precision studies (N=80 per analyte) showed low CVs. Linearity confirmed across claimed ranges (r > 0.999). Method comparison against AU5800 (N > 100 samples per analyte) showed high correlation (slope 0.98-1.03, r > 0.999). Matrix comparison (serum vs. plasma) confirmed equivalence. No clinical trials performed.

Technological Characteristics

Automated discrete photometric chemistry analyzer. Sensing: Ion Selective Electrodes (crown ether/PVC membranes) for electrolytes; colorimetric enzymatic for glucose; latex agglutination for CRP. Energy: Halogen lamp (340-800 nm). Connectivity: Barcode-based sample/reagent identification. Throughput: 800-1200 tests/hour. Software: Automated analysis, calibration, and QC monitoring.

Indications for Use

Indicated for quantitative measurement of sodium, potassium, chloride, glucose, and C-reactive protein (CRP) in human serum, plasma, urine, and cerebrospinal fluid (glucose only). Used for diagnosis/treatment of electrolyte/metabolic disorders, diabetes, cardiovascular risk assessment, and inflammatory conditions. Prescription use only.

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

• ISE Reagents : Potassium, Sodium and Chloride (K003721)
• ISE Reagents : Potassium (K112412)
• Glucose (K112412)
• OLYMPUS CRP Latex Immunoturbidimetric Reagent (K051564)
• AU5800 Clinical Chemistry Analyzer (K112412)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number
k161837

B. Purpose for Submission:
Sodium, potassium, chloride, glucose, and C-reactive protein (high sensitivity application) on the DxC 700 AU analyzer

C. Measurand:
Sodium, Potassium, Chloride, Glucose, Cardiac C-Reactive Protein

D. Type of Test:
Sodium, Potassium, and Chloride: Quantitative, ion selective electrodes
C-Reactive Protein (high sensitivity (cardiac) application): Quantitative, latex agglutination
Glucose: Quantitative, colorimetric enzymatic assay

E. Applicant:
Beckman Coulter, Inc.

F. Proprietary and Established Names:
ISE Reagent
CRP Latex
Glucose
DxC 700 AU Clinical Chemistry Analyzer

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G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JGS | II | 862.1665, Sodium Test System | 75-Chemistry |
| CEM | II | 862.1600, Potassium Test System | 75-Chemistry |
| CGZ | II | 862.1170, Chloride Test System | 75-Chemistry |
| CFR | II | 862.345, Glucose Test System | 75-Chemistry |
| NQD | II | 866.5270, Cardiac C-Reactive Protein | 82- Immunology |
| JJE | I | 862.2160, Discrete photometric chemistry analyzer for clinical use. | 75-Chemistry |

H. Intended Use:

1. Intended use(s):

See indications for use below.

2. Indication(s) for use:

ISE Reagent:

Reagent for the quantitative determination of Sodium, Potassium and Chloride concentrations in human serum, plasma, and urine on the Beckman Coulter ISE modules.

The sodium test system is intended for the quantitative measurement of 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.

The potassium test system is intended for the quantitative measurement of potassium in serum, plasma, and urine. Measurements obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of diseases and conditions characterized by low or high blood potassium levels.

The chloride test system is intended for the quantitative measurement of chloride in plasma, serum, and urine. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.

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Glucose Reagent:

The glucose test system is for the quantitative measurement of glucose in human serum, plasma, urine and cerebrospinal fluid on Beckman Coulter AU analyzers. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

CRP Latex Reagent:

System reagent for the quantitative determination of C-Reactive Protein in human serum and plasma on Beckman Coulter AU Analyzers. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. Measurements may also be useful as an aid in the identification of individuals at risk of future cardiovascular disease. High sensitivity CRP (hsCRP) measurements, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, maybe useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary Syndromes.

Analyzer:

The Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer is an automated chemistry analyzer that measures analytes in samples, in combination with appropriate reagents, calibrators, quality control (QC) material and other accessories. The system is for in vitro diagnostic use only. Applications include colorimetric, latex agglutination, and ion selective electrode.

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

DxC 700 AU Clinical Chemistry Analyzer

I. Device Description:

The ISE Reagent consists of the following:

ISE Low Serum Standard: 130 mmol/L sodium, 3.5 mmol/L potassium, 85 mmol/L chloride
ISE Mid-Standard: 4.3 mmol/L sodium, 0.13 mmol/L potassium, 3.1 mmol/L chloride
ISE High Serum Standard: 160 mmol/L sodium, 6 mmol/L potassium, 120 mmol/L chloride
ISE Low Urine Standard: 50 mmol/L sodium, 10 mmol/L potassium, 50 mmol/L chloride
ISE High Urine Standard: 200 mmol/L sodium, 100 mmol/L potassium, 180 mmol/L chloride

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ISE Buffer: Triethanolamine, 0.1 mol/L

ISE Reference: Potassium Chloride, 1.00 mol/L

ISE Na+ Selectivity Check: 150 mmol/L sodium

ISE K+ Selectivity Check: 5 mmol/L potassium

ISE Internal Reference: Potassium Chloride, 3.3 mol/L and saturated silver chloride

The CRP Latex reagent consists of the following:

Reactive Ingredients: Glycine buffer, 100 mmol/L; Latex coated with rabbit anti-CRP Antibodies, <0.5%.

The Glucose reagent consists of the following:

Reactive Ingredients: PIPES- buffer (pH 7.6), 24.0 mmol/L; NAD+, ≥ 1.32 mmol/L; Hexokinase, ≥ 0.59 KU/L; ATP, ≥ 2.0 mmol/L, Mg2+, 2.37 mmol/L; and, G6P-DH, ≥1.58 KU/L

Analyzer:

The five test systems being cleared in this submission include the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer. This Analyzer is a fully automated, random access chemistry analyzer used for the analysis of serum, plasma, urine, CSF, and other body fluids. The DxC 700 AU clinical chemistry analyzer measures analytes in samples using the same reagents, calibrators, quality control materials and other consumables used within the AU series of instruments. Applications include colorimetric, latex agglutination, and ion selective electrode. Electrolyte measurement is performed using a single cell Ion Selective Electrode which is also common among the other members of the AU family.

J. Substantial Equivalence Information:

1. Predicate device name(s) and 510(k) numbers:

| Predicate device name(s) | Predicate 510(k) numbers |
| --- | --- |
| ISE Reagent, Potassium (Beckman Coulter AU 5800) | k112412 |
| ISE Reagent, Sodium and Chloride (Olympus AU2700) | k003721 |
| Glucose (Beckman Coulter AU 5800) | k112412 |
| CRP Latex (Olympus AU 400/AU 400E, AU 600/AU 600E, AU 2700, and AU 5400) | k051564 |
| AU5800 Clinical Chemistry Analyzer | k112412 |

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2. Comparison with predicate:

These new tests systems on the DxC 700 AU Clinical Chemistry analyzer utilize the same reagents as the predicate systems on the AU5800 Clinical Chemistry analyzer for the quantitative measurement of sodium, potassium, chloride, glucose and C reactive protein. The differences in the test systems relate to the differences in the analyzer only. The following test system features are the same between the candidate and predicate devices for the analytes: intended use, test methodology, reagent stability and storage, acceptable specimen type, calibrators and measuring range.

| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device
Sodium, Potassium, Chloride, Glucose, and C-reactive Protein
(high sensitivity application) on the DxC 700 AU Clinical Chemistry Analyzer | Predicate Device
Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the AU5800 Clinical Chemistry Analyzer |
| Intended Use | **ISE reagent:**
The sodium, potassium, and chloride test systems are intended for the quantitative measurement of sodium, potassium, and chloride in serum, plasma, and urine.

**Glucose:**
The glucose test system is for the quantitative measurement of glucose in human serum, plasma, urine and cerebrospinal fluid

**C-Reactive Protein (high sensitivity application):**
System reagent for the quantitative determination of C-Reactive Protein in human serum and plasma

**Analyzer:**
An automated chemistry analyzer that measures analytes in samples in combination with appropriate reagents, calibrators, quality control (QC) material and other accessories. The system is for in | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the DxC 700 AU Clinical Chemistry Analyzer | Predicate Device Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the AU5800 Clinical Chemistry Analyzer |
| | vitro diagnostic use only. Applications include colorimetric, latex agglutination, and ion selective electrode. | |
| Test methodology | Colorimetric, latex agglutination, and ion selective electrode | Same |
| Reagent Storage Temperature | Refrigeration temperature: 4 to 12°C | Same |
| Sample containers | 10 sample tubes on a rack | Same |
| Sample identification | Sample barcode, sequential numbering and the position on the rack. | Same |
| Wavelengths (nm) | Halogen Lamp 340 to 800 nm 13 wavelengths: 340, 380, 410, 450, 480, 520, 540, 570, 600, 660, 700, 750, and 800 nm | Same |
| Reagent identification | Barcode and fixed position in the reagent carousel | Same |
| Differences | | |
| --- | --- | --- |
| Item | Candidate Device Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the DxC 700 AU Clinical Chemistry Analyzer | Predicate Device Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the AU5800 Clinical Chemistry Analyzer |
| Sample volume | 1.0 to 25.0 μL | 1.0 to 17.0 μL |
| Sample Input | Sample Rack, STAT Table, Direct-line Sample Aspiration (for automation connections) | Sample Rack |
| Single Sample Replicate Analysis | Ability to request test replicates for one sample, up to 20 replicates per sample per test. | None |
| Cuvette | Square, glass cuvette 5x5 mm | Square, glass cuvette 4x5 mm |

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| Differences | | |
| --- | --- | --- |
| Item | Candidate Device Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the DxC 700 AU Clinical Chemistry Analyzer | Predicate Device Sodium, Potassium, Chloride, Glucose, and C-reactive Protein (high sensitivity application) on the AU5800 Clinical Chemistry Analyzer |
| Number of Cuvettes | 165 | 408 |
| Throughput | Maximum 800 photometric tests/hour or 1200 tests/hour (photometric + ISE) | Maximum 2000 photometric tests/hour |
| Barcode Scanner | Able to scan a 2D barcode on a Calibrator Parameter sheet and auto-populate the calibrator parameters into the system and scan ISE reagent bottles and Electrode barcode for information entry. | Not available |
| Reagent Loading during analysis | Reagent bottles can be changed while the instrument continues to measure patient samples. | System must be in Pause Mode. |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition.

CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition.

CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition.

CLSI EP 17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline.

CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline.

CLSI EP28-A3c: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline; Third Edition.

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L. Test Principle:

The Ion Selective Electrode (ISE) module for sodium, potassium, and chloride measurement employs crown ether membrane electrodes for sodium and potassium and a molecular oriented PVC membrane for chloride that is specific for each ion of interest in the sample. An electrical potential is developed according to the Nernst Equation for a specific ion. When compared to the Internal Reference Solution, this electrical potential is translated into voltage and then into the ion concentration of the sample.

Glucose is phosphorylated by hexokinase in the presence of adenosine triphosphate (ATP) and magnesium ions to produce glucose-6-phospage (G-6-P) and adenosine diphosphate (ADP). Glucose-6-phosphate dehydrogenase specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide, reduced (NADH). For the DxC 700 AU the change in absorbance at 340/600 nm is proportional to the amount of glucose present in the sample.

The C-Reactive Protein assay high sensitive application uses the latex agglutination test principle. Immune complexes formed in solution scatter light in proportion to their size, shape, and concentration. Turbidimeters measure the reduction of incidence light due to reflection, absorption, or scatter. The measurement of the rate of decrease in light intensity transmitted (increase in absorbance) through particles suspended in solution is the result of complexes formed during the immunological reaction between the CRP of the patient serum and rabbit anti-CRP antibodies coated on latex particles.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

Note: The normal and high sensitivity CRP applications use the same CRP Latex reagent, but require separate calibrators and instrument settings, and have separate measuring ranges (normal, 1.0-480 mg/L and high sensitivity, 0.2-80 mg/L). Only the high sensitivity application (hs-CRP) was used for the CRP performance studies.

a. Precision/Reproducibility:

Repeatability (within-run) and total precision studies were performed in accordance with CLSI EP05-A3. The precision was evaluated using 1 lot of reagent and 1 lot of calibrator for each analyte tested. The samples for the ISE precision studies consisted of 3 to 4 levels of pooled human serum and pooled human urine. The glucose precision samples consisted of 5 concentrations of human serum samples and the CRP precision samples consisted of 4 concentrations of human serum samples. Some of the sample pools were spiked or diluted to achieve concentrations throughout the claimed measuring ranges of each analyte. The samples were run in duplicate, twice daily, over the course of 20 days for a total of 80 results per analyte on the DxC 700 AU analyzer. The results are summarized in the tables below:

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ISE Reagent

| | | | | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Test | Samples | N | Mean (mEq/L) | SD | %CV | SD | %CV |
| Na+ | Serum 1 | 80 | 61.8 | 0.324 | 0.52 | 0.879 | 1.42 |
| | Serum 2 | 80 | 109.7 | 0.318 | 0.29 | 0.638 | 0.58 |
| | Serum 3 | 80 | 139.5 | 0.212 | 0.15 | 0.552 | 0.40 |
| | Serum 4 | 80 | 167.8 | 0.309 | 0.18 | 0.834 | 0.50 |
| K+ | Serum 1 | 80 | 2.48 | 0.009 | 0.36 | 0.016 | 0.64 |
| | Serum 2 | 80 | 4.56 | 0.011 | 0.25 | 0.022 | 0.48 |
| | Serum 3 | 80 | 6.46 | 0.021 | 0.33 | 0.039 | 0.60 |
| | Serum 4 | 80 | 8.35 | 0.035 | 0.42 | 0.080 | 0.96 |
| Cl- | Serum 1 | 80 | 76.5 | 0.149 | 0.19 | 0.510 | 0.67 |
| | Serum 2 | 80 | 105.3 | 0.270 | 0.26 | 0.443 | 0.42 |
| | Serum 3 | 80 | 151.8 | 0.401 | 0.26 | 1.025 | 0.68 |
| Na+ | Urine 1 | 80 | 22.0 | 0.261 | 1.19 | 0.414 | 1.89 |
| | Urine 2 | 80 | 98.7 | 0.420 | 0.43 | 1.308 | 1.32 |
| | Urine 3 | 80 | 245.5 | 0.951 | 0.39 | 3.191 | 1.30 |
| | Urine 4 | 80 | 353.4 | 0.933 | 0.26 | 4.092 | 1.16 |
| K+ | Urine 1 | 80 | 10.5 | 0.047 | 0.45 | 0.127 | 1.21 |
| | Urine 2 | 80 | 33.6 | 0.128 | 0.38 | 0.611 | 1.82 |
| | Urine 3 | 80 | 101.1 | 0.596 | 0.59 | 1.308 | 1.29 |
| | Urine 4 | 80 | 171.4 | 1.145 | 0.67 | 2.435 | 1.42 |
| Cl- | Urine 1 | 80 | 25.5 | 0.173 | 0.68 | 0.559 | 2.19 |
| | Urine 2 | 80 | 84.5 | 0.249 | 0.29 | 0.508 | 0.60 |
| | Urine 3 | 80 | 148.5 | 0.383 | 0.26 | 0.758 | 0.51 |
| | Urine 4 | 80 | 291.0 | 1.737 | 0.60 | 3.640 | 1.25 |
| | Urine 5 | 80 | 364.1 | 1.716 | 0.47 | 4.157 | 1.14 |

Glucose Reagent

| | | | | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Test | Samples | N | Mean (mg/dL) | SD | %CV | SD | %CV |
| Glucose | Serum 1 | 80 | 25.9 | 0.326 | 1.26 | 0.628 | 2.43 |
| | Serum 2 | 80 | 60.6 | 0.501 | 0.83 | 0.815 | 1.35 |
| | Serum 3 | 80 | 101.7 | 0.754 | 0.74 | 1.184 | 1.16 |
| | Serum 4 | 80 | 280.6 | 2.386 | 0.85 | 2.530 | 0.90 |
| | Serum 5 | 80 | 643.9 | 4.269 | 0.66 | 4.821 | 0.75 |

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CRP Latex Reagent (high sensitivity (cardiac) application)

| | | | | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Test | Samples | N | Mean (mg/L) | SD | %CV | SD | %CV |
| hs-CRP | Serum 1 | 80 | 0.49 | 0.019 | 3.84 | 0.017 | 3.48 |
| | Serum 2 | 80 | 10.3 | 0.120 | 1.17 | 0.125 | 1.22 |
| | Serum 3 | 80 | 50.1 | 0.314 | 0.63 | 0.389 | 0.78 |
| | Serum 4 | 80 | 67.8 | 0.428 | 0.63 | 0.612 | 0.90 |

# b. Linearity/assay reportable range:

Linearity studies were performed in accordance with CLSI EP06-A. High pools were prepared by spiking a known concentration of analyte in serum and urine samples and low pools were prepared by dilution. The high and low pools were inter-diluted to achieve concentrations spanning the claimed measuring range as follows.

| Analyte | Sample concentrations tested |
| --- | --- |
| Sodium, serum (mEq/L) | 6.69, 29.15, 52.03, 75.90, 100.44, 124.17, 148.83, 172.65, 196.58, 220.44, 245.97 |
| Sodium, urine (mEq/L) | 9.04,13.37, 21.92, 31.67, 40.70, 50.10, 100.01, 150.42, 202.07, 253.84, 307.89, 361.83, 417.73 |
| Potassium, serum (mEq/L) | 0.14, 1.20, 2.39, 3.64, 4.89, 6.14, 7.40, 8.71, 9.88, 11.14, 12.44 |
| Potassium, urine (mEq/L) | 1.02, 2.04, 5.06, 10.17, 20.42, 25.69, 51.42, 76.86, 102.10, 126.89, 152.16, 176.03, 200.89, 223.47 |
| Chloride, serum (mEq/L) | 5.92, 26.20, 48.53, 72.64, 96.83, 121.45, 146.17, 171.17, 194.67, 220.90,246.78 |
| Chloride, urine (mEq/L) | 14.10, 22.42, 31.55, 40.79, 50.10, 100.35, 151.74, 203.87, 257.62, 311.36, 365.00, 421.31 |
| Glucose, serum (mg/dL) | 5.20, 9.73, 18.80, 46.58, 93.90, 192.03, 287.53, 374.80, 474.42, 569.10, 659.96, 751.01, 843.18 |
| hs-CRP, serum (mg/L) | 0.01, 0.96,1.90, 3.53, 8.98, 18.69, 37.39, 55.98, 76.57, 97.65 |

# Linear Regression Analysis

The samples were assayed in replicates of four and the mean result obtained for each sample concentration when run on the DxC 700 AU is shown in the table below were compared to the expected results determined by the dilution factor.

The linear regression results are summarized in the table below.

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| Analyte | Slope | Intercept | r |
| --- | --- | --- | --- |
| Na, serum | 1.0165 | -1.6158 | 0.9999 |
| Na, urine | 1.0506 | -2.7363 | 0.9994 |
| K, serum | 1.0207 | -0.1224 | 0.9996 |
| K, urine | 0.9883 | 0.0571 | 0.9999 |
| Cl, serum | 1.0362 | -3.6836 | 0.9995 |
| Cl, urine | 1.0476 | -3.5026 | 0.9994 |
| Glucose, serum | 0.9834 | -0.0628 | 0.9999 |
| hs-CRP, serum | 0.9894 | 0.0444 | 0.9995 |

The linearity studies support the following claimed measuring ranges:

| Analyte | Measuring range |
| --- | --- |
| Sodium, serum | 50-200 mEq/L |
| Potassium, serum | 1.0-10.0 mEq/L |
| Chloride, serum | 50-200 mEq/L |
| Sodium, urine | 10-400 mEq/L |
| Potassium, urine | 2.0-200 mEq/L |
| Chloride, urine | 15-400 mEq/L |
| Glucose, serum | 10-800 mg/dL |
| hs-CRP, serum | 0.2-80 mg/dL |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The ISE calibrator material for sodium, potassium and chloride was previously cleared under k921718. The Glucose calibrator material was previously cleared under k043460. The CRP calibrator material, high sensitivity application, was previously cleared under k051564.

d. Detection limit:

Detection limit studies were performed according to CLSI EP17-A2. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) for high sensitivity CRP and Glucose were determined by running replicate measurements on blank and low level serum samples using 2 lots of reagent across multiple days. A total of 60 blank replicates per reagent lot and 280 low level sample replicates per reagent lot were obtained. This was comprised of 4 blank samples run in replicates of 5 for 3 days, and 7 low level serum samples run in replicates of 5 for 8 days. The sponsor defines the LoQ for CRP and Glucose as the lowest concentration with an inter-assay precision of $\leq 20\%$ CV. The detection limits for Glucose and hs-CRP are summarized below:

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Detection Limit Summary

| Analyte | LoB | LoD | LoQ |
| --- | --- | --- | --- |
| Glucose (mg/dL) | 0 | 0.42 | 2.68 |
| hs-CRP (mg/L) | 0.04 | 0.08 | 0.08 |

The upper and lower limits of the measuring range for the ISE assays are supported by linearity studies above.

# e. Analytical specificity:

Interference studies were performed in accordance to CLSI EP07-A2. Different levels of intralipid, bilirubin and hemoglobin were spiked into human serum sample pools and tested on the DxC 700 AU. Samples were tested in replicates of four at one or two analyte concentrations using a single lot of reagent and calibrator. The results of the spiked samples were compared to the results of the non-spiked samples. The sponsor defines significant interference for each of the analytes as follows: Glucose, $\pm \geq 10\%$ bias; Chloride, $\pm 2.5\%$ bias; Potassium, $\pm 0.25\mathrm{mEq / L}$ ; and Sodium, $\pm 2$ $\mathrm{mEq / L}$ ; hs-CRP $\pm \geq 10\%$ bias for intralipid and $\pm \geq 5\%$ bias for hemolysis and bilirubin. The results are summarized in the table below:

| Analyte | Analyte concentrations tested | Interferent | Highest concentration of interferent tested that did not show significant interference |
| --- | --- | --- | --- |
| Na+ (serum) | 136 mEq/L 161 mEq/L | Intralipid | 500 mg/dL |
| | 139 mEq/L 161 mEq/L | Bilirubin | 40 mg/dL |
| | 139 mEq/L 162 mEq/L | Hemoglobin | 300 mg/dL |
| K+ (serum) | 3.40 mEq/L 4.79 mEq/L | Intralipid | 500 mg/dL |
| | 3.39 mEq/L 4.75 mEq/L | Bilirubin | 40 mg/dL |
| | 2.58 mEq/L 4.92 mEq/L | Hemoglobin | 70 mg/dL |
| Cl- (serum) | 97 mEq/L 115 mEq/L | Intralipid | 500 mg/dL |
| | 97 mEq/L 115 mEq/L | Bilirubin | 40 mg/dL |
| | 100 mEq/L 120 mEq/L | Hemoglobin | 500 mg/dL |

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| Analyte | Analyte concentrations tested | Interferent | Highest concentration of interferent tested that did not show significant interference |
| --- | --- | --- | --- |
| Glucose (serum) | 78 mg/dL
113 mg/dL | Intralipid | 700 mg/dL |
| | 78 mg/dL
113 mg/dL | Bilirubin | 40 mg/dL |
| | 78 mg/dL
113 mg/dL | Hemoglobin | 500 mg/dL |
| hs-CRP, (serum) | 1.46 mg/L | Intralipid | 1000 mg/dL |
| | 1.47 mg/L | Bilirubin | 40 mg/dL |
| | 1.44 mg/L | Hemoglobin | 500 mg/dL |

CRP (high sensitivity (cardiac) application) prozone study:

A study was performed to verify the CRP prozone performance on the DxC 700 AU. Human serum was spiked with human CRP to create a prozone high pool of >750 mg/L. The high pool was diluted with 5% BSA in 0.9% saline to obtain equally spaced concentrations of CRP as follows: approximately 0.0, 4.0, 8.2, 16.3, 40.7, 81.5, 163.0, 244.5, 326.0, 407.5, 488.9, 570.4, 651.9, 733.4, and 815.0 mg/L CRP. Each sample was run in triplicate to confirm prozone performance. The study demonstrated that no value within the measuring range (0.2-80 mg/L) is generated with CRP concentrations up to 815 mg/L and that all data flagged appropriately as being out of the measuring range (>80 mg/L).

The sponsor includes the following limitations in the labeling:

**ISE Reagent:**

"Separate serum from blood cells as soon as possible. Avoid hemolysis since it can lead to falsely elevated K+ values."

"Serum, free from hemolysis, is the recommended specimen."

"Certain anticoagulants, preservatives, drugs, and organophilic compounds may affect electrolyte determinations. For further information on interfering substances, refer to Young¹ for a compilation of reported interferences with this test. Visually turbid urine specimens should be centrifuged prior to analysis. Grossly lipemic samples may show an inappropriate decrease in sodium, potassium, and chloride results due to volume displacement. Such samples should be ultracentrifuged and the

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analysis performed on the infranatant (middle clear layer).”

“Care should be taken when interpreting results from patients with hyperproteinemia and hyperlipidemia due to the electrolyte exclusion effect.”

## Glucose Reagent:

“Fasting serum or plasma (EDTA, heparin or sodium fluoride) samples free from hemolysis, are the recommended specimens. Separate from red cells rapidly to minimize loss of glucose through glycolysis. Fresh random collections are recommended for urine specimens.”

“In rare cases gammopathy, especially monoclonal IgM (Waldenstrom’s macroglobulinemia), may cause unreliable results.”

## CRP Latex (high sensitivity (cardiac) application):

“Centrifuge samples containing precipitates before performing the assay.”

“In very rare cases gammopathy, especially monoclonal IgM (Waldenstrom’s macroglobulinemia), may cause unreliable results.”

“Samples containing heterophilic antibodies can cause falsely elevated results. Please note that oral contraceptives have been reported to affect results.”

“Sample carryover may occur when a high CRP sample >160 mg/L is run directly before a sample with low CRP. Sample contamination avoidance parameters should be programmed on the AU2700/5400/5800/480/680 and DxC 700 AU instruments and are available on the Beckman Coulter website.”

“When using the High Sensitive Application on the Beckman Coulter AU2700/5400/5800/DxC 700 AU systems, patients with CRP concentrations up to 750 mg/L will not generate false low results within the analytical range.”

“Patients with inflammatory and/or infectious conditions should have their CRP measured using the Normal Application, particularly when used for patient monitoring. When using the Normal Application on all Beckman Coulter AU systems, patients with CRP concentrations up to 750 mg/L will not generate false low results within the analytical range.”

## References:

1. Young, D.S., Effect of Drugs on Clinical Laboratory Tests, 5th Edition, AACC Press, 2000.

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f. Assay cut-off:

Not applicable.

## 2. Comparison studies:

a. Method comparison with predicate device:

A method comparison study was performed in accordance with CLSI EP09-A3. A minimum of 100 human serum samples with analyte concentration within the analytical ranges of sodium, potassium, chloride, glucose, and CRP (high sensitivity (cardiac) application) and a minimum of 100 urine samples for sodium, potassium, and chloride were tested on the DxC 700 AU and the AU5800. Less than 15% of the samples were altered by spiking and diluting human serum samples and urine. The regression analysis is summarized in the tables below:

Method Comparison Results

| Analyte | N | Slope | Intercept | R | Test Range | Claimed Measuring Range |
| --- | --- | --- | --- | --- | --- | --- |
| Na+, serum (mEq/L) | 120 | 1.007 | -0.779 | 0.999 | 52.4-197.8 | 50-200 |
| K+, serum (mEq/L) | 122 | 0.988 | 0.048 | 0.999 | 1.1-8.1 | 1.0-10 |
| Cl-, serum (mEq/L) | 118 | 0.999 | 0.224 | 0.999 | 59.4-179.7 | 50-200 |
| Na+, urine (mEq/L) | 130 | 1.014 | -1.392 | 1.000 | 11.1-386.2 | 10-400 |
| K+, urine (mEq/L) | 127 | 1.011 | -0.149 | 1.000 | 2.0-191.0 | 2.0-200 |
| Cl-, urine (mEq/L) | 129 | 1.036 | -3.679 | 1.000 | 15.8-383.7 | 15-400 |
| Glucose, serum (mg/dL) | 130 | 1.014 | 0.04 | 1.000 | 13.52-790.52 | 10-800 |
| hs-CRP, serum (mg/L) | 117 | 1.013 | -0.050 | 1.000 | 0.29-71.00 | 0.2-80 |

b. Matrix comparison:

Sodium, Potassium and Chloride :

A matrix comparison study was performed to demonstrate the equivalence between serum and plasma samples when measuring sodium, potassium and chloride on the

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DxC 700 AU analyzer. Blood was collected in-house using the following blood tube types: Serum, Ammonium Heparin, and Lithium Heparin. Fifty-one samples with analyte concentration within the analytical ranges of the applications were run on the DxC 700 AU analyzer. 16% of the total number of samples were altered by dilution or spiking in order to cover the claimed measuring range. The following regression equations were obtained from the matrix comparison study for sodium, potassium and chloride analytes:

DxC 700 AU matrix comparison results for ISE measurement

| Analyte | Matrix | N | Test range (mEq/L) | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- | --- |
| Na+ | Serum vs AmHep | 51 | 71-188 | 0.987 | 2.098 | 0.999 |
| K+ | Serum vs AmHep | 51 | 1.80-8.85 | 0.988 | -0.219 | 0.988 |
| Cl- | Serum vs AmHep | 51 | 51-193 | 0.993 | 0.590 | 0.999 |
| Na+ | Serum vs LiHep | 51 | 71-189 | 0.997 | 0.206 | 0.999 |
| K+ | Serum vs LiHep | 51 | 1.78-8.86 | 0.991 | -0.255 | 0.990 |
| Cl- | Serum vs LiHep | 51 | 51-193 | 0.994 | 0.721 | 0.999 |

The results of the matrix comparison studies support the sponsor's claim that serum, ammonium heparin, and lithium heparin samples can be used on the DxC 700 AU test systems for the measurement of sodium, potassium, and chloride.

## Glucose :

A matrix comparison study was performed on the DxC AU 700 analyzer to evaluate the equivalency of EDTA, Sodium Floride Potassium Oxalate, Sodium Floride EDTA, and Lithium Heparin plasma samples compared to serum samples for glucose measurement. Forty-two sets of matched samples were tested in the analysis, using one lot of glucose reagent. In order to cover the glucose measuring range of 10-800 mg/dL, the study included 16% contrived samples. The following regression equations were obtained from the matrix comparison study for the glucose analyte:

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DxC AU 700 matrix comparison results for glucose measurement

| Matrix | N | Test range (mg/dL) | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- |
| Serum vs K2-EDTA | 42 | 19.72-752.31 | 0.999 | -0.099 | 0.998 |
| Serum vs Sodium Fluoride Potassium Oxalate | 42 | 19.72-752.31 | 1.007 | 0.127 | 0.998 |
| Serum vs Lithium Heparin | 42 | 19.72-752.31 | 0.996 | -0.076 | 0.998 |
| Serum vs Sodium Fluoride EDTA | 42 | 19.72-752.31 | 1.005 | 0.133 | 0.998 |

The results of the matrix comparison studies support the sponsor's claim that serum, K2-EDTA, Sodium Fluoride Potassium Oxalate, SodiumFluoride EDTA, and lithium heparin samples can be used on the DxC 700 AU test systems for the measurement of glucose.

CRP high sensitivity (cardiac) application:

A matrix comparison study was performed on the DxC AU 700 analyzer to evaluate the equivalency of K2-EDTA and Lithium Heparin plasma samples compared to serum samples for CRP measurement (high sensitivity application). Fifty-two (52) sets of matched samples were tested in the analysis, using one lot of CRP Latex reagent. In order to cover the hs-CRP measuring range of $0.2 - 80\mathrm{mg / L}$ , the study included $15\%$ contrived samples. The following regression equations were obtained from the matrix comparison study for CRP analyte:

DxC AU 700 matrix comparison results for CRP measurement high sensitivity (cardiac) application

| Matrix | N | Test range (mg/L) | Slope | Intercept | r |
| --- | --- | --- | --- | --- | --- |
| Serum vs K2-EDTA | 52 | 0.34-73.11 | 0.990 | -0.059 | 0.999 |
| Serum vs Lithium Heparin | 52 | 0.34-73.11 | 0.985 | -0.013 | 0.999 |

The results of the matrix comparison studies support the sponsor's claim that serum,

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K2-EDTA, and lithium heparin samples can be used on the DxC 700 AU test systems for the measurement of CRP.

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable.

4. Clinical cut-off:

Not applicable.

5. Expected values/Reference range:

The sponsor performed studies in accordance to CLSI EP28-A3c to verify the reference ranges of the analytes. A minimum of 20 serum samples from healthy volunteers were used to verify the CRP high sensitivity (cardiac) application and Glucose reference ranges. The sodium, potassium and chloride reference range was verified using 20 serum, ammonium heparin, and lithium heparin samples from healthy volunteers. The samples were tested in duplicate on two DxC 700 AU analyzers, each using a different reagent lot. The mean of the duplicate results for each subject was compared against reference ranges cited in literature. The verification studies support the following reference ranges which were established through literature.

CRP high sensitivity (cardiac) application

The expected values of CRP concentrations, <1 mg/L were established though literature and the cardiac risk assessment categories are recommended by the American Heart Association (AHA) are as follows:

Low: <1 mg/L, Average 1.0 to 3.0 mg/L, and High: >3.0 mg/L¹

CRP expected values <10 mg/dL (established through literature)⁵

Newborns with no evidence of infection have CRP concentrations of <10 mg/L (established through literature).²

Sodium, serum and plasma: 136-145 mEq/L³

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Sodium, urine: 40-220 mEq/day³

Potassium, serum: 3.5-5.1 mEq/L³

Potassium, plasma: 3.4-4.5³

Potassium, urine: 25-125 mEq/day³

Chloride, serum and plasma: 98-107 mEq/L³

Chloride, urine: 110-250 mEq/day³

Glucose, serum, adult: 74-109 mg/dL⁴

Glucose, serum, newborn: 36-99 mg/dl⁴

Glucose, urine: none³

Glucose, cerebrospinal fluid, adult: 40-70 mg/dL³

Glucose, cerebrospinal fluid, child: 60-80 mg/dL³

## References:

1. Pearson TA et al. Markers of inflammation and cardiovascular disease. Application to clinical and public heal practice. A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. http://www.circulationaha.org.
2. Claudio Chiesa et al., C reactive protein and procalcitonin: Reference intervals for preterm and term newborns during the early neonatal period, Clinical Chemistry, Volume 412, 12 May 2011, pgs 1053-1059.
3. Tietz, N.W., editor, Clinical Guide to Laboratory Tests, 5th Edition, W.B Saunders 2012.
4. Thomas L, ed. Blutglucose. In: Thosmas L. ed. Laboratory and Diagnosis, 6th ed., Frankfurt/Main: TH-Books 2005; 193-199.
5. Raifai N, Ridker PM. Population Distributions of C-reactive Protein in Apparently Healthy Men and Women in the United States: Implications for Clinical Interpretation. Clin Chem 2006; 49:666-6691.

## N. Instrument Name:

DxC 700 AU Clinical Chemistry Analyzer

## O. System Descriptions:

1. Modes of Operation:

Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?

Yes ☐ X ☐ or No ☐

Does the applicant’s device transmit data to a computer, webserver, or mobile device

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using wireless transmission?

Yes _______ or No ☐ X

2. Software:

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

Yes ☐ X or No _______

3. Specimen Identification:

Sample barcode, sequential numbering and the position on the rack.

4. Specimen Sampling and Handling:

Instruction on sample handling is provided in the reagent labeling.

5. Calibration:

Instruction on calibration is provided in the reagent labeling.

6. Quality Control:

Beckman Coulter recommends that during operation of the DxC 700 AU analyzer, at least two levels of an appropriate quality control material should be tested a minimum of once a day. In addition, controls should be performed after calibration, with each new lot of reagent, and after specific maintenance or troubleshooting steps described in the appropriate User’s Guide. Quality control testing should be performed in accordance with regulatory requirements and each laboratory’s standard procedure.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

Not applicable

Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

R. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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