The Beckman Coulter DxC 500 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.

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

The Beckman Coulter DxC 500 AU Clinical Chemistry Analyzer carries out automated analysis of serum, plasma, urine samples and other body fluids and automatically generates results. The device is an automated photometric clinical 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. Electrolyte measurement is performed using a single cell lon Selective Electrode (ISE) which is also common among the other members of the AU family.

The ISE module for Na+, K+, and Cl- employs crown ether membrane electrodes for sodium and potassium and a molecular oriented PVC membrane for chloride that are 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.

In this Beckman Coulter procedure, glucose is phosphorylated by hexokinase (HK) in the presence of adenosine triphosphate (ATP) and magnesium ions to produce glucose-6-phosphate (G-6-P) and adenosine diphosphate (ADP). Glucose-6phosphate dehydrogenase (G6P-DH) specifically oxidizes G-6-P to 6phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide, reduced (NADH). The change in absorbance at 340/660 nm is proportional to the amount of glucose present in the sample.

The CRP Latex reagent is an in vitro diagnostic device that consists of ready to use buffer and latex particles coated with rabbit anti-CRP antibodies. In this procedure, the measurement of the rate of decrease in light intensity transmitted 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-CRPantibodies coated on latex particles. Two measuring range settings are available: Normal application (CRP Concentrations ranging between 5.0-480 mg/L) and Highly Sensitive (Cardiac) Application- (CRP concentrations ranging between 0.2-80mg/L).

AI/ML Overview

This document describes the acceptance criteria and supporting study for the Beckman Coulter DxC 500 AU Clinical Chemistry Analyzer and its associated reagents (Glucose, CRP Latex, ISE Reagents for Sodium, Potassium, and Chloride).

1. Table of Acceptance Criteria and Reported Device Performance

The device performance was evaluated across several metrics. The table below summarizes the acceptance criteria (often implied by the "Pass" result and the specific targets within the CLSI guidelines references) and the reported performance for key tests:

Reagent/ISE & Sample Type	Metric	Acceptance Criteria (Implied)	Reported Performance	Result
hsCRP (Cardiac) (Serum)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 0.990; Bias: 0.4% at 3mg/L; R: 0.9997	Pass
	Linearity	<12% or 0.15 mg/L difference	Range: 0.124 - 81.35 mg/L	Pass
	LOD	≤ 0.2 mg/L	LOB: 0.01 mg/L, LOD: 0.03 mg/L, LOQ: 0.06 mg/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.01-0.73; CV: 0.6-1.5% across 5 serum levels	Pass
	Interferences	<5% with Bilirubin, Haemoglobin; <10% with Lipemia, RF, Triglyceride	Met all specified thresholds	Pass
CRP Normal (Serum)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 0.993; Bias: 5.4% at 10 mg/L; R: 0.9995	Pass
	Linearity	<12% or 0.2 mg/L difference	Range: 0.78 - 516.408 mg/L	Pass
	LOD	≤ 5.0 mg/L	LOB: 0.28 mg/L, LOD: 0.48 mg/L, LOQ: 0.89 mg/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.04-4.33; CV: 0.6-1.5% across 5 serum levels	Pass
	Interferences	<5% with Bilirubin, Haemoglobin; <10% with Lipemia, RF, Triglyceride	Met all specified thresholds	Pass
Glucose (Serum)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 0.986; Bias: -1% at 100 mg/dL; R: 0.9999	Pass
	Linearity	<5% or 0.5 mg/dL difference	Range: 7.68 - 879.73 mg/dL	Pass
	LOD	≤ 10 mg/dL	LOB: 0.55 mg/dL, LOD: 1.02 mg/dL, LOQ: 1.42 mg/dL	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.2-2.9; CV: 0.3-1.0% across 3 serum levels	Pass
	Interferences	<10% intf. at Glucose conc. of 40 & 220 mg/dL for Lipemic, Icteric, Hemolytic	Met all specified thresholds	Pass
Glucose (Urine)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.001; Bias: -0.3% at 50 mg/dL; R: 1.0000	Pass
	Linearity	<5% or 0.5 mg/dL difference	Range: 7.39 - 760.22 mg/dL	Pass
	LOD	≤ 10 mg/dL	LOB: 0.48 mg/dL, LOD: 0.92 mg/dL, LOQ: 1.41 mg/dL	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.3-3.0; CV: 0.4-1.3% across 3 urine levels	Pass
	Interferences	<10% intf. at specified Glucose conc. for Icteric, Hemolytic	Met all specified thresholds	Pass
Glucose (CSF)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.009; Bias: 3% at 50 mg/dL; R: 0.9998	Pass
	Linearity	<5% or 0.5 mg/dL difference	Range: 7.23 - 901.37 mg/dL	Pass
	LOD	≤ 10 mg/dL	LOB: 0.4 mg/dL, LOD: 0.7 mg/dL, LOQ: 1.1 mg/dL	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.2-3.2; CV: 0.4-1.2% across 3 CSF levels	Pass
	Interferences	<10% intf. at specified Glucose conc. for Icteric, Hemolytic	Met all specified thresholds	Pass
Sodium (Serum)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.018; Bias: 0.2% at 130 mEq/L, 0.5% at 160 mEq/L; R: 0.9995	Pass
	Linearity	<2.5% or 3.25 mEq/L difference	Range: 47.11 - 205.87 mEq/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.23-0.57; CV: 0.2-0.8% across 4 serum levels	Pass
	Interferences	≤2 mEq/L at Sodium conc. of 130 & 150 mEq/L for Lipemic, Icteric, Hemolytic	Met all specified thresholds	Pass
Potassium (Serum)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.015; Bias: -0.1% at 3 mEq/L, 0.7% at 6 mEq/L; R: 0.9998	Pass
	Linearity	<4% or 0.12 mEq/L difference	Range: 0.727 - 10.835 mEq/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.01-0.05; CV: 0.2-0.5% across 4 serum levels	Pass
	Interferences	≤0.25 mEq/L at Potassium conc. of 3 & 5 mEq/L for Lipemic, Icteric, Hemolytic	Met all specified thresholds	Pass
Chloride (Serum)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.007; Bias: 0.3% at 90 mEq/L, 0.4% at 120 mEq/L; R: 0.9997	Pass
	Linearity	<4% or 3.6 mEq/L difference	Range: 27.66 - 223.58 mEq/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.21-0.81; CV: 0.3-0.5% across 4 serum levels	Pass
	Interferences	≤2.5 mEq/L at Chloride conc. of 90 & 110 mEq/L for Lipemic, Icteric, Hemolytic	Met all specified thresholds	Pass
Sodium (Urine)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.008; Bias: 0.6% at 60 mEq/L, 0.7% at 180 mEq/L; R: 0.9999	Pass
	Linearity	<5% or 1.2 mEq/L difference	Range: 7.93 - 441.48 mEq/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.24-2.18; CV: 0.3-1.7% across 4 urine levels	Pass
Potassium (Urine)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.000; Bias: 1.3% at 15 mEq/L, 0.2% at 80 mEq/L; R: 0.9998	Pass
	Linearity	<7% or 1 mEq/L difference	Range: 1.066 - 225.165 mEq/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.03-1.85; CV: 0.3-1.0% across 4 urine levels	Pass
Chloride (Urine)	Method Comparison	Slope: ~1.0; Bias: Low; R: ~1.0	Slope: 1.002; Bias: -0.4% at 50 mEq/L, 0.05% at 170 mEq/L; R: 0.9999	Pass
	Linearity	<6% or 3.6 mEq/L difference	Range: 11.42 - 433.78 mEq/L	Pass
	Precision	Repeatability (SD/CV) & Total Precision (SD/CV) at various levels	SD: 0.2-1.88; CV: 0.3-1.1% across 5 urine levels	Pass
Reference Interval	Transference	≥ 90% of reference individuals within cited range	CRP: 96% (24/25); Glucose Serum: 91% (21/23); Glucose Urine: 100% (24/24); ISE Na Serum: 100% (20/20); ISE K Serum: 100% (20/20); ISE Cl Serum: 95% (19/20)	Pass

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

The studies used various sample sizes for different tests, primarily patient samples and prepared sample pools. The provenance of the data is not explicitly stated in terms of country of origin, but it is implied to be clinical laboratory data. The studies are non-clinical (bench) studies following CLSI protocols, which suggests they were conducted in a controlled laboratory environment. The data is retrospective in the sense that it relies on established methods and samples to evaluate the new device against a predicate.

Method Comparison:
- hsCRP (Cardiac): 115 serum samples
- CRP Normal: 120 serum samples
- Glucose (Serum): 133 serum samples
- Glucose (Urine): 113 urine samples
- Glucose (CSF): 111 CSF samples
- ISE Sodium (Serum): 120 serum samples
- ISE Potassium (Serum): 119 serum samples
- ISE Chloride (Serum): 120 serum samples
- ISE Sodium (Urine): 117 urine samples
- ISE Potassium (Urine): 120 urine samples
- ISE Chloride (Urine): 114 urine samples
Linearity/Reportable Range: High and low sample pools were prepared and inter-diluted. Test samples were assayed in quadruplicate. The total number of unique samples is not specified, but multiple dilutions were tested.
Sensitivity (Detection Limits): Replicate measurements on blank and low-level samples across multiple days using multiple reagent lots. The specific number of samples is not detailed, but the method suggests an adequate number of replicates for statistical determination.
Precision/Reproducibility: Duplicate sample analysis, twice daily, over 20 days (n=80) for multiple sample levels (typically 3-5 levels per test).
Interferences: 5 replicates of test samples at two analyte levels.
Reference Interval: At least 20 reference individuals (e.g., 25 for CRP Latex Serum, 23 for Glucose Serum, 24 for Glucose Urine, 20 for ISE Serum tests).

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

This submission is for an in vitro diagnostic (IVD) device, specifically a clinical chemistry analyzer and its reagents. For such devices, "ground truth" is typically established by comparing the device's results to established, legally marketed predicate devices and reference methods, as well as adherence to recognized industry standards (CLSI guidelines).

Experts: The document does not describe the use of human experts to establish "ground truth" in the way it might for an AI-powered image analysis device (e.g., radiologists). Instead, the "ground truth" for the test set values themselves is derived from the established analytical performance of the predicate device and the reference methods outlined in the CLSI guidelines.
Qualifications: The "experts" in this context would be the skilled laboratory personnel performing the CLSI guideline-based studies and the manufacturers establishing the performance claims for both the candidate and predicate devices. Their qualifications align with standard laboratory practices and regulatory requirements for IVD development and validation.

4. Adjudication Method for the Test Set

No explicit adjudication method (like 2+1 or 3+1 consensus) is described, as this would typically apply to subjective interpretations (e.g., image reading by multiple human experts). For an IVD device measuring analytes, the evaluation is based on quantitative data comparison against established reference methods and performance specifications, using statistical analysis. The "pass" criteria for each test inherently serve as the "adjudication" against the set performance targets.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Reader Improvement with AI vs. Without AI Assistance

No MRMC study was done, nor is it applicable. This submission is for an automated clinical chemistry analyzer and its reagents, which quantitatively measure analytes. It is not an AI-assisted diagnostic imaging or interpretation device that clinicians would use to read cases or images. Therefore, there is no human-in-the-loop component for which an AI assistance effect size would be relevant.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies presented are essentially standalone performance evaluations of the DxC 500 AU Clinical Chemistry Analyzer and its associated reagents. The "algorithm" here refers to the instrument's automated analytical processes (photometric, ISE, etc.) and the reagent chemistries. The performance data (method comparison, linearity, precision, sensitivity, interference) directly reflects the device's analytical capability without direct human interpretation or intervention in the measurement process itself, beyond sample preparation and loading. Human oversight is involved in quality control and interpretation of results, but the core analytical performance is standalone.

7. The Type of Ground Truth Used

The ground truth for evaluating the device's performance is primarily established through:

Comparison to Predicate Device: The DxC 700 AU Clinical Chemistry Analyzer (K161837), which is a legally marketed device with established performance.
CLSI Guidelines: Standardized laboratory protocols (e.g., EP09C-ED3 for Method Comparison, EP06-ED2 for Linearity, EP17-A2 for Sensitivity, EP05-A3 for Precision) that define acceptable analytical performance.
Established Reference Ranges: For reference interval studies, existing medical literature or established clinical laboratory reference intervals are used, with verification that a high percentage of samples fall within these ranges on the new device.
Spiked Samples and Known Concentrations: For linearity, sensitivity, and interference studies, samples are engineered with known concentrations of analytes and/or interferents to challenge the device across its claimed range and conditions.

8. The Sample Size for the Training Set

This type of product (clinical chemistry analyzer and reagents) does not typically involve a "training set" in the context of machine learning or AI models. The development process for such devices relies on chemical and engineering principles, followed by rigorous analytical validation (the studies described above). Therefore, a "training set" size is not applicable.

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

As explained above, there is no "training set" for this type of medical device. The "ground truth" and performance establishment for the device's design and analytical methods would be rooted in fundamental scientific knowledge of chemistry, reagent interactions, and photometric/electrochemical detection, corroborated by extensive internal development and testing against established analytical standards and predicate devices.

Summary

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July 20, 2023

Beckman Coulter Laboratory Systems (Suzhou) Co., Ltd. Tracy Jin Sr. Regulatory Affairs No. 181 West Su Hong Road. Suzhou Industrial Park Suzhou, Jiangsu, CN 215021 China

Re: K220977

Trade/Device Name: ISE Reagents, Glucose, CRP Latex, DxC 500 AU Clinical Chemistry Analyzer Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium Test System Regulatory Class: Class II Product Code: JGS, CEM, CGZ, CFR, NQD, DCN, JJE Dated: January 12, 2023 Received: January 12, 2023

Dear Tracy Jin:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Paula V. Caposino -2

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K220977

Device Name

DxC 500 AU Clinical Chemistry Analyzer; Glucose; CRP Latex; ISE Reagents

Indications for Use (Describe)

The sodium test system is intended for the quantitative measurement of sodium in serum, plasma, and urine.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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1.0 Submitted By

Tracy Jin Sr. Regulatory Affairs Beckman Coulter Laboratory Systems (Suzhou) Co., Ltd. No. 181 West Su Hong Road, Suzhou Industrial Park, Suzhou, Jiangsu, CN 215021 Telephone: 86-512- 6895 5129 Fax: 86-512-6742 1069

2.0 Date of Preparation

July 19, 2023

3.0 Device Name(s)

DxC 500 AU Clinical Chemistry Analyzer 3.1

Proprietary Name:	DxC 500 AU Clinical Chemistry Analyzer
Common Name:	DxC 500 AU
510 (K) Number:	K220977
Class:	Class I
Classification Name:	Discrete photometric chemistry analyzer for clinical use
Regulation Number:	21 CFR § 862.2160
Product Code:	JJE

3.2 ISE Reagents

Proprietary Name:	ISE Reagents
Common Name:	ISE Reagents

Class: Class II Classification Name/Regulation Number/Product Code:

Sodium test system 21 CFR § 862.1665 [JGS] Potassium test system 21 CFR § 862.1600 [CEM] Chloride test system 21 CFR § 862.1170 [CGZ]

3.3 Glucose

Proprietary Name:	Glucose
Common Name:	Glucose
Class:	Class II
Classification Name:	Glucose test system
Regulation Number:	21 CFR § 862.1345
Product Code:	CFR

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3.4 CRP Latex

Proprietary Name: CRP Latex Common Name: CRP Latex Class: Class II Classification Name: C-reactive protein immunological test system Regulation Number: 21 CFR § 866.5270 Product Code: DCN, NQD

4.0 Predicate Devices

Candidate(s)	Predicate	Manufacturer
DxC 500 AU ClinicalChemistry Analyzer	DxC 700 AU Clinical ChemistryAnalyzer(K161837)	Beckman Coulter,Inc.
ISE Reagents:Sodium, Potassium andChloride	ISE Reagents:Sodium, Potassium and Chloride(K161837)
Glucose	Glucose(K161837)
CRP Latex	CRP Latex(K161837)

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5.0 Device Description

5.1 DxC 500 AU Clinical Chemistry Analyzer

5.2 ISE Reagents

5.3 Glucose

5.4 CRP Latex

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6.0 Indications for Use

DxC 500 AU Clinical Chemistry Analyzer 6.1

6.2 ISE Reagents (Sodium, Potassium and Chloride)

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 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.

6.3 Glucose

The Glucose test system is for the quantitative measurement of glucose in human serum, plasma, urine and cerebrospinal fluid on Beckman Coulter AU/DxC 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.

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6.4 CRP Latex

7.0 Comparison to the Predicate

The DxC 500 AU Clinical Chemistry Analyzer is a member of Beckman Coulter's AU/DxC AU series of automated photometric analyzers that includes the DxC 700 AU Clinical Chemistry Analyzer (K161837) to which the substantial equivalence is claimed. The devices share common design characteristics and modes of operation. The key features are summarized in Tables 7.1 through 7.4.

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	Predicate Device:	Predicate Device:
Feature	DxC 700 AU ClinicalChemistry Analyzer(K161837)	DxC 500 AU ClinicalChemistry Analyzer(K220977)
Intended Use:	Automated chemistryanalyzer that measuresanalytes in samples, incombination with appropriatereagents, calibrators, qualitycontrol (QC) material andother accessories. For in vitrodiagnostic use only.Applications includecolorimetric, latexagglutination and ionselective electrode.	Same (removal of testapplications only):Automated chemistryanalyzer that measuresanalytes in samples, incombination with appropriatereagents, calibrators, qualitycontrol (QC) material, andother accessories. Thissystem is for in vitrodiagnostic use only.
Classification:	Analyzer, chemistry(photometric, discrete), forclinical use has beenclassified as Class I, JJE bythe Clinical Chemistry andClinical Toxicology DevicesPanel, (21 CFR 862.2160).	Same
Sample Handling
Sample Containers	10 sample tubes on a Rack	7 sample tubes on a Rack
Sample Volume	1.0 to 25.0 µL	Same
Sample Types	Serum, plasma, urine, CSF,and whole blood (HbA1conly)	Same
Sample Input	Sample Rack, STAT Table,Direct-line Sample Aspiration(For AutomationConnections)	Sample Rack, STAT Table
	Predicate Device:	Candidate Device:
Feature	DxC 700 AU ClinicalChemistry Analyzer(K161837)	DxC 500 AU ClinicalChemistry Analyzer(K220977)
Single SampleReplicate Analysis	Ability to request testreplicates for one sample, upto 20 replicates per sampleper test.	Same
Sample Analysis
Wavelength (nm)	Halogen Lamp340 to 800 nm13 wavelengths:340, 380, 410, 450, 480, 520,540, 570, 600, 660, 700, 750and 800 nm (maximum of 2wavelengths)	Same
Type of Measurement	• End-point assay• Rate assay• Fixed point assay• Electrode method (ISE)	Same
Throughput	Maximum 800 photometrictests/hour or 1200 tests/hour(photometric + ISE)	Maximum 400 photometrictests/hour or 800 tests/hour(photometric + ISE)
Reagent Handling
Reagent Identification	Barcode and fixed position inthe reagent carousel	Same
Refrigerated ReagentOn-board Capacity	System has two ReagentRefrigerators:Reagent 1: 60 bottle capacityReagent 2: 48 bottle capacity	System has one ReagentRefrigerator with 76 bottlecapacity (Reagent 1+Reagent2)
	Predicate Device:	Candidate Device:
Feature	DxC 700 AU Clinical Chemistry Analyzer(K161837)	DxC 500 AU Clinical Chemistry Analyzer(K220977)
ISE Reagents	Three ISEs	Same
Reagent Storage Temperature	Refrigeration temperature: 4 to 12 °C (39.2 to 53.6 °F)	Same
Reagent Loading during Analysis	Reagent bottles can be changed while the instrument continues to measure patient samples. A reagent bottle can be added or changed within 5 minutes of request.	Reagent bottles can be changed while the instrument continues to measure patient samples. A reagent bottle can be added or changed within 5 minutes 30 seconds of request.
Computers/OS
CPU	Intel ProcessorrunningWindows 7 64bit	Intel ProcessorrunningWindows 10 64bit
Display/Monitor	24" displaywith touch screen	21.5" displaywith touch screen
Handheld Barcode Reader	Provided for reading 1D and 2D barcodes	Same
Software
GUI Application	User interface which will be common to new Beckman Coulter IVD systems	Re-engineered GUI; Latest common GUI design to Beckman Coulter IVD systems
User Help	HTML version of IFU is accessible with built-in interactive video.	HTML version of IFU is accessible in User Help
	Predicate Device:	Candidate Device:
Feature	DxC 700 AU ClinicalChemistry Analyzer	DxC 500 AU ClinicalChemistry Analyzer
	(K161837)	(K220977)
LaboratoryInformation System(LIS) Interfaces	Similar with LIS ASTM 1394and AU unique LIS protocol	Similar with LIS ASTM 1394protocol
LaboratoryAutomation System(LAS) Interfaces	Beckman LAS interface forDirect Track Sampling system	Not supported
Real-Time Solutions(RTS) support	Interface to RTS viaPROService protocol which ismade by Beckman CoulterRemote software installationcapabilities.	Interface to RTS via remoteservice protocol which ismade by Beckman Coulter
External printers	USB and LAN interfacedprinters	USB interfaced printers
	Predicate Device:	Candidate Device:
Feature	ISE – Sodium, Potassiumand Chloride(K161837)	ISE –Sodium, Potassiumand Chloride(K220977)
Intended Use	Reagent for the quantitativedetermination of Sodium,Potassium and Chlorideconcentrations in humanserum and urine on theBeckman Coulter ISEmodules.	Same
Measurement	Quantitative	Same
Instrument Required	DxC 700 AU BeckmanCoulter Analyzer	DxC 500 AU BeckmanCoulter Analyzer
Methodology	Indirect ISE	Same
Reagent form andstorage	Liquid, on-board storage	Same
Specimen Type	Serum, plasma, and urine	Same
Calibrator	Low Serum Standard (Cat #AUH1014) and High SerumStandard (Cat # AUH1015)Low/High Urine Standard(Cat # AUH1016)	Same
Calibration Stability	Calibrate daily.	Same
Reagent stability	ISE reagents are stable up to90 days when stored inaccordance with the IFUinstructions.	Same
	Predicate Device:	Candidate Device:
Feature	ISE – Sodium, Potassiumand Chloride	ISE–Sodium, Potassiumand Chloride
	(K161837)	(K220977)
Analytical Range	SerumNa+ 50 – 200 mEq/LK+ 1.0 – 10.0 mEq/LCl- 50 – 200 mEq/L	Same
	UrineNa+ 10 – 400 mEq/LK+ 2.0 – 200.0 mEq/LCl- 15 – 400 mEq/L
Interferences	Bilirubin (Na/K/Cl):NSI* up to 40 mg/dL.	Same
	Lipemia (Na/K/Cl):NSI up to 500 mg/dL.
	Hemoglobin (Na):NSI up to 250 mg/dL.
	Hemoglobin (K):NSI up to 70 mg/dL.
	Hemoglobin (Cl):NSI up to 500 mg/dL.
Precision(serum, urine)	Within-run CV < 3%Total Precision CV < 5%.	Same

Table 7.1 Predicate Device Comparison

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Image /page/12/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, resembling a stylized wave or ribbon. To the right of the circle are the words "BECKMAN" in a bold, sans-serif font, stacked above the word "COULTER," which is also in a bold, sans-serif font.

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Image /page/13/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, followed by the text "BECKMAN" in bold black letters above the text "COULTER" in bold black letters. The logo is simple and modern, and the colors are eye-catching.

Table 7.2 ISE (Sodium, Potassium & Chloride) Predicate Device Comparison

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*NSI – No significant interference (Chloride ±2.5%, Potassium ±0.25 mEq/L, Sodium ±2mEq/L)

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	Predicate Device:	Candidate Device:
Feature	Glucose(K161837)	Glucose(K220977)
Intended Use	The Glucose test system isfor the quantitativemeasurement of glucose inhuman serum, plasma, urine,and cerebrospinal fluid onBeckman Coulter AUanalyzers.	Same; updated instrumentfamily branding only.The Glucose test system isfor the quantitativemeasurement of glucose inhuman serum, plasma, urineand cerebrospinal fluid onBeckman Coulter AU/DxC AUanalyzers.
Measurement	Quantitative	Same
Instrument Required	DxC 700 AU BeckmanCoulter Analyzer.	DxC 500 AUBeckman Coulter Analyzer
Methodology	Photometric	Same
Reagent form andstorage	Liquid, on-board storage	Same
Specimen Type	Serum, plasma, urine, andcerebrospinal fluid	Same
Calibrator	Chemistry Calibrator (Cat #DR0070)Urine Calibrator (Cat #DR0090)	Same
Calibration Stability	30 days	Same
Onboard Stability	30 days refrigerated	Same
Feature	Predicate Device:Glucose(K161837)	Candidate Device:Glucose(K220977)
Analytical Range	Serum, plasma, and CSF:10 - 800 mg/dLUrine:10 - 700 mg/dL	Same
Interferences	Bilirubin:NSI* up to 40 mg/dL.Lipemia:NSI up to 700 mg/dL.Hemoglobin:NSI up to 500 mg/dL	Same
Precision(serum, urine)	Within-run CV < 3%Total Precision CV < 3%.	Same

Table 7.3 Glucose Predicate Device Comparison

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Image /page/16/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, resembling a stylized wave or heartbeat. To the right of the circle are the words "BECKMAN" stacked on top of "COULTER" in a bold, sans-serif font. The overall design is clean and corporate, conveying a sense of innovation and reliability.

*NSI – No significant interference designates recovery within 10% of the initial value.

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Feature	Predicate Device:CRP Latex(K161837)	Candidate Device:CRP Latex(K220977)
Intended Use	System reagent for thequantitative determination ofC-Reactive Protein in humanserum and plasma onBeckman Coulter AUAnalyzers. Measurement ofCRP is useful for thedetection and evaluation ofinfection, tissue injury,inflammatory disorders andassociated diseases.Measurements may also beuseful as an aid in theidentification of individuals atrisk for future cardiovasculardisease. High sensitivity CRP(hsCRP) measurements,when used in conjunction withtraditional clinical laboratoryevaluation of acute coronarysyndromes, may be useful asan independent marker ofprognosis for recurrentevents, in patients with stablecoronary disease or acutecoronary syndromes.	Same; updated instrumentfamily branding only.System reagent for thequantitative determinationof C-Reactive Protein inhuman serum and plasmaon Beckman CoulterAU/DxC AU analyzers.Measurement of CRP isuseful for the detection andevaluation of infection,tissue injury, inflammatorydisorders and associateddiseases. Measurementsmay also be useful as anaid in the identification ofindividuals at risk for futurecardiovascular disease.High sensitivity CRP(hsCRP) measurements,when used in conjunctionwith traditional clinicallaboratory evaluation ofacute coronary syndromes,may be useful as anindependent marker ofprognosis for recurrentevents, in patients withstable coronary disease oracute coronary syndromes.
Feature	Predicate Device:CRP Latex(K161837)	CandidateDevice:CRP Latex(K220977)
Measurement	Quantitative	Same
Instrument Required	DxC 700 AUBeckman Coulter Analyzer	DxC 500 AUBeckman Coulter Analyzer
Methodology	Latex enhancedImmunoturbidimetric	Same
Antibody	Rabbit Anti-CRP Antibodies	Same
Reagent form andstorage	Liquid, on-board storage	Same
Specimen Type	Serum and plasma	Same
Calibrator	CRP Latex Highly SensitiveCalibrator (Cat # ODC0027)for the Highly Sensitive(Cardiac) Application.CRP Latex Normal Calibrator(Cat # ODC0026) for theNormal Application	Same
Calibration Stability	90 days refrigerated	Same
Onboard Stability	90 days refrigerated	Same
Analytical Range	CRP High Sensitivity0.2 - 80 mg/LCRP Normal1.0 - 480 mg/L	CRP High Sensitivity0.2 - 80 mg/LCRP Normal5.0 - 480 mg/L
Feature	Predicate Device:CRP Latex(K161837)	Candidate Device:CRP Latex(K220977)
Interferences	Bilirubin:<5% at CRP concentrationsof 1 mg/L up to 40 mg/dLbilirubinLipemia:<10% at CRP concentrationsof 1 mg/L up to 1000 mg/dLintralipidHemoglobin:<5% at CRP concentrationsof 1 mg/L up to 500 mg/dLhemoglobin	Same
Precision(serum)	Within-run: SD ≤0.20 mg/LTotal Precision: SD ≤0.02mg/L	Same

Table 7.4 CRP Predicate Device Comparison

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8.0 Comparison Testing

Substantial equivalence was demonstrated through non-clinical (bench) studies as listed below. CLSI study protocols were used to verify the performance claims stated in the reagent IFUs and ensure that the technological differences between the candidate and predicate analyzer models did not adversely affect safety and effectiveness.

Method Comparison Linearity Precision Sensitivity Reference Interval Interference

9.0 Summary of Performance Data

The data contained in the Premarket Notification supports a finding of substantial equivalence to the measurand test systems already in commercial distribution.

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9.1 Method Comparison with Predicate Device

Method comparison and bias estimation experiments were designed in accordance with the CLSI Guideline EP09C-ED3 "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Third Edition". The patient correlation studies demonstrated equivalence between the representative assays on the candidate DxC 500 AU analyzer and the predicate DxC 700 AU analyzer. The study results in Table 9.1 are based on Weighted Deming regression analysis.

Reagent/ISE	SampleType	N	Slope	Bias	Intercept	R
hsCRP(Cardiac)	Serum	115	0.990	0.4% at 3mg/L	0.0421	0.9997
CRP Normal	Serum	120	0.993	5.4% at 10 mg/L	0.606	0.9995
Glucose	Serum	133	0.986	-1% at 100 mg/dL	0.227	0.9999
Glucose	Urine	113	1.001	-0.3% at 50 mg/dL	-0.216	1.0000
Glucose	CSF	111	1.009	3% at 50 mg/dL	0.891	0.9998
ISE Sodium	Serum	120	1.018	0.2% at 130 mEq/L0.5% at 160 mEq/L	-2.077	0.9995
ISE Potassium	Serum	119	1.015	-0.1% at 3 mEq/L0.7% at 6 mEq/L	-0.048	0.9998
ISE Chloride	Serum	120	1.007	0.3% at 90 mEq/L0.4% at 120 mEq/L	-0.379	0.9997
ISE Sodium	Urine	117	1.008	0.6% at 60 mEq/L0.7% at 180 mEq/L	-0.150	0.9999
ISE Potassium	Urine	120	1.000	1.3% at 15 mEq/L0.2% at 80 mEq/L	0.194	0.9998
ISE Chloride	Urine	114	1.002	-0.4% at 50 mEq/L0.05% at 170 mEq/L	-0.291	0.9999

Table 9.1 Method Comparison Data Summary

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9.2 Linearity/Reportable Range:

Analytical range (linearity) studies were designed in accordance with the CLSI guideline EP06-ED2 "Evaluation of the Linearity of Quantitative Measurement Procedures".

High and low sample pools were prepared and inter-diluted to achieve analyte concentrations spanning the claimed linear range of each assay. Test samples were assayed in quadruplicate on the DxC 500 AU analyzer. The study data demonstrates linearity throughout the claimed analytical measuring range of each assay, as represented in the Table 9.2 below.

Reagent andSample Type	Units	LinearRange	Acceptance CriteriaAllowableDifference (±)	Results		Pass/Fail
hsCRP(Cardiac)Serum	mg/L	0.2 - 80	12% or 0.15 mg/L	0.124	81.35	Pass
CRPNormalSerum	mg/L	1.0 - 480	12% or 0.2 mg/L	0.78	516.408	Pass
GlucoseSerum	mg/dL	10 - 800	5% or 0.5 mg/dL	7.68	879.73	Pass
GlucoseCSF	mg/dL	10 - 800	5% or 0.5 mg/dL	7.23	901.37	Pass
GlucoseUrine	mg/dL	10 - 700	5% or 0.5 mg/dL	7.39	760.22	Pass
SodiumSerum	mEq/L	50 - 200	2.5% or 3.25 mEq/L	47.11	205.87	Pass
PotassiumSerum	mEq/L	1.0 - 10.0	4% or 0.12 mEq/L	0.727	10.835	Pass
ChlorideSerum	mEq/L	50 - 200	4% or 3.6 mEq/L	27.66	223.58	Pass
SodiumUrine	mEq/L	10 - 400	5% or 1.2 mEq/L	7.93	441.48	Pass
PotassiumUrine	mEq/L	2.0 - 200.0	7% or 1 mEq/L	1.066	225.165	Pass
ChlorideUrine	mEq/L	15-400	6% or 3.6 mEq/L	11.42	433.78	Pass

Table 9.2 Linearity Data Summary

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9.3 Sensitivity (Detection Limits):

LOD and LOQ studies were designed in accordance with CLSI guideline EP17-A2 "Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures Approved Guideline - Second Edition". The experimental design consisted of replicate measurements on blank and low-level samples across multiple days using multiple reagent lots.

The LOB, LOD, and LOQ results are summarized in the Table 9.3 below. The representative reagents met the established LOQ specifications when tested on the DxC 500 AU analyzer, and the LOQ results were below the claimed measuring range for each assay.

Reagent andSample Type	Units	Low End ofMeasuringRange	LODSpec	LOQSpec	LOB	LOD	LOQ
CRPNormalSerum	mg/L	5.00	≤5.0	≤ 5.0 at≤ 20% CV	0.28	0.48	0.89
hsCRP(Cardiac)Serum	mg/L	0.20	≤ 0.2	≤ 0.2 at≤ 20% CV	0.01	0.03	0.06
GlucoseSerum	mg/dL	10	≤ 10	≤ 10 at≤ 20% CV	0.55	1.02	1.42
GlucoseUrine	mg/dL	10	≤ 10	≤ 10 at≤20% CV	0.48	0.92	1.41
GlucoseCSF	mg/dL	10	≤ 10	≤ 10 at≤20% CV	0.4	0.7	1.1

Table 9.3 Reagent Sensitivity Data Summary

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9.4 Precision/Reproducibility:

Repeatability (within-run) and within-laboratory (total) precision studies were designed from the CLSI guideline EP05-A3 "Evaluation of Quantitative Measurement Procedures; Approved Guideline - Third Edition". The precision was verified on the DxC 500 AU using one lot of reagent and one lot of calibrator and utilized duplicate sample analysis, twice daily, over the course of 20 days (n=80) for multiple sample levels.

All assays met the performance precision specifications and provided data to support the precision claims in the IFUs. The results are summarized in Tables 9.4.1 and 9.4.2 below:

Reagent andUnits	SampleLevels	Mean(n=80)	Repeatability(Within Run)		Within Laboratory(Total)
			SD	% CV	SD	% CV
hsCRP(Cardiac)(mg/L)	Serum 1	1.06	0.01	1.2	0.01	1.3
	Serum 2	3.01	0.02	0.6	0.03	0.8
	Serum 3	9.10	0.08	0.9	0.09	1.0
	Serum 4	10.5	0.10	0.9	0.15	1.5
	Serum 5	70.0	0.53	0.8	0.73	1.0
CRPNormal(mg/L)	Serum 1	5.62	0.04	0.7	0.06	1.1
	Serum 2	10.12	0.06	0.6	0.11	1.1
	Serum 3	36.18	0.35	1.0	0.56	1.5
	Serum 4	248.10	1.49	0.6	2.70	1.1
	Serum 5	422.85	3.34	0.8	4.33	1.0
Glucose(mg/dL)	Serum 1	51.1	0.2	0.4	0.5	0.9
	Serum 2	121.4	0.4	0.3	1.1	0.9
	Serum 3	288.9	0.7	0.3	2.9	1.0
Glucose(mg/dL)	CSF 1	36.9	0.2	0.5	0.4	1.2
	CSF 2	122.7	0.4	0.4	1.0	0.8
	CSF 3	317.2	1.3	0.4	3.2	1.0
Glucose(mg/dL)	Urine 1	56.8	0.3	0.5	0.4	0.7
	Urine 2	131.4	0.6	0.4	1.7	1.3
	Urine 3	341.8	1.5	0.4	3.0	0.9

Table 9.4.1 Reagent Precision Data Summary

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Section 5 510(k) Summary DxC 500 AÚ

Reagent andUnits	SampleLevels	Mean(n=80)	Repeatability(Within Run)		Within Laboratory(Total)
			SD	% CV	SD	% CV
Sodium(mEq/L)	Serum 1	60	0.23	0.4	0.48	0.8
	Serum 2	110	0.24	0.2	0.53	0.5
	Serum 3	140	0.28	0.2	0.40	0.3
	Serum 4	172	0.36	0.2	0.57	0.3
Potassium(mEq/L)	Serum 1	2.5	0.01	0.2	0.01	0.3
	Serum 2	4.5	0.01	0.2	0.01	0.3
	Serum 3	6.4	0.01	0.2	0.02	0.4
	Serum 4	8.5	0.02	0.2	0.05	0.5
Chloride(mEq/L)	Serum 1	51	0.21	0.4	0.26	0.5
	Serum 2	76	0.23	0.3	0.28	0.4
	Serum 3	104	0.35	0.3	0.47	0.5
	Serum 4	150	0.70	0.5	0.81	0.5
Sodium(mEq/L)	Urine 1	21	0.24	1.1	0.37	1.7
	Urine 2	99	0.26	0.3	0.40	0.4
	Urine 3	251	0.69	0.3	1.17	0.5
	Urine 4	352	1.42	0.4	2.18	0.6
Potassium(mEq/L)	Urine 1	10	0.03	0.3	0.05	0.5
	Urine 2	32	0.13	0.4	0.25	0.8
	Urine 3	100	0.27	0.3	1.02	1.0
	Urine 4	178	0.77	0.4	1.85	1.0
Chloride(mEq/L)	Urine 1	26	0.20	0.8	0.28	1.1
	Urine 2	87	0.30	0.3	0.36	0.4
	Urine 3	152	0.49	0.3	0.72	0.5
	Urine 4	303	1.38	0.5	1.88	0.6
	Urine 5	375	1.59	0.4	2.32	0.6

Table 9.4.2 ISE Precision Data Summary

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0.5 Interferences (Analytical Specificity):

Interference studies were designed in accordance with CLSI Guideline EP07, 3ª Edition "Interference Testing in Clinical Chemistry; Approved Guideline". All test samples were assayed (n=5) at two analyte levels. The sample pools were tested at different levels of interferents to determine the magnitude of their effect. The data analysis involved calculating the recovery difference between samples with and without the potential interfering substances. The results for Glucose and ISE are summarized in Table 9.5 below. The results for CRP Normal and CRP Highly Sensitive (Cardiac) applications are summarized on page 5-27 and 5-28. All assays met the performance specifications and provided data to support the interference claims in the IFUs.

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Reagent/SampleType	Interference Threshold
	Lipemic¹	Icteric²	Hemolytic³	Results
GlucoseSerum	Intralipid(700 mg/dL)intf. ≤10%at Glucose conc. of40 & 220 mg/dL	Bilirubin(40 mg/dL)intf. ≤10%at Glucose conc. of40 & 220 mg/dL	Hemolysate(500 mg/dL)intf. ≤10%at Glucose conc. of40 & 220 mg/dL	Pass
GlucoseCSF	N/A	Bilirubin(40 mg/dL)intf. ≤10%at Glucose conc. of36 & 216 mg/dL	Hemolysate(500 mg/dL)intf. ≤10%at Glucose conc. of36 & 216 mg/dL	Pass
GlucoseUrine	N/A	Bilirubin(40 mg/dL)intf. ≤10%at Glucose conc. of20 & 200 mg/dL	Hemolysate(500 mg/dL)intf. ≤10%at Glucose conc. of20 & 200 mg/dL	Pass
SodiumSerum	Intralipid(500 mg/dL)intf. ≤2 mEq/L atSodium conc. of130 & 150 mEq/L	Bilirubin(40 mg/dL)intf. ≤2 mEq/L atSodium conc. of130 & 150 mEq/L	Hemolysate(250 mg/dL)intf. ≤2 mEq/L atSodium conc. of130 & 150 mEq/L	Pass
ChlorideSerum	Intralipid(500 mg/dL)intf. ≤2.5 mEq/Lat Chloride conc. of90 & 110 mEq/L	Bilirubin (40 mg/dL)intf. ≤2.5 mEq/L atChloride conc. of90 & 110 mEq/L	Hemolysate(500 mg/dL)intf. ≤2.5 mEq/L atChloride conc. of90 & 110 mEq/L	Pass
PotassiumSerum	Intralipid(500 mg/dL)intf. ≤0.25 mEq/Lat Potassium conc. of3 & 5 mEq/L	Bilirubin (40 mg/dL)intf. ≤0.25 mEq/L atPotassium conc. of3 & 5 mEq/L	Hemolysate(70 mg/dL)intf ≤0.25 mEq/L atPotassium conc. of3 & 5 mEq/L	Pass

Table 9.5 Interference Data Summary

1 Intralipid is a 20% fat emulsion used to emulate extremely turbid samples.

² Unconjugated bilirubin, (porcine source)

3 Lysed human red blood cells

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CRP Normal and CRP Highly Sensitive (Cardiac) Applications

Results of studies show that the following substances may interfere with this C-reactive procedure. Normal Application Icterus: Interference less than 5% up to 40 mg/dL bilirubin Haemolysis: Interference less than 5% up to 5 g/L haemoglobin Lipemia: Interference less than 10% up to 1,000 mg/dL Intralipid Rheumatoid Factor: Interference less than 10% up to 500 IU/mL Rheumatoid Factor Triglyceride: Interference less than 10% up to 500 mg/dL Triglyceride

Highly Sensitive (Cardiac) Application Icterus: Interference less than 5% up to 40 mq/dL bilirubin Haemolysis: Interference less than 5% up to 5 g/L haemoglobin Lipemia: Interference less than 10% up to 1,000 mg/dL Intralipid Rheumatoid Factor: Interference less than 10% up to 500 IU/mL Rheumatoid Factor Triglyceride: Interference less than 10% up to 500 mg/dL Triglyceride

Intralipid, manufactured by Pharmacia, is a 20% fat emulsion used to emulate extremely turbid samples.

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Results of studies conducted to evaluate the susceptibility of the method to interference from common or known drugs that could interfere with the CRP (Normal and CRP Highly Sensitive (Cardiac) Applications) are listed below. The criteria for no significant interference is recovery within 10% of the initial value (sample containing no interferent).

No significant interference is observed from substances up to the following concentrations:

Acetaminophen	15.6 mg/dL
Acetylsalicylic Acid	3 mg/dL
Amoxicillin	5.4 mg/dL
Ascorbic Acid	5.25 mg/dL
Atorvastatin	0.075 mg/dL
Azithromycin	1.11 mg/dL
Cephalexin	12.6 mg/dL
Ciprofloxacin	1.2 mg/dL
Fluconazole	2.55 mg/dL
Ibuprofen	21.9 mg/dL
Lisinopril	0.0246 mg/dL
Metformin	1.2 mg/dL
Methotrexate	136 mg/dL
Naproxen	36 mg/dL
Omeprazole	0.84 mg/dL
Prednisone	0.0099 mg/dL

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9.6 Reference Interval

The Reference Interval study utilized a transference approach in accordance with the CLSI guideline EP028-A3c "Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline – Third Edition". The purpose of the study was to validate the acceptability of the original adult reference intervals for use on the candidate DxC 500 AU analyzer. The use of a transference approach was based on the demonstrated comparability between the candidate and predicate tests systems via the CLSI EP09c study. The approach used a sampling of at least 20 reference individuals to verify that ≥ 90% of the test samples recovered within the reference intervals cited in the respective assay IFUs. Verification studies were not performed for sample types difficult to source (CSF and 24hour urine collections); these applications are supported by the original literature references in their IFUs. Refer to Table 9.6 below for a summary of results.

Product andSample Type	Units	Reference Range	Within Range	Result
CRP LatexSerum	mg/L	<10	96% (24/25)	Pass
GlucoseSerum (Adult)	mg/dL	74 - 109	91% (21/23)	Pass
GlucoseUrine	mg/dL	No detectableGlucose	100% (24/24)	Pass
GlucoseCSF (Adult)	mg/dL	40 - 70	N/A*	N/A*
ISE NaSerum	mEq/L	136 - 145	100% (20/20)	Pass
ISE KSerum	mEq/L	3.5 - 5.1	100% (20/20)	Pass
ISE CISerum	mEq/L	98 - 107	95% (19/20)	Pass
ISE NaUrine	mEq/day	40 - 220	N/A*	N/A*
ISE KUrine	mEq/day	25 - 125	N/A*	N/A*
ISE CIUrine	mEq/day	110 - 250	N/A*	N/A*

Table 9.6 Reference Interval Summary

Literature reference used

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10.0 Substantial Equivalence Conclusion

The data contained in the Premarket Notification supports a finding of substantial equivalence to the measurand test systems already in commercial distribution. The performance testing on the DxC 500 AU Clinical Chemistry Analyzer presented in this submission demonstrates that the measurand test systems continue to be safe and effective in their Intended Use.

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.