K Number
K161837
Device Name
ISE Reagent, Glucose, CRP Latex, DxC 700 AU Clinical Chemistry Analyzer
Date Cleared
2016-12-16

(164 days)

Product Code
Regulation Number
862.1665
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended 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 Description
The Beckman Coulter DxC 700 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 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. Electrolyte measurement is performed using a single cell Ion 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-6-phosphate dehydrogenase (G6P-DH) specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide, reduced (NADH). 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. Depending on the application used (different instrument settings), two measuring ranges are available: Normal application (CRP Concentrations ranging between 1.0-480 mg/L) and Highly Sensitive (Cardiac/ Neonatal) Application- (CRP concentrations ranging between 0.2- 80mg/L).
More Information

Not Found

No
The summary describes a standard automated clinical chemistry analyzer using established methods (colorimetric, latex agglutination, ISE) and does not mention any AI or ML components.

No
This device is an in vitro diagnostic (IVD) chemistry analyzer that measures analytes in samples for diagnostic purposes, not for direct therapeutic intervention.

Yes
The "Intended Use / Indications for Use" section explicitly states that the system is "for in vitro diagnostic use only" and that measurements are "used in the diagnosis and treatment of carbohydrate metabolism disorders," "detection and evaluation of infection, tissue injury, inflammatory disorders," and "diagnosis and treatment of electrolyte and metabolic disorders." These uses directly relate to diagnosing diseases or conditions.

No

The device is a physical automated chemistry analyzer that measures analytes in samples using hardware components like ISE modules and reagents. It is not solely software.

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

The document explicitly states multiple times that the system and its components are "for in vitro diagnostic use only." The intended use describes measuring analytes in human samples (serum, plasma, urine, cerebrospinal fluid) to aid in the diagnosis and treatment of various medical conditions. This aligns directly with the definition of an in vitro diagnostic device, which is used to examine specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.

N/A

Intended Use / 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.

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

JGS, CEM, CGZ, CFR, NQD, JJE

Device Description

The Beckman Coulter DxC 700 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 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. Electrolyte measurement is performed using a single cell Ion Selective Electrode (ISE) which is also common among the other members of the AU family.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

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

Not Found

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

A minimum of 100 serum, urine and CSF samples were tested over five days. No more than 20% of samples were either spiked or diluted to ensure a uniform distribution over the analytical range.

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

Method Comparison Matrix Comparison Linearity Sensitivity Precision Interference In use (On board) & Calibrator Stability Prozone Sample Dilution
Method comparison and bias estimation experiments were designed using CLSI Guideline EP09-A3 "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline". These patient correlation studies demonstrate equivalence between the predicate AU5800 and the candidate DxC 700 AU. All method comparisons met the required specifications.

Anticoagulation Studies were designed using CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples: Approved Guideline - Third Edition. All results passed specification.

Analytical range (linearity) studies were designed to meet the requirements of CLSI quidelines EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline". The performance data for the study demonstrates linearity throughout the claimed dynamic range of each assay.

LoB, LoD and LoQ studies were designed primarily from CLSI quideline 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 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 generated. All representative reagents met specifications and were below the claimed measuring range of the reagent.

Repeatability (within-run) and within-laboratory (total) precision studies were designed from CLSI guideline EP05-A3 "Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition". The precision was verified on the DxC 700 AU using 1 lot of reagent and 1 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.

In-Use and Calibration Stability Verification (EP25-A): This protocol followed CLSI EP25-A quideline "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline"; The aim was to verify the 30 and 90 day on-board claim for the representative reagents and to verify the 1 day calibration stability claim for the ISEs on the DxC 700 analyzer. All results were within specification.

Interference studies were designed based on CLSI Guideline EP07-A2: "Interference Testing in Clinical Chemistry: Approved Guideline - Second Edition". All interferences met the required specifications on the DxC 700 AU analyzer.

Prozone: Testing was carried out to verify the prozone performance on the DxC 700 AU using CRP Latex (High Sensitivity application) as the representative assay. Testing demonstrates that samples with CRP concentrations up to 750 mg/L will not generate falsely low results within the analytical range.

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

Slope, Intercept, r, Bias, SD, %CV

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

K112412, K003721, K051564

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

Not Found

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

Not Found

§ 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.

0

Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the circle is a stylized image of three human profiles facing to the right, with a flowing, wave-like design connecting them.

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

December 16, 2016

BECKMAN COULTER INC. GERALDINE FUENTESPINA MANAGER, REGULATORY AFFAIRS 250 S. KRAEMER BLVD. MAILS STOP E1.SE.01 BREA, CA 92821

Re: K161837

Trade/Device Name: ISE Reagents, Glucose, and CRP Latex on the DxC 700 AU Clinical Analyzer Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium Test System Regulatory Class: II Product Code: JGS, CEM, CGZ, CFR, NQD, JJE Dated: December 2, 2016 Received: December 5, 2016

Dear Geraldine Fuentespina:

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

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

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

1

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

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

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

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

Sincerely yours,

Courtney H. Lias -S

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

Enclosure

2

Indications for Use

510(k) Number (if known) K161837

Device Name

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

Indications for Use (Describe)

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.

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.

3

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

4

Image /page/4/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape on the left, with two curved white lines running through it. To the right of the oval is the company name, "BECKMAN COULTER," written in a bold, sans-serif font. The word "BECKMAN" is placed above the word "COULTER."

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

1.0 Submitted By

Geraldine Fuentespina Manager, Requlatory Affairs Beckman Coulter, Inc. 250 S. Kraemer Blvd. Mail Stop: E1.SE.01 Brea, CA 92821 Telephone: (714) 961-3777 Fax: (714) 961-4234

2.0 Date of Preparation

14 December 2016

3.0 Device Name(s)

3.1 ISE Reagent

Proprietary Name:ISE Reagents
Common Name:ISE Reagents
Class:2
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]

3.2 Glucose

Proprietary Name:Glucose
Common Name:Glucose
Class:2
Classification Name:Glucose test system
Regulation Number:21 CFR § 862.1345
Product Code:CFR

3.3 CRP Latex

Proprietary Name:CRP Latex
Common Name:CRP Latex
Class:2
Classification Name:C-reactive protein immunological test system
Regulation Number:21 CFR § 866.5270
Product Code:NQD

5

Image /page/5/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 company name "BECKMAN COULTER" in black, with "BECKMAN" on the top line and "COULTER" on the bottom line. The font is bold and sans-serif.

3.4 DxC 700 AU Clinical Chemistry Analyzer

Proprietary Name:DxC 700 AU Clinical Chemistry Analyzer
Common Name:DxC 700 AU
Class:1
Classification Name:Discrete photometric chemistry analyzer for clinical use
Regulation Number:21 CFR § 862.2160
Product Code:JJE

4.0 Predicate Devices

Candidate(s)PredicateManufacturer
ISE Reagents : Sodium and
ChlorideISE Reagents : Potassium,
Sodium and Chloride
(K003721)Beckman Coulter,
Inc.
ISE Reagents : PotassiumISE Reagents : Potassium
(K112412)Beckman Coulter,
Inc.
GlucoseGlucose
(K112412)Beckman Coulter,
Inc.
CRP LatexOLYMPUS CRP Latex
Immunoturbidimetric Reagent
(K051564)Beckman Coulter,
Inc.
DxC 700 AU Clinical
Chemistry AnalyzerAU5800 Clinical Chemistry
Analyzer
(K112412)Beckman Coulter,
Inc.

5.0 Device Description

5.1 ISE Reagents

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.

Reactive Ingredients: ISE Buffer (Triethanolamine), Mid-Standard (Na, K, CI), Reference (Potassium Chloride), High Serum Standard (Na, K, CI), Low Serum Standard (Na, K, CI), High/Low Urine Standard (Na, K, CI), Internal Reference Solution (Potassium Chloride, Silver Chloride), and Na*/K* Selectivity Check Solution (Na, K).

5.2 Glucose

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-6-phosphate dehydrogenase (G6P-DH) specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide, reduced (NADH).

6

Image /page/6/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, placed to the left of the company name. The text "BECKMAN" is stacked on top of "COULTER" in a bold, sans-serif font.

For the AU400/AU640/AU600 the change in absorbance at 340/380 nm is proportional to the amount of glucose present in the sample. For the AU5800/AU5400/AU2700/AU680/AU480/DxC 700 AU the change in absorbance at 340/660 nm is proportional to the amount of glucose present in the sample.

Reactive Ingredients: PIPES- buffer (pH 7.6), NAD*, Hexokinase, ATP, Mg4*, G6P-DH

5.3 CRP Latex

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. Depending on the application used (different instrument settings), two measuring ranges are available: Normal application (CRP Concentrations ranging between 1.0-480 mg/L) and Highly Sensitive (Cardiac/ Neonatal) Application- (CRP concentrations ranging between 0.2- 80mg/L).

Reactive Ingredients: Glycine buffer, Latex coated with anti-CRP Antibodies.

5.4 DxC 700 AU Clinical Chemistry Analyzer

The Beckman Coulter DxC 700 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 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. Electrolyte measurement is performed using a single cell lon Selective Electrode (ISE) which is also common among the other members of the AU family.

6.0 Indications for Use

6.1 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 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

7

Image /page/7/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, placed to the left of the company name. The text "BECKMAN" is on the top line, and "COULTER" is on the bottom line, with both words in a bold, sans-serif font.

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 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.

6.2 Glucose

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.

6.3 CRP Latex

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.

6.4 DxC 700 AU Clinical Chemistry 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. This system is for in vitro diagnostic use only. Applications include colorimetric, latex agglutination, and ion selective electrode.

8

Image /page/8/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape on the left side, with two white curved lines inside. To the right of the oval is the company name, "BECKMAN COULTER," written in bold, black letters. The word "BECKMAN" is on the top line, and "COULTER" is on the bottom line.

7.0 Comparison to the Predicate

The DxC 700 AU Clinical Chemistry System is a family member of the AU series of analyzers, including the AU5800 (K112412) to which the substantial equivalence comparison is claimed. The devices have same / similar design and modes of operation. The key features are summarized in the following tables:

| Feature | Predicate Device:
ISE Reagents – Sodium and
Chloride
(K003721) | Proposed Device:
ISE Reagents - Sodium and
Chloride |
|-----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------|
| Item Number | AUH1011, AUH1012, AUH1013,
AUH1014, AUH1015, AUH1016,
AUH1017, AUH1018 | Same |
| Intended Use | Reagent for the quantitative
determination of Sodium,
Potassium and Chloride
concentrations in human serum
and urine on the Beckman
Coulter ISE modules. | Same |
| Measurement | Quantitative | Same |
| Instrument
Required | AU400/400°, AU600/640/640°,
AU800,AU1000, AU5200 and
AU2700 Beckman Coulter
Analyzers | AU400/400°/480,
AU600/640/640°/680,
AU2700/5400/AU5800 and DxC
700 AU Beckman Coulter
Analyzers. |
| Methodology | Indirect ISE | Same |
| Reagent form and
storage | Liquid, on-board storage | Same |
| Specimen Type | Serum, plasma and urine | Same |
| Calibrator | AUH1014 Low Serum Standard
AUH1015 High Serum Standard
AUH1016 High/Low Urine
Standard | Same |
| Calibration Stability | Calibrate daily. | Same |
| Reagent stability | AUH1011, AUH1012, and
AUH1013 are stable for 90 days
when opened and stored in the
ISE reagent compartment of the
analyzer.
After opening AUH1014,
AUH1015, AUH1016, and
AUH1018 may be stored at 2 -
25°C for up to 90 days, provided
the cap is replaced immediately
after each use. After opening,
AUH1017 may be stored at 15 -
25°C for up to 90 days. | Same |
| Feature | Predicate Device:
ISE Reagents - Sodium and
Chloride
(K003721) | Proposed Device:
ISE Reagents - Sodium and
Chloride |
| Analytic Range | Serum
$Na^+ 50 - 200$ mEq/L
$Cl^- 50 - 200$ mEq/L
Urine
$Na^+ 10 - 400$ mEq/L
$Cl^- 15 - 400$ mEq/L | Same |

7.1 ISE Reagents (Sodium & Chloride) Predicate Device Comparison Table

9

Image /page/9/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, placed to the left of the company name. The text "BECKMAN COULTER" is written in bold, black letters, with "BECKMAN" on the top line and "COULTER" on the bottom line.

7.2 ISE Reagents (Potassium) Predicate Device Comparison Table

| Feature | Predicate Device:
ISE Reagents - Potassium
(K112412) | Proposed Device:
ISE Reagents – Potassium |
|-----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------|
| Item Number | AUH1011, AUH1012, AUH1013,
AUH1014, AUH1015, AUH1016,
AUH1017, AUH1018 | Same |
| Intended Use | Reagent for the quantitative
determination of Sodium,
Potassium and Chloride
concentrations in human serum
and urine on the Beckman
Coulter ISE modules. | Same |
| Measurement | Quantitative | Same |
| Instrument
Required | AU400/400e/480,
AU600/640/640o/680 and
AU2700/5400/AU5800 Beckman
Coulter Analyzers | AU400/400e/480,
AU600/640/640o/680,
AU2700/5400/AU5800 and DxC
700 AU Beckman Coulter
Analyzers. |
| Methodology | Indirect ISE | Same |
| Reagent form and
storage | Liquid, on-board storage | Same |
| Specimen Type | Serum, plasma and urine | Same |
| Calibrator | AUH1014 Low Serum Standard
AUH1015 High Serum Standard
AUH1016 High/Low Urine
Standard | Same |
| Calibration Stability | Calibrate daily. | Same |
| Reagent stability | AUH1011, AUH1012, and
AUH1013 are stable for 90 days
when opened and stored in the
ISE reagent compartment of the
analyzer.
After opening AUH1014,
AUH1015, AUH1016, and
AUH1018 may be stored at 2 –
25°C for up to 90 days, provided
the cap is replaced immediately
after each use. After opening,
AUH1017 may be stored at 15 –
25°C for up to 90 days. | Same |

10

Image /page/10/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, resembling a stylized letter "B". To the right of the oval is the company name, "BECKMAN COULTER", written in bold, black capital letters. The overall design is clean and professional.

| Feature | Predicate Device:
ISE Reagents - Potassium
(K112412) | Proposed Device:
ISE Reagents - Potassium |
|----------------|---------------------------------------------------------------------|----------------------------------------------|
| Analytic Range | Serum
$K^+ 1.0 - 10.0$ mEq/L
Urine
$K^+ 2.0 - 200.0$ mEq/L | Same |

7.3 Glucose Predicate Device Comparison Table

| Feature | Predicate Device:
Glucose
(K112412) | Proposed Device:
Glucose |
|-----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------|
| Item Number | Glucose (OSR6121, OSR6221,
OSR6621) | Same |
| Intended Use | System reagent for the
quantitative determination of
Glucose in human serum,
plasma, urine and cerebrospinal
fluid on Beckman Coulter AU
analyzers. | Same |
| Measurement | Quantitative | Same |
| Instrument
Required | AU400/400 e/480,
AU600/640/6406/680 and
AU2700/5400/AU5800 Beckman
Coulter Analyzers | AU400/400 e/480,
AU600/640/6406/680,
AU2700/5400/AU5800 and DxC
700 AU Beckman Coulter
Analyzers. |
| Methodology | Photometric | Same |
| Reagent form and
storage | Liquid, on-board storage | Same |
| Specimen Type | Serum, plasma, urine and
cerebrospinal fluid | Same |
| Calibrator | Chemistry Calibrator (Cat #
DR0070)
Urine Calibrator (Cat # DR0090) | Same |
| Calibration
Stability | 30 days | Same |
| Onboard Stability | 30 days refrigerated | Same |
| Analytic Range | Serum, plasma and CSF:
10 - 800 mg/dL
Urine:
10 - 700 mg/dL | Same |

11

Image /page/11/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, resembling a stylized wave or ribbon. To the right of the oval, the words "BECKMAN" are stacked on top of "COULTER" in a bold, sans-serif font.

| Feature | Predicate Device:
CRP Latex | Proposed Device: |
|---------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | (K051564) | CRP Latex |
| Item Number | CRP Latex (OSR6199) | Same |
| Intended Use | Olympus System Reagent and
calibrators for the quantitative
determination of C-Reactive
Protein in human serum and
plasma on OLYMPUS
Analyzers. Measurement of
CRP is useful for the detection
and evaluation of infection,
tissue injury, inflammatory
disorders and associated
diseases. Measurements may
also be used 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. | Same
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. |
| Measurement | Quantitative | Same |
| Instrument Required | AU400/400°/480,
AU600/640/640°/680 and
AU2700/5400/AU5800
Beckman Coulter Analyzers | AU400/400°/480,
AU600/640/640°/680,
AU2700/5400/AU5800 and
DxC 700 AU Beckman Coulter
Analyzers. |
| Methodology | Latex enhanced
Immunoturbidimetric | Same |
| Antibody | Rabbit Anti-CRP Antibodies | Same |
| Reagent form and
storage | Liquid, on-board storage | Same |
| Specimen Type | Serum and plasma | Same |
| Calibrator | CRP Latex Highly Sensitive
Calibrator (Cat # ODC0027)
for the Highly Sensitive
(Cardiac / Neonatal)
Application. | Same |
| Calibration Stability | 30 days refrigerated | 90 days refrigerated |
| Onboard Stability | 30 days refrigerated | 90 days refrigerated |
| Analytic Highly Sensitive Range | 0.2 - 160 mg/L | 0.2 to 80 mg/L |

CRP Predicate Device Comparison Table 7.4

12

Image /page/12/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, placed to the left of the company name. The text "BECKMAN" is stacked on top of "COULTER" in a bold, sans-serif font.

7.5 AU5800 versus the DxC 700 AU Predicate Device Comparison Table
FeaturePredicate Device:
AU5800 Clinical Chemistry
Analyzer
(K112412)Proposed Device:
DXC 700 AU Clinical
Chemistry Analyzer
Intended Use:The Beckman Coulter AU5800
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,
turbidimetric, latex agglutination,
homogeneous enzyme
immunoassay, and ion selective
electrode.Similar to predicate.
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.
Classification:Analyzer, chemistry
(photometric, discrete), for
clinical use has been classified
as Class I, JJE by the Clinical
Chemistry and Clinical
Toxicology Devices Panel, (21
CFR 862.2160).Identical to predicate.
Sample Handling
Sample Containers10 sample tubes on a RackIdentical to predicate.
Sample Volume1.0 to 17.0 µL1.0 to 25.0 µL
Sample TypesSerum, urine, CSF and PlasmaIdentical to predicate.
Sample InputSample RacksSample Rack, STAT Table,
Direct-line Sample Aspiration
(For Automation Connections)
Single Sample
Replicate AnalysisNone.Ability to request test replicates
for one sample, up to 20
replicates per sample per test.
Sample Analysis
Wavelength (nm)Halogen Lamp
340 to 800 nm
13 wavelengths:
340, 380, 410, 450, 480, 520,
540, 570, 600, 660, 700, 750
and 800 nm (maximum of 2
wavelengths)Identical to predicate.
Type of
Measurement• End point assay
• Rate assay
• Fixed point assay
• Electrode method (ISE)Identical to predicate.
ThroughputMaximum 2000 photometric
tests/hour/unitMaximum 800 photometric
tests/hour or 1200 tests/hour
(photometric + ISE)
FeaturePredicate Device:
AU5800 Clinical Chemistry
Analyzer
(K112412)Proposed Device:
DxC 700 AU Clinical
Chemistry Analyzer
Reagent Handling
Reagent
IdentificationBarcode and fixed position in the
reagent carouselIdentical to predicate
RefrigeratedSystem has 2 Reagent
RefrigeratorsSystem has 2 Reagent
Refrigerators:
Reagent On-board
CapacityReagent 1: 54 bottle capacity
Reagent 2: 54 bottle capacityReagent 1: 60 bottle capacity
Reagent 2: 48 bottle capacity
ISE Reagents3 ISEsIdentical to predicate.
Reagent Storage
TemperatureRefrigeration temperature: 4 to
12 °C (39.2 to 53.6 °F)Identical to predicate
Reagent Loading
during AnalysisNot available.Reagent bottles can be changed
on the DxC 700 AU while the
instrument continues to measure
patient samples.
Prior to replacing reagent
bottles, the AU5800 existing
analysis must be completed and
system must be in Pause Mode.
This may take up to 24 minutes
after customer requests reagent
replacement.On the DxC 700 AU, a reagent
bottle can be added or changed
within 5 minutes of request.
Computers/OS
CPUSingle Intel Processor
running
Windows XP Pro 32bitIntel Processor
running
Windows 7 64bit
Display/Monitor19" display
with touch screen24" display
with touch screen
Handheld Barcode
ReaderNot AvailableProvided for reading 1D and 2D
barcodes
Software
GUI ApplicationUser interface unique to AU
Chemistry systemsUser interface which will be
common to new Beckman
Coulter IVD systems
Result Database
Capacity300 (Index)
9999 (Sample / Index)
400000 (test)Identical to predicate.
User HelpPDF of IFU is availableHTML version of IFU is
accessible with built-in
interactive video.
Laboratory
Information System
(LIS) InterfacesSimilar with LIS ASTM 1394 and
AU unique LIS protocolIdentical to predicate.
Laboratory
Automation System
(LAS) InterfacesBeckman LAS interface for Rack
BuilderBeckman LAS interface for
Direct Track Sampling system
FeaturePredicate Device:
AU5800 Clinical Chemistry
Analyzer
(K112412)Proposed Device:
DxC 700 AU Clinical
Chemistry Analyzer
Real-Time
Solutions
(RTS) supportInterface to RTS via
PRO Service protocol which is
made by Beckman CoulterInterface to RTS via
PRO Service protocol which is
made by Beckman Coulter
Remote software installation
capabilities.
External printersParallel port and USB
interfaced printersUSB and LAN
interfaced printers

AU5800 versus the DxC 700 AU Predicate Device Comparison Table 7 5

13

Image /page/13/Picture/0 description: The image contains the logo for Beckman Coulter. The logo consists of a red circular graphic on the left, with two curved white lines inside. To the right of the graphic are the words "BECKMAN" in a larger, bold font, stacked above the word "COULTER" in a smaller, bold font. The text and graphic are all in black and white.

14

Image /page/14/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, placed to the left of the company name. The text "BECKMAN COULTER" is written in bold, black letters, with "BECKMAN" on the top line and "COULTER" on the bottom line.

8.0 Comparison testing

In order to further demonstrate the comparability of the predicate device, AU5800 and the candidate device, DxC 700 AU, the following reagent performance testing was performed on a representative number of assays:

  • Method Comparison Matrix Comparison Linearity Sensitivity Precision Interference In use (On board) & Calibrator Stability Prozone Sample Dilution
    The DxC 700 AU chemistry analyzer uses the same lon Selective Electrode (ISE) and reagents, as well as the same menu of reagents currently available on the AU5800. Representative assays from the AU chemistry menu were selected to demonstrate equivalency between the predicate device, AU5800, and the candidate device, DxC 700 AU.

The CRP Latex reagent can be used to measure CRP on the DxC 700 AU chemistry analyzer using two applications, a normal application and a high sensitivity (cardiac) application. Only the CRP high sensitivity (cardiac) application was reviewed in this submission as a representative assay.

15

Image /page/15/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 flow. To the right of the circle, the words "BECKMAN" and "COULTER" are written in bold, black, sans-serif font, with "BECKMAN" on top of "COULTER".

Summary of Performance Data 9.0

This 510(k) submission provides the data necessary to demonstrate equivalence of the predicate device to the candidate device based on the performance validations and comparisons conducted between the representative reagents and analyzer platforms. Based on this data. the new DxC 700 AU Chemistry Analyzer is substantially equivalent to the referenced predicate.

9.1 Method Comparison with Predicate Device:

Method comparison and bias estimation experiments were designed using CLSI Guideline EP09-A3 "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline". These patient correlation studies demonstrate equivalence between the predicate AU5800 and the candidate DxC 700 AU. A minimum of 100 serum, urine and CSF samples were tested over five days. No more than 20% of samples were either spiked or diluted to ensure a uniform distribution over the analytical range. Each spiked or diluted sample was made from an individual sample. All method comparisons met the required specifications as detailed in the tables below.

Analyte# of samplesUnitsSlopeInterceptr
Sodium, Serum120mEq/L1.007-0.7790.999
Sodium, Urine130mEq/L1.014-1.3921.000
Potassium, Serum122mEq/L0.9880.0480.999
Potassium, Urine127mEq/L1.011-0.1491.000
Chloride, Serum118mEq/L0.9990.2240.999
Chloride, Urine129mEq/L1.036-3.6791.000
Glucose Serum130mg/dL1.0140.0401.000
CRP Latex (HS) Serum117mg/L1.013-0.0501.000

Table 9.1.1 Reagent Method Comparison Data

16

Image /page/16/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape on the left, with two white curved lines inside. To the right of the oval are the words "BECKMAN" on the top line and "COULTER" on the bottom line, both in a bold, sans-serif font.

9.2 Matrix Comparison Study

Anticoagulation Studies were designed using CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples: Approved Guideline - Third Edition.

9.2.1 Glucose

The serum recovery from the Glucose test was compared to the corresponding EDTA, Sodium Fluoride Potassium Oxalate, Sodium Fluoride EDTA and Lithium Heparin for the same donor.

| Anticoagulant | No. of
Samples
tested | Sample Range
(mg/dL) | Regression
analysis | Specification | Result |
|--------------------------------------------|-----------------------------|-------------------------|---------------------------------------------------------------|-----------------------------------------------------------------------------------|--------|
| EDTA | 50 | 19.72 - 752.31 | Slope: 0.999
Intercept: -0.099
R: 0.998
Bias: -0.199 | | Pass |
| Sodium
Fluoride
Potassium
Oxalate | 50 | 19.72 - 752.31 | Slope: 1.007
Intercept: 0.127
R: 0.998
Bias: 0.827 | Slope: 0.95-1.05
Intercept: ± 3.8mg/dL
R: ≥ 0.95
Bias: ± 3% at 100 mg/dL | Pass |
| Lithium Heparin | 50 | 19.72 - 752.31 | Slope: 0.996
Intercept:-0.076
R: 0.998
Bias: -0.476 | | Pass |
| Sodium
Fluoride EDTA | 50 | 19.72 - 752.31 | Slope: 1.005
Intercept: 0.133
R: 0.998
Bias: 0.633 | | Pass |

Table 9.2.1 Anticoagulant study results for Glucose reagent (OSR6x21)

17

Image /page/17/Picture/0 description: The image contains the logo for Beckman Coulter. The logo consists of a red circular shape with two curved white lines inside, positioned to the left of the company name. The text "BECKMAN" is stacked on top of "COULTER" in a bold, sans-serif font.

9.2.2 CRP Latex

The serum recovery from the CRP Latex test (highly sensitive application) was compared to the corresponding EDTA and Lithium Heparin for the same donor.

Table 9.2.2 Anticoagulant study results for CRP Latex reagent (OSR6x99)
--------------------------------------------------------------------------------

| Anticoagulant | No. of
Samples
tested | Sample Range
(mg/dL) | Regression
analysis | Specification | Result |
|-----------------|-----------------------------|-------------------------|---------------------------------------------------------------|-----------------------------------------------------------------------------|--------|
| EDTA | 52 | 0.34 - 73.11 | Slope: 0.990
Intercept: -0.059
R: 0.9992
Bias: -2.97 | Slope: 0.9-1.1
Intercept: ± 0.2 mg/L
R: ≥ 0.95
Bias: ± 6% at 3mg/L | Pass |
| Lithium Heparin | 52 | 0.34 - 73.11 | Slope: 0.985
Intercept: -0.013
R: 0.9995
Bias: -1.93 | | Pass |

18

Image /page/18/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, resembling a stylized wave or ribbon. To the right of the oval, the words "BECKMAN" and "COULTER" are stacked on top of each other in a bold, sans-serif font. The overall design is clean and modern, conveying a sense of innovation and technology.

9.3 Linearity/Assay Reportable Range:

Analytical range (linearity) studies were designed to meet the requirements of CLSI quidelines EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline".

High and low pools were prepared and inter-diluted to achieve concentrations spanning the required linear range. Each dilution was assayed in quadruplicate on the DxC 700 AU. The performance data for the study demonstrates linearity throughout the claimed dynamic range of each assay, as represented in the tables below.

Results
AnalyteUnitsSlopeInterceptrLinear
FromLinear
to
Sodium,
SerummEq/L1.0165-1.61580.99996.69245.97
Sodium,
UrinemEq/L1.0506-2.73630.99949.04417.43
Potassium,
SerummEq/L1.0207-0.12240.99960.1412.44
Potassium,
UrinemEq/L0.98830.05710.99991.02223.47
Chloride,
SerummEq/L1.0362-3.68360.99955.92246.78
Chloride,
UrinemEq/L1.0476-3.50260.999414.10421.31
Glucose
Serummg/dL0.9834-0.06280.99995.20843.18
CRP Latex
(HS) Serummg/L0.98940.04440.99950.1592.49

Table 9.3.1 Linearity Data

19

Image /page/19/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circular shape with two white curved lines inside, resembling a stylized wave or flow pattern. To the right of the circular shape, the words "BECKMAN" and "COULTER" are written in bold, black, sans-serif font, with "BECKMAN" on the top line and "COULTER" on the bottom line.

9.4 Sensitivity (Detection Limits):

LoB, LoD and LoQ studies were designed primarily from CLSI quideline 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 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 generated. This was comprised of 4 blank samples run 5-fold for 3 days, and 7 low level samples run 5-fold for 8 days.

The LoB, LoD, and LoQ results are summarised in the table below. All representative reagents met specifications and were below the claimed measuring range of the reagent.

| Reagent | Units | Low End of
Measuring
Range | LoB | LoD | LoQ |
|--------------------------|-------|----------------------------------|------|------|------|
| Glucose,
Serum | mg/dL | 10 | 0 | 0.42 | 2.68 |
| CRP Latex
(HS), Serum | mg/L | 0.2 | 0.04 | 0.08 | 0.08 |

Table 9.4.1 Sensitivity

0.5 Precision/Reproducibility:

Repeatability (within-run) and within-laboratory (total) precision studies were designed from CLSI guideline EP05-A3 "Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition". The precision was verified on the DxC 700 AU using 1 lot of reagent and 1 lot of calibrator and utilized duplicate sample analysis, twice daily, over the course of 20 days (n=80) for multiple sample levels. There was a minimum interval of two hours between the two runs each day.

All assays met the performance precision specifications and provide data to support the precision claims in the IFUs. The results are summarized in the below tables:

20

Image /page/20/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, placed to the left of the company name. The text "BECKMAN" is stacked on top of "COULTER" in a bold, sans-serif font.

Table 9.5.1. Precision

| Reagent | Sample
Levels | Mean | Repeatability
(Within-run) | | Within Laboratory
(Total) | |
|-----------------------------|------------------|--------|-------------------------------|------|------------------------------|------|
| | | (n=80) | SD | % CV | SD | % CV |
| CRP Latex
(HS)
(mg/L) | Serum 1 | 0.49 | 0.019 | 3.84 | 0.017 | 3.48 |
| | Serum 2 | 10.28 | 0.120 | 1.17 | 0.125 | 1.22 |
| | Serum 3 | 50.08 | 0.314 | 0.63 | 0.389 | 0.78 |
| | Serum 4 | 67.82 | 0.428 | 0.63 | 0.612 | 0.90 |
| Glucose
(mg/dL) | Serum 1 | 25.87 | 0.326 | 1.26 | 0.628 | 2.43 |
| | Serum 2 | 60.55 | 0.501 | 0.83 | 0.815 | 1.35 |
| | Serum 3 | 101.73 | 0.754 | 0.74 | 1.184 | 1.16 |
| | Serum 4 | 280.55 | 2.386 | 0.85 | 2.530 | 0.90 |
| | Serum 5 | 643.89 | 4.269 | 0.66 | 4.821 | 0.75 |
| Sodium
(mEq/L) | Serum 1 | 61.83 | 0.324 | 0.52 | 0.879 | 1.42 |
| | Serum 2 | 109.70 | 0.318 | 0.29 | 0.638 | 0.58 |
| | Serum 3 | 139.51 | 0.212 | 0.15 | 0.552 | 0.40 |
| | Serum 4 | 167.78 | 0.309 | 0.18 | 0.834 | 0.50 |
| Potassium
(mEq/L) | Serum 1 | 2.48 | 0.009 | 0.36 | 0.016 | 0.64 |
| | Serum 2 | 4.56 | 0.011 | 0.25 | 0.022 | 0.48 |
| | Serum 3 | 6.46 | 0.021 | 0.33 | 0.039 | 0.60 |
| | Serum 4 | 8.35 | 0.035 | 0.42 | 0.080 | 0.96 |
| Chloride
(mEq/L) | Serum 1 | 76.47 | 0.149 | 0.19 | 0.510 | 0.67 |
| | Serum 2 | 105.25 | 0.270 | 0.26 | 0.443 | 0.42 |
| | Serum 3 | 151.82 | 0.401 | 0.26 | 1.025 | 0.68 |
| Sodium
(mEq/L) | Urine 1 | 21.98 | 0.261 | 1.19 | 0.414 | 1.89 |
| | Urine 2 | 98.73 | 0.420 | 0.43 | 1.308 | 1.32 |
| | Urine 3 | 245.49 | 0.951 | 0.39 | 3.191 | 1.30 |
| | Urine 4 | 353.40 | 0.933 | 0.26 | 4.092 | 1.16 |
| Potassium
(mEq/L) | Urine 1 | 10.50 | 0.047 | 0.45 | 0.127 | 1.21 |
| | Urine 2 | 33.62 | 0.128 | 0.38 | 0.611 | 1.82 |
| | Urine 3 | 101.11 | 0.596 | 0.59 | 1.308 | 1.29 |
| | Urine 4 | 171.44 | 1.145 | 0.67 | 2.435 | 1.42 |
| Chloride
(mEq/L) | Urine 1 | 25.50 | 0.173 | 0.68 | 0.559 | 2.19 |
| | Urine 2 | 84.46 | 0.249 | 0.29 | 0.508 | 0.60 |
| | Urine 3 | 148.47 | 0.383 | 0.26 | 0.758 | 0.51 |
| | Urine 4 | 290.56 | 1.737 | 0.60 | 3.640 | 1.25 |
| | Urine 5 | 364.05 | 1.716 | 0.47 | 4.157 | 1.14 |

21

Image /page/21/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, the words "BECKMAN" and "COULTER" are written in bold, black, sans-serif font, with "BECKMAN" on the top line and "COULTER" on the bottom line.

9.6 In-Use and Calibration Stability Verification (EP25-A):

This protocol followed CLSI EP25-A quideline "Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline"; The aim was to verify the 30 and 90 day on-board claim for the representative reagents and to verify the 1 day calibration stability claim for the ISEs on the DxC 700 analyzer.

Testing was performed using one reagent lot (where appropriate) and one calibrator lot on the DxC 700 analyzer. Calibration (as required) was performed on the initial day of testing and controls were run in duplicate. At each timepoint the reagents were calibrated (if required) and controls were run in duplicate. Controls were run in duplicate on Day 1 + greater than 2hrs for the ISEs. The mean of the control replicates was calculated and the bias of this result to the mean of the control on Day 0 was calculated. The final time-points exceeded the claims on the reagent and ISE IFUs. For the reagents, linearity was assessed at the final time point.

A summary of in-use and calibration stability specifications and results are detailed in the tables below. All results were within specification and provide data to support the on-board and calibrations stability claims in the reagent and ISE IFUs.

| Reagent | Application | Onboard
Stability
Claim
(Days) | Calibration
Stability
Claim
(Days) |
|-------------------|-------------|-----------------------------------------|---------------------------------------------|
| CRP Latex
(HS) | Serum | 90 | 90 |
| Glucose | Serum | 30 | 30 |

Table 9.6.1 Reagent In-Use and Calibration Stability Specifications

Table 9.6.2 ISE Calibration Stability Specifications

| Product Name | Sample
Type | Calibration
Stability Claim
(Days) |
|--------------|----------------|------------------------------------------|
| Sodium | Serum | 1 |
| Sodium | Urine | 1 |
| Potassium | Serum | 1 |
| Potassium | Urine | 1 |
| Chloride | Serum | 1 |
| Chloride | Urine | 1 |

22

Image /page/22/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 words "BECKMAN" in bold black letters on the first line and "COULTER" in bold black letters on the second line. The logo is simple and modern, and the use of red and black gives it a strong and professional look.

9.7 Interferences (Analytical specificity):

Interference studies were designed based on CLSI Guideline EP07-A2: "Interference Testing in Clinical Chemistry: Approved Guideline - Second Edition".

All test samples were assayed in quadruplicate at two analyte levels. The sample pools tested were at different levels of interferents to determine the magnitude of their effect (if any). The data analysis involved calculating the difference in recovery of the samples with and without the potential interfering substances. The results are summarized below. All interferences met the required specifications on the DxC 700 AU analyzer.

Table 9.7.1 Chloride LIH Tolerance

| SUBSTANCE | SOURCE | LEVEL
TESTED* | OBSERVED
EFFECT |
|--------------------------|----------------|------------------|--------------------|
| Bilirubin (unconjugated) | Porcine | 40 mg/dL | NSIa |
| Hemoglobin | RBC hemolysate | 500 mg/dL | NSI |
| Lipemia | Intralipidb | 500 mg/dL | NSI |

Table 9.7.2 Potassium LIH Tolerance

| SUBSTANCE | SOURCE | LEVEL
TESTED* | OBSERVED
EFFECT |
|--------------------------|----------------|------------------|--------------------|
| Bilirubin (unconjugated) | Porcine | 40 mg/dL | NSIa |
| Hemoglobin | RBC hemolysate | 70 mg/dL | NSI |
| Lipemia | Intralipidb | 500 mg/dL | NSI |

Table 9.7.3 Sodium LIH Tolerance

| SUBSTANCE | SOURCE | LEVEL
TESTED* | OBSERVED
EFFECT |
|--------------------------|----------------|------------------|--------------------|
| Bilirubin (unconjugated) | Porcine | 40 mg/dL | NSIa |
| Hemoglobin | RBC hemolysate | 250 mg/dL | NSI |
| Lipemia | Intralipidb | 500 mg/dL | NSI |

*Level Tested represents the maximum concentration of interferent tested where no significant interference was observed.

a = NSI = No Significant Interference (Chloride ±2.5%, Potassium ±0.25 mEq/L, Sodium ±2mEq/L)

b = Intralipid is a registered trademark of KabiVitrum, Inc., Clayton, NC 27250

Table 9.7.4 Glucose and CRP (HS) Interference Data

Interference Threshold
Reagent*Lipemic
(Intralipid) ±Icteric
(Unconjugated) ±Hemolytic ±
Glucose,
Serum10% at
700 mg/dL10% at
40 mg/dL10% at
500 mg/dL
CRP Latex
(HS), SerumIntralipid
(1000 mg/dL)
intf. 750 mg/L. The CRP concentration was verified using three replicates of three dilutions within the measuring range. Eleven dilutions of the high prozone pool were then prepared and ran n=3 to confirm prozone performance. Testing demonstrates that samples with CRP concentrations up to 750 mg/L will not generate falsely low results within the analytical range.

10.0 Conclusion

The submission provides the data necessary to demonstrate this equivalence based on the performance validations and comparisons conducted between the representative reagents and analyzer platforms. Based on this data, the new DxC 700 AU Chemistry Analyzer is substantially equivalent to the referenced predicate(s).

This 510(k) summary is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.