Bicarbonate measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

For In Vitro Diagnostic Use

Device Description

The AU Bicarbonate reagent kit is a liquid, ready to use and consists of four R1 reagent vials in vanous fill volumes. The calibrator is a Beckman Coulter lyophilized chemistry calibrator packaged as catalog number DR0070 and sold separately. The AU Bicarbonate reagent is an enzymatic method utilizing Bicarbonate (HCO3) and phosphoenolpyruvate (PEP), which are converted to oxaloacetate to malate with the concomitant oxidation of reduced nicotinamide adenine dinucleotide (NADH). This oxidation of NADH results in a decrease in absorbance of the reaction mixture measured bichromatically at 380/410nm proportional to the Bicarbonate content of the sample.

The AU Bicarbonate reagent is designed for optimal performance on Beckman Coulter AU analyzers.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the AU Bicarbonate Reagent, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

Study Category	Acceptance Criteria	Reported Device Performance
Method Comparison	Slope: 0.900-1.100Intercept: ±2.0 mEq/Lr (correlation coefficient): ≥ 0.95N (sample size): > 100	Slope: 0.922Intercept: 1.148 mEq/Lr: 0.9909N: 133
Precision	Within-run (Low Pool): ≤3%CV or SD≤1Within-run (Med Pool): ≤3%CV or SD≤1Within-run (High Pool): ≤3%CV or SD≤1Total (Low Pool): ≤7%CV or SD≤1.5 mEq/LTotal (Med Pool): ≤7%CV or SD≤1.5 mEq/LTotal (High Pool): ≤7%CV or SD≤1.5 mEq/L	Within-run (Low Pool): %CV 2.5, SD 0.30Within-run (Med Pool): %CV 1.1, SD 0.35Within-run (High Pool): %CV 0.8, SD 0.34Total (Low Pool): %CV 7.5, SD 0.92Total (Med Pool): %CV 4.0, SD 1.23Total (High Pool): %CV 3.6, SD 1.47
Sensitivity	Not explicitly stated as acceptance criteria, but reported values are: LoB = 1.20 mEq/L, LoD = 1.95 mEq/L	LoB = 1.20 mEq/LLoD = 1.95 mEq/L
Interfering Substances	Unconjugated Bilirubin: No significant interference up to 40 mg/dL (defined as recovery within 10% of initial value)Conjugated Bilirubin: No significant interference up to 20 mg/dL (defined as recovery within 10% of initial value)Hemolysis: No significant interference up to 500 mg/dL (defined as recovery within 10% of initial value)Lipemia: No significant interference up to 1000 mg/dL Intralipid (defined as recovery within 10% of initial value)	Unconjugated Bilirubin: No significant interference up to 40 mg/dLConjugated Bilirubin: No significant interference up to 20 mg/dLHemolysis: No significant interference up to 500 mg/dLLipemia: No significant interference up to 1000 mg/dL Intralipid (No significant interference is recovery within 10% of initial value)
Linearity Range	2.0 - 45.0 mEq/L	2.0 - 45.0 mEq/L (implied, as this is the stated range)
Expected Values	23 - 29 mEq/L	23 - 29 mEq/L (implied, as this is the stated range)

All reported device performances met their respective acceptance criteria as indicated by "Pass" in the Method Comparison and Precision tables.

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

Method Comparison Test Set: N = 133 samples.
Precision Test Set: The document refers to "Low pool," "Med pool," and "High pool" samples. It doesn't specify an overall sample size for the precision study, but implies multiple measurements were taken for each pool (e.g., within-run and total precision across multiple runs/days).
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is clinical laboratory data, likely gathered prospectively during validation studies.

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

This document describes an in vitro diagnostic reagent for quantitative determination of bicarbonate, not an imaging or diagnostic device requiring expert interpretation for ground truth.
The "ground truth" for method comparison is a reference method (Thermo Scientific, TR28321) and for precision is based on statistical measures of reproducibility. No human expert "ground truth" establishment is described for these types of studies.

4. Adjudication Method for the Test Set:

Not applicable. This is a quantitative chemical assay, not an interpretative diagnostic task requiring adjudication. The performance is assessed against predefined statistical and analytical criteria.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically for evaluating the impact of an AI algorithm on human reader performance, which is not relevant for an in vitro diagnostic reagent.

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

Yes, this entire study represents the standalone performance of the AU Bicarbonate Reagent on Beckman Coulter AU analyzers. There is no human-in-the-loop component in the measurement and quantification of bicarbonate by this automated system.

7. The Type of Ground Truth Used:

Quantitative Reference Measurement: For the method comparison, the "ground truth" is a comparison against a commercially available and presumably validated reference method (Thermo Scientific TR28321).
Statistical Definitions: For precision, the "ground truth" is based on statistical definitions of within-run and total precision, where the target values are the mean concentrations of the control pools.
Defined Standards/Limits: For sensitivity, linearity, and interfering substances, the ground truth is established against predefined analytical limits and standards (e.g., NIST standard for calibrator traceability).

8. The Sample Size for the Training Set:

The document does not explicitly refer to a "training set" in the context of machine learning. This is a chemical reagent and instrument system, not an AI/ML algorithm that undergoes a distinct training phase with a labeled dataset. The development and optimization of the reagent itself would involve internal R&D studies, but these are not referred to as a "training set" in this context.

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

Not applicable, as this device does not involve a machine learning "training set." The performance characteristics are established through analytical validation studies rather than machine learning model training.

Summary

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OCT 0 9 2013

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510k Summary AU Bicarbonate Reagent

1.0 Submitted By:

David G. Davis Director Regulatory Affairs Beckman Coulter Inc. 250 S. Kraemer Boulevard Brea, CA 92821. Telephone: (469) 236-8180 Fax: (714) 961-4234 Email: dgdavis@beckman.com

Date Submitted:

April 24, 2013

3.0 Device Name(s):

2.0

3.1 Proprietary Names AU Bicarbonate Reagent

3.2 Classification Name

Bicarbonate/carbon dioxide test system (21 CFR § 862.1160)

4.0 Predicate Device:

Candidate(s)	Predicate	Manufacturer	Docket Number
AU Bicarbonate Reagent	Carbon Dioxide - DST	Trace	K960035

5.0 Description:

The AU Bicarbonate reagent is designed for optimal performance on Beckman Coulter AU analyzers.

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6.0 Intended Use:

AU Bicarbonate reagent is intended for the quantitative determination of Bicarbonate in human serum and plasma on Beckman Coulter AU analyzers.

Bicarbonate measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acidbase balance.

For in vitro diagnostic use.

Clinical Significance

Bicarbonate measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acidbase balance.

7.0 Comparison to Predicate(s):

The following tables shows similarities and differences between the predicate identified in Section 4.0 of this summary. 1 T

	Similarities
Feature	AU Bicarbonate Reagent	Predicate
Intended Use	System reagent for the quantitativedetermination of Bicarbonate inhuman serum and plasma onBeckman Coulter AU analyzers.	SimilarThis reagent is intended for in vitroquantitative determination of totalcarbon dioxide in human serum onboth automated and manualsystems.
Measurement	Quantitative	Same
Reagent	Liquid, Ready for use	Same
AssayMethodology/OperatingPrinciple	Enzymatic Photometric	Same
Calibration	Serum based calibrator traceable toNIST standard(Cat #DR0070)	SimilarRecommended to use an aqueousor serum based calibrator traceableto a primary standard (e.g. NIST orIRMM)
Linearity Range	2.0 - 45.0 mEq/L	Similar3 - 50 mEq/L
ExpectedValues	23 - 29 mEq/L	Same23.0 - 29.0 mEq/L

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Differences
Feature	AU Bicarbonate Reagent	Predicate
Instrumentation	Beckman Coulter AU Analyzers	Automated and manual systems
Specimen Type	Serum and Plasma(Sodium Heparin and Lithium Heparin)	Serum
Reagent On Board Stability	Opened reagents are stable for seven days when stored in the refrigerated compartment of the analyzer	Not specified
Calibration Frequency	Daily	Not specified
Sensitivity	LoB = 1.20 mEq/LLoD = 1.95 mEq/L	Analytical 0.01 ΔA per mEq/L
Interfering Substances	Unconjugated Bilirubin:No significant interference up to 40 mg/dL	Unconjugated Bilirubin:No interference up to 18.6 mg/dL
	Conjugated Bilirubin:No significant interference up to 20 mg/dL	Conjugated Bilirubin:No interference up to 18.7 mg/dL
	Hemolysis:No significant interference up to 500 mg/dL	Haemoglobin:No interference up to 520 mg/dL
	Lipemia:No significant interference up to 1000 mg/dL Intralipid	Lipemia:No interference measured at absorbance 630 nm, up to 1.77 AU
	No significant interference is recovery within 10% of initial value

8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to a predicate chemistry test systems already in commercial distribution. Equivalence is demonstrated through performance characteristics testing. Experiments included: Method Comparison, Precision, Linearity, Sensitivity, Interferences, Stability and Expected Values, as outlined in FDA's guidance entitled "In Vitro Diagnostic Bicarbonate/Carbon Dioxide Test System."

Performance on method comparison and precision are summarized below:

Reference	Test	SampleRange:	Specifications	Results	Pass/Fail
ThermoScientific(TR28321)	AU Bicarbonate(OSR6x37)	Ref:5.63 mEq/L -45.44 mEq/LTest:4.69 mEq/L -41.85 mEq/L	Slope:0.900-1.100Intercept:±2.0mEq/Lr: ≥ 0.95N: >100	Slope: 0.922Intercept:1.148mEq/Lr: 0.9909N: 133	PassPassPassPass

Method Comparison Study Results

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Sample	ConcentrationmEq/L	Within run precision		Total precision			Pass/Fail
		%CV	SD	Specification	%CV	SD	Specification
Lowpool	12.3	2.5	0.30	≤3%CVor SD≤1	7.5	0.92	≤7%CV or SD≤1.5mEq/L	Pass
Medpool	31.0	1.1	0.35	≤3%CVor SD≤1	4.0	1.23	≤7%CV or SD≤1.5mEq/L	Pass
Highpool	40.3	0.8	0.34	≤3%CVor SD≤1	3.6	1.47	≤7%CV or SD≤1.5mEq/L	Pass

Precision Study Results

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

Section 5 - Page 4 of 4

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

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

October 9, 2013

Beckman Coulter Ireland, Inc. c/o David G. Davis 250 S. Kraemer Blvd. BREA CA 92821

Re: K131546

Trade/Device Name: AU Bicarbonate Reagent Regulation Number: 21 CFR 862.1160 Regulation Name: Bicarbonate/carbon dioxide test system Regulatory Class: II Product Code: KHS Dated: August 21, 2013 Received: August 29, 2013

Dear Mr. Davis:

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 conceming your device in the Federal Register.

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

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Page 2-Mr. Davis

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

Sincerely yours,

Carol C. Benson -S for

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

Enclosure

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Indications for Use

510(k) Number: K131546

Device Name: AU Bicarbonate Reagent

Indications for Use: AU Bicarbonate reagent is intended for the quantitative determination of Bicarbonate in human serum and plasma on Beckman Coulter AU analyzers.

Bicarbonate measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

For In Vitro Diagnostic Use

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Yung ADAhan -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k) and the comments of the comments of the comments of the comments of the comments of the comments of the contribution of the contribution of the contribution of the first of t

Regulation Number and Section

§ 862.1160 Bicarbonate/carbon dioxide test system.

(a)
Identification. A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.(b)
Classification. Class II.