For in vitro diagnostic use with the CARESIDE Analyzer™ to measure total CO2 from anticoagulated whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with respiratory and metabolic disorders associated with acid-base imbalance.

Device Description

CARESIDE™ CO2 cartridges are used with the CARESIDE Analyzer™ to measure total CO2 in whole blood, serum or plasma specimens. The CARESIDE™ CO2 cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of total CO2 The film cartridge (patent pending) contains all reagents necessary to measure total CO2.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CARESIDE™ CO2 device, based on the provided text:

CARESIDE™ CO2 Device: Acceptance Criteria and Performance Study

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion	Predicate Device Specification (Vitros CO2 DT Slides)	CARESIDE™ CO2 Performance (as reported)
Detection Limit	5 mmol/L	5 mmol/L
Reportable Range	5 to 50 mmol/L	5 to 40 mmol/L
Accuracy	Not provided	Mean recovery 101%
Precision	Total CV, 22 mmol/L, 6.6%	Total CV, 19 mmol/L, 6.6%
Method Comparison	Not specified (this is the comparison equation)	CARESIDE™ = 1.06 (Vitros CO2 DT) - 1.94 mmol/L, r = 0.97
Linearity	Not provided	Linearity yielded slope and correlation coefficient within acceptable limits.
Interference	Bromide, iodide, nitrate, diatrizoate may cause positive interference.	No significant interference observed at tested concentration of interferent: Ascorbic Acid (20 mg/dL), Bilirubin (15 mg/dL), Hemoglobin (300 mg/dL), Total Protein (15 g/dL), Triglycerides (3000 mg/dL)

Note: The document explicitly states, "The nonclinical and clinical data provided demonstrate that the CARESIDE™ CO2 product is as safe, effective, and performs as well as or better than the legally marketed predicate device." This indicates that the predicate's performance served as the "acceptance criteria" for demonstrating substantial equivalence.

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

Sample Size: Not explicitly stated for the "clinical data" or "method comparison" studies.
Data Provenance: Not explicitly stated (e.g., country of origin). The document refers to "nonclinical and clinical data provided," implying internal studies by CARESIDE, Inc. It does not indicate if the data was retrospective or prospective.

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

This information is not provided in the document. The document describes an in vitro diagnostic device for quantitative measurement, and ground truth would typically be established by laboratory reference methods rather than expert consensus for individual results.

4. Adjudication Method for the Test Set

This information is not provided. Given it's a quantitative diagnostic device, adjudication methods like 2+1 or 3+1 are not typically applicable. The comparison is against established laboratory methods.

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

No, an MRMC study was not done. This type of study is for evaluating human performance, often with AI assistance, in interpreting medical images or data. The CARESIDE™ CO2 device is an automated in vitro diagnostic device, not one requiring human interpretation in this manner.

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

Yes, this was a standalone performance study. The CARESIDE™ CO2 cartridge, used with the CARESIDE Analyzer™, is an automated system designed to quantitatively measure total CO2 without human intervention in the measurement process itself, beyond sample loading. The performance characteristics (accuracy, precision, linearity, method comparison, interference) reported are indicative of the device's standalone performance.

7. The Type of Ground Truth Used

The ground truth for the method comparison and accuracy studies would have been established by comparing the CARESIDE™ CO2 results against a legally marketed predicate device (Vitros CO2 DT Slides) or other established reference methods in a clinical laboratory setting. The "Method comparison" section directly compares the CARESIDE™ results to the Vitros CO2 DT, indicating the Vitros results served as a comparative ground truth.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" sample size. For in vitro diagnostic devices, method validation studies typically encompass "development" or "internal validation" phases which are analogous to a training set, but explicit sample sizes for these are rarely detailed in 510(k) summaries. The reported performance data would generally come from a separate "test set" after method development is complete.

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

As a quantitative diagnostic test, the "ground truth" during any developmental or training phase would typically be established against existing, well-established reference methods or predicate devices in a laboratory. The document does not describe the specific process for establishing ground truth during initial development or "training" phases, if any specific "training set" was used for the algorithm. The fundamental principle is that the device is calibrated and its performance evaluated against established, accurate measurements of CO2.

Summary

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SEP 1 5 1999 CARESIDE, Inc. Page 10

510(K) SUMMARY: CARESIDE™ CO2 SAFETY AND V. EFFECTIVENESS

I. Applicant Information

Applicant Name A.
Applicant/Manufacturer Address B.
Telephone Number C.
Contact Person D.
FAX Number E.
e-Mail Address F.
Date 510(k) Summary prepared G.

II. Device Information

A. Device Name (Trade)
B. Device Name (Classification)
C. Device Classification

CARESIDE, Inc.

6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 AsarchK@CARESIDE.com Date July 23, 1999

CARESIDE™ CO2, Total

Bicarbonate/Carbon dioxide test system Clinical chemistry panel Bicarbonate/Carbon dioxide test system Regulation Number: 21 CFR 862.1160 Regulatory Class 2 Classification Number: 75KHS None applicable

D. Special controls and performance standards

Substantial Equivalence Claim III.

General equivalency claim A.
The ability to monitor analyte-specific biochemical reactions in dry film and other formats is widely recognized and has gained widespread acceptance for use in chemistry assays.

CO2 in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market. CO2 products include those that use dry film using a PEP carboxylase coupled enzyme reaction and reflectance photometry technology.

B. Specific equivalency claim

This CARESIDE™ CO2 test is substantially equivalent in intended use and clinical performance to the currently marketed Vitros CO2 DT slides for the quantitative measurement of total CO2 on the Vitros DT 60 II / DTE II system. The CARESIDE CO2 utilizes the principle of reflectance photometry and the Vitros DT 60 II / DTE II system utilizes differential potentiometry.

Name of Predicate Devices:

Johnson and Johnson's (formerly Eastman Kodak, Inc.): Vitros CO2 DT Slides for Johnson and Johnson's (formerly Eastman Kodak) Vitros DT 60 II / DTE II system and Vitros ECO2 DT Slides for Johnson and Johnson's Vitros Chemistry Analyzers.

Predicate Device 510K number: K912844/A - K903144 Predicate Product Code: 75KHS i

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IV. Device Description

CARESIDE™ CO2 cartridges are used with the CARESIDE Analyzer™ to measure total CO2 in whole blood, serum or plasma specimens. The CARESIDE™ CO2 cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of total CO2 The film cartridge (patent pending) contains all reagents necessary to measure total CO2.

Explanation of Device Function A.
Each CARESIDE™ CO2 cartridge consists of a CO2-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge Sample Well, closes the lid and inserts the cartridge into the CARESIDE Analyzer™.

Once loaded, the CARESIDE Analyzer™ scans the cartridge barcode, brings the cartridge and the contained specimen to 37°C, and spins the cartridge to move the sample from the Sample Well into the cartridge channels and chambers where separation of cells, if present, occurs. 8.5 microliters of sample remains in the metering channel. Any excess sample flows into an overflow well.

The 8.5 microliters of sample is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the specimen uniformly. The color intensity of the resulting yellow dye, as measured by the amount of reflected light at 425 nanometers, directly relates to the total CO2 concentration of the specimen.

Test Reaction Sequence:

Carbon dioxide in the form of bicarbonate ion combines with phosphoenolpyruvate in a reaction catalyzed by PEP-carboxylase (PEPC) to form oxaloacetate (OAC) and inorganic phosphate (PO4-3) as shown below. Oxaloacetate reacts with thio-NADH (t-NADH) and hydrogen ion (H) in a malate dehydrogenase (MDH) catalyzed reaction to form L-malate and thio-NAD+ (t-NAD*).

$$\begin{aligned} \text{HCO}_3^- + \text{PEP} & \xrightarrow{\text{PEPC} \atop \text{M} \text{O}^-} \text{OAC} + \text{PO}_4^{\cdot 3} \ \text{OAC} + \text{t-NADH} & + \text{H}^+ \xrightarrow{\text{MDH}} \text{L-Malate} + \text{t-NAD}^+ \end{aligned}$$

As the cartridges spin, a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time. The analyzer uses the reflectance measurements and the lot-specific standard curve to calculate total carbon dioxide concentration.

B. Test Summary

Carbon dioxide is a gas, and as such occurs in very low concentrations in this form in the blood. Bicarbonate ion (HCO3) as well as other ions are in equilibrium with CO2 in the blood. At physiological pH, CO2 occurs in the largest concentration while carbonate and carbamino compounds are present in such low quantities that they are generally not considered separately. The bicarbonate ion concentration in blood is related to the total carbon dioxide concentration and the pH according to the Henderson-Hasselbach equation.

The bicarbonate ion/carbonic acid pair represents the most important buffer system of plasma. Clinical conditions characterized as metabolic disturbances of acid-base balance are classified as primary disturbances in HCO5 ion concentration. Primary disturbances in the total dissolved CO2 are characterized as respiratory disturbances. Changes in the bicarbonate ion, dissolved CO2 concentration, or both occur as a result of various compensatory mechanisms attempting to re-establish the normal ratio of bicarbonate ion to total dissolved CO2.

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V. Intended Use

Intended Use A.
The CARESIDE™ CO2 cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer™ to quantitatively measure total CO2 in whole blood, serum or plasma.
Indications for Use B.
This product is indicated for use in the diagnosis and treatment of patients with respiratory and metabolic disorders associated with acid-base imbalance.

Technological Characteristics VI.

Similarities A.

	CARESIDE™ CO2	Vitros CO2 DT Slides
Intended Use	Primarily to aid in thediagnosis and treatment ofpatients with respiratory andmetabolic disorders associatedwith acid-base imbalance	Primarily to aid in theevaluation of acid-base status.
Indications	For in vitro diagnostic use.For professional laboratoryuse: not for point of care orphysician office laboratoryuse.	For in vitro diagnostic use
Measurement	Quantitative	Same
Method Principle	Dry film, reflectancephotometry	Differential potentiometry
Specimen dilution	Not required	Same
Materials	PEP, PEP carboxylase, thio-NADH, and malatedehydrogenase.	Silver, silver chloride, sodiumchloride, potassium chloride,trioctylpropylammoniumchloride, anddecyltrifluoroacetophenone
Detector	Photodiode (425 nm)	Ion-selective electrode
Test time	Approx. 4 minute warm-up(on-board) plus 5 minute testtime.	15 minutes slide warm-up(off-line) plus 3 minutes testtime.
Sample Type	Anti-coagulated whole blood,heparinized plasma, orserum.	Serum or plasma
Specimen volume	8.5 µl test volume(85 ± 15 µl applied volume)	10 µl
Calibration	Calibration information bar-coded on each cartridge.Calibration information maychange with each lot.	Run Vitros DT II calibratorswhenever a new slide lot isused or when necessary.
Quality Control	2 levels	Same
Reporting Units	mmol/L	Same
Reaction Temp.	37 °C	Same

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B. Differences

	CARESIDE™ CO2	Vitros CO2 DT Slides
SpecimenProcessing	Not required	Required
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

C. Comparative Performance Characteristics

	CARESIDE™ CO2	Vitros CO2 DT Slides
Detection limit	5 mmol/L	5 mmol/L
Reportable range	5 to 40 mmol/L	5 to 50 mmol/L
Accuracy	Mean recovery 101%	Not provided
Precision	Total CV, 19 mmol/L, 6.6%	Total CV, 22 mmol/L, 6.6%
Methodcomparison	CARESIDE™ = 1.06 (Vitros CO2 DT) - 1.94 mmol/L, r = 0.97
Linearity	Linearity yielded slope andcorrelation coefficient withinacceptable limits.	Not provided
Interference	No significant interferenceobserved at testedconcentration of interferent:Ascorbic Acid, ........20 mg/dLBilirubin, ........15 mg/dLHemoglobin, ........300 mg/dLTotal Protein, ........15 g/dLTriglycerides ........3000 mg/dL	Bromide, iodide, nitrate,diatrizoate may cause positiveinterference.

D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE™ CO2 product is as safe, effective, and performs as well as or better than the legally marketed predicate device

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a stylized human figure, composed of three curved lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 1 5 1999

Kenneth B. Asarch, Ph.D. VP Quality Systems and Regulatory Affairs Careside, Inc. 6100 Bristol Parkway Culver City, California 90230

Re: K992475

Trade Name: CARESIDE™ CO, Total for use on the Careside Analyzer™ Regulatory Class: II Product Code: KHS Dated: July 23, 1999 Received: July 26, 1999

Dear Dr. Asarch:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Image /page/5/Picture/6 description: The image contains a signature and some text. The signature is on the left side of the image and appears to be a stylized letter. To the right of the signature, there are three lines of text, but the content of the text is not clear enough to read.

Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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VII. INDICATIONS FOR USE

992475 510(k) Number: CARESIDE™ CO2 Device Name:

Indications for use: For in vitro diagnostic use with the CARESIDE Analyzer™ to measure total CO2 from anticoagulated whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with respiratory and metabolic disorders associated with acid-base imbalance.

ecom Cerope

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K992475

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use (Optional Format 1-2-96)

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.