For in vitro diagnostic use with Exigent Diagnostics' CARESIDE™ Analyzer to measure total cholesterol from anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of patients with disorders of lipid and lipoprotein metabolism

Device Description

CARESIDE™ Total Cholesterol cartridges are used with the Exigent Diagnostics CARESIDE™ Analyzer to measure total cholesterol concentration in anti-coagulated whole blood, plasma or serum specimens. The CARESIDE™ Total Cholesterol cartridge, a single use disposable in vitro diagnostic test cartridge, aids in specimen separation and delivers a measured volume of plasma or serum to a dry film to initiate the measurement of total cholesterol concentration. The film cartridge (patent pending) contains all reagents necessary to measure total concentration of cholesterol.

AI/ML Overview

The Exigent Diagnostics CARESIDE™ Total Cholesterol device is a quantitative in vitro diagnostic system for measuring total cholesterol in anti-coagulated whole blood, plasma, or serum specimens when used with the CARESIDE™ Analyzer. The device's performance was evaluated by comparing it to the legally marketed predicate device, Johnson and Johnson’s Vitros CHOL Slides for the Vitros DT 60 II. The study focused on accuracy, precision, and method comparison.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are not explicitly defined in terms of specific performance targets (e.g., "accuracy must be >95%"). Instead, the document demonstrates substantial equivalence by presenting comparative performance characteristics against a predicate device. The implicit acceptance criterion is that the CARESIDE™ device performs as well as or better than the predicate device for key metrics.

Performance Characteristic	Acceptance Criteria (Implicit: As good as or better than predicate)	CARESIDE™ Total Cholesterol Performance	Predicate Device (Vitros CHOL DT Slides) Performance
Detection Limit	50 mg/dL	50 mg/dL	50 mg/dL
Reportable Range	At least 50 to 325 mg/dL	50 to 450 mg/dL	50 to 325 mg/dL
Accuracy	Not explicitly defined, but assumed to be acceptable	Mean recovery 106%	Not provided
Precision	Comparable to predicate (e.g., CV%)	Total CV, 203 mg/dL, 5.2%	Total CV, 202 mg/dL, 3.4%
Method Comparison	Strong correlation with predicate	CARESIDE™ = 1.04 (Vitros CHOL DT) + 23 mg/dL, r = 0.94	Not provided
Linearity	Within acceptable limits	Linearity by mixing and by dilution yielded slope and correlation coefficient within acceptable limits	Not provided
Interference	No significant interference at specified concentrations	No significant interference observed at:Ascorbic acid 1 mg/dLBilirubin 10 mg/dLHemoglobin 250 mg/dLProtein 5 to 9 g/dLTriglyceride 600 mg/dL	Very high protein > 10 mg/dL

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

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

The document does not explicitly state the sample size used for the test set in the provided sections. Details regarding the number of patient samples (e.g., for accuracy, precision, or method comparison studies) are not given.

The data provenance is not explicitly stated in terms of country of origin or whether it was retrospective or prospective. Given the context of a 510(k) summary for a diagnostic device seeking U.S. market clearance, it is highly probable that the studies were conducted in the U.S. or followed U.S. regulatory guidelines for clinical data. The studies would typically be prospective for clinical performance evaluations.

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

This information is not applicable to this type of device and study. The Exigent Diagnostics CARESIDE™ Total Cholesterol is an in vitro diagnostic (IVD) device for quantitative measurement of a biochemical analyte (total cholesterol). The "ground truth" for measuring cholesterol concentration is established by a reference method (Abell Kendall in this case) and validated laboratory procedures, not by expert consensus or interpretation of images.

4. Adjudication Method for the Test Set

This is not applicable as the ground truth is based on quantitative chemical measurements against a reference method (Abell Kendall), not subjective interpretations requiring adjudication.

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 relevant for diagnostic imaging devices where human readers interpret medical images. The CARESIDE™ device is an automated in vitro diagnostic test for measuring a chemical concentration; therefore, MRMC studies are not applicable.

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

Yes, the performance presented for the CARESIDE™ device is standalone performance. The device automatically measures cholesterol concentration by processing the sample and uses its internal algorithm (based on reflectance measurements and a lot-specific standard curve) to calculate the total cholesterol concentration. The performance metrics (accuracy, precision, linearity, method comparison, interference) represent the device's capability to provide measurements independently of human interpretation of the final result, beyond the initial sample application and instrument operation.

7. The Type of Ground Truth Used

The ground truth for the performance evaluation of the CARESIDE™ Total Cholesterol device typically relies on established reference methods and laboratory standards. Specifically, the document states:

Reference Method: Abell Kendall. This method is a widely accepted and rigorous chemical method for determining cholesterol concentration and serves as the gold standard for accuracy comparisons.
Comparative Method: Vitros CHOL DT Slides (predicate device), which itself is compared to and validated against established reference methods.

Therefore, the ground truth is primarily based on chemical reference methods/laboratory standards.

8. The Sample Size for the Training Set

The document does not provide information on the sample size used for the training set. For an IVD device, the "training set" would typically refer to data used during the development and calibration of the device's algorithms and standard curves. This information is generally part of the internal development process and not always detailed in the 510(k) summary unless specific machine learning components require it for regulatory review, which is less common for enzymatic assays like this.

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

The document does not explicitly state how the ground truth for the training set was established. However, based on typical IVD development, the ground truth for establishing calibration curves and optimizing the enzymatic reactions would involve:

Known concentration standards: Using commercially available or internally prepared solutions with precisely known cholesterol concentrations.
Reference laboratory measurements: Analyzing samples using established reference methods (like Abell Kendall or other highly accurate laboratory methods) to determine their true cholesterol levels, which are then used to develop and validate the device's calibration.

This process ensures that the device's measurements are accurate across its reportable range.

Summary

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111 2 / 1998

Exigent Diagnostics, Inc. Page 10

May 29, 1998

K982/118

510(K) SUMMARY: CARESIDE™ TOTAL IV. CHOLESTEROL SAFETY AND EFFECTIVENESS

Applicant Information I.

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

II. Device Information

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

D. Special controls and performance standards

III. Substantial Equivalence Claim

A. General equivalency claim
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.

Total cholesterol in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including total cholesterol products which utilize enzymatic (cholesterol oxidase) generation of hydrogen peroxide from free and liberated cholesterol which reacts with chromogens in a peroxidase catalyzed reaction to form a dye.

B. Specific equivalency claim
This CARESIDE™ Total Cholesterol test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of total cholesterol on the Vitros DT 60 II.

Name of Predicate Device:	Johnson and Johnson's (formerly Eastman Kodak,Inc.) Vitros CHOL Slides for Johnson andJohnson's Vitros DT 60 (formerly Eastman Kodak'sDT 60 II).
Predicate Device 510K number:	K912844/A
Product Code:	75CHH

Exigent Diagnostics, Inc. 6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 asarchk@worldnet.att.net May 29, 1998

CARESIDE™ Total Cholesterol

Total Cholesterol test system Clinical chemistry panel Total cholesterol test system Regulation Number: 21 CFR 862.1175 Regulatory Class I Classification Number: 75CHH None applicable

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IV. Device Description

A. Explanation of Device Function

Each Exigent Diagnostics CARESIDE™ Total Cholesterol cartridge consists of a total cholesterol-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the anti-coagulated whole blood, serum, or plasma specimen into the cartridge sample deposition well, closes the lid and inserts the cartridge into the Exigent Diagnostics CARESIDE™ Analyzer.

Once loaded, the CARESIDE™ Analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. As the cartridge continues to spin, the blood cells are separated from the plasma/serum and the cells accumulate in the separation well. Approximately ten microliters of plasma (or serum, as applicable) remain in the metering passage. Any excess sample flows into an overflow well.

The plasma (or serum, as applicable) is automatically dispensed onto the multi-layer reagent film. The spreading layer distributes the sample evenly on the film, and the sample moves through a reflection layer into the detection layer. Cholesterol is dissociated from protein by the action of lipoprotein lipase (LPL) and a surfactant. Cholesterol esterase (CHE) hydrolyzes the cholesterol esters (CHOL-ester) into free cholesterol. Endogenous cholesterol and the liberated cholesterol react with oxygen and water to produce hydrogen peroxide in a cholesterol oxidase (CO) catalyzed reaction. Peroxidase (POD) then catalyzes the reaction of the hydrogen peroxide with a diarylimidazole leuco dye to produce a blue chromogen. The color intensity of the resulting blue dye, as measured by the amount of reflected light at 505 nanometers, directly relates to the total cholesterol concentration of the specimen.

Test Reaction Sequence: Total Cholesterol ------------------------------------------------------------------------------------------------------------------------------------------------------------CHE -> CHOL (free) CHOL-Ester -CHOL + O2 + H2O2 + Cholesten-3one POD Fe .... > Blue dye Leuco dye + H2O2 -

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

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Exigent Diagnostics, Inc. Page 12

B. Test Summary

Total cholesterol in blood comprises all of the cholesterol found in various lipoproteins. Cholesterol is the major component of the low density lipoprotein (LDL) fraction, and a minor component of the very low density lipoprotein (VLDL) and high density lipoprotein (HDL) fractions. Cholesterol measurements are used in classifying patients according to risk of coronary heart disease, in the diagnosis and treatment of various primary or secondary hyperlipidemias, and to monitor changes in cholesterol levels resulting from treatment. Elevated LDL-cholesterol has consistently been associated with incidence of atherosclerosis. There is also a strong correlation between considerably elevated cholesterol levels and an increased tendency for atherosclerosis. Conversely, HDL-cholesterol concentration and cardiovascular disease risk are inversely related. Measurement of total and HDL-cholesterol in serum is useful in evaluating cardiovascular disease risk.

V. Intended Use

A. Intended Use
The CARESIDE™ Total Cholesterol cartridge is intended for in vitro diagnostic use in conjunction with the Exigent Diagnostics CARESIDE™ Analyzer to quantitatively measure total cholesterol concentration in anti-coagulated whole blood, plasma or serum.
B. Indications for Use
This product is indicated for use in the diagnosis and treatment of patients with disorders of lipid and lipoprotein metabolism.

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VI. Technological Characteristics

Similarities A.

	CARESIDE™ TotalCholesterol	Vitros CHOL DT Slides
Intended Use	Primarily to aid in the diagnosisand treatment of patients withdisorders of lipid andlipoprotein metabolism.	Used in classifying patientsaccording to risk of coronaryheart disease, in the diagnosisand treatment of various primaryor secondary hyperlipidemias,and to monitor changes incholesterol and levels resultingfrom treatment.
Indications	For in vitro diagnostic use.For professional laboratory use.	For in vitro diagnostic use
Measurement	Quantitative	Same
Method Principle	Dry film based already on theU.S. market, including totalcholesterol products whichutilize enzymatic (cholesteroloxidase) generation - ofhydrogen peroxide from freeand liberated cholesterolwhich reacts with chromogensin a peroxidase catalyzedreaction to form a dye.	Same
Specimen dilution	Not required	Same
Materials	Lipoprotein lipase, surfactant,cholesterol esterase,cholesterol oxidase,peroxidase, anddiarylimidazole leuco dye	Surfactant, cholesterolesterase, cholesterol oxidase,peroxidase, and leuco dye
Detector	Reflectance (505 nm)	Reflectance (555 nm)
Test time	Approx. 4 minute warm-up (on-board) plus 6 minute test time.	15 minutes slide warm-up (off-line) plus 5 minutes test time.
Reference Method	Abell Kendall	Abell Kendall
Sample Type	Serum, plasma, whole blood[whole blood applied sample,plasma test sample]	serum, plasma
Specimen volume	10 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	mg/dL or mmol/L	Same
Reaction Temp.	37 °C	Same
	CARESIDE™ TotalCholesterol	Vitros CHOL DT Slides
Direct bloodspecimen	Yes, whole blood	No, requires separation ofwhole blood prior to sampleapplication
Reportable range	50 to 450 mg/dL	50 to 325 mg/dL
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

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B. Differences

C. Comparative Performance Characteristics

	CARESIDE™ TotalCholesterol	Vitros CHOL DT Slides
Detection limit	50 mg/dL	50 mg/dL
Reportable range	50 to 450 mg/dL	50 to 325 mg/dL
Accuracy	Mean recovery 106%	Not provided
Precision	Total CV, 203 mg/dL, 5.2%	Total CV, 202mg/dL, 3.4%
Method comparison	CARESIDE™ = 1.04 (Vitros CHOL DT) + 23 mg/dL, r = 0.94
Linearity	Linearity by mixing and bydilution yielded slope andcorrelation coefficient withinacceptable limits.	Not provided
Interference	No significant interference observed at tested concentration of interferent:Ascorbic acid 1 mg/dLBilirubin 10 mg/dLHemoglobin 250 mg/dLProtein 5 to 9 g/dLTriglyceride 600 mg/dL	Very high protein > 10 mg/dL

D. Conclusion

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

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Image /page/5/Picture/2 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features the department's name in a circular arrangement around an emblem. The emblem is a stylized representation of a human figure embracing a bird, symbolizing care and protection.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 24 1998

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

K982118 Re: CARESIDE™ Total Cholesterol Regulatory Class: I Product Code: CHH Dated: May 29, 1998 June 3, 1998 Received:

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 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 The general controls provisions of the Act 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 requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ದ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) 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 In addition, FDA may publish further announcements action. 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/dsmamain.html".

Sincerely yours,
Steven Litman

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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INDICATIONS FOR USE VI.

510(k) Number:

Device Name:

CARESIDE™ Total Cholesterol

Indications for use:

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K982118

(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)

Regulation Number and Section

§ 862.1175 Cholesterol (total) test system.

(a)
Identification. A cholesterol (total) test system is a device intended to measure cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.