CARESIDE ANALYZER

K982118 · Exigent Diagnostics, Inc. · CHH · Jul 24, 1998 · Clinical Chemistry

Device Facts

• Record ID: K982118
• Device Name: CARESIDE ANALYZER
• Applicant: Exigent Diagnostics, Inc.
• Product Code: CHH · Clinical Chemistry
• Decision Date: Jul 24, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1175
• Device Class: Class 1

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.

Device Story

CARESIDE™ Total Cholesterol is a single-use disposable cartridge used with the CARESIDE™ Analyzer. It accepts anti-coagulated whole blood, plasma, or serum. The analyzer heats the cartridge to 37°C and spins it to separate blood cells from plasma/serum. Plasma is metered and dispensed onto a multi-layer reagent film. Lipoprotein lipase and surfactant dissociate cholesterol from protein; cholesterol esterase hydrolyzes esters; cholesterol oxidase produces hydrogen peroxide; peroxidase reacts with a diarylimidazole leuco dye to form a blue chromogen. A photodiode measures reflectance at 505 nm. The analyzer uses lot-specific standard curves to calculate total cholesterol concentration. Used in professional laboratory settings to assist clinicians in diagnosing and monitoring lipid metabolism disorders and cardiovascular risk. Benefits include direct whole blood testing without manual separation and rapid results.

Clinical Evidence

Method comparison study against the predicate device yielded a correlation of r = 0.94 (y = 1.04x + 23 mg/dL). Precision testing showed a total CV of 5.2% at 203 mg/dL. Accuracy demonstrated a mean recovery of 106%. Interference testing showed no significant impact from ascorbic acid (1 mg/dL), bilirubin (10 mg/dL), hemoglobin (250 mg/dL), protein (5-9 g/dL), or triglyceride (600 mg/dL).

Technological Characteristics

Dry film reagent cartridge containing lipoprotein lipase, cholesterol esterase, cholesterol oxidase, peroxidase, and diarylimidazole leuco dye. Sensing via reflectance photometry at 505 nm. Operates at 37°C. Features on-board barcode calibration. Connectivity via analyzer-integrated system. Quantitative measurement of total cholesterol in whole blood, plasma, or serum.

Indications for Use

Indicated for in vitro diagnostic use to measure total cholesterol from anti-coagulated whole blood, plasma, or serum to aid in the diagnosis and treatment of patients with disorders of lipid and lipoprotein metabolism.

Regulatory Classification

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.

Predicate Devices

• Johnson and Johnson's Vitros CHOL Slides for Vitros DT 60 (K912844/A)

Submission Summary (Full Text)

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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,<br>Inc.) Vitros CHOL Slides for Johnson and<br>Johnson's Vitros DT 60 (formerly Eastman Kodak's<br>DT 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 [e-mail] 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

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.

#### 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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i

### VI. Technological Characteristics

- Similarities A.

| | CARESIDE™ Total<br>Cholesterol | Vitros CHOL DT Slides |
|--------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Primarily to aid in the diagnosis<br>and treatment of patients with<br>disorders of lipid and<br>lipoprotein metabolism. | Used in classifying patients<br>according to risk of coronary<br>heart disease, in the diagnosis<br>and treatment of various primary<br>or secondary hyperlipidemias,<br>and to monitor changes in<br>cholesterol and levels resulting<br>from treatment. |
| Indications | For <i>in vitro</i> diagnostic use.<br>For professional laboratory use. | For <i>in vitro</i> diagnostic use |
| Measurement | Quantitative | Same |
| Method Principle | Dry film based already on the<br>U.S. market, including total<br>cholesterol products which<br>utilize enzymatic (cholesterol<br>oxidase) generation - of<br>hydrogen peroxide from free<br>and liberated cholesterol<br>which reacts with chromogens<br>in a peroxidase catalyzed<br>reaction to form a dye. | Same |
| Specimen dilution | Not required | Same |
| Materials | Lipoprotein lipase, surfactant,<br>cholesterol esterase,<br>cholesterol oxidase,<br>peroxidase, and<br>diarylimidazole leuco dye | Surfactant, cholesterol<br>esterase, cholesterol oxidase,<br>peroxidase, and leuco dye |
| Detector | Reflectance (505 nm) | Reflectance (555 nm) |
| Test time | Approx. 4 minute warm-up (on-<br>board) plus 6 minute test time. | 15 minutes slide warm-up (off-<br>line) plus 5 minutes test time. |
| Reference Method | Abell Kendall | Abell Kendall |
| Sample Type | Serum, plasma, whole blood<br>[whole blood applied sample,<br>plasma test sample] | serum, plasma |
| Specimen volume | 10 µl test volume<br>(85 ± 15 µl applied volume) | 10 µl |
| Calibration | Calibration information bar-<br>coded on each cartridge.<br>Calibration information may<br>change with each lot. | Run Vitros DT II calibrators<br>whenever a new slide lot is<br>used or when necessary. |
| Quality Control | 2 levels | Same |
| Reporting Units | mg/dL or mmol/L | Same |
| Reaction Temp. | 37 °C | Same |
| | CARESIDE™ Total<br>Cholesterol | Vitros CHOL DT Slides |
| Direct blood<br>specimen | Yes, whole blood | No, requires separation of<br>whole blood prior to sample<br>application |
| Reportable range | 50 to 450 mg/dL | 50 to 325 mg/dL |
| Accurate<br>pipetting | Not required | Required |
| Reagent pre-<br>warming | Not required | Required |

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### B. Differences

C. Comparative Performance Characteristics

| | CARESIDE™ Total<br>Cholesterol | 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 by<br>dilution yielded slope and<br>correlation coefficient within<br>acceptable limits. | Not provided |
| Interference | No significant interference observed at tested concentration of interferent:<br><br>Ascorbic acid 1 mg/dL<br>Bilirubin 10 mg/dL<br>Hemoglobin 250 mg/dL<br>Protein 5 to 9 g/dL<br>Triglyceride 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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone] 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:

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

(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)