CARESIDE HDL-CHOLESTEROL

K981899 · Exigent Diagnostics, Inc. · LBS · Jul 14, 1998 · Clinical Chemistry

Device Facts

• Record ID: K981899
• Device Name: CARESIDE HDL-CHOLESTEROL
• Applicant: Exigent Diagnostics, Inc.
• Product Code: LBS · Clinical Chemistry
• Decision Date: Jul 14, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1475
• Device Class: Class 1

Intended Use

The CARESIDE™ HDL-Cholesterol cartridge is intended for in vitro diagnostic use in conjunction with the Exigent Diagnostics CARESIDE™ Analyzer to quantitatively measure HDL-cholesterol concentration in pre-treated serum or plasma.

Device Story

CARESIDE™ HDL-Cholesterol is a single-use disposable cartridge used with the Exigent Diagnostics CARESIDE™ Analyzer. Input: pre-treated serum or plasma specimen. Operation: user deposits sample into cartridge; analyzer heats to 37°C, spins to distribute sample onto multi-layer reagent film. Enzymatic reaction (lipoprotein lipase, cholesterol esterase, cholesterol oxidase, peroxidase) produces blue chromogen proportional to HDL-cholesterol concentration. Output: reflectance measurement at 615 nm converted to concentration via lot-specific standard curve. Used in clinical laboratory settings by professionals. Output aids clinicians in evaluating cardiovascular disease risk and managing hyperlipidemias.

Clinical Evidence

Bench testing only. Comparison study against Vitros HDLC DT slides showed correlation (r=0.97, y=0.97x-1.5 mg/dL). Precision (total CV) was 6.5% at 33 mg/dL. Mean recovery 109%. Interference testing showed no significant interference from ascorbic acid, bilirubin, hemoglobin, protein, or triglycerides at tested concentrations.

Technological Characteristics

Dry film reagent cartridge containing lipoprotein lipase, cholesterol esterase, cholesterol oxidase, peroxidase, and diarylimidazole leuco dye. Sensing principle: reflectance photometry at 615 nm. Energy source: analyzer-integrated heating and spinning mechanism. Connectivity: barcode-based lot-specific calibration. Reaction temperature: 37°C.

Indications for Use

Indicated for use in the diagnosis and treatment of patients with disorders of lipid and lipoprotein metabolism using pre-treated serum or plasma specimens.

Regulatory Classification

Identification

A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.

Predicate Devices

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

Submission Summary (Full Text)

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81899

Exigent Diagnostics, Inc. Page 11

CARESIDE™ HDL-Cholesterol Premarket Notification May 29, 1998

# 510(K) SUMMARY: CARESIDE™ HDL-CHOLESTEROL IV. SAFETY AND EFFECTIVENESS

#### I. Applicant Information

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

#### II. Device Information

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

# 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 Mav 29, 1998

## CARESIDE™ HDL-Cholesterol

HDL-Cholesterol test system Clinical chemistry panel HDL-Cholesterol test system Regulation Number: 21 CFR 862.1475 Regulatory Class I Classification Number: 75LBS None applicable

- 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.

HDL-Cholesterol in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including HDL-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™ HDL-Cholesterol test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of HDL-cholesterol on the Vitros DT 60 II.

| Name of Predicate Device: | Johnson and Johnson's (formerly Eastman Kodak,<br>Inc.) Vitros HDLC Slides for Johnson and Johnson's<br>Vitros DT 60 (formerly Eastman Kodak's DT 60 II). |
|-------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Predicate Device 510K number: | K912844/A |
| Product Code: | 75LBS |

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#### IV. Device Description

CARESIDE™ HDL-Cholesterol cartridges are used with the Exigent Diagnostics CARESIDE™ Analyzer to measure HDL-cholesterol concentration in pre-treated serum or plasma specimens. The CARESIDE™ HDL-Cholesterol cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of pre-treated serum or plasma to a dry film to initiate the measurement of HDL-cholesterol concentration. The film cartridge (patent pending) contains all reagents necessary to measure HDL-cholesterol concentration.

#### Explanation of Device Function A.

Each Exigent Diagnostics CARESIDE™ HDL-Cholesterol cartridge consists of a HDL-cholesterol-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the pre-treated 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°C, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. Ten microliters of sample remains in the metering passage. Any excess sample flows into an overflow well.

The ten microliters of pre-treated sample 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) to liberated 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 615 nanometers directly relates to the HDL-cholesterol concentration of the specimen.

Test Reaction Sequence:

LPL> CHOL + CHOL-Ester+ Protein HDL-Cholesterol -CHOL-Ester - CHE > CHOL (free) -> H2O2 + Cholesten-3one CHOL + O2 + H2O -POD Fe+2 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 HDL-cholesterol concentration.

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#### B. Test Summary

HDL-Cholesterol in blood comprises all of the cholesterol found in various lipoproteins. Cholesterol is the major component of the low-density lipoprotein fraction, and a minor component of the very low-density lipoprotein and high-density lipoprotein 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 LDLC 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. However, HDL- cholesterol concentration and cardiovascular disease risk are inversely related. Measurement of total and HDLcholesterol in serum is useful in evaluating cardiovascular disease risk.

#### V. Intended Use

- A. Intended Use
The CARESIDE™ HDL-Cholesterol cartridge is intended for in vitro diagnostic use in conjunction with the Exigent Diagnostics CARESIDE™ Analyzer to quantitatively measure HDL-cholesterol concentration in pre-treated serum or plasma.

- 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™<br>HDL-Cholesterol | Vitros HDLC DT Slides |
|-------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------|
| Intended Use | Primarily to aid in the diagnosis<br>and treatment of patients with<br>disorders of lipid and<br>lipoprotein metabolism. | Same |
| Indications | For in vitro diagnostic use.<br>For professional laboratory. | For in vitro diagnostic use |
| Measurement | Quantitative | Same |
| Method Principle | Dry film based already on the<br>U.S. market, including<br>HDL-cholesterol products<br>which utilize cholesterol<br>esterase sample treatment<br>followed by cholesterol oxidase<br>generation of hydrogen<br>peroxide from free and<br>liberated cholesterol which<br>reacts with a leuco dye in a<br>peroxidase catalyzed reaction to<br>form a blue dye. | Same |
| Specimen dilution | Not required | Same |
| Materials | Lipoprotein lipase, cholesterol<br>esterase, cholesterol oxidase,<br>peroxidase, and diarylimidazole<br>leuco dye | Cholesterol esterase,<br>cholesterol oxidase, peroxidase,<br>and diarylimidazole leuco dye |
| Detector | Reflectance (615 nm) | Reflectance (660 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 | Not known |
| Sample Type | Pre-treated serum or plasma | Same |
| 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 |

## B. Differences

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

| | CARESIDE™<br>HDL-Cholesterol | Vitros HDLC DT Slides |
|----------------------------|------------------------------|-----------------------|
| Specimen pre-<br>treatment | Required | Required |
| Reportable range | 10 to 110 mg/dL | 1 to 110 mg/dL |
| Accurate<br>pipetting | Not required | Required |
| Reagent pre-<br>warming | Not required | Required |

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、

## Comparative Performance Characteristics C.

| | CARESIDE™<br>HDL-Cholesterol | Vitros HDLC DT Slides |
|----------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------|
| Detection limit | 10 mg/dL | 1 mg/dL |
| Reportable range | 10 to 110 mg/dL | 1 to 110 mg/dL |
| Accuracy | Mean recovery 109% | Not provided |
| Precision | Total CV, 33 mg/dL, 6.5% | Total CV, 41 mg/dL, 3.2% |
| Method<br>comparison | CARESIDE™ = 0.97 (Vitros HDLC DT) - 1.5 mg/dL, r = 0.97 | |
| Linearity | Linearity by mixing and by<br>dilution yielded slope and<br>correlation coefficient within<br>acceptable limits. | Not provided |
| Interference | No significant interference<br>observed at tested<br>concentration of interferent:<br>Ascorbic Acid, 1 mg/dL<br>Bilirubin, 10 mg/dL<br>Hemoglobin, 250 mg/dL<br>Protein 5 - 9 g/dL<br>Triglycerides 1500 mg/dL | Ascorbic Acid interferes<br>(non-interfering concentration<br>undefined) |

### D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE™ HDL-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 logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The eagle is positioned to the right of a circular emblem that contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the circle's perimeter.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 1 4 1998

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

K981899 Re : CARESIDE™ HDL-Cholesterol Regulatory Class: I Product Code: LBS Dated: May 29, 1998 Received: June 1, 1998

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, qood 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 Requlations, Title 21, Parts 800 to 895. ਸੋ 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 requlation (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 [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 requlation (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" Other general information on your (21 CFR 807.97). 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 Butman

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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# VI. INDICATIONS FOR USE

510(k) Number:

Device Name:

CARESIDE™ HDL-Cholesterol

For in vitro diagnostic use with Exigent Diagnostics' CARESIDE™ Analyzer to Indications for use: measure HDL-cholesterol from pre-treated serum or plasma 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 | K981899 |

# (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)

OR

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