CARESIDE TOTAL BILIRUBIN

K981588 · Careside, Inc. · CIG · Jun 23, 1998 · Clinical Chemistry

Device Facts

• Record ID: K981588
• Device Name: CARESIDE TOTAL BILIRUBIN
• Applicant: Careside, Inc.
• Product Code: CIG · Clinical Chemistry
• Decision Date: Jun 23, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1110
• Device Class: Class 2

Intended Use

The CARESIDE™ Total Bilirubin cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE™ Analyzer to quantitatively measure the total concentration of bilirubin in anti-coagulated whole blood, plasma or serum. The CARESIDE™ Total Bilirubin test aids in the diagnosis and treatment of patients with liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder blockage.

Device Story

CARESIDE™ Total Bilirubin cartridge is a single-use disposable in vitro diagnostic test used with the CARESIDE™ Analyzer. Input: anti-coagulated whole blood, plasma, or serum. Operation: user deposits sample into cartridge; analyzer scans barcode, heats to 37°C, and spins to separate blood cells from plasma/serum. Plasma is automatically metered onto a multi-layer reagent film containing dyphilline and 2,4-dichlorobenzene diazonium salt. Bilirubin reacts to form a red azo dye. Output: reflectance measured at 505 nm by photodiodes; analyzer calculates total bilirubin concentration using lot-specific standard curve. Used in professional laboratories; results assist clinicians in diagnosing liver, hemolytic, and metabolic disorders. Benefits include rapid, automated quantitative measurement from whole blood without manual sample preparation.

Clinical Evidence

Bench testing only. Performance evaluated via method comparison against Vitros TBIL DT slides (r=0.96; CARESIDE = 1.04 * Vitros + 1.0 mg/dL). Precision reported as total CV of 12% at 1.1 mg/dL. Accuracy demonstrated by 96% mean recovery. Interference testing showed no significant impact from ascorbic acid (20 mg/dL), hemoglobin (100 mg/dL), or protein (9 mg/dL). Reportable range 0.2–24 mg/dL.

Technological Characteristics

Dry film-based diazo reaction. Reagents: dyphilline, 2,4-dichlorobenzene diazonium salt. Detection: reflectance at 505 nm. Sample volume: 10 μL. Reaction temperature: 37°C. Calibration: lot-specific barcoded information on cartridge. Connectivity: barcode scanning. Form factor: single-use disposable cartridge.

Indications for Use

Indicated for professional laboratory use to quantitatively measure total bilirubin in anti-coagulated whole blood, plasma, or serum to aid in diagnosis/treatment of liver, hemolytic, hematological, and metabolic disorders (e.g., hepatitis, gall bladder blockage). Not for point-of-care or physician office laboratory use.

Regulatory Classification

Identification

A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Predicate Devices

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

Submission Summary (Full Text)

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CARESIDE, Inc. Page 6

CARESIDE™ Total Bilirubin (K981588) CO Premarket Notification Addendum June 11, 1998

JUN 23 1998

# Attachment 3

(Revised 510(k) Summary)

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### CARESIDE™ TOTAL BILIRUBIN 510(K) SUMMARY: SAFETY AND EFFECTIVENESS

#### I. Applicant Information

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

#### 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 @ worldnet.att.net June 11, 1998

### CARESIDE™ Total Bilirubin

Total Bilirubin test system Clinical chemistry panel Total Bilirubin test system Regulation Number: 21 CFR 862.1110 Regulatory Class II Classification Number: 75CIG None applicable

- D. Special controls and performance standards
#### III. Substantial Equivalence Claim

- 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.

Total bilirubin in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market, including total bilirubin products which utilize diphylline to dissociate conjugated bilirubin and diazonium salts to combine with bilirubin to form an azo dye.

#### B. Specific equivalency claim

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

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

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#### IV. Device Description

CARESIDE™ Total Bilirubin cartridges are used with the CARESIDE™ Analyzer to quantitatively measure the total concentration of bilirubin in anti-coagulated whole blood, plasma or serum specimens. The CARESIDE™ Total Bilirubin 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 the total concentration of bilirubin. The film cartridge (patent pending) contains all reagents necessary to measure the total concentration of bilirubin.

#### Explanation of Device Function A.

Each CARESIDE™ Total Bilirubin cartridge consists of a bilirubin-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the anticoagulated whole blood, serum, or plasma specimen into the cartridge sample deposition 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℃, 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. Excess sample flows into an overflow well.

The plasma (or serum, as applicable) is automatically dispensed onto the multi-layer reagent film. The spreading and reaction layer distributes the sample evenly on the film and dissociates the unconjugated bilirubin from albumin. Conjugated and unconjugated bilirubin reacts with 2,4-dichlorobenzene diazonium salt to form a red azo dye. The color intensity, as measured by the amount of light reflected at 505 nanometers, directly relates to the total concentration of bilirubin in the specimen.

Test Reaction Sequence:

Image /page/2/Figure/9 description: This image shows a reaction scheme. Direct bilirubin and indirect bilirubin react with 2,4-dichlorobenzen diazonium salt in a reaction of diazo. This reaction produces a red azo dye. Dyphilline is also present in the reaction.

As the cartridge spins, a photodiodes measures reflectance of light emitted from 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 the total bilirubin concentration.

#### B. Test Summary

Bilirubin is formed by the reticuloendothelial system as a by-product of the breakdown of hemoglobin. Bilirubin circulates in multiple forms: (1) unconjugated, also known as indirect, bilirubin which circulates non-covalently bound to albumin, (2) direct or conjugated bilirubin that is covalently bound to glucuronic acid, and (3) covalently protein bonded bilirubin. Conjugated bilirubin, excreted into the bile by the liver, gives the bile its major pigmentation.

In healthy individuals, a small amount of bilirubin is found in the serum. An increase in unconjugated bilirubin is more frequently associated with increased destruction of red blood cells (hemolysis); and an increase in conjugated bilirubin is more likely seen in dysfunction of the liver or bile ducts.

Total bilirubin may be measured as part of a routine examination. A normal level of total bilirubin rules out any significant impairment of the excretory function of the liver or excessive hemolysis of red blood cells. Only when the total bilirubin levels are elevated is it indicated to determine the direct bilirubin level in order to discriminate between the

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relative levels of conjugated and unconjugated bilirubin levels above 2.5 mg/dL are associated with jaundice.

#### v. Intended Use

- A. Intended Use
The CARESIDE™ Total Bilirubin cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE™ Analyzer to quantitatively measure the total concentration of bilirubin in anti-coagulated whole blood, plasma or serum. The CARESIDE™ Total Bilirubin test aids in the diagnosis and treatment of patients with liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder blockage.

#### Indications for Use B.

This product is for in vitro diagnostic use with the CARESIDE™M Analyzer to quantitatively measure total bilirubin concentration in anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of patients with liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder blockage. It is intended for professional laboratory use: not for point of care use or physician office laboratory use.

#### VI. Technological Characteristics

- A. Similarities

| | CARESIDE™ Total Bilirubin | Vitros TBIL DT Slides |
|-------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|
| Intended Use | Primarily to aid in the diagnosis and<br>treatment of patients with liver,<br>hemolytic, hematological and<br>metabolic disorders. | Same |
| Indications | For in vitro diagnostic use.<br>For professional laboratory use: not<br>for point of care or physician office<br>laboratory use. | For in vitro diagnostic use |
| Measurement | Quantitative | Same |
| Method Principle | Dry film based diazo reaction. | Same |
| Specimen dilution | Not required | Same |
| Materials | Dyphilline<br>2,4-dichlorobenzene diazonium salt | Dyphilline<br>[4-(N-carboxymethylsulfamyl)- benzene diazonium<br>hexafluorophosphate] |
| Detector | Reflectance (505 nm) | Reflectance (555 nm) |
| Test time | Approximately 4 minute warm-up<br>(on-board) plus 5 minute test time. | 15 minutes slide warm-up (off-line)<br>plus 5 minutes test time. |
| Reference Method | Diazotized sulfanilic acid reaction in<br>presence of caffeine-benzoate-acetate<br>(candidate ref. method for serum total<br>bilirubin determination) | Unknown |
| Sample Type | Serum, plasma, anti-coagulated<br>whole blood (wb) [wb applied<br>sample, plasma test sample] | serum, plasma |
| Specimen volume | 10 μl test volume<br>(85 ± 15 μl applied volume) | 10 μl |
| Calibration | Calibration information bar-coded on<br>each cartridge. Calibration<br>information may change with each<br>lot. | Run Vitros DT II calibrators<br>whenever a new slide lot is used or<br>when necessary. |
| Quality Control | 2 levels | Same |
| Reporting Units | mg/dL or mmol/L | Same |
| Reaction Temp. | 37 °C | Same |

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#### B. Differences

| | CARESIDE™ Total<br>Bilirubin | Vitros TBIL DT Slides |
|--------------------------|------------------------------|--------------------------------------------------------------------------|
| Direct blood<br>specimen | Yes, whole blood | No, requires separation of<br>whole blood prior to sample<br>application |
| Reportable range | 0.2 to 24 mg/dL | 0.1 to 20 mg/dL |
| Accurate<br>pipetting | Not required | Required |
| Reagent pre-<br>warming | Not required | Required |

C. Comparative Performance Characteristics

| | CARESIDE™ Total<br>Bilirubin | Vitros TBIL DT Slides |
|------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|
| Detection limit | 0.2 mg/dL | Not provided |
| Reportable range | 0.2 to 24 mg/dL | 0.1 to 20 mg/dL |
| Accuracy | Mean recovery 96% | Not provided |
| Precision | Total CV, 1.1 mg/dL, 12% | Total CV, 1.2 mg/dL, 6% |
| Method comparison | CARESIDE™ = 1.04 (Vitros TBIL DT) + 1.0 mg/dL, | r = 0.96 |
| Linearity | Linearity by mixing and by<br>dilution yielded results within<br>acceptable limits | Not provided |
| Interference | No significant interference<br>observed at tested<br>concentration of interferent:<br>Ascorbic Acid, 20 mg/dL<br>Hemoglobin, 100 mg/dL<br>Protein, 9 mg/dL | Not provided |
| Specimen Types<br>& Anticoagulants | No clinically significant<br>difference between anti-<br>coagulated whole blood,<br>serum, sodium heparin<br>plasma, and EDTA plasma. | No clinically significant<br>difference between serum,<br>heparin plasma, or EDTA<br>plasma. Whole blood is<br>unsuitable. |
| Expected Values | 0.2 to 1.3 mg/dL<br>Central 95% interval | 0.1-1.4 mg/dL (male)<br>Central 95% interval |

#### D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE™ Total Bilirubin 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/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the logo is an abstract symbol that resembles a stylized caduceus or a representation of human figures.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 23 1998

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

K981588 Re : CareSide™ Total Bilirubin Regulatory Class: II CIG Product Code: Dated: April 30, 1998 Received: May 4, 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, 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 Requlations, 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 Requlation (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 requlations.

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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 Bitman

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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CARESIDE, Inc. Page 5

### INDICATIONS FOR USE VI.

510(k) Number: K981588

CARESIDE™ Total Bilirbuin Device Name:

with the diagnostic use for in vitro product is Indications for use: This CARESIDE™ Analyzer to quantitatively measure total bilirubin concentration in anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of patients with liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder blockage. It is intended for professional laboratory use: not for point of care use or physician office laboratory use.

Division Sign-Off)
Vivision of Clinical Laboratory Devices
(k) Number k981588

## (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)