CARESIDE DIRECT BILIRUBIN

K993771 · Careside, Inc. · CIG · Dec 27, 1999 · Clinical Chemistry

Device Facts

• Record ID: K993771
• Device Name: CARESIDE DIRECT BILIRUBIN
• Applicant: Careside, Inc.
• Product Code: CIG · Clinical Chemistry
• Decision Date: Dec 27, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1110
• Device Class: Class 2

Intended Use

The CARESIDE™ Direct Bilirubin cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer™ to quantitatively measure direct bilirubin in whole blood, plasma or serum.

Device Story

CARESIDE™ Direct Bilirubin is a single-use disposable cartridge used with the CARESIDE Analyzer™ for quantitative measurement of direct bilirubin in whole blood, plasma, or serum. The user introduces the specimen into the cartridge sample well and inserts it into the analyzer. The analyzer scans the barcode, heats the cartridge to 37°C, and spins it to move the sample into channels. A measured volume (8.5 µl) is automatically dispensed onto a multi-layer reagent film. The diazo reaction (sodium nitrite and sulfanilic acid) produces a bluish dye. A photodiode measures light reflectance at 570 nm. The analyzer uses reflectance measurements and a lot-specific standard curve to calculate concentration. Results aid clinicians in diagnosing hepatic, hemolytic, and metabolic diseases. The system is designed for point-of-care use, eliminating the need for manual specimen processing, pipetting, or reagent pre-warming.

Clinical Evidence

Bench testing only. Performance evaluated via method comparison against the Boehringer Mannheim/Hitachi 902 (y = 0.99x + 0.019, r = 0.997). Precision reported as 3.1% CV at 2.2 mg/dL. Linearity established up to 16 mg/dL. Interference testing showed no significant impact from ascorbic acid (10 mg/dL), hemoglobin (300 mg/dL), total protein (9 g/dL), or triglycerides (3000 mg/dL). Mean recovery 97%.

Technological Characteristics

Dry film reagent cartridge containing sulfanilic acid and sodium nitrite. Reflectance photometer detector (570 nm). Operates at 37°C. Sample volume 8.5 µl. Calibration via lot-specific barcode on cartridge. Connectivity: Standalone analyzer. Quantitative measurement.

Indications for Use

Indicated for use in the diagnosis and treatment of patients with hepatic, hemolytic hematological, and metabolic disease, including hepatitis and gall bladder blockage.

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

• Trace America, Inc. Direct Bilirubin (K870365)

Reference Devices

• Boehringer Mannheim/Hitachi 902

Submission Summary (Full Text)

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CARESIDE, Inc. Page 10

# DEC 27 1999

### 510(K) SUMMARY: CARESIDE™ DIRECT BILIRUBIN V. 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.

#### Device Information II.

- 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 [e-mail] November 5, 1999

### CARESIDE™ Direct Bilirubin

Direct bilirubin test system Clinical chemistry panel Bilirubin (total or direct) test system Regulation Number: 21 CFR 862.1110 Regulatory Class 2 Classification Number: 75CIG 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. As well, the ability to measure direct bilirubin via reaction with sodium nitrite and sulfanilic acid is used in other commercial methods.

Direct billrubin in vitro diagnostic products are already on the U.S. market, including spectrophotometric methods from Trace America, Inc. and from Boehringer Mannheim/Hitachi 902.

- B. Specific equivalency claim
This CARESIDE™ Direct Bilirubin test is substantially equivalent in intended use and clinical performance to the currently marketed reagents for the quantitative measurement of direct bilirubin.on the Trace America Direct Bilirubin. Both are based on the diazo method; however, the Trace America method is based upon liquid reagents while the CARESIDE method is based dry reagents.

| Name of Predicate Device: | Trace America, Inc. Direct Bilirubin. |
|-------------------------------|---------------------------------------|
| Predicate Device 510K number: | K870365 |
| Product Code: | 75CIW |

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#### IV. Device Description

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

- A. Explanation of Device Function
Each CARESIDE™ Direct Bilirubin cartridge consists of a direct bilirubin-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℃, and spins the cartridge to move the sample from the Sample Well into the cartridge channels and chambers. 8.5 microliters of sample remains in the metering passage. 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 layer distributes the specimen uniformly before it passes through to the absorption layer. The color intensity of the resulting bluish dye, as measured by the amount of reflected light at 570 nanometers, directly relates to the direct bilirubin concentration of the specimen.

Test Reaction Sequence:

### Sodium Nitrite + Sulfanilic Acid ---------------------------------------------------------------------------------------------------------------------------------------------

### Conjugated Bilirubin + 4-sulfo-benzenediazonium ------------------------------------------------------------------------------------------------------------------------------

As the cartridges spin, a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time period. The instrument uses the reflectance measurements and the lot-specific standard curve to calculate direct 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 bilirubin. sometimes referred to as indirect bilirubin, which circulates non-covalently bound to albumin, (2) conjugated or direct bilirubin which is covalently bound to glucuronic acid and circulates freely, and (3) covalently protein bound. Conjugated bilirubin, excreted into the bile by the liver, imparts to 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 is commonly 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. If the total bilirubin level is elevated, the direct bilirubin level may be measured in order to discriminate between the levels of conjugated and unconjugated bilirubin.

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### V. Intended Use

#### A. Intended Use

The CARESIDE™ Direct Bilirubin cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer™ to quantitatively measure direct bilirubin in whole blood, plasma or serum.

- B. Indications for Use
This product is indicated for use in the diagnosis and treatment of patients with hepatic, hemolytic hematological, and metabolic disease, including hepatitis and gall bladder blockage.

### VI. Technological Characteristics

- A. Similarities

| | CARESIDE™ Direct<br>Bilirubin | Trace Direct Bilirubin |
|------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------|
| Intended Use | Primarily to aid in the<br>diagnosis and treatment of<br>patients with hepatic,<br>hemolytic hematological, and<br>metabolic disease, including<br>hepatitis and gall bladder<br>blockage. | Same |
| Indications | For in vitro diagnostic use.<br>For point of care use | For in vitro diagnostic use |
| Measurement | Quantitative | Same |
| Method Principle | Dry film, diazo method | Acid diazo method |
| Materials | Sulfanilic acid, sodium nitrite | Sulphanilic acid, sodium<br>nitrite |
| Detector | Reflectance photometer (570<br>nm) | Spectrophotometer (550 nm) |
| Test time | Approx. 4 minute warm-up<br>(on-board) plus approximately<br>5 minute test time. | 10 minutes |
| Sample Type | Anti-coagulated whole blood,<br>plasma, or serum plasma. | Serum |
| Specimen volume | 8.5 µl test volume<br>(90 ± 10 µl applied volume) | 10 µl |
| Calibration | Calibration information bar-<br>coded on each cartridge.<br>Calibration information may<br>change with each lot. | Calibration required. |
| Quality Control | 2 levels | Same |
| Reporting Units | mg/dL | Same |
| Reaction Temp. | 37 °C | Constant |

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### B. Differences

| | CARESIDE™ Direct<br>Bilirubin | Trace Direct Bilirubin |
|-------------------------|-------------------------------|------------------------|
| Specimen<br>Processing | Not required | Required |
| Accurate<br>pipetting | Not required | Required |
| Reagent pre-<br>warming | Not required | Required |

### C. Comparative Performance Characteristics

| | CARESIDE™ Direct<br>Bilirubin | Trace Direct Bilirubin |
|----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------|
| Detection limit | 0.2 mg/dL | Depends on instrumentation |
| Reportable range | 0.1 to 16 mg/dL | to 20 mg/dL |
| Accuracy | Mean recovery 97% | Not provided |
| Precision | Total CV, 2.2 mg/dL, 3.1% | Total CV, 1.2 mg/dL, 8.7% |
| Method<br>comparison | CARESIDETM = 0.99 (BM/Hitachi 902 Direct Bilirubin) + 0.019 mg/dL, r = 0.997 | |
| Linearity | Linear up to 16 mg/dL. | Linear up to 20 mg/dL |
| Interference | No significant interference observed at tested concentration of interferent:<br>Ascorbic Acid,......... 10 mg/dL<br>Hemoglobin,......... 300 mg/dL<br>Total Protein,......... 9 g/dL<br>Triglycerides .........3000 mg/dL | No reported interference |

### D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE™ Direct 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/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized image of three wavy lines, which are meant to represent the human form.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 2 7 1999

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

Re: K993771 Trade Name: CARESIDE™ Direct Bilirubin Regulatory Class: II Product Code: CIG Dated: November 5, 1999 Received: November 8, 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 Ouality 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 [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/dsma/dsmamain.html".

Sincerely yours,

Steven Routman

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

510(k) Number:

Device Name:

CARESIDE™ Direct Bilirubin

Indications for use:

For in vitro diagnostic use with the CARESIDE Analyzer™ to measure direct bilirubin from whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with hepatic, hemolytic hematologic, and metabolic diseases, including hepatitis and gall bladder blockage.

Sean Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K963771

(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)