CARESIDE ANALYZER

K981610 · Careside, Inc. · CEO · Jun 25, 1998 · Clinical Chemistry

Device Facts

• Record ID: K981610
• Device Name: CARESIDE ANALYZER
• Applicant: Careside, Inc.
• Product Code: CEO · Clinical Chemistry
• Decision Date: Jun 25, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1580
• Device Class: Class 1

Intended Use

The CARESIDE™ Phosphorus cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE™ Analyzer to quantitatively measure phosphorus concentration in anti-coagulated whole blood, plasma or serum. The CARESIDE™ Phosphorus test aids in the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance.

Device Story

CARESIDE™ Phosphorus cartridge is a single-use disposable test used with the CARESIDE™ Analyzer. Input: anti-coagulated whole blood, plasma, or serum. Operation: user loads specimen into cartridge; analyzer scans barcode, heats to 37°C, and spins to separate blood cells from plasma/serum. Plasma is automatically metered and dispensed onto a multi-layer reagent film. Principle: enzymatic reaction where purine nucleoside phosphorylase (PNP) reacts with inorganic phosphorus and xanthosine; xanthine oxidase (XOD) oxidizes xanthine to produce uric acid and hydrogen peroxide; peroxidase (POD) converts leuco dye and hydrogen peroxide to imidazole blue dye. Output: reflectance measurement at 655 nm, converted to phosphorus concentration via lot-specific standard curve. Used in professional laboratories; results assist clinicians in diagnosing/treating parathyroid, kidney, and vitamin D disorders.

Clinical Evidence

Bench testing only. Comparison study against Vitros PHOS DT slides showed high correlation (r=1.00, slope=0.99). Precision (total CV) was 4.0% at 3.5 mg/dL. Mean recovery was 97%. Interference testing showed no significant impact from ascorbic acid, bilirubin, hemoglobin, d-mannitol, or triglycerides. Reportable range 0.5 to 15 mg/dL.

Technological Characteristics

Dry film-based enzymatic assay. Reagents: xanthosine, purine nucleoside phosphorylase, diarylimidazole leuco-dye. Sensing: reflectance photometry at 655 nm. Energy: 37°C thermal control. Connectivity: barcode-based lot-specific calibration. Form factor: single-use disposable cartridge. Software: automated sample processing and reflectance-based concentration calculation.

Indications for Use

Indicated for professional laboratory use to quantitatively measure inorganic phosphorus in anti-coagulated whole blood, plasma, or serum to aid in the diagnosis and treatment of disorders including parathyroid gland disease, kidney disease, and vitamin D imbalance. Not for point-of-care or physician office laboratory use.

Regulatory Classification

Identification

A phosphorus (inorganic) test system is a device intended to measure inorganic phosphorus in serum, plasma, and urine. Measurements of phosphorus (inorganic) are used in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance.

Predicate Devices

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

Submission Summary (Full Text)

{0}------------------------------------------------

JUN 25 1998

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

#### I. Applicant Information

- Applicant Name A.
- B. Applicant/Manufacturer Address
- 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

## 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™ Phosphorus

Phosphate test system Clinical chemistry panel Phosphate test system Regulation Number: 21 CFR 862.1580 Regulatory Class I Classification Number: 75CEO 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.

Phosphorus in vitro diagnostic products, in both dry film and other formats, are already on the U.S. market. These products utilize dry film and other formats. These products utilize either direct complexation of inorganic phosphate or coupled reactions to form a chromogen. For example,

- complexation of inorganic phosphate with ammonium l. Dry film molybdate coupled to conversion to heteropolymolbydate blue dye by reaction with p-methylaminophenol sulfate.
Vitros PHOS DT 60 slides for Vitros DT 60 II example: (formerly Kodak DT 60 II), Johnson & Johnson Clinical Diagnostics, Inc.

- 2. Wet chemistry complexation of inorganic phosphate with ammonium molybdate. Ammonium molybdate complex is reduced and the resulting change in absorbance at 340/660 nanometers is proportional to the amount of inorganic phosphorous present in the sample.
- Phosphate XTS™ for Olympus AU5200, example: Olympus America, Inc.

{1}------------------------------------------------

#### Specific equivalency claim B.

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

| Name of Predicate Device: | Johnson and Johnson's (formerly Eastman Kodak,<br>Inc.) Vitros PHOS 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: | 75CEO |

#### IV. Device Description

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

#### Explanation of Device Function A.

Each CARESIDE™ Phosphorus cartridge consists of a phosphorus-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. Any excess sample flows into an overflow well.

The plasma (or serum, as applicable) is automatically dispensed onto the multi-layer reagent film. The test specimen is distributed uniformly by the spreading layer. Large molecular components, such as proteins and dye components are filtered out as the specimen passes into the reaction layer. Purine nucleoside phosphorylase (PNP) catalyzes the reaction of the inorganic phosphorus (H2PO4, HPO4") reacts with xanthosine to form xanthine and ribose-1-phosphoric acid. Xanthine oxidase (XOD) then catalyzes the oxidation of xanthine in the presence of water and oxygen to produce uric acid and hydrogen peroxide. Peroxidase (POD) then catalyzes the conversion of leuco dye and hydrogen peroxide to produce an imidazole blue dye and water. The intensity of the color as measured by the amount of reflected light at 655 nanometers directly relates to the specimen inorganic phosphorus concentration.

Test Reaction Sequence:

Xanthosine + inorganic phosphate -> Xanthine + Ribose-1-phosphoric acid

Xanthine + H2O + Oxygen -> Uric Acid + Hydrogen Peroxide

Hydrogen Peroxide + Leuco-dye -> Imidazole Blue Dye + 2 H20

As the cartridge spins, a photodiode measures film 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 phosphorus concentration.

{2}------------------------------------------------

#### B. Test Summary

Phosphate is required for generation of bony tissue and functions in the metabolism of glucose and lipids, in the maintenance of acid-base balance, and in the storage and transfer on energy from one site in the body to another. Phosphate enters the cell with glucose and is lowered after carbohydrate ingestion. For these reasons, blood phosphate levels must be controlled within narrow limits.

Determination of whole blood, serum or plasma phosphorus levels is used in the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance. Phosphorus levels are always evaluated in relation to calcium levels because there is an inverse relationship between the two. When phosphate rises rapidly and calcium drops, there is a high risk of arrhythmias and muscle twitching. Excess serum levels of one causes the kidneys to excrete the other.

Hypophosphatemia may be seen in hyperparathyroidism, Fanconi's syndrome, vitamin D deficiency in children (rickets) and adults (osteomalacia), chronic use of antacids, chronic alcoholism, malabsorption syndromes, hyperinsulinism and occasionally during hyperalimentation therapy.

Causes of hyperphosphatemia include chronic renal failure, Addison's disease, excessive ingestion of vitamin D. cytotoxic treatment of certain leukemias and lymphomas, metastatic bone tumors, hypocalcemia, diabetic ketoacidosis, and healing bone fractures.

#### V. Intended Use

- A. Intended Use
The CARESIDE™ Phosphorus cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE™ Analyzer to quantitatively measure phosphorus concentration in anti-coagulated whole blood, plasma or serum. The CARESIDE™ Phosphorus test aids in the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance.

#### B. Indications for Use

For in vitro diagnostic use with the CARESIDE™ Analyzer to quantitatively measure inorganic phosphorus from anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of various disorders. including parathyroid gland and kidney diseases, and vitamin D imbalance. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

{3}------------------------------------------------

#### VI. Technological Characteristics

- Similarities A.

| | CARESIDETM Phosphorus | Vitros PHOS DT Slides |
|-------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Primarily to aid in the diagnosis<br>and treatment of phosphate<br>regulation disorders such as<br>parathyroid gland disease,<br>kidney disease, or vitamin D<br>imbalance. | Same |
| Indications | For in vitro diagnostic use.<br>For laboratory professional use:<br>not for point of care or<br>physician office laboratory use. | For in vitro diagnostic use |
| Measurement | Quantitative | Same |
| Method Principle | Dry film based enzymatic<br>generation of hydrogen<br>peroxide from inorganic<br>phosphate. Reaction of<br>chromogen with hydrogen<br>peroxide to form blue. Dye<br>quantitated by reflectance<br>measurement after fixed time. | Dry film, complexation of<br>inorganic phosphate with<br>ammonium molybdate coupled<br>to conversion to<br>heteropolymolbydate blue dye<br>by reaction with p-<br>methylaminophenol sulfate |
| Specimen dilution | Not required | Same |
| Materials | Xanthosine purine nucleoside<br>phosphorylase,<br>Diarylimidazole leuco-dye | p-methylaminophenol sulfate,<br>ammonium molybdate |
| Detector | Reflectance (655 nm) | Reflectance (660 nm) |
| Test time | Approximately 4 minute warm-<br>up (on-board) plus 5 minute test<br>time. | 15 minutes slide warm-up (off-<br>line) plus 5 minutes test time. |
| Reference Method | Phosphomolybdate Reduced | Phosphomolybdate Reduced |
| Sample Type | Serum, plasma, anti-coagulated<br>(wb) [wb 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 |

{4}------------------------------------------------

…

#### B. Differences

| | CARESIDE™ Phosphorus | Vitros PHOS DT Slides |
|--------------------------|----------------------|--------------------------------------------------------------------------|
| Direct blood<br>specimen | Yes, whole blood | No, requires separation of<br>whole blood prior to sample<br>application |
| Reportable range | 0.5 to 15 mg/dL | 0.5 to 13 mg/dL |
| Accurate<br>pipetting | Not required | Required |
| Reagent pre-<br>warming | Not required | Required |

#### C. Comparative Performance Characteristics

| | CARESIDE™ Phosphorus | Vitros PHOS DT Slides |
|------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|
| Detection limit | 0.5 mg/dL | 0.5 mg/dL |
| Reportable range | 0.5 to 15 mg/dL | 0.5 to 13 mg/dL |
| Accuracy | Mean recovery 97% | Not provided |
| Precision | Total CV, 3.5 mg/dL, 4.0% | Total CV, 4.9 mg/dL, 3.7% |
| Method<br>comparison | CARESIDE™ = 0.99 (Vitros PHOS DT) + 0.49, r = 1.00 | |
| Linearity | Linearity by mixing and by<br>dilution yielded slope and<br>correlation coefficients within<br>acceptable limits. | Not provided |
| Interference | No significant interference<br>observed at tested<br>concentration of interferent:<br>Ascorbic Acid, 10 mg/dL<br>Bilirubin, 20 mg/dL<br>Hemoglobin, 100 mg/dL<br>d-Mannitol 800 mg/dL<br>Triglycerides 1500 mg/dL | Not provided |
| Specimen Types<br>& Anticoagulants | No clinically significant<br>difference between sodium<br>heparinized 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 | 2.2 to 4.4 mg/dL<br>Central 95% | 2.5 to 4.5 mg/dL<br>Central 95% |

#### D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDETM Phosphorus product is as safe, effective, and performs as well as or better than the legally marketed Vitros DT 60.

{5}------------------------------------------------

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name arranged in a circular fashion around a symbol. The symbol is a stylized representation of three human figures, possibly symbolizing health and well-being. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

## JUN 25 1998

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

K981610 Re: CareSide™ Phosphorus Regulatory Class: I Product Code: CEO Dated: April 27, 1998 Received: April 30, 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 aqainst 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. ਸਿ 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 Reqister. 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.

{6}------------------------------------------------

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 Sitman

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

{7}------------------------------------------------

CARESIDE, Inc. Page 5

# INDICATIONS FOR USE

K981610 510(k) Number:

Device Name:

CARESIDE™ Phosphorus

For in vitro diagnostic use with the CARESIDE™ Analyzer to quantitatively Indications for use: measure inorganic phosphorus from anti-coagulated whole blood, plasma or serum specimens to aid in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance. It is intended for professional laboratory use: not for point of care or physician office laboratory use.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K981610

## (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)