CARESIDE PT

K991065 · Careside, Inc. · GJS · Jul 26, 1999 · Hematology

Device Facts

• Record ID: K991065
• Device Name: CARESIDE PT
• Applicant: Careside, Inc.
• Product Code: GJS · Hematology
• Decision Date: Jul 26, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7750
• Device Class: Class 2

Intended Use

The CARESIDE™ PT cartridge is intended for in vitro diagnostic use in conjunction with CARESIDE Analyzer™ to quantitatively measure prothrombin time in applied citrated whole blood or citrated plasma.

Device Story

CARESIDE™ PT is a single-use disposable cartridge used with the CARESIDE Analyzer™ for point-of-care prothrombin time (PT) testing. Input consists of citrated whole blood or citrated plasma. The cartridge contains dried recombinant rabbit tissue factor, calcium ions, and synthetic phospholipids. Upon insertion, the analyzer heats the cartridge to 37°C and uses centrifugal force to separate blood cells from plasma. A metered volume of plasma is mixed with reagents in a cuvette. Coagulation is monitored optically via 570nm LED scattering. An onboard timer records the time to clot formation. The device reports PT in seconds, PT ratio, and INR. Results assist clinicians in managing patients on vitamin K antagonist therapy (e.g., warfarin) or screening for coagulation factor deficiencies. The system eliminates the need for manual sample preparation and pipetting.

Clinical Evidence

Method comparison study performed against the Innovin/Electra 900C predicate. Results showed high correlation (r=0.98) with a regression equation of y = 0.98x + 0.60 sec. Precision testing reported a total CV of 4.1% at 10.2 seconds. Interference testing confirmed no significant impact from bilirubin (20 mg/dL), hemoglobin (500 mg/dL), or triglycerides (300 mg/dL). Reportable range is 9 to 75 seconds.

Technological Characteristics

Materials: Dried recombinant rabbit brain tissue factor, synthetic phospholipids, calcium. Principle: Photometric optical clot detection via 570nm LED. Energy: Electrical (analyzer-powered). Form factor: Single-use disposable cartridge. Connectivity: Standalone analyzer. Software: Embedded algorithm for optical monitoring. Reaction temperature: 37°C.

Indications for Use

Indicated for use with the CARESIDE Analyzer™ to measure prothrombin time from citrated whole blood or citrated plasma as a general screening procedure for detecting extrinsic pathway clotting deficiencies or monitoring patients on anticoagulant therapy.

Regulatory Classification

Identification

A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).

Predicate Devices

• Innovin (K974343)
• MLA Electra 900C (K884863)

Submission Summary (Full Text)

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CARESIDE, Inc. Page 10

# CARESIDE™ PT Premarket March 30 1999

### 510(K) SUMMARY: CARESIDE™ PROTHROMBIN IV. TIME SAFETY AND EFFECTIVENESS

#### I. Applicant Information

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

#### II. Device Information

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

### CARESIDE, Inc.

6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Kenneth B. Asarch, Pharm.D., Ph.D. 310-338-6789 [e-mail] March 30, 1999

### CARESIDE™ PT

Prothrombin Time test system Hematology panel Prothrombin Time test system Regulation Number: 21 CFR 864.7750 Regulatory Class 2 Classification Number: 81GJS Performance Standards

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

- A. General equivalency claim
The ability to monitor coagulation events optically is widely recognized and accepted for use in coagulation tests.

Prothrombin time in vitro diagnostic products using optical and other detection technologies are already on the U.S. market.

#### B. Specific equivalency claim

This CARESIDE™ PT test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Innovin reagent for the quantitative measurement of prothrombin time on the MLA Electra 900C.

Dade Innovin on the MLA Electra 900C. Name of Predicate Device: K974343 (Innovin)/K884863-(Electra 900C) Predicate Device 510K number: 81GJS (Innovin)/81GKP (Electra 900C) Product Code:

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#### IV. Device Description

CARESIDE™ PT cartridges are used with the CARESIDE Analyzer™ to measure prothrombin time in citrated plasma with the sample applied either as citrated whole blood or citrated plasma. The CARESIDE™ PT cartridge, a single use disposable in vitro diagnostic test cartridge, aids in specimen separation and delivers a measured volume of plasma to a cartridge cuvette to initiate the measurement of prothrombin time. The cartridge (patent pending) contains all reagents necessary to measure prothrombin time.

#### A. Explanation of Device Function

Each CARESIDE™ PT cartridge consists of a cuvette with dried recombinant rabbit tissue factor with calcium ions mounted in a plastic cartridge with a hinged lid. The user opens the pouch, introduces the citrated whole blood or citrated plasma 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. As the cartridge continues to spin. the blood cells are separated from the plasma and the cells accumulate in the separation well. Forty microliters of citrated plasma remain in the metering passage. Any excess sample flows into an overflow well. Once the analyzer completes any other tests, the sample is added to begin the coagulation test. The metered volume of sample is dispensed into the cuvette by a plunger that displaces a flexible seal that covers the Sample Well while a second plunger seals the cartridge vent. As the flexible seal is displaced, air is forced through the metering passage, forcing the sample out and into the cuvette to mix with the reagent. The cuvette is then positioned over an LED and the coagulation event is optically monitored. An onboard timer measures the coagulation time.

Test Cartridge Architecture: '' '''' '''' ''' ' ' ' ' '

Diluent > Reconstituted PT Reagent Dried PT Reagent -PT Reagent + Plasma --> Stable Clot

Photodiodes monitor the amount of scattered light transmitted by a 570 nanometer light emitting diode to optically monitor the progress of the clot formation. The time at which a clot is detected is reported as the prothrombin time. The results are also reported as the prothrombin ratio (% PT/mean normal PT reference interval) or as the INR (International Normalized Ratio).

- B. Test Summary
The prothrombin time is a screening test for the extrinsic and common coagulation pathway that was originally described by Quick in 1935. The prothrombin time test is sensitive to the coagulation factor abnormalities and to factor inhibitors affecting coagulation II, V, VII, and X, plus proteins C and S. Each component of the prothrombin reagents (calcium ions, tissue factor, and phospholipids) is required to initiate clotting. Differences among PT reagent preparations affect their sensitivity to reductions in coagulation factors. Accordingly, PT reagents are characterized by an international sensitivity index (ISI).

Various methods have been used historically to report and interpret prothrombin time results in order to account for differences in thromboplastin sensitivity. For example, prothrombin time results have been expressed as the ratio between a patient's prothrombin time and the mean normal prothrombin time reference interval.

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Prothrombin time results are also reported as the International Normalized Ratio as recommended by the International Committee on Thrombosis and Hemostasis and the International Council for Standardization in Hematology. The INR is the equivalent PT ratio that would be obtained if the appropriate International Reference Preparation (ISI = 1.0. World Health Organization) were used as the source of thromboplastin in the performance of the prothrombin time.

The time required for the formation of a fibrin clot provides information regarding the presence and activity of coagulation factors I (fibrinogen), II, V, VII, and X. The factors II. VII. and X are dependent upon the co-factor vitamin K for activation by posttranslational carboxylation. The prothrombin time may be increased in patients with hepatic disease, vitamin K deficiency or in patients on vitamin K antagonist anticoagulant therapy such as warfarin. Likewise, significant alterations in the intake of vitamin K will affect the prothrombin time.

### EXTRINSIC COAGULATION PATHWAY

Tissue Factor > Factor VIIa Factor VII

VIIa, Ca" Factor Xa Factor X -

Xa Va > Thrombin Prothrombin -

Thrombin > Fibrin monomers Fibrinogen

_xilla_ca_2___________________________________________________________________________________________________________________________________________________________________ Fibrin

--

Ca*2 > Crosslinked fibrin (Stable clot) Fibrin polymers -

#### V. Intended Use

- A. Intended Use
The CARESIDE™ PT cartridge is intended for in vitro diagnostic use in conjunction with CARESIDE Analyzer™ to quantitatively measure prothrombin time in applied citrated whole blood or citrated plasma.

#### B. Indications for Use ~

To be used with the CARESIDE Analyzer™ to measure PT from applied citrated whole blood or citrated plasma specimens as a general screening procedure for the detection of possible clotting deficiencies in the extrinsic pathway or to monitor patients receiving anticoagulant therapy.

- - 10 - 10 8 1. - . .

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#### VI. Technological Characteristics

- Similarities A.

| | CARESIDE™ PT | Innovin on Electra 900C |
|--------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------|
| Intended Use | A general screen for the detection of clotting deficiencies in the extrinsic pathway or to monitor patients receiving anticoagulant therapy. | For use in prothrombin time determinations and prothrombin time-based assays. |
| Indications | For <i>in vitro</i> diagnostic use.<br>For professional laboratory use. | Same |
| Measurement | Quantitative | Same |
| Method Principle | Classical one-stage prothrombin time (optical clot detection in the presence of recombinant rabbit tissue factor and synthetic phospholipids.) | Same, except type recombinant tissue factor is human in lieu of rabbit |
| Clot Detection Algorithm | Peak of second derivative of optical time course | Peak of second derivative of optical time course |
| Specimen dilution | Not required | Same |
| Materials | Dried recombinant rabbit brain tissue factor, synthetic phospholipids, and calcium. | Dried recombinant human tissue factor and phospholipids (thromboplastin) with calcium |
| Detection principle | Photometric | Same |
| Test time | Approx. 4 minute warm-up (on-board) plus clot time. | Approx. 1 minute warm-up (on-board) plus clot time |
| Sample Type | Applied citrated whole blood or citrated plasma | Citrated plasma |
| Specimen volume | 40 µl test volume<br>(300 ± 50 µl applied volume whole blood or plasma) | 100 µl (plasma) |
| Quality Control | 2 levels | Same |
| Reporting Units | Sec, PT Ratio, INR | Sec and (PT Ratio or INR) |
| Reaction Temp. | 37 °C | 37.6 °C |

#### B. Differences

| | CARESIDE™ PT | Innovin on Electra 900C |
|--------------------------|------------------|--------------------------------------------------------------------------|
| Direct blood<br>specimen | Yes, whole blood | No, requires separation of<br>whole blood prior to sample<br>application |
| Accurate<br>pipetting | Not required | Required |
| Reagent pre-<br>warming | On-board | On-board |

·

.

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i

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#### C. Comparative Performance Characteristics

| | CARESIDE™ PT | Innovin on Electra 900C |
|--------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|
| Detection limit | 9 sec | 7 sec |
| Reportable range | 9 to 75 sec | 7 to 106 sec |
| Precision | Total CV, 10.2 sec, 4.1% | Not available |
| Accuracy via<br>Method<br>comparison | CARESIDE™ = 0.98 (Innovin on Electra 900C ) + 0.60 sec,<br>r = 0.98 | |
| Interference | No significant interference observed at tested concentration of interferent:<br>Bilirubin 20 mg/dL<br>Hemoglobin 500 mg/dL<br>Triglyceride 300 mg/dL | No data provided. |

#### D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE™ PT 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/0 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. In the center of the seal is a stylized image of an eagle with its wings spread, which is a common symbol of the United States. The eagle is depicted in a simple, graphic style, with bold lines and a minimalist design.

### DEPARTMENT OF HEALTH & HUMAN SERVICES

JUL 26 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Kenneth B. Asarch, Pharm. D., Ph.D. Vice President, Quality Systems and Regulatory Affairs Careside Inc. 6100 Bristol Parkway Culver City, California 90230

Re: K991065 Trade Name: CARESIDE™ PT Regulatory Class: II Product Code: GJS Dated: June 17, 1999 Received: June 21, 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 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 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/cdrl/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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:

K991065

CARESIDE™ PT

Indications for use:

For in vitro diagnostic use with the CARESIDE Analyzer™ to measure prothrombin time from applied citrated whole blood or citrated plasma as a general screening procedure for the detection of possible clotting deficiencies in the extrinsic pathway or to monitor patients receiving anticoagulant therapy.

### (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Lita E. Madson

Prescription Use M (Per 21 CFR 801.109)

OR

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