INRATIO2 PI/NR MONITORING SYSTEM; INRATIO PT/INR TEST STRIP

K110212 · Alere San Diego, Inc (Formally Biosite Incorporate · GJS · May 1, 2012 · Hematology

Device Facts

• Record ID: K110212
• Device Name: INRATIO2 PI/NR MONITORING SYSTEM; INRATIO PT/INR TEST STRIP
• Applicant: Alere San Diego, Inc (Formally Biosite Incorporate
• Product Code: GJS · Hematology
• Decision Date: May 1, 2012
• Decision: SESU
• Submission Type: Traditional
• Regulation: 21 CFR 864.7750
• Device Class: Class 2

Intended Use

Alere INRatio®2 PT/INR Monitoring System (Professional Use): The Alere INRatio®2 PT/INR Monitoring System (Professional Use), consisting of the INRatio®2 Monitor and INRatio®2 PT/INR test strip, is used for quantitative determination of international normalized ratio (INR) in fresh capillary whole blood to monitor the effect of warfarin on clotting time by health care professionals. The Alere INRatio®2 PT/INR Monitoring System (Professional Use) is intended for use outside of the body (in vitro diagnostic use). The Alere INRatio®2 PT/INR Monitoring System (Professional Use) is not intended to be used for screening purposes. Limitations: The Alere INRatio®2 PT/INR Monitoring System (Professional Use) is not intended for use in patients who are transitioning from heparin treatment to warfarin therapy. Alere INRatio®2 PT/INR Home Monitoring System: The Alere INRatio®2 PT/INR Home Monitoring System, consisting of the INRatio®2 Home Monitor and INRatio®2 PT/INR test strip, is used for quantitative determination of international normalized ratio (INR) in fresh capillary whole blood to monitor the effect of warfarin therapy on clotting time by properly selected suitably trained users (by prescription for home use or other order of a treating physician). Patients must be stabilized (>6 weeks) on warfarin therapy. The Alere INRatio®2 PT/INR Home Monitoring System is intended for use outside of the body (in vitro diagnostic use). The Alere INRatio®2 PT/INR Home Monitoring System is not intended to be used for screening purposes. Limitations: The Alere INRatio®2 PT/INR Home Monitoring System is not intended for use in patients who are transitioning from heparin treatment to warfarin therapy.

Device Story

System performs modified one-stage Prothrombin Time (PT) test using recombinant human thromboplastin (rhTP). Input: fresh capillary whole blood sample applied to disposable test strip. Operation: monitor heats strip to reaction temperature; detects clot formation via change in electrical impedance across 3 electrode pairs; calculates INR from measured PT. Output: INR value displayed on monitor screen. Used in professional clinical settings or home environments by trained patients. Healthcare providers use output to adjust warfarin dosage. Benefits: enables convenient, point-of-care monitoring of anticoagulant therapy, facilitating patient management.

Clinical Evidence

Multi-center clinical studies (4 sites) evaluated accuracy and precision for professional and home-use settings. Professional study (n=288) compared fingerstick INR to venous plasma reference (Sysmex CA-560); Deming regression: y=1.05x-0.05, r=0.91. Home-use study (n=105) compared patient-performed fingerstick INR to central lab reference; Deming regression: y=1.07x-0.19, r=0.93. Precision (CV%) for professional users was 8.16% (normal) and 6.16% (therapeutic); for home users, 5.68% (therapeutic). Bench testing confirmed linearity (0.7-7.5 INR), hematocrit range (25-53%), and lack of interference from common substances/drugs.

Technological Characteristics

System uses electrical impedance sensing with 3 electrode pairs. Recombinant human thromboplastin reagent. Dimensions/form factor: handheld monitor with disposable test strips. Connectivity: standalone. Sterilization: N/A. Software: embedded firmware with Prothrombin Time Finding Algorithm (PTFA). Calibration: factory-calibrated monitor; strip-specific coefficients per WHO 889:1999.

Indications for Use

Indicated for quantitative determination of INR in fresh capillary whole blood to monitor warfarin therapy. Professional use or home use by trained patients stabilized on warfarin (>6 weeks). Not for screening. Contraindicated for patients transitioning from heparin to warfarin.

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

• INRatio® PT Monitoring System (k020679, k021923)
• INRatio®2 PT/INR Monitoring System (k072727)
• INRatio® PT/INR Test Strip (k092987)

Submission Summary (Full Text)

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

# 510(K) SUMMARY

# MAY - 1 2012

This 510(k) summary is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: k110212

A. Submitter: Alere San Diego, Inc 9975 Summers Ridge Road San Diego, CA 92121 USA

- Contact: Telephone: Fax: Email:
Mara Caler Regulatory Affairs 858.805.2083 858.805.7100 [e-mail]

April 12, 2012 Date Prepared:

- B. Device Names:
Classification name Common/usual name Proprietary name

Prothrombin Time Test Prothrombin Time Test

Alere INRatio 2 PT/INR Monitoring System (Professional Use) Alere INRatio®2 PT/INR Home Monitoring System Alere INRatio®2 PT/INR Test Strip

- INRatio® PT Monitoring System, K020679 C. Predicate Devices: INRatio® PT Monitoring System, K021923 INRatio® 2 PT/INR Monitoring System, K072727 INRatio® PT/INR Test Strip, K092987
#### D. Device Description:

The INRatio2 PT/INR Monitoring Systems (Professional and Home) perform a modified version of the one-stage Prothrombin Time test, using commercially available recombinant human thromboplastin (rhTP) reagent. The clot formed in the Prothrombin Time (PT) reaction is detected by a change in the electrical impedance of the sample during the coagulation process. The system consists of a monitor and disposable test strips. The monitor heats the test strip to the proper reaction temperature; a measure clot impedance and provides a result on a screen (user interface). The clotting reaction occurs on the Test Strip after the blood sample is applied. An International Normalized Ratio (INR) value is calculated from measured Prothrombin Time and the INR is displayed on the monitor to the user/patient.

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

# E. Intended Uses:

Alere INRatio 2 PT/INR Monitoring System (Professional Use): The Alere INRatio 2 PT/INR Monitoring System (Professional Use), consisting of the INRatio®2 Monitor and INRatio®2 PT/INR test strip, is used for quantitative determination of international normalized ratio (INR) in fresh capillary whole blood to monitor the effect of warfarin on clotting time by health care professionals. The Alere INRatio 2 PT/INR Monitoring System (Professional Use) is intended for use outside of the body (in vitro diagnostic use). The Alere INRatio 2 PT/INR Monitoring System (Professional Use) is not intended to be used for screening purposes.

Limitations: The Alere INRatio 2 PT/INR Monitoring System (Professional Use) is not intended for use in patients who are transitioning from heparin treatment to warfarin therapy.

Alere INRatio®2 PT/INR Home Monitoring System: The Alere INRatio®2 PT/INR Home Monitoring System, consisting of the INRation2 Home Monitor and INRatio®2 PT/NR test strip, is used for quantitative determination of international normalized ratio (INR) in fresh capillary whole blood to monitor the effect of warfarin therapy on clotting time by properly selected suitably trained users (by prescription for home use or other order of a treating physician). Patients must be stabilized (>6 weeks) on warfarin therapy. The The Alere INRatio 2 PT/INR Home Monitoring System is intended for use outside of the body (in vitro diagnostic use). The Alere INRatio®2 PT/INR Home Monitoring System is not intended to be used for screening purposes.

Limitations: The Alere INRatio®2 PT/INR Home Monitoring System is not intended for use in patients who are transitioning from heparin treatment to warfarin therapy.

### Comparison with the Predicate Devices: F.

The intended use (assay type and intended users) and the operation of the INRatio2 PT/INR Monitoring Systems (Professional and Home) and associated accessories and reagents have not changed. The INRatio2PT/INR Monitoring Systems (Professional or Home) are intended to measure International Normalized Ratio (INR) from fresh, capillary whole blood samples by both healthcare professional users and lay (trained patient users. The systems are not intended for screening. Based on the data and information presented here, the INRatio2 PT/INR Monitoring Systems (Professional or Home), when used with the User Guide by both Healthcare Professionals and Trained Patients, performed equivalently to the INRatio2 PT/INR Monitoring System K072727).

Furthermore, the INRatio2 PT/INR Test Strip is substantially equivalent to the previously cleared INRatio PT/INR Test Strip (K092987) currently marketed and distributed by Alere

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

North America. The current and modified INRatio2 PT/INR Test Strips both catalyze a clotting reaction in fresh, finger stick capillary whole blood samples The INRatio2 PT/INR Test Strips have a lower blood volume requirement. The INRatio2 PT/INR Test Strips can be used with the INRatio2 PT/INR monitors (Professional or Home). .

The INRatio®2 PT/INR Monitoring Systems (Professional Use and Home-use) are not intended for use in the quantitative determination of the international normalized ratio (INR) to monitor the effect of oral anticoagulant (warfarin) therapy on clotting time on patients who are transitioning from heparin treatment to warfarin therapy.

# Nonclinical Data:

Performance testing verified that the modified INRatio2 PT/INR Test Strips have equivalent or better performance compared to the previously cleared INRatio PT/INR Test Strips with respect to precision, accuracy, and potential interferents when used with the INRatio2 PT/INR Monitoring Systems (Professional or Home). The performance claims currently in the labeling have been changed to reflect the performance of the INRatio2 PT/INR Test Strips.

# G. Clinical Data

Clinical testing validated that the INRatio2 PT/INR Monitoring Systems (Professional and Home) utilizing the INRatio2 PT/INR Test Strips, when used by trained patient users or healthcare professionals, performed with acceptable accuracy compared to the reference method (the Sysmex CA-560 Anticoagulation Analyzer). Both user populations generated INR values with the INRatio2 PT/INR Monitoring Systems (Professional or Home), utilizing the INRatio2 PT/INR Test Strip, that were deemed accurate relative to the reference method. per ISO 17593:2007.

# H. Conclusions Drawn from Testing

Based on the data and information presented here, the INRatio2 PT/INR Monitoring Systems (Professional and Home) , when used with the INRatio2 PT/INR Test Strip, are substantially equivalent to the INRatio (K020679; K021923) and INRatio2 (K072727) PT/INR Monitoring System and the INRatio PT/INR Test Strip (K092987) currently manufactured and distributed by Alere. The INRatio2 PT/INR Monitoring Systems (Professional and Home) have been verified and validated for ease of use by both Healthcare Professionals and Trained Patients in multiple healthcare professional and patient self-test user clinical trials (K020679: K021923, K072727 and this submission).

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

| Alere | Traditional 510(K) Application | INRatio2PT/INR Monitoring System | | | |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------|--|
| Comparison Table of the INRatio/INRatio® 2 Monitoring PT/INR Test Systems utilizing the Current INRatio® PT/INR Test Strip vs.<br>the Alere™ INRatio®2 PT/INR Test Strip | | | | | |
| Parameter | Current INRatio/INRatio2<br>PT/INR Monitoring Test Systems<br>utilizing current INRatio PT/INR<br>Test Strip<br>(K020679, K021923, K072727 and<br>K092987) | INRatio2 PT/INR Monitoring<br>System utilizing modified<br>Alere™ INRatio 2 PT/INR Test<br>Strip<br>(This submission) | Alere INRatio®2 PT/INR<br>Monitoring System ( <i>Professional<br/>Use</i> ): The Alere INRatio®2<br>PT/INR Monitoring System<br>( <i>Professional Use</i> ), consisting of<br>the INRatio®2 Monitor and<br>INRatio®2 PT/INR test strip, is | Comment/Explanation of<br>difference | |
| Intended Use | The Alere INRatio/INRatio2<br>PT/INR Monitoring System is used<br>for the quantitative measurement of<br>Prothrombin Time (PT) in fresh,<br>capillary whole blood. The<br>INRatio/INRatio2 PT/INR<br>Monitoring system is intended for<br>use outside the body (in vitro<br>diagnostic use). The<br>INRatio/INRatio2 PT/INR<br>Monitoring System is intended for<br>professional and home use by<br>people taking warfarin and other<br>oral anticoagulant (blood thinning)<br>therapy who need to monitor the<br>clotting time of their blood. The<br>INRatio/INRatio2 PT/INR<br>Monitoring System is not intended<br>to be used for screening purposes. | Alere INRatio®2 PT/INR<br>Monitoring System ( <i>Professional<br/>Use</i> ): The Alere INRatio®2<br>PT/INR Monitoring System<br>( <i>Professional Use</i> ), consisting of<br>the INRatio®2 Monitor and<br>INRatio®2 PT/INR test strip, is<br>used for quantitative<br>determination of international<br>normalized ratio (INR) in fresh<br>capillary whole blood to monitor<br>the effect of warfarin on clotting<br>time by health care professionals.<br>The Alere INRatio 2 PT/INR<br>Monitoring System ( <i>Professional<br/>Use</i> ) is intended for use outside of<br>the body (in vitro diagnostic use).<br>The Alere INRatio®2 PT/INR<br>Monitoring System ( <i>Professional<br/>Use</i> ) is not intended to be used<br>for screening purposes. | Limitations: The Alere INRatio®2<br>PT/INR Monitoring System<br>( <i>Professional Use</i> ) is not intended<br>for use in patients who are<br>transitioning from heparin<br>treatment to warfarin therapy. | Addition of patient self<br>testing to the intended use of<br>INRatio2 PT/INR Monitoring<br>System | |

:

:

·

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

| | Traditional 510(K) Application | INRatio2PT/INR Monitoring System | | |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|
| | Comparison Table of the INRatio/INRatio®2 Monitoring PT/INR Test Systems utilizing the Current INRatio® PT/INR Test Strip vs.<br>the Alere™ INRatio®2 PT/INR Test Strip | | | |
| Parameter | Current INRatio/INRatio2<br>PT/INR Monitoring Test Systems<br>utilizing current INRatio PT/INR<br>Test Strip<br>(K020679, K021923, K072727 and<br>K092987) | INRatio2 PT/INR Monitoring<br>System utilizing modified<br>Alere™ INRatio®2 PT/INR Test<br>Strip<br>(This submission) | Comment/Explanation of<br>difference | |
| Alere INRatio®2 PT/INR Home<br>Monitoring System: The Alere<br>INRatio®2 PT/INR Home<br>Monitoring System, consisting of<br>the INRatio®2 Home Monitor and<br>INRatio®2 PT/INR test strip, is<br>used for quantitative<br>determination of international<br>normalized ratio (INR) in fresh<br>capillary whole blood to monitor<br>the effect of warfarin therapy on<br>clotting time by properly selected<br>suitably trained users (by<br>prescription for home use or other<br>order of a treating physician).<br>Patients must be stabilized (>6<br>weeks) on warfarin therapy. The<br>The Alere INRatio®2 PT/INR<br>Home Monitoring System is<br>intended for use outside of the<br>body (in vitro diagnostic use).<br>The Alere INRatio®2 PT/INR<br>Home Monitoring System is not<br>intended to be used for screening | | | | |
| Alere | Traditional 510(K) Application | INRatio2PT/INR Monitoring System | | |
| | Comparison Table of the INRatio/INRatio®2 Monitoring PT/INR Test Systems utilizing the Current INRatio® PT/INR Test Strip vs.<br>the Alere™ INRatio®2 PT/INR Test Strip | | | |
| Parameter | Current INRatio/INRatio2<br>PT/INR Monitoring Test Systems<br>utilizing current INRatio PT/INR<br>Test Strip<br>(K020679, K021923, K072727 and<br>K092987) | INRatio2 PT/INR Monitoring<br>System utilizing modified<br>Alere™ INRatio®2 PT/INR Test<br>Strip<br>(This submission) | Comment/Explanation of<br>difference | |
| Intended Users | Healthcare professionals and trained<br>patients on the prescription or other<br>order of a treating physician. | same | Limitations: The Alere INRatio®2<br>PT/INR Home Monitoring<br>System is not intended for use in<br>patients who are transitioning<br>from heparin treatment to<br>warfarin therapy. | |
| Intended Sample | capillary whole blood | Capillary whole blood | Addition of patient self testing<br>to the intended use of the<br>Alere INRatio2 PT/INR<br>Monitoring System | |
| Test Strip Monitor<br>Compatibility | INRatio (professional and patient<br>self test) and INRatio2<br>(professional) monitors | INRatio2 (professional and patient<br>self-test) | Addition of patient self tesing<br>to the intended use of Alere<br>INRatio2 PT/INR Monitoring<br>System | |
| Mode of Measurement | Electrical Impedance | same | No change | |
| Number of Reaction<br>Sites (and pairs of<br>electrodes) | 3 (3 Pairs of Electrodes) | same | No change | |
| Test Strip Layout | "Trident" | same | No change | |
| Quality Control | Integrated in Test Strip | same | No change | |
| | HIGH QC (therapeutic range) | same | No change | |
| | LOW QC (normal range) | same | No change | |
| Test Strip Graphics | Name of product | same | Name of product and thumbprint<br>Thumbprint and directional | |
| Alere | Traditional 510(K) Application | INRatio2PT/INR Monitoring System | | |
| Comparison Table of the INRatio/INRatio®2 Monitoring PT/INR Test Systems utilizing the Current INRatio® PT/INR Test Strip vs. the Alere™ INRatio®2 PT/INR Test Strip | | | | |
| Parameter | Current INRatio/INRatio2<br>PT/INR Monitoring Test Systems<br>utilizing current INRatio PT/INR<br>Test Strip<br>(K020679, K021923, K072727 and<br>K092987) | INRatio2 PT/INR Monitoring<br>System utilizing modified<br>Alere™ INRatio®2 PT/INR Test<br>Strip<br>(This submission) | Comment/Explanation of<br>difference | |
| Minimum Sample<br>Volume | 15 μL | 9.5 μL | and directional leading arrow | |
| Test Time<br>Measurement Range | Approximately 1 min for INRatio2<br>INR: 0.7 - 7.5<br>PT: 7 - 75 sec | Approximately I min for INRatio2<br>INR: 0.7 - 7.5 | leading arrow graphic added<br>to test strip for ease of use<br>Miniaturized micro-fluidic<br>design of Test Strip channels<br>allows for reduction in<br>minimum sample volume and<br>increases ease of use | |
| Reference Range | INR: 0.7 - 1.2<br>PT: 6.5 - 11.9 sec | INR: 0.8 - 1.3 | No change<br>No change; PT seconds units<br>are no longer reported in<br>package insert; INR units are<br>now industry standard<br>Reflects verified normal<br>reference range. PT range is<br>no longer reported in package<br>insert; INR units are now<br>industry standard | |
| Strip Calibration | Per WHO889:1999, using normal<br>and therapeutic capillary whole<br>blood samples vs. reference method<br>using normal and therapeutic venous<br>whole blood samples processed to<br>plasma | same | No change | |
| Accuracy | Slope = 0.9 – 1.1<br>Intercept ± 0.5 INR | Slope = 0.9 – 1.1<br>Intercept ± 0.5 INR | No change | |
| Alere | Traditional 510(K) Application | INRatio2PT/INR Monitoring System | | |
| Comparison Table of the INRatio/INRatio®2 Monitoring PT/INR Test Systems utilizing the Current INRatio® PT/INR Test Strip vs. the Alere™ INRatio®2 PT/INR Test Strip | | | | |
| Parameter | Current INRatio/INRatio2<br>PT/INR Monitoring Test Systems<br>utilizing current INRatio PT/INR<br>Test Strip<br>(K020679, K021923, K072727 and K092987) | INRatio2 PT/INR Monitoring<br>System utilizing modified<br>Alere™ INRatio®2 PT/INR Test<br>Strip<br>(This submission) | Comment/Explanation of<br>difference | |
| Precision (Repeatability) | Normal subjects<br>Capillary %CV - 7.6% | Normal subjects<br>Capillary %CV - 8.2% | Minor change; reflects current<br>performance of the test strip | |
| | Therapeutic<br>Capillary %CV - 5.9% | Therapeutic<br>Capillary %CV - 6.2% | | |
| Between Day Precision | Normal Subjects %CV - 8.5% | Therapeutic Patient Self Testers<br>Capillary %CV - 5.7%<br>Not Applicable | No longer reported on<br>package insert as this number<br>is not clinically useful;<br>Between Day Precision can<br>only be determined for normal<br>subjects who are not the<br>intended test population; This<br>is now industry standard | |
| Endogenous Interfering<br>Factors:<br>- Bilirubin | • None up to 20 mg/dL | • None up to 30 mg/dL | • Reflects current performance<br>of the test strip | |
| - Hemoglobin/Hemolysis | • None up to 500 mg/dL | • None up to 1000 mg/dL | • Reflects current performance<br>of the test strip | |
| - Lipemia/triglycerides | • None up to 1500 mg/dL | • None up to 1500 mg/dL | • No change | |
| Factor Sensitivity:<br>- Factor II | • <49% of normal factor level | • <56% of normal factor level | • Reflects current performance<br>of the test strip | |
| Alere | INRatio2PT/INR Monitoring System | | | |
| | Traditional 510(K) Application | | | |
| | Comparison Table of the INRatio/INRatio®2 Monitoring PT/INR Test Systems utilizing the Current INRatio® PT/INR Test Strip vs. the Alere™ INRatio®2 PT/INR Test Strip | | | |
| Parameter | Current INRatio/INRatio2<br>PT/INR Monitoring Test Systems<br>utilizing current INRatio PT/INR<br>Test Strip<br>(K020679, K021923, K072727 and K092987) | INRatio2 PT/INR Monitoring<br>System utilizing modified<br>AlereTM INRatio®2 PT/INR Test<br>Strip<br>(This submission) | Comment/Explanation of difference | |
| • Factor VII | <74% of normal factor level | <78% of normal factor level | of the test strip<br>• Reflects current performance of the test strip | |
| • Factor X | <72% of normal factor level | <74% of normal factor level | • Reflects current performance of the test strip | |
| Exogenous Interfering<br>Factors:<br>• Fondaparinux…