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/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 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 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.

AI/ML Overview

The Alere INRatio2 PT/INR Monitoring System and INRatio2 PT/INR Test Strips were evaluated for performance against acceptance criteria. The study aimed to demonstrate equivalent or better performance compared to previously cleared devices.

Here's a breakdown of the information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document provides a comparison table (pages 3-6) showing the performance of the new INRatio2 PT/INR Monitoring System utilizing the modified Alere™ INRatio2 PT/INR Test Strip against the previous INRatio/INRatio2 Monitoring PT/INR Test Systems.

Parameter	Acceptance Criteria (Previous INRatio/INRatio2 Systems)	Reported Device Performance (INRatio2 PT/INR System with modified strip)	Comment/Explanation of Difference
Intended Use	Quantitative measurement of PT in fresh capillary whole blood for professional and home use to monitor warfarin therapy. Not for screening.	Same, but with added specificity for "International Normalized Ratio (INR)" and "monitoring the effect of warfarin on clotting time by health care professionals" (Professional Use) and "by properly selected suitably trained users (by prescription for home use or other order of a treating physician)" (Home Use). Patients must be stabilized (>6 weeks) for Home Use.	Addition of patient self-testing to the intended use of the INRatio2 PT/INR Monitoring System (for Home Use). Clarification of limitations for both professional and home use regarding patients transitioning from heparin treatment to warfarin therapy.
Intended Users	Healthcare professionals and trained patients.	Same	No change.
Intended Sample	Capillary whole blood	Capillary whole blood	No change.
Test Strip Monitor Compatibility	INRatio (professional and patient self test) and INRatio2 (professional) monitors	INRatio2 (professional and patient self-test)	Addition of patient self-testing to the intended use of Alere INRatio2 PT/INR Monitoring System. The new strip is specifically designed for the INRatio2 monitors.
Mode of Measurement	Electrical Impedance	Same	No change.
Number of Reaction Sites	3 (3 Pairs of Electrodes)	Same	No change.
Test Strip Layout	"Trident"	Same	No change.
Quality Control	Integrated in Test Strip	Same	No change.
Test Strip Graphics	Name of product	Name of product and thumbprint and directional leading arrow	Thumbprint and directional leading arrow graphic added to test strip for ease of use.
Minimum Sample Volume	15 µL	9.5 µL	Miniaturized micro-fluidic design of Test Strip channels allows for reduction in minimum sample volume and increases ease of use.
Test Time	Approximately 1 min for INRatio2	Approximately 1 min for INRatio2	No change.
Measurement Range (INR)	0.7 - 7.5	0.7 - 7.5	No change.
Measurement Range (PT)	7 - 75 sec	Not reported	PT seconds units are no longer reported in package insert; INR units are now industry standard.
Reference Range (INR)	0.7 - 1.2	0.8 - 1.3	Reflects verified normal reference range. PT range is no longer reported in package insert; INR units are now industry standard.
Reference Range (PT)	6.5 - 11.9 sec	Not reported	PT seconds units are no longer reported in package insert; INR units are now industry standard.
Strip Calibration	Per WHO889:1999, using normal and therapeutic capillary whole blood samples vs. reference method using normal and therapeutic venous whole blood samples processed to plasma	Same	No change.
Accuracy	Slope = 0.9 – 1.1, Intercept ± 0.5 INR	Slope = 0.9 – 1.1, Intercept ± 0.5 INR	No change.
Precision (Repeatability) - Normal subjects Capillary %CV	7.6%	8.2%	Minor change; reflects current performance of the test strip. This is likely still within acceptable analytical variation.
Precision (Repeatability) - Therapeutic Capillary %CV	5.9%	6.2%	Minor change; reflects current performance of the test strip. This is likely still within acceptable analytical variation.
Between Day Precision - Normal Subjects %CV	8.5%	Not Applicable (Therapeutic Patient Self Testers Capillary %CV - 5.7%)	No longer reported on package insert as this number is not clinically useful; Between Day Precision can only be determined for normal subjects who are not the intended test population; This is now industry standard. The reported value (5.7%) for Therapeutic Patient Self Testers suggests good between-day precision in the relevant population.
Endogenous Interfering Factors:
- Bilirubin	None up to 20 mg/dL	None up to 30 mg/dL	Reflects current performance of the test strip, indicating improved resistance to bilirubin interference.
- Hemoglobin/Hemolysis	None up to 500 mg/dL	None up to 1000 mg/dL	Reflects current performance of the test strip, indicating improved resistance to hemoglobin interference.
- Lipemia/triglycerides	None up to 1500 mg/dL	None up to 1500 mg/dL	No change.
Factor Sensitivity:
- Factor II	<49% of normal factor level	<56% of normal factor level	Reflects current performance of the test strip. The slightly higher percentage suggests a minor change in sensitivity, which needs to be clinically acceptable.
- Factor VII	<74% of normal factor level	<78% of normal factor level	Reflects current performance of the test strip. The slightly higher percentage suggests a minor change in sensitivity, which needs to be clinically acceptable.
- Factor X	<72% of normal factor level	<74% of normal factor level	Reflects current performance of the test strip. The slightly higher percentage suggests a minor change in sensitivity, which needs to be clinically acceptable.
Exogenous Interfering Factors:
- Fondaparinux	Not previously characterized	Up to 5 mg/L	Further characterization of potential interfering factors; reflects values to appear in labeling. This is an improvement in known interference profiles.
- Acetylsalicylic acid	Not previously characterized	Up to 4 mmol/L	Further characterization of potential interfering factors; reflects values to appear in labeling. This is an improvement in known interference profiles.
- Clopidogrel	Not previously characterized	Up to 20 mg/dL	Further characterization of potential interfering factors; reflects values to appear in labeling. This is an improvement in known interference profiles.
- Atovastatin	Not previously characterized	Up to 600 µg/L	Further characterization of potential interfering factors; reflects values to appear in labeling. This is an improvement in known interference profiles.
- Unfractionated Heparin	Not previously characterized	≥ 2 IU/mL	Further characterization of potential interfering factors; reflects values to appear in labeling. This is an improvement in known interference profiles.
- Low molecular weight Heparin	Not previously characterized	≥ 3 IU/mL	Further characterization of potential interfering factors; reflects values to appear in labeling. This is an improvement in known interference profiles.
Hematocrit range	30 - 55%	25 - 53%	Expanded range on low end to include a larger patient population; decreased range on upper end. Accuracy was established up to 55% HCT. This allows use in a broader patient population.
Operating conditions: Temperature	10 - 35°C (50 - 95°F)	10 - 32°C (50 - 90°F)	Reflects current performance of the system (monitor and strip). The narrower upper temperature limit indicates less temperature tolerance than the previous system, but is likely still within acceptable limits for typical use environments.
Operating conditions: Humidity	10%-95% RH	15%-90% RH	Reflects current performance of the system (monitor and strip). The narrower humidity range indicates less humidity tolerance than the previous system, but is likely still within acceptable limits for typical use environments.
Strip warm-up time (Refrig storage)	5 min at RT, if stored refrig	Same	No change.
Strip warm-up time (RT storage)	N/A, if stored at RT	Same	No change.
Strip Stability (Out of pouch)	10 minutes	Same	No change.
Strip Stability (Pouched)	15 months at recommended storage conditions	11 months at recommended storage conditions	Shelf Life at room temperature based on currently available real time stability data. This indicates a shorter shelf life for the new strips.

Study Proving Acceptance Criteria:

The document states that "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) per ISO 17593:2007." (Section G. Clinical Data).

Furthermore, "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." (Nonclinical Data section).

Missing Information (Not explicitly stated in the provided text):

While the document states clinical and performance testing was done, several specific details requested in the prompt are not explicitly provided in the text:

2. Sample size used for the test set and the data provenance:

Sample Size: Not explicitly stated for the clinical or performance testing.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). However, "Clinical testing validated" implies prospective collection for that specific validation.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not explicitly stated. The ground truth is established by a reference method (Sysmex CA-560 Anticoagulation Analyzer), not by human experts.

4. Adjudication method for the test set:

Not applicable as the ground truth is an objective measurement from a reference analyzer.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. This is an in-vitro diagnostic device for measuring INR, not an imaging device requiring human reader interpretation or AI assistance in that context. The "users" are healthcare professionals or trained patients operating the device. The comparison is between the device's output and a reference method.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

The device inherently operates as an algorithm-only system to generate INR values from the applied blood sample. Its "standalone" performance is assessed by comparing its output directly to the reference standard, as implied by the accuracy statements. The "human-in-the-loop" refers to applying the sample and reading the result, but not interpreting raw data from the device itself.

7. The type of ground truth used:

Reference Method: Sysmex CA-560 Anticoagulation Analyzer. This is a recognized laboratory instrument for coagulation testing, providing objective, quantitative data.

8. The sample size for the training set:

Not explicitly stated. The document focuses on validation/performance testing, not on the specific "training" that would be typical for machine learning models. For a device like this, the "training" would be the development and calibration of the assay, likely involving a different set of samples than the final performance validation.

9. How the ground truth for the training set was established:

Not explicitly stated. Similar to point 8, the ground truth for internal development and calibration would typically be established using a gold standard laboratory method. The document mentions "Strip Calibration per WHO889:1999, using normal and therapeutic capillary whole blood samples vs. reference method using normal and therapeutic venous whole blood samples processed to plasma," which describes the general method for calibrating the strips.

Summary

{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 mara.caler@alere.com

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:

{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.the Alere™ INRatio®2 PT/INR Test Strip
Parameter	Current INRatio/INRatio2PT/INR Monitoring Test Systemsutilizing current INRatio PT/INRTest Strip(K020679, K021923, K072727 andK092987)	INRatio2 PT/INR MonitoringSystem utilizing modifiedAlere™ INRatio 2 PT/INR TestStrip(This submission)	Alere INRatio®2 PT/INRMonitoring System ( ProfessionalUse ): The Alere INRatio®2PT/INR Monitoring System( Professional Use ), consisting ofthe INRatio®2 Monitor andINRatio®2 PT/INR test strip, is	Comment/Explanation ofdifference
Intended Use	The Alere INRatio/INRatio2PT/INR Monitoring System is usedfor the quantitative measurement ofProthrombin Time (PT) in fresh,capillary whole blood. TheINRatio/INRatio2 PT/INRMonitoring system is intended foruse outside the body (in vitrodiagnostic use). TheINRatio/INRatio2 PT/INRMonitoring System is intended forprofessional and home use bypeople taking warfarin and otheroral anticoagulant (blood thinning)therapy who need to monitor theclotting time of their blood. TheINRatio/INRatio2 PT/INRMonitoring System is not intendedto be used for screening purposes.	Alere INRatio®2 PT/INRMonitoring System ( ProfessionalUse ): The Alere INRatio®2PT/INR Monitoring System( Professional Use ), consisting ofthe INRatio®2 Monitor andINRatio®2 PT/INR test strip, isused for quantitativedetermination of internationalnormalized ratio (INR) in freshcapillary whole blood to monitorthe effect of warfarin on clottingtime by health care professionals.The Alere INRatio 2 PT/INRMonitoring System ( ProfessionalUse ) is intended for use outside ofthe body (in vitro diagnostic use).The Alere INRatio®2 PT/INRMonitoring System ( ProfessionalUse ) is not intended to be usedfor screening purposes.	Limitations: The Alere INRatio®2PT/INR Monitoring System( Professional Use ) is not intendedfor use in patients who aretransitioning from heparintreatment to warfarin therapy.	Addition of patient selftesting to the intended use ofINRatio2 PT/INR MonitoringSystem

{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.the Alere™ INRatio®2 PT/INR Test Strip
Parameter	Current INRatio/INRatio2PT/INR Monitoring Test Systemsutilizing current INRatio PT/INRTest Strip(K020679, K021923, K072727 andK092987)	INRatio2 PT/INR MonitoringSystem utilizing modifiedAlere™ INRatio®2 PT/INR TestStrip(This submission)	Comment/Explanation ofdifference
Alere INRatio®2 PT/INR HomeMonitoring System: The AlereINRatio®2 PT/INR HomeMonitoring System, consisting ofthe INRatio®2 Home Monitor andINRatio®2 PT/INR test strip, isused for quantitativedetermination of internationalnormalized ratio (INR) in freshcapillary whole blood to monitorthe effect of warfarin therapy onclotting time by properly selectedsuitably trained users (byprescription for home use or otherorder of a treating physician).Patients must be stabilized (>6weeks) on warfarin therapy. TheThe Alere INRatio®2 PT/INRHome Monitoring System isintended for use outside of thebody (in vitro diagnostic use).The Alere INRatio®2 PT/INRHome Monitoring System is notintended 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.the Alere™ INRatio®2 PT/INR Test Strip
Parameter	Current INRatio/INRatio2PT/INR Monitoring Test Systemsutilizing current INRatio PT/INRTest Strip(K020679, K021923, K072727 andK092987)	INRatio2 PT/INR MonitoringSystem utilizing modifiedAlere™ INRatio®2 PT/INR TestStrip(This submission)	Comment/Explanation ofdifference
Intended Users	Healthcare professionals and trainedpatients on the prescription or otherorder of a treating physician.	same	Limitations: The Alere INRatio®2PT/INR Home MonitoringSystem is not intended for use inpatients who are transitioningfrom heparin treatment towarfarin therapy.
Intended Sample	capillary whole blood	Capillary whole blood	Addition of patient self testingto the intended use of theAlere INRatio2 PT/INRMonitoring System
Test Strip MonitorCompatibility	INRatio (professional and patientself test) and INRatio2(professional) monitors	INRatio2 (professional and patientself-test)	Addition of patient self tesingto the intended use of AlereINRatio2 PT/INR MonitoringSystem
Mode of Measurement	Electrical Impedance	same	No change
Number of ReactionSites (and pairs ofelectrodes)	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 thumbprintThumbprint 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/INRatio2PT/INR Monitoring Test Systemsutilizing current INRatio PT/INRTest Strip(K020679, K021923, K072727 andK092987)	INRatio2 PT/INR MonitoringSystem utilizing modifiedAlere™ INRatio®2 PT/INR TestStrip(This submission)	Comment/Explanation ofdifference
Minimum SampleVolume	15 μL	9.5 μL	and directional leading arrow
Test TimeMeasurement Range	Approximately 1 min for INRatio2INR: 0.7 - 7.5PT: 7 - 75 sec	Approximately I min for INRatio2INR: 0.7 - 7.5	leading arrow graphic addedto test strip for ease of useMiniaturized micro-fluidicdesign of Test Strip channelsallows for reduction inminimum sample volume andincreases ease of use
Reference Range	INR: 0.7 - 1.2PT: 6.5 - 11.9 sec	INR: 0.8 - 1.3	No changeNo change; PT seconds unitsare no longer reported inpackage insert; INR units arenow industry standardReflects verified normalreference range. PT range isno longer reported in packageinsert; INR units are nowindustry standard
Strip Calibration	Per WHO889:1999, using normaland therapeutic capillary wholeblood samples vs. reference methodusing normal and therapeutic venouswhole blood samples processed toplasma	same	No change
Accuracy	Slope = 0.9 – 1.1Intercept ± 0.5 INR	Slope = 0.9 – 1.1Intercept ± 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/INRatio2PT/INR Monitoring Test Systemsutilizing current INRatio PT/INRTest Strip(K020679, K021923, K072727 and K092987)	INRatio2 PT/INR MonitoringSystem utilizing modifiedAlere™ INRatio®2 PT/INR TestStrip(This submission)	Comment/Explanation ofdifference
Precision (Repeatability)	Normal subjectsCapillary %CV - 7.6%	Normal subjectsCapillary %CV - 8.2%	Minor change; reflects currentperformance of the test strip
	TherapeuticCapillary %CV - 5.9%	TherapeuticCapillary %CV - 6.2%
Between Day Precision	Normal Subjects %CV - 8.5%	Therapeutic Patient Self TestersCapillary %CV - 5.7%Not Applicable	No longer reported onpackage insert as this numberis not clinically useful;Between Day Precision canonly be determined for normalsubjects who are not theintended test population; Thisis now industry standard
Endogenous InterferingFactors:- Bilirubin	• None up to 20 mg/dL	• None up to 30 mg/dL	• Reflects current performanceof the test strip
- Hemoglobin/Hemolysis	• None up to 500 mg/dL	• None up to 1000 mg/dL	• Reflects current performanceof the test strip
- Lipemia/triglycerides	• None up to 1500 mg/dL	• None up to 1500 mg/dL	• No change
Factor Sensitivity:- Factor II	• <49% of normal factor level	• <56% of normal factor level	• Reflects current performanceof 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/INRatio2PT/INR Monitoring Test Systemsutilizing current INRatio PT/INRTest Strip(K020679, K021923, K072727 and K092987)	INRatio2 PT/INR MonitoringSystem utilizing modifiedAlereTM INRatio®2 PT/INR TestStrip(This submission)	Comment/Explanation of difference
• Factor VII	<74% of normal factor level	<78% of normal factor level	of the test strip• 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 InterferingFactors:• Fondaparinux	• Not previously characterized	• Up to 5 mg/L	Further characterization of potential interfering factors; reflects values to appear in labeling
• Acetylsalicylic acid	• Not previously characterized	• Up to 4 mmol/L
• Clopidogrel	• Not previously characterized	• Up to 20 mg/dL
• Atovastatin	• Not previously characterized	• Up to 600 µg/L
• Unfractionated Heparin	• Not previously characterized	• ≥ 2 IU/mL
• Low molecular weightHeparin	• Not previously characterized	• ≥ 3 IU/mL
Hematocrit range	30 - 55%	25 - 53%	Expanded range on low end to include a larger patient population; decreased range on upper end. Accuracy was established up to 55% HCT
Operating conditions:• Temperature	10 - 35°C (50 - 95°F)	10 - 32°C (50 - 90°F)	• Reflects current performance of the system (monitor and strip)
• Humidity	• 10%-95% RH	• 15%-90% RH
Alere	Traditional 510(K) ApplicationINRatio2PT/INR Monitoring System
Parameter	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	Current INRatio/INRatio2 PT/INR Monitoring Test Systems utilizing current INRatio PT/INR Test Strip(K020679, K021923, K072727 and K092987)	INRatio2 PT/INR Monitoring System utilizing modified Alere™ INRatio 2 PT/INR Test Strip(This submission)	Comment/Explanation of difference

• Room Temp		• Below 90°F (32°C) until expiration date	• Below 90°F (32°C) until expiration date	No change
Strip warm-up time:• Refrig storage		• 5 min at RT, if stored refrig	• same	• No change
• RT storage		• N/A, if stored at RT	• same	• No change
Strip Stability:• Out of pouch		• 10 minutes	• Same	• No change
• Pouched		• 15 months at recommended storage conditions	• 11 months at recommended storage conditions	• Shelf Life at room temperature based on currently available real time stability data

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

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

。

. . . . .

100 - 100

and the commend of the comments of

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

{8}------------------------------------------------

Alere

{9}------------------------------------------------

{10}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/10/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus or a representation of human figures.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Alere San Diego, Inc. c/o Ms. Mara Caler Regulatory Affairs 9975 Summers Ridge Road San Diego, CA 92121

MAY 0 1 2012

Re: K110212

Trade/Device Name: Alere INRatio®2 PT/INR Monitoring System (Professional Use); Alere INRatio®2 PT/INR Home Monitoring System; Alere INRatio®2 PT/INR Test Strip Regulation Number: 21 CFR § 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: Class II Product Code: GJS Dated: April 27, 2012 Received: April 27, 2012

Dear Ms. Caler:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA): 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.

The Office of In Vitro Diagnostic Device Evaluation and Safety has determined that there is a reasonable likelihood that this device will be used for an intended use not identified in the proposed labeling and that such use could cause harm. Therefore, in accordance with Section 513(i)(1)(E) of the Act, the following limitation must appear under the Indications for Use section of the device's labeling, the patient test report and any promotional materials:

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.

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.

Please note that the above labeling limitations are required by Section 513(i)(1)(E) of the Act. Therefore, a new 510(k) is required before these limitations are modified in any way or removed from the device's labeling.

{11}------------------------------------------------

Page 2 - Ms. Mara Caler

The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and permits your device to proceed to the market. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification if the limitation statement described above is added to your labeling.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 1 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

m chan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{12}------------------------------------------------

INRatio2 PT/INR Monitoring System

Traditional 510(K) Application

INDICATIONS FOR USE

510(k) Number (if known): _ k110212_ _________________________________________________________________________________________________________________________________________

Device Name: Alere INRatio®2 PT/INR Monitoring System (Professional Use), ___

Indications for 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.

Prescription Use X (21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510(k) K11021

Page 1 of 2

{13}------------------------------------------------

INRatio2 PT/INR Monitoring System

Traditional 510(K) Application

INDICATIONS FOR USE

510(k) Number (if known): K110212

Device Name: Alere INRatio 2 PT/INR Home Monitoring System

Indications for Use:

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/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 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.

AND/OR

Prescription Use X (21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign Off

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K / 1021

Page 2 of 2

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
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).(b)
Classification. Class II (performance standards).