The CoaguChek® Vantus System measures an INR (International Normalized Ratio) based on a prothrombin time (PT) response to monitor the effect of a therapy with vitamin K antagonists by using the CoaguChek XS PT test strips. The CoaguChek Vantus System uses fresh capillary whole blood from a finger stick.

The system is intended for properly selected and suitable trained users on the prescription of the treating doctor.

Users should be stabilized on anticoagulation with vitamin K antagonists for at least 6 weeks prior to single patient self-testing with the CoaguChek Vantus System.

The CoaguChek Vantus System is intended for single patient self-testing only for adults, age 22 years and older.

Device Description

The CoaguChek Vantus consists of a handheld meter and associated test strips.

The CoaguChek Vantus meter is a small handheld instrument intended for the quantitative measurement of INR (International Normalized Ratio) based on a prothrombin time (PT) response, by using a single electrochemical test strip. It is designed for ease of use and is intended for patient self-testing only.

The CoaguChek XS PT Test strip contains a lyophilized reagent in dried form). The reactive components of this reagent consist of thromboplastin and a peptide substrate. When a sample is applied, thromboplastin activates coagulation, which leads to the formation of thrombin. At the same time, the meter starts to measure the time. The enzyme thrombin cleaves the peptide substrate, generating an electrochemical signal. Depending on the time elapsed when it first appears, this signal is then converted by means of an algorithm into customary coagulation units and the result is displayed.

AI/ML Overview

The document describes the CoaguChek Vantus System, a device for measuring INR (International Normalized Ratio) based on prothrombin time (PT) response to monitor the effect of vitamin K antagonist therapy. It uses fresh capillary whole blood from a finger stick and is intended for single patient self-testing for adults aged 22 years and older, who have been stabilized on anticoagulation for at least 6 weeks.

1. A table of acceptance criteria and the reported device performance:

The document does not explicitly state "acceptance criteria" in a table format with pass/fail results for each criterion. However, it presents various performance study results for the CoaguChek Vantus System, comparing it against the predicate device (CoaguChek XS System) and a reference laboratory analyzer (Sysmex CA-1500). The implication is that meeting these performance benchmarks supports substantial equivalence.

Here's a summary of the reported device performance from various studies:

Performance Characteristic	Acceptance Criteria (Implied/Benchmark)	Reported Device Performance (CoaguChek Vantus System)
Measuring Range (INR)	Not explicitly stated as acceptance criteria, but defines operational range.	0.8 to 6.0 INR
Repeatability (CV%)	Not explicitly stated as acceptance criteria, but low CV indicates good repeatability.	< 2.0 INR: Mean 1.1 INR, SD 0.04 INR, CV 3.8% 2.0-3.5 INR: Mean 2.6 INR, SD 0.08 INR, CV 3.1% > 3.5 - 4.5 INR: Mean 4.0 INR, SD 0.12 INR, CV 3.2% > 4.5 - 6.0 INR: Mean 4.9 INR, SD 0.07 INR, CV 1.5%
Reproducibility (Overall CV%)	Not explicitly stated as acceptance criteria, but low CV indicates good reproducibility.	Control Level 1 (1.32 INR): 4.0% Control Level 2 (2.79 INR): 4.2% Control Level 3 (5.85 INR): 4.0% Control Level 4 (3.39 INR): 3.2%
Method Comparison vs. Predicate (CoaguChek XS System)	Not explicitly stated, but typically a slope close to 1, intercept close to 0, and high Pearson r are desired.	All Sites (N=207): Slope: 1.00 (95% CI: 1.00, 1.03) Intercept: 0.1 (95% CI: 0.1, 0.1) Pearson r: 0.99
Method Comparison vs. Reference System (Sysmex CA-1500 w/ Dade Innovin)	Not explicitly stated, but typically a slope close to 1, intercept close to 0, and high Pearson r are desired.	All Sites (N=200): Slope: 0.98 (95% CI: 0.93, 1.03) Intercept: 0.1 (95% CI: 0.0, 0.3) Pearson r: 0.91
Expected Values / Reference Range (Healthy Subjects)	N/A (establishing a normal range)	95% of INRs ranged between 0.9 - 1.1 for healthy subjects not on anticoagulation therapy.
Factor Sensitivity	Verifies specific factor levels that do not significantly affect test results.	Factor II <31%; Factor V <46%; Factor VII <44%; and Factor X <50% (Verified)
Interference (Bilirubin)	No significant effect up to specified concentration.	No significant effect up to 30 mg/dL
Interference (Hemolysis)	No significant effect up to specified concentration.	No significant effect up to 1000 mg/dL
Interference (Heparin)	Unaffected by specified concentration.	Unaffected by concentrations up to 0.8 U/mL
Interference (LMWH)	Insensitive up to specified activity.	Insensitive up to 2 IU anti-factor Xa activity/mL
Interference (Triglycerides)	No significant effect up to specified concentration.	No significant effect up to 500 mg/dL
Interference (Other Drugs)	Not explicitly stated as criteria, but lists drugs where testing is not applicable or results are unaffected.	Clopidogrel (up to 20 mg/dL), Fondaparinux (up to 0.5 mg/L) - no significant effect. Rivaroxaban, Apixaban, Dabigatran, Edoxaban - Cannot be tested with system.

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

Repeatability Study: A total of 688 specimens from subjects on oral anticoagulation therapy and coagulation healthy subjects. There were 344 repeatability series performed at four Point-of-Care (PoC) sites. Data provenance is implied to be clinical samples collected for this study, likely in a prospective manner given the nature of repeatability testing. The document does not specify the country of origin.
Reproducibility Study: Data was obtained from HCP measurements of three lots of CoaguChek XS PT controls covering four levels of controls, at all 4 PoC sites. The specific number of individual measurements is large (e.g., N=1040 for control levels 1 & 2, N=708/712 for control levels 3 & 4), indicating a substantial test set. Data provenance is implied to be clinical performance testing, likely prospective. Country of origin not specified.
Method Comparison vs. Predicate: 207 samples were used, collected from both subjects not receiving anticoagulant and those on warfarin therapy. The study was conducted across 4 PoC sites. Data provenance is implied to be clinical samples, likely prospective. Country of origin not specified.
Method Comparison vs. Reference System: 200 samples in total (67 from Site 1, 43 from Site 2, 47 from Site 3, 43 from Site 4). These were capillary whole blood samples measured on the CoaguChek Vantus System compared against venous plasma samples measured on the Sysmex CA 1500 laboratory analyzer. The study was performed across four (4) sites. Data provenance is implied to be clinical samples, likely prospective. Country of origin not specified.
Expected Values / Reference Range Study: 121 healthy subjects were tested. Data provenance is implied to be clinical samples, likely prospective. Country of origin not specified.
Endogenous and Exogenous Interferences: Not explicitly stated, but performed using "up to four CoaguChek XS PT Test strip lots, using fresh citrated venous whole blood from both normal and warfarin blood samples spiked separately with the interferents." The number of samples for each interferent is not detailed.
Factor Sensitivity: Not explicitly stated in terms of sample size for human plasma, but states "Standard human plasma was mixed with varying amounts of factor II, V, VII or X deficient plasma to obtain plasma samples with different factor activities (0, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 %)." For each test strip lot, "at least 4 measurements were performed per coagulation factor and dilution level." This suggests a controlled laboratory study.

The overall data provenance for the non-clinical and clinical performance evaluation sections points to controlled laboratory and point-of-care studies, suggesting a prospective data collection approach for the device validation.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

This device is an in-vitro diagnostic (IVD) device that measures a quantitative parameter (INR). The "ground truth" for such devices is typically established through reference methods and calibrated instruments, not through expert human review in the same way an imaging AI device's ground truth would be established.

For Method Comparison studies: The ground truth was established by:
- The predicate device (CoaguChek XS System), which is an already regulated and accepted device.
- A reference laboratory analyzer (Sysmex CA-1500) using a specific reagent (Dade Innovin recombinant human tissue thromboplastin reagent). This laboratory method serves as the gold standard reference for PT/INR measurement.
For other performance studies (Repeatability, Reproducibility, Linearity, Interference): The "ground truth" or reference is the precise and accurate measurement capabilities of the laboratory instruments and standardized clinical protocols.

Therefore, the concept of "experts" establish ground truth in this context typically refers to the expertise of the laboratory personnel performing the reference measurements and the established validity of the reference methods themselves, rather than a panel of diagnosticians reviewing cases. No specific number or qualifications of "experts" for reviewing individual data points are mentioned because the ground truth is analytically derived.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Adjudication methods like "2+1" or "3+1" are typically used for qualitative or subjective assessments, such as in imaging studies where multiple readers interpret a finding and discrepancies are resolved by an adjudicator.

For this IVD device, the results are quantitative measurements (INR values). Therefore, there is no human "adjudication" of the test results in the sense of resolving differences in interpretation. The comparisons are statistical (e.g., Pearson r, slope, intercept from regression analysis, SD, CV). The "adjudication" is inherent in the statistical analysis and comparison to established reference methods.

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:

No, an MRMC comparative effectiveness study was not conducted. This type of study is relevant for AI devices that assist human readers in tasks like image interpretation (e.g., radiology AI). The CoaguChek Vantus System is an in-vitro diagnostic device that provides a direct quantitative measurement (INR) for self-testing, not an AI system designed to assist human interpretation of complex data like medical images. Therefore, the concept of human readers "improving with AI assistance" does not apply to this device.

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

Yes, the performance studies described in the document are effectively "standalone" performance evaluations of the device itself. The CoaguChek Vantus System is a standalone measurement device. It provides an INR result based on an electrochemical principle and internal algorithm. The human "in the loop" is the patient performing the finger stick and applying the blood, and the physician prescribing and managing the therapy. The device's measurement and output are not subject to real-time human interpretation or modification of the result before being displayed. The accuracy, precision, and interference studies directly assess the "algorithm only" performance (i.e., the instrument's ability to accurately measure and produce a result).

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth for this device's performance evaluation was established using:

Reference laboratory methods: Specifically, the Sysmex CA-1500 laboratory analyzer using Dade Innovin recombinant human tissue thromboplastin reagent was used as the reference method for PT/INR determinations in venous plasma samples. This is considered the analytical gold standard.
Predicate device: The CoaguChek XS System (K062925) served as another comparison point, indicating substantial equivalence to an already marketed device.
Standardized control materials and spiked samples: Used in precision, linearity, and interference studies to assess the device's accuracy and resistance to various factors.

This is a form of analytical ground truth derived from established, validated laboratory methods and reference materials, which is standard for IVD devices.

8. The sample size for the training set:

The document describes premarket notification (510(k)) and focuses on the performance studies (validation) rather than the development phase (training). The CoaguChek Vantus System utilizes an electrochemical detection principle and factory calibration rather than a machine learning model that would typically have a "training set." Therefore, the concept of a "training set" in the context of machine learning does not apply to this device as described.

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

As the device's operating principle is based on electrochemical measurements and factory calibration rather than a machine learning model, there isn't a "training set" with associated "ground truth" to be established in the sense of supervised learning. The calibration of each lot of test strips is "factory calibrated to a reference lot of human recombinant thromboplastin traceable to the World Health Organization International Reference Preparation," with this calibration information embedded in a code chip. This factory calibration is likely based on extensive internal studies and validated reference standards.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 25, 2017

Roche Diagnostics Justin Davis Regulatory Affairs Principal 9115 Hague Road Indianapolis, Indiana 46250

Re: K170960

Trade/Device Name: CoaguChek Vantus System Regulation Number: 21 CFR 864.7750 Regulation Name: Prothrombin time test Regulatory Class: Class II Product Code: GJS Dated: November 24, 2017 Received: November 27, 2017

Dear Justin Davis:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Leonthena R. Carrington -S

Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K170960

Device Name CoaguChek Vantus System

Indications for Use (Describe)

The system is intended for properly selected and suitable trained users on the treating doctor.

Users should be stabilized on anticoagulation with vitamin K antagonists for at least 6 weeks prior to single patient selftesting with the CoaguChek Vantus System.

The CoaguChek Vantus System is intended for single patient self-testing only for adults, age 22 years and older.

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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CoaguChek Vantus System 510(k) Summary

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

In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).

The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the CoaguChek Vantus System.

Submitter Name	Roche Diagnostics
Address	9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0457
Contact	Justin DavisPhone: (317) 521-6024FAX: (317) 521-2324Email: justin.davis@roche.com
Date Prepared	March 30, 2017
Proprietary Name	CoaguChek Vantus System
Common Name	CoaguChek Vantus System
Classification Name	Test Time ProthrombinProthrombin Time Test
Product Codes, Regulation Numbers	GJS, 21 CFR 864.7750
Predicate Devices	CoaguChek XS System, K062925
Establishment Registration	For the CoaguChek Vantus System, the establishment registrationnumber for Roche Diagnostics GmbH in Mannheim, Germany is9610126.The establishment registration number for Roche Diagnostics in theUnited States is 1823260.

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DEVICE DESCRIPTION 1.

1.1. CoaguChek Vantus System

The CoaguChek Vantus consists of a handheld meter and associated test strips.

1.2. CoaquChek XS PT Test Strip

2. INTENDED USE

The system is intended for properly selected and suitable trained users on the prescription of the treating doctor.

Users should be stabilized on anticoagulation with vitamin K antagonists for at least 6 weeks prior to single patient self-testing with the CoaguChek Vantus System.

The CoaguChek Vantus System is intended for single patient self-testing only for adults, age 22 years and older.

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TECHNOLOGICAL CHARACTERISTICS 3.

The following tables compare the CoaguChek Vantus System with its predicate device,

CoaguChek XS System (K062925).

Candidate Device Name	Predicate Device Name	K-Number
CoaguChek Vantus System	CoaguChek XS System	K062925

Table 1: Instrument and Assay Comparison

Feature	CoaguChek XS System (K062925)	CoaguChek Vantus System
Intended Use	The CoaguChek XS PT test strips are part of theCoaguChek XS System. The CoaguChek XS Systemmeasures blood clotting time for people who aretaking anticoagulation medications such asCoumadin® or warfarin. The CoaguChek XS Systemuses blood from a finger stick. The system isintended for properly selected and suitably trainedusers or their caregivers on the prescription orother order of the treating doctor. Users should bestabilized on anticoagulation medications such asCoumadin® or warfarin prior to self- testing withthe CoaguChek XS System.	The CoaguChek® Vantus System measures an INR(International Normalized Ratio) based on aprothrombin time (PT) response to monitor theeffect of a therapy with vitamin K antagonists byusing the CoaguChek XS PT test strips. TheCoaguChek Vantus System uses fresh capillarywhole blood from a finger stick.The system is intended for properly selected andsuitable trained users on the prescription of thetreating doctor.Users should be stabilized on anticoagulation withvitamin K antagonists for at least 6 weeks prior tosingle patient self-testing with the CoaguChekVantus System.The CoaguChek Vantus System is intended forsingle patient self-testing only for adults, age 22years and older.
Indications for Use	Same as Intended Use	Same as Intended Use
Test Strip	CoaguChek XS PT Test Strip	Same
Sample Type	Capillary Whole Blood	Same
Operating Principle	Electrochemical technology with amperometric(electric current) detection of thrombin activity	Same
Reagent Test StripPrinciple	Human recombinant thromboplastin	Same
Sample Volume	The blood drop must be a minimum of 8 µl	Same
Measuring Range	0.8 to 8.0 INR	0.8 to 6.0 INR
On-Board Control	Built into each CoaguChek XS PT Test Strip	Same
Hematocrit Range	Hematocrit ranges between 25-55% have nosignificant effect on test results	Same
Bilirubin	Bilirubin up to 30 mg/dL have no significant effecton test results	Same

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Feature	CoaguChek XS System (K062925)	CoaguChek Vantus System
Triglyceride	Lipemic samples containing up to 500 mg/dL oftriglycerides have no significant effect on testresults	Same
Hemolysis	Hemolysis up to 1000 mg/dL have no significanteffect on test results	Same
Heparin	Test results are unaffected by heparinconcentrations up to 0.8 U/mL	Same
Low MolecularWeight Heparin	The CoaguChek XS PT Test is insensitive to lowmolecular weight heparins (LMWH) up to 2 IU anti-factor Xa activity/mL	Same
Memory Capacity	300 test results with date and timeNo test strip lot information stored (code chipdata)	300 test results with date and timeCode chip data from up to 5 test strip lots can bestored
CommunicationInterface	Infrared	Bluetooth, USB

NON-CLINICAL PERFORMANCE EVALUATION 4.

The following internal performance data were provided in support of the substantial equivalence determination:

Endogenous Interferences Hematocrit/Bilirubin/Triglycerides/Hemolysis/Heparin .
Exogenous Interferences Drugs .
Stability .

4.1. Linearity/Assay Reportable Range

4.1.1. -Linearity
A linearity study is not applicable for the CoaguChek Vantus System.

4.1.2. Assay Reportable Range

The assay reportable range (0.8 - 6.0 INR) of the CoaguChek Vantus System was established through method comparison studies against both the predicate (Roche CoaguChek XS System) and the reference device (Sysmex CA-1500 laboratory analyzer). Dade Innovin Reagent was used for prothrombin time (PT) determinations.

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Test Strip Stability 4.2.

4.2.1. Traceability

Each lot of CoaguChek XS PT Test Strips is factory calibrated to a reference lot of human recombinant thromboplastin traceable to the World Health Organization International Reference Preparation.

4.2.1.1. Closed Vial and Transport Stability

The CoaguChek XS PT Test strips were stored at +2-8 °C and +26-30°C and tested after a storage time of 3, 6, 16, and 25 months. The 25 month time point captures the component of transport stability, as the 25 months includes a 5-day period of stressed storage at +45 °C (±2 °C).

4.2.1.2. Open Vial Stability

Open vial stability simulates the repeated opening and closing of the vial by the customer when strips are removed from the vial for measurement. Open vial stability was tested by opening the vials once per day for at least 1 minute at +32 °C, 85 % relative humidity (RH) over a period of 30 days.

4.2.1.3. Out of Vial Stability

Out of vial stability was tested to prove that the test strips can be kept outside the vial before measurement for at least 10 minutes when directly exposed to +32 ℃, 85 % RH. This was verified by storing the test strip outside the vial under the specified environmental conditions for 14 minutes before measurement

Detection Limit/Factor Sensitivity 4.3.

For Factor Sensitivity studies, four CoaguChek XS PT Test strip lots were used.

Standard human plasma was mixed with varying amounts of factor II, V, VII or X deficient plasma to obtain plasma samples with different factor activities (0, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 %). For each test strip lot, at least 4 measurements were performed per coagulation factor and dilution level.

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Factor sensitivities were calculated according to CLSI guidelines (CLSI H47-A2; Vol.28, Appendix D). The study verifies Factor Sensitivity at the following levels: Factor II <31%; Factor V <46%; Factor VII <44%; and Factor X <50%.

Analytical Specificity 4.4.

Endogenous and Exogenous Interferences 4.4.1.

The interference studies were performed for the following interferents: bilirubin, hemolysis, heparin, low molecular weight heparin, triglycerides. In addition, an interference study was conducted to characterize the levels of other known drugs: clopidogrel , fondaparinux, rivaroxaban, apixaban, dabigatran, edoxaban.

Interference limits were established using up to four CoaguChek XS PT Test strip lots, using fresh citrated venous whole blood from both normal and warfarin blood samples spiked separately with the interferents.

Interferent	Concentration
Bilirubin	Up to 30 mg/dL
Hemolysis	Up to 1000 mg/dL
Heparin	Up to 0.8 U/mL
Low Molecular Weight Heparin	Up to 2 IU anti-factor XA activity/mL
Triglycerides	Up to 500 mg/dL
Clopidogrel	Up to 20 mg/dL
Fondaparinux	Up to 0.5 mg/L
Rivaroxaban	Cannot be tested with system
Apixaban	Cannot be tested with system
Dabigatran	Cannot be tested with system
Edoxaban	Cannot be tested with system

Assay Cut-Off 4.5.

Not applicable.

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EXTERNAL (CLINICAL) TESTING 5.

5.1. Precision

5.1.1. Repeatability

A total of 688 specimens from subjects on oral anticoagulation therapy with vitamin K antagonists and coagulation healthy subjects were collected. In total 344 repeatability series were performed at four PoC sites. Data analysis was carried out by PoC site, by test strip lot and by clinically relevant ranges (<2.0, 2.0-3.5, >3.5-4.5, >4.5 INR).

Blood	< 2.0 INR	2.0-3.5 INR	> 3.5 - 4.5 INR	> 4.5 - 6.0 INR
N	200	394	70	24
Mean (INR)	1.1	2.6	4.0	4.9
SD (INR)	0.04	0.08	0.12	0.07
CV (%)	3.8	3.1	3.2	1.5

Summary of Repeatability for CoaguChek Vantus Table 2:

5.1.2. Reproducibility

The intermediate precision experiment according to the CLSI Guideline EP05-A3 was conducted at all 4 PoC sites, with three lots of CoaguChek XS PT Test strips. The data was obtained from HCP measurements of three lots of CoaguChek XS PT controls covering four levels of controls.

Table 3: Summary of Reproducibility for CoaguChek Vantus

		Repeatability(Within Run)		BetweenRun		BetweenStrip Lot		BetweenDay		BetweenSite		Reproducibility
ControlLevel	N	Mean	SD	% CV	SD	% CV	SD	% CV	SD	% CV	SD	% CV	SD	% CV
1	1040	1.32	0.03	2.4	0.01	0.6	0.04	2.9	0.01	0.7	0.01	1.0	0.05	4.0
2	1040	2.79	0.11	4.0	0.00	0.0	0.02	0.7	0.00	0.0	0.03	1.0	0.12	4.2
3	708	5.85	0.17	2.9	0.07	1.2	0.14	2.3	0.04	0.8	0.02	0.4	0.24	4.0
4	712	3.39	0.09	2.7	0.04	1.2	0.03	1.0	0.00	0.0	0.03	0.9	0.11	3.2

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Method Comparison 5.2.

5.2.1. Method Comparison versus Predicate

Accuracy was evaluated by comparing the CoaguChek Vantus System against the predicate device, the CoaguChek XS System. The clinical method comparison study was performed using capillary whole blood samples from subjects not receiving warfarin or any other anticoagulant and from subjects currently on warfarin therapy. The method comparison study was conducted across 4 PoC sites using three 3 CoaguChek XS PT Test strip lots.

Table 4: CoaguChek Vantus System vs CoaguChek XS System

Site	N	Slope(95% CI)	Intercept(95% CI)	Pearsonr
All	207	1.00(1.00, 1.03)	0.1(0.1, 0.1)	0.99

5.2.2. Method Comparison versus Reference System

Accuracy was also evaluated by comparing the INR results of capillary samples measured on the CoaguChek Vantus System against the INR of venous plasma samples measured on Sysmex CA 1500 laboratory analyzer using Dade Innovin recombinant human tissue thromboplastin reagent (reference device). The method comparison study was performed s across four (4) sites using CoaguChek XS PT Test strip lots. Results of INR values measured on CoaguChek Vantus System fingerstick capillary whole blood samples were compared to the INR measured on Innovin using venous plasma samples. The data from individual sites were combined and a Passing-Bablok regression analysis was performed.

Table 5: CoaguChek Vantus System vs Innovin

Site	N	Slope(95% CI)	Intercept(95% CI)	Pearson r
1	67	0.94(0.85,1.02)	0.2(-0.0,0.4)	0.86
2	43	1.02(0.92,1.15)	0.1(-0.2,0.3)	0.97
3	47	1.03(0.94,1.12)	0.0(-0.2,0.2)	0.97

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Site	N	Slope(95% CI)	Intercept(95% CI)	Pearson r
4	43	0.95(0.82,1.13)	0.2(-0.3,0.5)	0.93
All	200	0.98(0.93, 1.03)	0.1(0.0, 0.3)	0.91

5.3. Sample Matrix Comparison

Not applicable, as the CoaguChek Vantus System is intended for use with capillary whole blood samples only.

5.4. Expected Values / Reference Range

A normal range study was conducted on 121 healthy subjects not on anticoagulation therapy. Capillary whole blood sample testing performed on the subjects not using vitamin K antagonist drugs demonstrated that 95% of the INRs ranged between 0.9 - 1.1.

6. SYSTEM DESCRIPTIONS

6.1. Modes of Operation

The CoaguChek Vantus System is a closed system, which only uses the CoaguChek XS PT Test Strip; other test strips will not work with the instrument.

6.2. Software

The user interface of the CoaguChek Vantus instrument guides the user through the test procedure step by step. The user only needs to insert the code chip, turn the meter on, insert the test strip, and apply a blood sample. The CoaguChek Vantus meter measures the coagulation time and displays the result. After the test is completed, the meter automatically saves the test result.

The system also includes Bluetooth connectivity to allow transfer of INR results.

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Specimen Sampling and Handling 6.3.

The CoaguChek XS PT Test strip is intended for single-use only. Once the test strip is inserted into the analyzer, a drop of fresh capillary whole blood sample collected by fingerstick is manually applied to the test strip target area and analyzed by the CoaguChek Vantus instrument.

6.4. Calibration

Each lot of CoaguChek XS PT Test strips is factory calibrated to a reference lot of human recombinant thromboplastin traceable to the World Health Organization International Reference Preparation. This lot-specific calibration information is embedded within the code chip, which is required by the CoaguChek Vantus instrument prior to using the specific lot of the CoaguChek XS PT Test strip.

Quality Control 6.5.

The CoaguChek Vantus System provides On-Board Controls (OBC), which provide a quality control check for each individual CoaguChek XS PT Test strip used with the CoaguChek Vantus instrument. There are no additional steps required by the user to activate the OBC.

When a test strip is inserted, the CoaguChek Vantus instrument, the first check assesses potential issues with the reagent. The second check ensures that the test strip has not been exposed to environmental conditions or physical stresses, like bending. If either of these checks does not pass, then no PT/INR result is provided.

CONCLUSIONS 7.

The submitted information in this premarket notification supports a substantial equivalence decision.

The results of these studies demonstrate that the CoaguChek Vantus System is similar to the predicate. The data presented are a summary of external clinical evaluation, internal laboratory evaluation, and software development information.

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).