Assure Titanium Blood Glucose Monitoring System

K200788 · Arkray, Inc. · PZI · May 23, 2022 · Clinical Chemistry

Device Facts

• Record ID: K200788
• Device Name: Assure Titanium Blood Glucose Monitoring System
• Applicant: Arkray, Inc.
• Product Code: PZI · Clinical Chemistry
• Decision Date: May 23, 2022
• Decision: SESE
• Submission Type: Dual Track
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The Assure Titanium Blood Glucose Monitoring System consists of the Assure Titanium Blood Glucose meter and the Assure Titanium Blood Glucose test strips. The Assure Titanium Blood Glucose Monitoring System is intended for use in the quantitative measurement of glucose in fresh capillary whole blood samples drawn from the fingertips. The system is intended for in vitro diagnostic, point of care use in endocrinology clinics and nursing or skilled nursing facilities, for multiple patient use. This system should only be used with single-use, auto-disabling lancing devices for drawing finger stick capillary blood. The system is not intended for the screening or diagnosis of diabetes mellitus but is indicated for use in determining dysglycemia. The system is not intended for use in acute care or hospital settings. The system is not intended for neonatal use. The system is for prescription use only.

Device Story

System consists of battery-powered meter, disposable test strips, and control solutions; used in endocrinology clinics and nursing facilities by healthcare professionals. Input: fresh capillary whole blood via finger stick. Principle: amperometric biosensor; glucose oxidase (GOD) reacts with glucose in sample to produce electric current proportional to glucose concentration. Meter measures current, calculates glucose level, and displays result. Output: quantitative glucose concentration. Benefits: provides rapid point-of-care glucose monitoring for clinical decision-making in non-acute settings. Device includes test strip ejector and error flagging for out-of-range samples, short samples, or sample perturbation.

Clinical Evidence

Multi-center study (1 nursing facility, 2 endocrinology clinics) with 396 patients. Compared Assure Titanium results to YSI 2300 reference analyzer. Results showed strong linear correlation (r=0.99). Accuracy: 99.2% of samples ≥75 mg/dL within ±15% of reference; 100% of samples <75 mg/dL within ±15 mg/dL. Bench testing confirmed precision (%CV ≤4.2%), linearity (10-600 mg/dL), hematocrit range (10-70%), and interference resistance.

Technological Characteristics

Amperometric electrochemical biosensor; glucose oxidase enzyme; hexaammineruthenium (III) chloride mediator; battery-powered meter; capillary action sample intake; 0.5 μL sample volume; 7-second measurement time; 10-600 mg/dL measuring range; automated calibration; 10-70% hematocrit range; compliant with IEC 60601-1-2 for EMC.

Indications for Use

Indicated for quantitative glucose measurement in fresh capillary whole blood from fingertips in endocrinology clinics and nursing/skilled nursing facilities. For prescription, point-of-care, multiple-patient use. Not for diabetes screening/diagnosis, acute care, hospital settings, or neonatal use. Contraindicated for patients undergoing tight glycemic control or those with severe hypotension, shock, hyperosmolar-hyperglycemia, or severe dehydration.

Regulatory Classification

Identification

A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Special Controls

*Classification.* Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Predicate Devices

• Statstrip Glucose Hospital Meter System (k132121)

Submission Summary (Full Text)

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May 23, 2022

Arkray, Inc. Dhwani Thakkar Regulatory Affairs Project Manager 5182 West 76th Street Minneapolis, MN 55439

Re: K200788

Trade/Device Name: Assure® Titanium Blood Glucose Monitoring System Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose Test System Regulatory Class: Class II Product Code: PZI Dated: June 14, 2021 Received: June 15, 2021

Dear Dhwani Thakkar:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone [phone] or 301-796-7100).

Sincerely,

Kellie Kelm, Ph.D. Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) K200788

#### Device Name

Assure® Titanium Blood Glucose Monitoring System

Indications for Use (Describe)

· The Assure Titanium Blood Glucose Monitoring System consists of the Assure Titanium Blood Glucose meter and the Assure Titanium Blood Glucose test strips. The Assure Titanium Blood Glucose Monitoring System is intended for use in the quantitative measurement of glucose in fresh capillary whole blood samples drawn from the fingertips. The system is intended for in vitro diagnostic, point of care use in endocrinology clinics and nursing facilities, for multiple patient use. This system should only be use, auto-disabling lancing devices for drawing finger stick capillary blood.

• The system is not intended for the screening or diagnosis of diabetes mellitus but is indicated for use in determining dysglycemia.

- · The system is not intended for use in acute care or hospital settings.
- · The system is not intended for neonatal use.
- · The system is for prescription use only.

Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)

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

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# 1. Administrative Information

| Applicant's Name<br>and Address | Yoshiharu Uehata<br>ARKRAY, Inc.<br>Yousuien-nai, 59 Gansuin-cho<br>Kamigyo-ku, Kyoto 602-0008 Japan<br>Establishment Registration # 3003422726 |
|---------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|
| Primary Contact | Dhwani Thakkar<br>Regulatory Affairs Project Manager<br>[e-mail] |
| Secondary Contact | Daya Ranamukhaarachchi, PhD<br>V.P. Regulatory and Scientific Affairs<br>[e-mail] |
| Phone | 408-234-0804 |
| Fax | 1-855-924-2725 |
| Email | [e-mail] |
| Date Prepared | June 14, 2021 |

# 2. Device Information

# Device

| Trade Name | Assure® Titanium Blood Glucose Monitoring System |
|--------------------------|------------------------------------------------------------------|
| 510(k) Number | K200788 |
| Classification Name | Prescription Use Blood Glucose Meter for Near-Patient<br>Testing |
| Common Name | Glucose Test System |
| Product Code | PZI |
| Classification Panel | 75 – Clinical Chemistry |
| Device<br>Classification | 21 CFR § 862.1345 |

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## 3. Predicate Device Information

| Predicate Device Name | Predicate Device<br>510(k) Number |
|-----------------------------------------|-----------------------------------|
| StatStrip Glucose Hospital Meter System | K132121 |

## 4. Device Description

The Assure Titanium Blood Glucose Monitoring System consists of a battery-powered meter, disposable test strips Assure Titanium Blood Glucose Test Strips, and control solutions. The Assure Titanium Blood Glucose Test Strips utilizes biosensor technology for the quantitative determination of glucose concentrations in capillary blood samples. Glucose in the blood reacts with the reagent in the test strip, and this produces a small electric current (amperometry). The strength of this current is proportional to the concentration of glucose in the blood. The meter measures this current and calculates the patient's glucose level.

#### Test principle:

The sample (whole blood) is drawn by capillary action at the tip of the test strip. As depicted in the chemical reactions listed below in Figure 1, glucose in the sample reacts with glucose oxidase (GOD) and Hexaammineruthenium (III) chloride in the test strip. This produces Hexaammineruthenium (II) chloride. Hexaammineruthenium (II) chloride is produced in proportion to the glucose concentration of the blood sample. Oxidation of the Hexaammineruthenium (II) chloride produces an electric current. The meter converts the current to the glucose concentration and displays it as the test result.

B-D-glucose + Hexaammineruthenium (II) chloride -> D-Glucono-δLactone + Hexaammineruthenium (II) chloride Hexaammineruthenium (II) chloride Electrical Charge Hexaammineruthenium (III) chloride + e-

#### Figure 1: Principle of Action for Assure Titanium Blood Glucose Monitoring System

A similar test principle is used in StatStrip Glucose Hospital Meter System previously cleared under K132121.

## 5. Indications for Use

The Assure Titanium Blood Glucose Monitoring System consists of the Assure Titanium Blood Glucose meter and the Assure Titanium Blood Glucose test

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strips. The Assure Titanium Blood Glucose Monitoring System is intended for use in the quantitative measurement of glucose in fresh capillary whole blood samples drawn from the fingertips. The system is intended for in vitro diagnostic, point of care use in endocrinology clinics and nursing or skilled nursing facilities, for multiple patient use. This system should only be used with single-use, auto-disabling lancing devices for drawing finger stick capillary blood.

The system is not intended for the screening or diagnosis of diabetes mellitus but is indicated for use in determining dysglycemia.

The system is not intended for use in acute care or hospital settings.

The system is not intended for neonatal use.

The system is for prescription use only.

### 6. Substantial Equivalence Information

The Assure Titanium Blood Glucose Monitoring Device uses similar intended use as the predicate, StatStrip Glucose Hospital Meter System. Also, test principle and technology are similar for both devices. Table 1 below provides a comparison between the Assure Titanium Blood Glucose Monitoring System and its predicate device.

As described in the performance testing summary below, the verification and validation (bench and clinical) testing successfully demonstrated substantial equivalence for the Assure Titanium Blood Glucose Monitoring System to the predicate device as required per 21 CFR § 807.92(b)(3).

| Table 1: Similarities and Differences Table | | | | |
|---------------------------------------------|--|--|--|--|
| | | | | |

| COMPONENT/<br>CHARACTERISTIC | PROPOSED | PREDICATE |
|-----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K200788 | K132121 |
| Device/Measuring<br>System | Assure® Titanium<br>Blood Glucose<br>Monitoring System | StatStrip Glucose<br>Hospital Meter<br>System |
| COMPONENT/<br>CHARACTERISTIC | PROPOSED | PREDICATE |
| Intended Use and<br>Indications for Use | The Assure Titanium<br>Blood Glucose<br>Monitoring System<br>consists of the Assure<br>Titanium Blood<br>Glucose meter and the<br>Assure Titanium<br>Blood Glucose test<br>strips. The Assure<br>Titanium Blood<br>Glucose Monitoring<br>System is intended for<br>use in the quantitative<br> | For the quantitative<br>determination of<br>glucose in capillary<br>finger stick, venous<br>whole blood, arterial<br>whole blood, neonate<br>arterial whole blood<br>and neonate heel stick<br>specimens. Also for<br>the quantitative<br>determination of<br>glucose in venous<br>whole blood, arterial<br>whole blood,<br>neonatal heel stick,<br>and neonatal arterial<br>whole blood<br>throughout all<br>hospital and all<br>professional<br>healthcare settings. |
| | intended for neonatal<br>use.<br>The system is for<br>prescription use only. | |
| Population limitation | Not intended for<br>neonatal use, acute<br>care or hospital<br>settings, nor for use<br>with patients<br>receiving intensive<br>medical<br>intervention/therapy. | Not intended for<br>patients receiving<br>intensive medical<br>intervention/therapy.<br>This system is<br>intended for use with<br>neonatal arterial whole<br>blood but has not been<br>validated for neonatal<br>venous blood. |
| Sample Type | Fresh capillary whole<br>blood* | Whole Blood:<br>Capillary, Venous,<br>Arterial, and Neonate<br>arterial whole blood |
| Test Strip Ejector | Yes | No |
| Controls | 3 levels of Assure<br>Control- Control<br>Solutions | 3 levels of Nova<br>StatStrip Control<br>Solutions |
| Maximum<br>Altitude | 10,000 ft (3,048<br>meters) | 15,000 ft (4500<br>meters) |
| Sample Volume | 0.5 µL | 1.2 µL |
| Weight | 4.1 oz with batteries | 9.6 oz |
| Dimensions | 4.7 x 2.4 x 1.2 inch | 6.0 x 3.25 x 1.8 inch |
| Battery/Power<br>source | Two 1.5V alkaline<br>AAA batteries | 3.7V Li Polymer<br>battery<br>(Rechargeable/Replace<br>able) |
| Operating<br>Temperature range | 46-104°F (8-40°C) | 59-104 °F (15-40°C) |
| Hematocrit Range | 10-70% | 20-65% |
| Data Storage | 1,000 test results | 1,000 Patient Tests<br>200 QC Tests<br>4000 Operators |
| Measuring Time | 7 seconds | 6 seconds |
| Electrical<br>Compliance | Conforms to<br>ANSI/AAMI IEC<br>60601-1-2:2014 | Conforms to:<br>IEC 61010-1:2001 and<br>IEC 61010-2-101:2002 |
| Measuring Range | 10-600 mg/dL | 10-600 mg/dL |
| Relative Humidity | 10-90% (no condensation) | 10-90% (no condensation) |
| Enzyme | Glucose oxidase<br>(Aspergillus niger sourced) | Glucose Oxidase<br>(Aspergillus sourced) |
| Test Principle | Electro-chemical<br>biosensor<br>(Amperometric) | Electro-chemical<br>biosensor<br>(Amperometric) |
| Calibration | Automatic coded<br>calibration | Automatic, no<br>calibration code |
| Wi-Fi network<br>connectivity | No | No |

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* Although whole blood samples are used for measurement, displayed results are equivalent to plasma glucose levels.

## 7. Summary of Performance Testing

Performance testing was conducted on the proposed Assure Titanium Blood Glucose Monitoring System in accordance with the FDA guidance Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use, 2016 and 2020 using final product. Performance testing demonstrated that the device meets the performance requirements for its intended use.

#### PRECISION

Within-run and intermediate precision for the Assure Titanium Blood Glucose Monitoring System were evaluated to assess imprecision of the system across the glucose measuring range and under normal use conditions.

Briefly, within-run precision was evaluated using venous whole blood spiked with high concentration glucose solution or allowed to glycolyze to 5 glucose concentrations. These whole blood samples were tested on at least 10 vials of 3 test strip lots using at least 10 Assure Titanium Blood Glucose Meters. Test strips were taken from the same bottle for each meter. This resulted in 500 results on each lot, for a total of 1500 tests.

Results for the within-run precision testing are shown in Table 2, mean results for each glucose level are presented for each lot with associated standard deviation (SD), percent coefficient of variation (%CV) and the 95% confidence intervals.

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| Lot # | Glucose Level<br>(mg/dL) | Mean (mg/dL) | SD | 95% CI | %CV |
|-------|--------------------------|--------------|------|-------------|------|
| 280-2 | 30-50 | 45.7 | 1.2 | 1.0 to 1.4 | 2.6% |
| | 51-110 | 96.3 | 2.0 | 1.6 to 2.4 | 2.1% |
| | 111-150 | 140.2 | 3.1 | 2.5 to 3.6 | 2.2% |
| | 151-250 | 203.7 | 6.2 | 5 to 7.5 | 3.1% |
| | 251-400 | 324.3 | 10.1 | 8.1 to 12.1 | 3.1% |
| 280-4 | 30-50 | 44.4 | 1.3 | 1.0 to 1.5 | 2.9% |
| | 51-110 | 95.7 | 2.0 | 1.6 to 2.4 | 2.1% |
| | 111-150 | 139.6 | 2.8 | 2.2 to 3.3 | 2.0% |
| | 151-250 | 204.9 | 3.8 | 3.1 to 4.6 | 1.9% |
| | 251-400 | 324.2 | 7.5 | 6.1 to 9 | 2.3% |
| 280-5 | 30-50 | 42.6 | 1.0 | 0.8 to 1.2 | 2.4% |
| | 51-110 | 92.8 | 2.3 | 1.8 to 2.7 | 2.4% |
| | 111-150 | 137.8 | 3.2 | 2.6 to 3.9 | 2.3% |
| | 151-250 | 202.7 | 4.9 | 3.9 to 5.8 | 2.4% |
| | 251-400 | 324.1 | 8.7 | 7 to 10.4 | 2.7% |

Table 2: Within-Run Precision Results for Assure Titanium Blood Glucose Monitoring System

The data in Table 2 demonstrate the within-run precision met the overall acceptance criteria for %CV ≤ 4.2% for the Assure Titanium Blood Glucose Monitoring System.

Intermediate precision was evaluated using control solution adjusted to the same 5 glucose concentrations. Multiple operators tested the control solution over 10 days using at least 10 bottles of 3 test strip lots and 10 Assure Titanium meters. Test strips were taken from the same bottle for each meter. This resulted in 50 tests per lot per day for a total of 1500 tests.

Results for intermediate precision testing for all lots are shown in Table 3. Mean results for each glucose level are presented with associated standard deviation (SD), percent coefficient of variation (%CV) and the 95% confidence intervals.

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| | Glucose Level<br>(mg/dL) | Mean (mg/dL) | SD | 95% CI | %CV |
|----------------------|--------------------------|--------------|-----|------------|-----|
| All Lots<br>Combined | 30-50 | 42.4 | 0.8 | 0.6 to 0.9 | 1.9 |
| | 51-110 | 87.0 | 1.4 | 1.1 to 1.7 | 1.6 |
| | 111-150 | 129.3 | 1.8 | 1.4 to 2.1 | 1.4 |
| | 151-250 | 254.7 | 3.9 | 3.2 to 4.7 | 1.5 |
| | 251-400 | 360.6 | 7.5 | 6.0 to 9.0 | 2.1 |

Table 3: Intermediate Precision Results for Assure Titanium

The data in Table 3 show that Intermediate precision met the overall acceptance criteria.

#### LINEARITY

Linearity for the Assure Titanium Blood Glucose Monitoring System was evaluated using glucose concentrations across the claimed glucose measuring range and data was analyzed according to CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement: A Statistical Approach; An Approved Guideline.

Briefly, linearity was evaluated using venous whole blood spiked with high concentration glucose solution or allowed to glycolyze to eleven evenly spaced glucose concentrations. The target glucose concentrations were verified by the YSI 2300 reference analyzer. These whole blood samples were tested on 3 test strip lots using 5 Assure Titanium Blood Glucose Meters. This resulted in 5 replicates per level per lot tested, for a total of 165 results.

Data analysis included linear regression with regression equation and coefficient of determination (R2) presented for each lot tested and presented in Table 4.

| Lot | Linear Regression Equation | R2 |
|------------|----------------------------|--------|
| Type 280-1 | y = 1.0079x + 3.9485 | 0.9988 |
| Type 302-1 | y = 1.0063x + 3.3727 | 0.9993 |
| Type 302-2 | y = 0.9902x + 2.1839 | 0.9999 |

Table 4: Linear Regression Equation for All Assure Titanium Blood Glucose Monitoring System Lots

Data analysis showed that linearity testing met the acceptance criteria in that all measurements fell within the ranges shown in Table 5, demonstrating linearity of the Assure Titanium Blood Glucose Monitoring System across the claimed measuring range of 10-600 mg/dL.

Table 5: Assure Titanium Blood Glucose Monitoring System Comparison to YSI 2300 Reference

| Lot | Within ±15% at <75 mg/dL and<br>±12% at ≥75 mg/dL from reference |
|------------|------------------------------------------------------------------|
| Type 280-1 | 100% |
| Type 302-1 | 100% |
| Type 302-2 | 100% |

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#### HEMATOCRIT

The effect of hematocrit on the performance of the Assure Titanium Blood Glucose Monitoring System was evaluated to establish that it can be safely used across the claimed hematocrit range. Briefly, percent hematocrit effect on Assure Titanium Blood Glucose Monitoring System results was evaluated using venous whole blood adjusted to five glucose levels and thirteen hematocrit levels spaced 5% apart spanning the claimed hematocrit range.

The target acceptance criteria are as follows: For glucose levels ≥ 75 mg/dL, the average bias to comparator method should be <5% with no individual value exceeding 10%. For glucose levels <75 mg/dL, the absolute bias should be reported with 95% confidence intervals justified for clinical impact.

The results for glucose levels ≥75 mg/dL met the target acceptance criteria. In addition, the absolute bias for results for glucose levels <75 mg/dL ranged from -1.5 to 2.2 mg/dL, an error so small that this error would not impact patient safety. The results of the Hematocrit Evaluation study support the safe use of the Assure Titanium Blood Glucose Monitoring System across the claimed hematocrit range of 10- 70% in the intended use population.

#### INTERFERENCE

The effect of potentially interfering endogenous and exogenous substances was evaluated on the Assure Titanium Blood Glucose Monitoring System. The study was designed using whole blood samples spiked or allowed to glycolyze to 3 target ranges. Eachinterferent was tested at clinically relevant concentrations. For each concentration of potential interferent, average percent bias to untreated control samples and 95% confidence intervals were calculated. If interference was observed additional testing was performed to determine the concentration at which the interference starts to occur. Table 6 lists potentially interfering substances and the maximum concentrations tested and the highest tested concentration at which no interference was observed.

| | Potential Interfering<br>Substance | Highest concentration with no<br>interference | Maximum Test<br>Concentration |
|----|------------------------------------|-----------------------------------------------|-------------------------------|
| 1 | Acetaminophen | 20 mg/dL | 20 mg/dL |
| 2 | Ascorbic acid | 4 mg/dL | 6 mg/dL |
| 3 | Conjugated Bilirubin | 50 mg/dL | 50 mg/dL |
| 4 | Unconjugated Bilirubin | 40 mg/dL | 40 mg/dL |
| 5 | Cholesterol | 500 mg/dL | 500 mg/dL |
| 6 | Creatinine | 15 mg/dL | 15 mg/dL |
| 7 | Dopamine | 20 mg/dL | 20 mg/dL |
| 8 | EDTA | 180 mg/dL | 200 mg/dL |
| 9 | Galactose | 60 mg/dL | 60 mg/dL |
| 10 | Gentisic acid | 700 mg/dL | 1,000 mg/dL |
| 11 | Reduced Glutathione | 92 mg/dL | 92 mg/dL |
| 12 | Hemoglobin | 20,000 mg/dL | 20,000 mg/dL |
| 13 | Heparin | 500 IU/dL | 500 IU/dL |
| 14 | Ibuprofen | 50 mg/dL | 50 mg/dL |
| 15 | Icodextrin | 1094.4 mg/dL | 1094.4 mg/dL |
| 16 | L-Dopa | 0.75mg/dL | 0.75 mg/dL |
| 17 | Maltose | 5,000 mg/dL | 10,000 mg/dL |
| 18 | Methyl-L-dopa | 1000 mg/dL | 1000 mg/dL |
| 19 | Salicylic acid | 60 mg/dL | 60 mg/dL |
| 20 | Sodium | 414 mg/dL | 414 mg/dL |
| 21 | Tolbutamide | 100 mg/dL | 100 mg/dL |
| 22 | Tolazamide | 40 mg/dL | 40 mg/dL |
| 23 | Triglycerides | 1,500 mg/dL | 1,500 mg/dL |
| 24 | Uric acid | 24 mg/dL | 24 mg/dL |
| 25 | Xylose | 300 mg/dL | 600 mg/dL |
| 26 | Xylitol | 0.09 mg/dL | 0.09 mg/dL |
| 27 | Mannitol | 1,800 mg/dL | 1,800 mg/dL |
| 28 | Fenofibric Acid | 1.8 mg/dL | 1.8 mg/dL |
| 29 | Canagliflozin | $15\times10^{-4}$ mg/dL | $15\times10^{-4}$ mg/dL |
| 30 | Amlodipine Besylate | $18\times10^{-4}$ mg/dL | $18\times10^{-4}$ mg/dL |
| 31 | Atorvastatin Calcium | $84\times10^{-4}$ mg/dL | $84\times10^{-4}$ mg/dL |
| 32 | Cilostazol | $21\times10^{-2}$ mg/dL | $21\times10^{-2}$ mg/dL |
| 33 | Prasugrel | $105\times10^{-3}$ mg/dL | $105\times10^{-3}$ mg/dL |
| 34 | Nortriptyline HCl | $45 \times 10^{-6}$ mg/dL | $45 \times 10^{-6}$ mg/dL |
| 35 | Budesonide | $36\times10^{-5}$ mg/dL | $36\times10^{-5}$ mg/dL |
| 36 | Dextromethorphan | $9\times10^{-4}$ mg/dL | $9\times10^{-4}$ mg/dL |
| 37 | Oxcarbazepine | $258\times10^{-2}$ mg/dL | $258\times10^{-2}$ mg/dL |
| 38 | Trihexyphenidyl HCL | $15\times10^{-3}$ mg/dL | $15\times10^{-3}$ mg/dL |
| 39 | Fluphenazine Decanoate | $81\times10^{-5}$ mg/dL | $81\times10^{-5}$ mg/dL |
| 40 | Levoflaxicin | $183\times10^{-5}$ mg/dL | $183\times10^{-5}$ mg/dL |
| 41 | Glimiperide | $576\times10^{-4}$ mg/dL | $576\times10^{-4}$ mg/dL |
| 42 | Benazeprilat | 297 nmol/dL | 297 nmol/dL |
| 43 | Saxagliptin | $72\times10^{-4}$ mg/dL | $72\times10^{-4}$ mg/dL |
| 44 | Morphine | 28.3 nmol/dL | 84.9 nmol/dL |
| 45 | Ursodiol | $7,836\times10^{-4}$ mg/dL | $9,795\times10^{-4}$ mg/dL |
| 46 | Silodosin | $1848\times10^{-5}$ mg/dL | $1848\times10^{-5}$ mg/dL |
| 47 | Letrozole | 31.2 nmol/dL | 31.2 nmol/dL |

Table 6: Maximum Concentrations Tested

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The results were compared to the following target acceptance criteria: for each concentration of potential interferent the average percent bias and 95% confidence interval of test sample to untreated control sample must be within ±10% at each glucose level.

Interfering Substances

- Patients with high doses of Vitamin C intake (ascorbic acid; blood levels higher than . 4 mg/dL) may yield inaccurate results.
- Patients undergoing oxygen therapy may yield inaccurate results. ●

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#### CLEANING AND DISINFECTION VIRAL ELIMINATION EFFECTIVENESS

The cleaning and disinfection viral elimination effectiveness study for the Assure Titanium Blood Glucose Monitoring System was conducted by Microbac Laboratories (Sterling, VA).

The elimination of duck hepatitis B virus, as a surrogate for human hepatitis B virus, using the disinfection product, PDI Super Sanicloth (EPA# 9480-4), has been evaluated with the constituent surface materials of the Assure Titanium Blood Glucose Monitoring System.

The PDI Super Sanicloth Wipes were proven to be effective in eliminating the duck hepatitis B virus from all tested surfaces.

### CLEANING AND DISINFECTION ROBUSTNESS/DURABILITY

Cleaning and disinfection durability testing were performed to demonstrate that the Assure Titanium Blood Glucose Monitoring System can withstand multiple cleaning and disinfection cycles to validate a three-year use life or "warranty" for the Assure Titanium Blood Glucose Monitoring System. The number of cleaning and disinfection cvcles performed for this testing was based ten cleaning and disinfection cycles per day for three years for a total of 10.950 cycles (10 cycles/day * 365 days/year * 3 years = 10,950).

To demonstrate that the Assure Titanium Blood Glucose Monitoring System is not adversely affected by the recommended cleaning and disinfection cvcles applied over a three-vear use life. five meters were cleaned and disinfected 10,950 times with PDI Super Sanicloth Wipes (EPA# 9480-4) and examined to detect any performance issues and signs of physical deterioration.

A physical inspection and performance testing of each of the five meters was performed at the beginning of the study, midway through the study (approximately 5,480 cleaning anddisinfection cvcles), and after the 10.950 cleaning and disinfection cycles were complete. The five meters were inspected at the three time points to determine if there were signs of physical and/or performance deterioration.

The venous blood performance met the acceptance criteria at each time point. All external material passed physical and performance inspection after cleaning and disinfecting 10.950 times with PDI Super Sanicloth Wipes.

#### INTERMITTENT SAMPLING

Intermittent sampling occurs when a short sample is applied to a test strip, a glucose measurement begins, and more sample is applied to the test strip before the glucose measurement is complete. Briefly, intermittent sampling was evaluated using venous whole blood spiked with high concentration glucose solution or allowed to glycolyze to three concentrations: 50-65 mg/dL, 100-120 mg/dL, 200-250 mg/dL. The glucose levels were verified by the YSI 2300 reference analyzer.

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The results demonstrated that the Assure Titanium Blood Glucose Monitoring System provides accurate glucose measurements or an error when the sample is intermittently applied to an Assure Titanium Blood Glucose Test Strip.

#### ENVIRONMENTAL/SYSTEM OPERATING CONDITIONS

A study to assess the performance of the Assure Titanium Blood Glucose Monitoring System when used under various operating temperature and humidity conditions was performed. These studies were designed to represent actual use conditions experienced by Blood Glucose Monitoring The tested temperature and humidity ranges covered the system operating System users. conditions and also included ranges outside the claimed operating range. The testing incorporated eight extreme temperature and humidity combinations (high temperature/low humidity; high temperature/high humidity; low temperature/low humidity; low temperature/high humidity) within and outside the claimed operating range.

### ALTITUDE

ARKRAY evaluated the effect of altitude on the performance of the Assure Titanium Blood Glucose Monitoring System. Three lots of Assure Titanium test strips were tested with venous blood samples at three glucose levels at two altitude conditions. Sea level (203 feet) and high altitude (10.000 feet) were tested using a custom-made pressure chamber to create the effects of altitude.

The results demonstrated that the Assure Titanium Blood Glucose Monitoring System performance is unaffected by altitudes up to and equal to an elevation of 10,000 feet.

### ERROR CODES FOR SAMPLES OUTSIDE THE MEASURING RANGE

ARKRAY performed analyses to demonstrate that the Assure Titanium Blood Glucose Monitoring System provides the appropriate error codes when measured glucose concentrations are outside of the Blood Glucose Monitoring System's claimed measuring range. Three lots of Assure Titanium test strips were tested with venous blood samples at two glucose levels (<10 and >600 mg/dL). The acceptance criteria were as follows: All meters to display "Lo" at glucose levels <10 mg/dL, all meters to display "HI" at glucose levels >600 mg/dL.

All results met the acceptance criteria demonstrating that the Assure Titanium Blood Glucose Monitoring System will supply the user with the appropriate error codes when measuring blood glucose concentrations outside of the claimed measuring range.

### ERROR CODES AND FLAGGING

ARKRAY performed evaluations to demonstrate that the Assure Titanium Blood Glucose Monitoring System provides error codes and flags according to the design specification. Please see Table 7 below for details on the error codes/flags evaluated.

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| Table 7: Assure Titanium Blood Glucose Monitoring System Error Codes and Flags | |
|--------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------|
| Error Code | Description |
| E-1 | Test strip was previously used. Retest with a new test strip. |
| E-2 | Meter malfunction. Contact customer service. |
| E-3 | Temperature too high or too low. Move to an area with a temperature between 50°F and 104°F (10°C and 40°C) and retest. |
| E-4 | Test strip is damaged or was not properly inserted. Retest with a new test strip. |
| E-5 | Blood sample was applied before the flashing blood drop symbol appeared. Retest with a new test strip. |
| E-6 | Not enough blood was applied to the test strip. Retest with a new test strip. |
| E-7 | Control solution test result is out of range. Repeat the control solution test. |
| E-8 | Meter malfunction. Contact customer service. |
| E-9 | Test strip error. Retest with a new test strip. |
| E-10 | Meter malfunction. Contact customer service. |

| E6 | Occurs when the temperature is outside the<br>temperature operating range |
|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------|
| E5 | Occurs when an abnormal sample is detected,<br>the contact bars of the test strips are dirty, or<br>an incorrect sample type is used |
| E0 | Occurs when measurement of blood sample is<br>attempted during QC lockout |
| Control Solution Flag | Meter displays control flag when control<br>solution is tested |
| Temperature Flag | Occurs alongside E6 when the temperature is<br>outside the temperature operating range |

For each error code/flag listed in Table 7, the appropriate conditions that trigger the error code/flag were tested and the error code/flag was verified. Additionally, conditions that should not trigger the error code/flag were also tested and the absence of the error code/flag was verified.

### SHORT SAMPLE DETECTION

Blood glucose measurement from short samples of reduced sample volume) can lead to inaccurate results. To avoid the risk of inaccurate results, Blood Glucose Monitoring Systems should be able to detect that a short blood sample has been applied to the test strip and should not provide a result.

Three lots of Assure Titanium test strips were tested with venous blood samples at three glucose levels (50-65. 100-120, 200-250 mg/dL) that were verified using the YS1 2300. Approximately 0.1. 0.3. 0.5. 1. 5. or 10 uL of sample was applied to the test strip. Once the countdown was completed (if initiated), an error or the test result displayed on the meter.

The results demonstrated that the Assure Titanium Blood Glucose Monitoring System will either produce an error or an accurate result when short sampled.

### SAMPLE PERTURBATION

Sample perturbation occurs when an appropriate volume of blood is applied to the test strip for glucose measurement, but an event such as wicking of blood away from the test strip, flicking of the test strip or flipping of the meter occurs during the start of the measurement and potentially alters the volume of the initial sample application.

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Three lots of Assure Titanium test strips were tested with venous blood samples at three glucose levels (50-65, 100-120, 200-250 mg/dL) that were verified using the YSI 2300. The samples were applied to the test strip and then perturbed by flicking the test strip, flipping the meter on theside, and wicking the sample away using a tissue.

The results demonstrated that the Assure Titanium Blood Glucose Monitoring System either provides an error or an accurate result when the sample is perturbed.

### TESTING WITH USED TEST STRIP

The Assure Titanium Blood Glucose Monitoring System is designed to automatically detect the insertion of used Assure Titanium Blood Glucose Test Strips into the Assure Titanium Blood Glucose Meter. Insertion of used Assure Titanium Blood Glucose Test Strips into the system should not provide glucose measurement results.

Three lots of Assure Titanium test strips were dosed with either capillary finger-stick blood or control solution. The used test strips were then re-inserted into Assure Titanium meters to produce an error. The target acceptance criteria are as follow: All used test strips shall produce the E1 error upon re-insertion. All test results met the acceptance criteria.

#### SUMMARY OF CLINICAL STUDY (METHOD COMPARISON)

The Assure Titanium Blood Glucose Meter and Assure Titanium Blood Glucose Test Strips for the Assure Titanium Blood Glucose Monitoring System were tested in a multi-center study conducted at one (1) nursing/skilled nursing facility and two (2) endocrinology clinics to demonstrate clinical performance with patients/subjects in whom routine glucose monitoring is done in these settings.

Nursing/skilled nursing facility (Site #1) is a 475-bed institution in the state of Massachusetts. The study took place across both long-term care nursing and temporary care/rehabilitation units. The study was conducted by Point-of-Care operators who took capillary blood samples from 130 patients . Patients in this study represented 390 medical conditions and 239 different medications. Site #2 is an endocrinology clinic located in the state of California. Point-of-Care operators took capillary blood samples from 165 patients in this study represented 18 medical conditions and 245 different medications. Site #3 is an endocrinology clinic located in the state of Georgia. Point-of-Care operators took capillary blood samples from 101 patients. Patients in this study comprised 61 medical conditions and 196 different medications.

In total, capillary blood samples from 396 patients were measured and the results were compared to the YSI Model 2300 Glucose Analyzer, a lab instrument (comparator method). The tables 8-12 below show differences in glucose values between the Assure Titanium Blood Glucose Meter and the YSI method.

The slope, correlation, intercept, standard error, and 95% confidence interval as shown in Table 8 represent a strong linear correlation between the Assure Titanium Blood Glucose Monitoring System and the YSI 2300 reference analyzer.

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| | Results obtained by healthcare professionals | |
|-------------------|----------------------------------------------|----------------------|
| | Nursing/Skilled<br>Nursing Facility | Endocrinology Clinic |
| Slope | 0.98 | 0.98 |
| Correlation 'r' | 0.99 | 0.99 |
| Intercept | 3.24 | 2.83 |
| Number of Samples | 130 | 266 |
| Range Tested | 29.0 - 405.5 mg/dL | 43.7 - 492.5 mg/dL |

Table 8: Assure Titanium Blood Glucose Monitoring System Correlation

Table 9: Nursing/Skilled Nursing Facility Accuracy results for glucose concentrations <75 mg/dL:

| Difference range between the true<br>blood glucose level and the Assure<br>Titanium Blood Glucose<br>Monitoring System result | Within<br>±5 mg/dL | Within<br>±10 mg/dL | Within<br>±12 mg/dL | Within<br>±15 mg/dL | Exceeds<br>±15 mg/dL |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|---------------------|---------------------|---------------------|----------------------|
| The percent (and number) of<br>samples for which the difference<br>between the Assure Titanium Blood<br>Glucose Meter and the YSI<br>comparator method were within the<br>difference range shown in the top<br>row | 1/1<br>(100%) | 1/1<br>(100%) | 1/1<br>(100%) | 1/1<br>(100%) | 0/1<br>(0%) |

Table 10: Nursing/Skilled Nursing Facility Accuracy results for glucose concentrations ≥75 mg/dL:

| Difference range between the true<br>blood glucose level and the Assure<br>Titanium Blood Glucose<br>Monitoring System result | Within<br>±5 % | Within<br>±10 % | Within<br>±12 % | Within<br>±15 % | Within<br>±20 % | Exceeds<br>±20 % |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------|--------------------|--------------------|--------------------|-------------------|------------------|
| The percent (and number) of<br>samples for which the difference<br>between the Assure Titanium Blood<br>Glucose Meter and the YSI<br>comparator method were within the<br>difference range shown in the top<br>row | 80/129<br>(62%) | 122/129<br>(94.6%) | 125/129<br>(96.9%) | 128/129<br>(99.2%) | 129/129<br>(100%) | 0/129<br>(0%) |

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Table 11: Endocrinology Clinic Accuracy results for glucose concentrations <75 mg/dL:

| Difference range between the true<br>blood glucose level and the Assure<br>Titanium Blood Glucose<br>Monitoring System result | Within<br>$\pm$ 5 mg/dL | Within<br>$\pm$ 10 mg/dL | Within<br>$\pm$ 12 mg/dL | Within<br>$\pm$ 15 mg/dL | Exceeds<br>$\pm$ 15 mg/dL |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|--------------------------|--------------------------|--------------------------|---------------------------|
| The percent (and number) of<br>samples for which the difference<br>between the Assure Titanium Blood<br>Glucose Meter and the YSI<br>comparator method were within the<br>difference range shown in the top<br>row | 17/26<br>(65.4%) | 25/26<br>(96.2%) | 26/26<br>(100%) | 26/26<br>(100%) | 0/26<br>(0%) |

Table 12: Endocrinology Clinic Accuracy results for glucose concentrations ≥75 mg/dL:

| Difference range between the true<br>blood glucose level and the Assure<br>Titanium Blood Glucose<br>Monitoring System result | Within<br>$\pm$ 5 % | Within<br>$\pm$ 10 % | Within<br>$\pm$ 12 % | Within<br>$\pm$ 15 % | Within<br>$\pm$ 20 % | Exceeds<br>$\pm$ 20 % |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------|----------------------|----------------------|----------------------|----------------------|-----------------------|
| The percent (and number) of<br>samples for which the difference<br>between the Assure Titanium Blood<br>Glucose Meter and the YSI<br>comparator method were within the<br>difference range shown in the top<br>row | 163/240<br>(67.9%) | 224/240<br>(93.3%) | 230/240<br>(95.8%) | 235/240<br>(97.9%) | 240/240<br>(100%) | 0/240<br>(0%) |

### Medications and Medical Conditions:

The clinical studies included patients representative of each clinical setting. A detailed analysis of medical conditions and medications was performed on the clinical data set from all three (3) clinical study sites to identify any potential safety issues with the use of the Assure Titanium Blood Glucose Monitoring System within the intended use population. A frequency distribution table (Table 13) for each Drug Class as well as a table for medical conditions (Table 14) are presented below.

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| | Table 13: Medications Table | |
|--|-----------------------------|--|

| Assure Titanium Method Comparison Study Drug Table | | |
|----------------------------------------------------------------------|----------------------------------------------------------------------------|--------------------------|
| Therapeutic Drug Class 2 | Therapeutic Drug Class 3 | Number<br>of<br>Patients |
| Agents Acting on the Renin-<br>Angiotensin System | ACE Inhibitors, Plain | 107 |
| Agents Acting on the Renin-<br>Angiotensin System | Angiotensin II Receptor Blockers<br>(ARBs), Plain | 62 |
| All Other Therapeutic Products | Angiotensin II Receptor Blockers<br>(ARBs), Combinations | 11 |
| All Other Therapeutic Products | All Other Therapeutic Products | 13 |
| Anabolic Agents for Systemic Use | Other Mineral Supplements | 29 |
| Analgesics | Opioids | 66 |
| Analgesics | Other Analgesics and Antipyretics | 132 |
| Anesthetics | Anesthetics, General | 1 |
| Anesthetics | Anesthetics, Local | 23 |
| Antianemic Preparations | Iron Preparations | 32 |
| Antianemic Preparations | Vitamin B12 and Folic Acid | 42 |
| Antibacterials for Systemic Use | Beta-Lactam Antibacterials,<br>Penicillins | 13 |
| Antibacterials for Systemic Use | Other Antibacterials | 8 |
| Antibacterials for Systemic Use | Other Beta-Lactam Antibacterials | 5 |
| Antibacterials for Systemic Use | Quinolone Antibacterials | 7 |
| Antibacterials for Systemic Use | Sulfonamides | 6 |
| Antibacterials for Systemic Use | Tetracyclines | 1 |
| Antibiotics and Chemotherapeutics<br>for Determatological Use | Antibiotics for Topical Use | 2 |
| Antibiotics and Chemotherapeutics<br>for Determatological Use | Chemotherapeutics for Topical Use | 1 |
| Antidiarrheals, Intestinal<br>Inflammatory/Antiinfective Agents | Antidiarrheal Microorganisms | 10 |
| Antidiarrheals, Intestinal<br>Inflammatory/Antiinfective Agents | Antipropulsives | 7 |
| Antidiarrheals, Intestinal<br>Inflammatory/Antiinfective Agents | Intestinal Adsorbents | 1 |
| Antidiarrheals, Intestinal<br>Inflammatory/Antiinfective Agents | Intestinal Antiinflammatory Agents | 35 |
| Antidiarrheals, Intestinal<br>Inflammatory/Antiinfective Agents | Other Antidiarrheals | 2 |
| Antiemetics and Antinauseants | Antiemetics and Antinauseants | 19 |
| Antiepileptics | Antiepileptics | 110 |
| Antifungals for Dermatologic Use | Antifungals for Systemic Use | 1 |
| Antifungals for Dermatologic Use | Antifungals for Topical Use | 23 |
| Antigout Preparations | Antigout Preparations | 21 |
| Antihistamines for Systemic Use | Antihistamines for Systemic Use | 24 |
| Antihypertensives | Antiadrenergic Agents, Generally<br>Acting | 5 |
| | Antiadrenergic Agents, Peripherally<br>Acting | 6 |
| | Arteriolar Smooth Muscle, Agents<br>Acting on | 8 |
| | Other Antihypertensives | 1 |
| Antiinflammatory and Antirheumatic<br>Products | Antiinflammatory and Antirheumatic<br>Products, Non-Steroids | 34 |
| Antimycotics for Systemic Use | Antimycotics for Systemic Use | 5 |
| Antiobesity Preparations, Excl. Diet<br>Products | Antiobesity Preparations, Excl. Diet<br>Products | 3 |
| | Anticholinergic Agents | 2 |
| Anti-Parkinson Drugs | Dopaminergic Agents | 16 |
| | Agents Against Amoebiasis and Other<br>Protozoal Diseases | 1 |
| Antiprotozoals | Antimalarials | 5 |
| Antiseptics and Disinfectants | Antiseptics and Disinfectants | 1 |
| Antithrombotic Agents | Antithrombotic Agents | 237 |
| Antivirals for Systemic use | Direct Acting Antivirals | 5 |
| | Beta Blocking Agents | 147 |
| Beta Blocking Agents | Beta Blocking Agents and Thiazides | 1 |
| Bile and Liver Therapy | Bile Therapy | 1 |
| Blood Substitutes and Perfusion<br>Solutions | Irrigating Solutions | 4 |
| | Selective Calcium Channel Blockers<br>with Direct Cardiac Effects | 16 |
| Calcium Channel Blockers | Selective Calcium Channel Blockers<br>with Mainly Vascular Effects | 64 |
| Calcium Homeostasis | Anti-Parathyroid Agents | 1 |
| | Parathyroid Hormones and Analogues | 1 |
| | Antiarrhythmics, Class I and III | 10 |
| | Cardiac Glycosides | 6 |
|…