EZ SMART-168 GLUCOSE MONITORING SYSTEM

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k052818 B. Purpose for Submission: Premarket Notification 510(k) of intention to manufacture and market the Tyson Bioresearch, Inc. EZ SMART-168 Blood Glucose Monitoring System. C. Measurand: Whole Blood Glucose D. Type of Test: Quantitative, utilizing Glucose Oxidase technology E. Applicant: Tyson Bioresearch, Inc. F. Proprietary and Established Names: EZ SMART-168 Blood Glucose Monitoring System EZ SMART-168 Blood Glucose Test Strips EZ SMART-168 Control Solutions G. Regulatory Information: 1. Regulation section: 21 CFR §862.1345, Glucose test system 21 CFR §862.1660, Single (Specified) Analyte Controls (Assayed and Unassayed) 2. Classification: Class II (analyte) {1} Class I, reserved (controls) 3. Product code: - NBW (over-the-counter, blood glucose) - CGA (glucose oxidase, glucose) - JJX (control material) 4. Panel: - 75 (Chemistry) H. Intended Use: 1. Intended use(s): See Indications for use below. 2. Indication(s) for use: The EZ SMART-168 Blood Glucose Test Strips are used with the EZ SMART-168 Meter for quantitatively measuring glucose (sugar) in fresh capillary whole blood obtained from the fingertip. The EZ SMART-168 Test Strips are for testing outside the body (in vitro diagnostic use). The EZ SMART-168 Blood Glucose Monitoring System is intended for use in the home and in the professional setting to monitor blood glucose levels for better glucose control among diabetics. 3. Special conditions for use statement(s): For over-the-counter use - This blood glucose monitoring system is not for use for testing blood samples from alternate sites. - This blood glucose monitoring system is not to be used for Neonatal Testing and is not to be used with critical ill patients. 4. Special instrument requirements: EZ SMART-168 Blood Glucose Meter {2} 3 I. Device Description: The EZ SMART-168 Blood Glucose Monitoring System contains the following: 1. EZ SMART-168 Blood Glucose Meter 2. EZ SMART-168 Test Strip containing glucose oxidase and potassium ferricyanide 3. Lancets and Lancing device 4. Glucode Chip 5. EZ SMART-168 Glucose Control Solutions are not included with the meter; however 3 levels of control solution are available. The sponsor recommends using a normal and high level control of the user's choice. 6. Carrying Case 7. User's Manual will be included with the meter. 8. Quick Reference Guide 9. Log Book J. Substantial Equivalence Information: 1. Predicate device name(s): VIP International EZ Smart Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k040848 3. Comparison with predicate: | Similarities and Differences | | | | --- | --- | --- | | Item | New Device EZ SMART-168 Blood Glucose Monitoring System k052818 | Predicate VIP International EZ Smart Blood Glucose Monitoring System k040848 | | Measuring Range | 20 – 600 mg/dL | 20 - 600 mg/dL | | Operating Principle | Electrochemical biosensor | Electrochemical biosensor | | Intended Use | The EZ SMART-168 Meter is used for in vitro diagnostic use for the quantitative measurement of glucose in fresh capillary whole blood obtained from the fingertip. The EZ SMART-168 Blood Glucose Monitoring System is intended for use in the home and in the professional setting to monitor blood glucose | The EZ Smart Blood Glucose Test Strips are used with the EZ Smart Blood Glucose Meter to measure glucose (sugar) in whole blood. The EZ Smart Test Strips are for testing outside the body (in vitro diagnostic use). The EZ Smart Blood Glucose Monitoring System is intended for use in the home and in | {3} | Similarities and Differences | | | | --- | --- | --- | | Item | New Device EZ SMART-168 Blood Glucose Monitoring System k052818 | Predicate VIP International EZ Smart Blood Glucose Monitoring System k040848 | | | levels for better glucose level control among diabetics. | professional settings to monitor blood glucose levels for better glucose level control among diabetics. | | Test Principle | Electrochemical Biosensor with Glucose Oxidase | Electrochemical Biosensor with Glucose Oxidase | | Operating Temperature | 10-40 °C (50-104 °F) | 10-40 °C (50-104 °F) | | Test Strips | EZ SMART-168 Glucose Test Strip | EZ SMART Glucose Test Strip | | Specimen type | Capillary whole blood | Capillary whole blood | | Sample volume | ≥ 1.5 μL | ≥ 1.5 μL | | Measuring time | 10 seconds | 10 seconds | | Measuring range | 20-600 (mg/dL) | 20-600 (mg/dL) | | Hematocrit range | 35-55% | 35-55% | | Power source | One 3 V Lithium CR 20322 | One 3 V Lithium CR 20322 | | Strip storage temp | 4 to 30 °C (40-86 °F) | 4 to 30 °C (40-86 °F) | | EMC test standard | EN60601-1-2 | EN60601-1-2 | | Memory storage | Only 28 test results | 300 results with date, time, and year stamp | | 14-Day Average | None, only 28 test average | Calculate 14-day test average | | Meter Coding | Check Glucode Chip | Check Strip | | Button Design | One Button | Two Button | | Meter Dimensions | 76 x 47 x 16 (mm) | 94 x 49 x 17 (mm) | | Weight | 44 grams | 50 grams | | LCD Display | 40 x 21.5 (mm) | 42 x 41 (mm) | K. Standard/Guidance Document Referenced (if applicable): EP5-A2 CLSI: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline, Second Edition 2004 EP6-A CLSI: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline Evaluation of Matrix Effects; Approved Guideline, Second Edition 2003 EP7-A CLSI: Interference Testing in Clinical Chemistry; Approved Guideline. EP9-A CLSI: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. Vol. 15, No. 17, 1995 {4} FDA Guidance Document Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, May 11, 2005 EN60601-1-2 Electromagnetic Compatibility – Medical electrical equipment EN61000-4-2 Electromagnetic Discharge EN61000-4-3 Radiated Electromagnetic Fields EN61000-4-8 Power frequency Magnetic Immunity Test IEC 61000-4-3 Electromagnetic compatibility (EMC) ## L. Test Principle: The Test Principle used by this device is electrochemical biosensor technology using Glucose Oxidase. Glucose is oxidized to gluconic acid and electrons are produced from the reaction. The electrons are then trapped by a chemical mediator, potassium ferricyanide. Once the enzymatic reaction is complete, a potential is provided by the meter for a further electrochemical reaction in order to generate a current from the release of trapped electrons. This current is then measured and correlated to the glucose concentration in the whole-blood sample. ## M. Performance Characteristics (if/when applicable): ### 1. Analytical performance: #### a. Precision/Reproducibility: According to the sponsor precision studies were based on CLSI Document EP5-A2, The following precision results were obtained from spiked venous blood specimens assayed at Tyson Bioresearch, Inc. This study included a measurement of strip-to-strip (within-run) reproducibility by calculating the mean, standard deviation, and % CV for tests conducted on strips from different lots (between-run). Whole blood samples from volunteers were collected with heparinized tubes and were spiked with β-D-Glucose to the desired glucose concentration of 30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, and 251-400 mg/dL. The YSI 2300 glucose analyzer was used to measure the glucose concentrations in venous samples. All measurements were done in “Normal Mode” and a calibration mode of “5/15” (calibrating every 5 measurements or every 15 minutes) #### Results: Within Run and Between Run precision of the EZ SMART-168 Test Strips were measured with venous blood samples in the laboratory. The precision data for fifty test strip lots (n = 50) is shown in the tables below: {5} | | | EZ SMART-168 | | | | --- | --- | --- | --- | --- | | | YSI (mg/dL) | Mean (mg/dL) | SD (mg/dL) | CV% | | | 45.9 | 50.6 | 2.3 | 4.5 | | | 79.3 | 81.1 | 2.9 | 3.6 | | Lot 1 | 120 | 113 | 3.3 | 2.9 | | | 233 | 226 | 5.5 | 2.4 | | | 376 | 380 | 12.1 | 3.2 | | | | EZ SMART-168 | | | | --- | --- | --- | --- | --- | | | YSI (mg/dL) | Mean (mg/dL) | SD (mg/dL) | CV% | | | 49.9 | 49.7 | 2.7 | 5.5 | | | 86.9 | 86.5 | 4.2 | 4.8 | | Lot 2 | 130 | 128 | 3.9 | 3.0 | | | 235 | 237 | 6.8 | 2.9 | | | 385 | 385 | 8.7 | 2.3 | | | | EZ SMART-168 | | | | --- | --- | --- | --- | --- | | | YSI (mg/dL) | Mean (mg/dL) | SD (mg/dL) | CV% | | | 44.5 | 45.6 | 2.4 | 5.3 | | | 79.7 | 82.1 | 3.3 | 4.0 | | Lot 3 | 118 | 109 | 3.2 | 2.9 | | | 233 | 237 | 6.5 | 2.7 | | | 386 | 384 | 9.0 | 2.3 | Within Run Precision of EZ SMART-168 Blood Glucose Monitoring System | Average Glucose Concentration (mg/dL) | 49.9 | 86.9 | 130 | 235 | 385 | | --- | --- | --- | --- | --- | --- | | SD (mg/dL) | 2.7 | 4.2 | 3.9 | 6.8 | 8.7 | | CV% | 5.5 | 4.8 | 3 | 2.9 | 2.3 | Between Run Precision of EZ SMART-168 Blood Glucose Monitoring System | Average Glucose Concentration (mg/dL) | 46.8 | 82 | 123 | 234 | 382 | | --- | --- | --- | --- | --- | --- | | SD (mg/dL) | 2.5 | 3.5 | 3.5 | 6.3 | 9.9 | | CV% | 5.1 | 4.1 | 2.9 | 2.7 | 2.6 | Variability in tests from strip to strip was 5.1% or less b. Linearity/assay reportable range: The sponsor indicated that the linearity studies protocol was developed using CLSI {6} Document, EP6-A. Venous blood was drawn from healthy volunteers and collected into lithium heparin tubes. The blood was then placed in a room temperature environment overnight, until glycolysis occurred and reduced the glucose concentration to nearly zero. The blood was then pooled and allocated to lithium heparin tubes. A small amount of high concentration glucose (10,000 mg/dL) was added to each tube to obtain the desired blood glucose levels needed to perform the test. Recovery tests were performed by confirming the blood glucose concentration with the YSI 2300. Blood samples with glucose concentrations ranging from 20 to 600 mg/dL were then tested with the EZ Smart Blood Glucose Monitoring System. Three lots of EZ Smart Test Strips, chosen at random, were used during the test. The test results were evaluated to describe recovery over the entire range of blood glucose values. A linear regression analysis was performed by the method of least squares (Y = 0.98X + 3.1, r² = 0.9986). The sponsor's acceptance criteria were: All measurements determined by the EZ Smart System are within a 15% bias of the reference (YSI 2300) results (glucose concentration > 100 mg/dL) and a 15 mg/dL bias of the reference (YSI 2300) results (glucose concentration < 100 mg/dL) see table below: | YSI (mg/dL) | 20.0 | 45.2 | 80.6 | 130 | 230 | 380 | 600 | | --- | --- | --- | --- | --- | --- | --- | --- | | Test Results (mg/dL) | 23 | 47 | 73 | 120 | 231 | 383 | 584 | | | 24 | 51 | 82 | 127 | 229 | 389 | 588 | | | 22 | 42 | 80 | 135 | 219 | 392 | 600 | | | 25 | 48 | 75 | 126 | 234 | 382 | 596 | | | 20 | 44 | 76 | 128 | 237 | 374 | 575 | | | 23 | 49 | 85 | 124 | 231 | 388 | 600 | | | 20 | 45 | 83 | 137 | 239 | 384 | 570 | | | 26 | 52 | 76 | 129 | 239 | 376 | 581 | | MEAN | 22.88 | 47.25 | 78.75 | 128.25 | 232.38 | 383.50 | 586.75 | | SD | 2.17 | 3.45 | 4.33 | 5.55 | 6.61 | 6.23 | 11.32 | | CV% | 9.47% | 7.31% | 5.50% | 4.33% | 2.84% | 1.63% | 1.93% | | Bias% | 14.38% | 4.54% | 2.30% | -1.35% | 1.03% | 0.92% | -2.21% | c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability has been referenced by the manufacturer to ISO 17511. The three control solutions consist of buffered aqueous solutions of D (+)-glucose containing stabilizers, preservatives, and other non-reactive ingredients. Lot-specific ranges are printed on the EZ Smart-168 Test Strip bottle label. The control values are assigned by repeat testing. Mean values are obtained and ranges are assigned based upon the mean value ± a pre-determined value for each control concentration. {7} 8 # Closed Vial Stability of Control Solution Control solution stability studies were assessed by the sponsor using accelerated and real time aging studies. Five EZ Smart-168 meters and the YSI 2300 Stat Plus analyzer were used during the testing procedure. The shelf life of closed vial stability claim is 24 months. # Opened Vial Stability of Control Solution The sponsor conducted open vial stability studies of control solutions (Level 1, 2, and 3) that were stored at room temperature (15°-28°C). Samples were tested every week for 4 consecutive weeks, then every other week for the second month, and every month for the 3rd to 6th months. Five EZ Smart-168 glucose meters and the YSI 2300 STAT PLUS were used during the testing procedure. The open vial stability claim of the control solutions is 3 months after opening. # Closed Vial Stability of Test Strips According to the sponsor the EZ Smart-168 Test Strips are identical to the previously cleared EZ Smart Test Strips (k040848) that utilize glucose oxidase technology. The test strip stability was assessed using accelerated and real time aging studies. The closed vial glucose test strip stability claim is 24 months. # Open Vial Stability of Test Strips The open vial stability of Test Strips stored at room temperature (15°-28°C) were performed every week for 4 consecutive weeks, then every other week for the second month, and every month for the 3rd to 6th months. The open vial stability claim for the EZ Smart Test Strips is 3 months when stored as indicated. ## d. Detection limit: The detection range from 20 – 600 mg/dL was demonstrated by measuring recovery at the low and high end of the range. See linearity/assay detection limit above. ## e. Analytical specificity: According to the sponsor, data were analyzed for chemical interference according to the guidelines given by CLSI document EP7-P. Several compounds were studied to determine if their presence affected the reporting of glucose results in whole blood. Blood samples drawn from healthy donors were collected in to lithium heparin tubes, pooled and mixed. Drugs were added to whole blood to obtain the desired test concentrations. Control samples were made by substituting an equal amount of saline for the volume of drug added to the whole-blood sample, so that the dilutions of the spiked and control samples were identical. The sponsor’s results are shown in the table below. {8} | Interferent | Therapeutic Test Level (mg/dL) | High Test Level (mg/dL) | Interferent Level that does not Interfere (mg/dL) | | --- | --- | --- | --- | | Acetaminophen | 2 | 4 | 3 | | Alcohol | --- | 3500 | 3500 | | Ascorbic acid | 2 | 15 | 7.5 | | Bilirubin | 1.2 | 20 | 20 | | Caffeine | --- | 100 | 100 | | Cholesterol | 30 | 500 | 500 | | Creatinine | 1.5 | 30 | 30 | | EDTA | --- | 4 | 4 | | Ibuprofen | 4.2 | 40 | 40 | | L-Dopa | 0.3 | 2 | 1 | | Salicylate | 30 | 125 | 125 | | Sodium Fluoride | --- | 500 | 500 | | Tetracycline | 0.4 | 4 | 4 | | Tolazamide | 2.5 | 5 | 3.75 | | Tolbutamide | 10 | 100 | 100 | | Triglyceride | 190 | 2000 | 2000 | | Urea | --- | 5000 | 5000 | | Uric acid | 7.7 | 20 | 20 | Acetaminophen, Uric Acid, Ascorbic Acid (vitamin C), and other reducing substances when occurring in normal blood or normal therapeutic concentrations do not significantly affect results. However, abnormally high concentrations in blood may cause inaccurately high results. Lipemic samples: Cholesterol up to $500\mathrm{mg / dL}$ or Triglycerides up to $2000\mathrm{mg / dL}$ do not significantly affect test results. However, glucose values in specimens beyond these levels should be interpreted with caution. Temperature and humidity studies were conducted by the sponsor to evaluate the EZ SMART-168 meter for acceptable performance after exposure to environmental conditions of $44^{\circ}\mathrm{F}$ ( $7^{\circ}\mathrm{C}$ ) or $109^{\circ}\mathrm{F}$ ( $43^{\circ}\mathrm{C}$ ) and $90\%$ relative humidity for 0-12 hours. The sponsors environmental studies were conducted over a temperature range from $(10 - 40^{\circ}\mathrm{C})$ to $(50 - 104^{\circ}\mathrm{F})$ with increasing and decreasing intervals of $5^{\circ}\mathrm{C}$ . Samples containing four levels of glucose concentrations $(68\mathrm{mg / dL})$ , $(156\mathrm{mg / dL})$ , $(329\mathrm{mg / dL})$ , and $(446\mathrm{mg / dL})$ were used. Values obtained were averaged and standard deviations were calculated and the results were compared with those from the YSI 2300 glucose analyzer performed at room temperature $(23^{\circ}\mathrm{C})$ . The sponsor defined a significant deviation from the reference result as a result larger than $10\%$ bias from the YSI result. The claimed operating range is $10 - 40^{\circ}\mathrm{C}$ and $10 - 90\%$ relative humidity. {9} Altitude studies were conducted by the sponsor at 164 feet, 7545 feet and 9875 feet above sea level. Venous samples from healthy volunteers were collected into EDTA tubes and allocated into 2 ml vials. A small amount of glucose high concentration (10,000 mg/dL) was added to each vial to obtain the desired glucose levels of 70 mg/dL, 150 mg/dL, 330 mg/dL, and 400 mg/dL. The samples were then tested using the EZ SmART-168 Blood Glucose Monitoring System and YSI 2300 analyzer. A linear regression analysis was performed by the method of least squares. The Bias % results of the EZ SMART-168 Test Strip by venous blood at different altitudes are shown in the table below. | Altitude (feet) | 70 mg/dL | 150 mg/dL | 250 mg/dL | 330 mg/dL | 400 mg/dL | | --- | --- | --- | --- | --- | --- | | 164 | 10.5% | -2.2% | -3.4% | -1.2% | 1.9% | | 7545 | 3.2% | -4.2% | -11.9% | -6.0% | -4.7% | | 9875 | 16.3% | 6.8% | 14.0% | 16.3% | 22.1% | The sponsor determined from the above results that the Bias % is below ± 15% when the altitude is below 7545 feet. Based on the sponsor's criteria the EZ SMART-168 Blood Glucose Monitoring System should not be used at altitudes above 7545 feet. f. Assay cut-off: Not Applicable for this type of device. 2. Comparison studies: a. Method comparison with predicate device: The sponsor compared the clinical accuracy of the EZ Smart-168 Blood Glucose Monitoring System to the predicate EZ Smart Blood Glucose Monitoring System (k040848) and the YSI 2300 Stat Plus Glucose Analyzer. A 100 patient in house consumer study was performed at QC laboratory in Tyson Bioresearch Inc. to assess the readability of the user's manual, testing accuracy, and user's satisfaction of the EZ Smart-168 Blood Glucose Monitoring System. The patient profiles were recorded by the technician consisting of sex, age and education. The technician provided the subject with the EZ Sart-168 User's Manual and quick reference guide and asked the subject to perform a glucose test based on the instructions provided. The subject then performed their own finger stick and ran the test with the EZ Smart-168 glucose meter and the predicate EZ Smart meter from the original finger stick and record their results on the questionnaire provided. The technician then performed the test with the EZ Smart-168 and predicate EZ Smart meter using blood from the original fingerstick and recorded the results. The technician then collected a venous blood sample from the subject for analysis on the YSI 2300 Stat Plus analyzer. The subject was then required to complete the {10} questionnaire. A linear regression analysis against the YSI 2300 Stat Plus was performed by the method of least squares. EZ Smart-168 Blood Glucose Monitoring System | N = 100 | Lay User | Technician | Lay User/ and Technician | | --- | --- | --- | --- | | Slope | 0.98 | 0.99 | 1.00 | | Intercept | 2.6 | 3.5 | 2.6 | | r² | 0.9380 | 0.9702 | 0.9833 | # Clarke's Error-Grid Analysis The sponsor determined the clinical accuracy of the estimation of glucose concentrations measured by the blood glucose monitors using the error-grid analysis proposed by Clarke et al. The table below outlines the percentage of samples that fell within each portion of the grid: | | Total Points | A | B | C | D | E | | --- | --- | --- | --- | --- | --- | --- | | Lay User | 100 | 99.0% | 1.0% | 0.0% | 0.0% | 0.0% | | Technician | 100 | 100% | 0.0% | 0.0% | 0.0% | 0.0% | b. Matrix comparison: Not Applicable - finger stick capillary whole blood only. 3. Clinical studies: a. Clinical Sensitivity: Not Applicable b. Clinical specificity: Not Applicable c. Other clinical supportive data (when a. and b. are not applicable): 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: The sponsor's Expected values/Reference ranges were derived from published literature. {11} The Normal fasting blood glucose range for a non-diabetic adult is 70-110 mg/dL (3.9 to 6.1 mmol/L). One to two hours after meals, normal glucose values should be less than 120 mg/dL (6.7 mmol/L). Consult your physician or healthcare professional for the target glucose values that are right for you. Expected blood glucose levels for people without diabetes: | Time | Range mg/dL | Range mmol/L | | --- | --- | --- | | Before breakfast | 70-105 | 3.9-5.8 | | Before lunch or dinner | 70-110 | 3.9-6.1 | | 1 hour after meals | Less than 160 | Less than 8.9 | | 2 hours after meals | Less than 120 | Less than 6.7 | | Between 2 and 4 AM | Greater than 70 | Greater than 3.9 | N. Instrument Name: Tyson Bioresearch, Inc. EZ Smart-168 Blood Glucose Monitoring System O. System Descriptions: 1. Modes of Operation: Manual operation 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ☐ X ☐ or No ☐ 3. Specimen Identification: Manual identification is used. The memory will store 28 Patient Tests, 28 days Test Average 4. Specimen Sampling and Handling: A fresh capillary sample is taken from the fingertip and used immediately. Refer to the Tyson Bioresearch, Inc. EZ Smart-168 Blood Glucose Monitoring System User’s Manual for the test procedure. 5. Calibration: Lot Specific adjusted calibration with the Check Glucode Chip. 12 {12} 6. Quality Control: The EZ Smart-168 control solutions are used to check the performance of the EZ Smart-168 meter, Test Strips, and testing technique. The EZ Smart-168 Blood Glucose Monitoring System is performing correctly if the control solution test results fall within the specific control solution range listed on the EZ Smart-168 Test Strip Vial. Note: EZ Smart-168 Control Solutions are required but not supplied with Test Strips for checking the system. There are three aqueous EZ Smart-168 Control Solutions (Low, Normal, and High) that are available for the user to choose from. The sponsor recommends the use of at least a normal and high control solution to check the accuracy of the system. For more information about the EZ Smart-168 Control Solution, see the EZ Smart-168 Control Solution package insert. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above: Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 13