Nova Max Uric Acid Monitoring System

{0} 1 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k160990 B. Purpose for Submission: New device C. Measurand: Uric acid in capillary whole blood D. Type of Test: Quantitative, enzymatic, electrode reading E. Applicant: Nova Biomedical Corporation F. Proprietary and Established Names: Nova Max Uric Acid Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1775, Uric acid test system 2. Classification: Class I, reserved 3. Product code: PTC {1} 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): The Nova Max Uric Acid Monitoring System consists of the Nova Max Uric Acid Monitor, Nova Max Uric Acid Test Strips and Nova Max Uric Acid Control Solutions. The Nova Max Uric Acid Monitoring System is intended to be used for the quantitative measurement of uric acid in fresh capillary whole blood obtained from the fingertip of gout patients. It is intended for single-patient home use by prescription and should not be shared. It is intended for self-testing outside the body (in vitro diagnostic use) by people with gout as an aid to monitor the effectiveness of uric acid control. It is intended for use by patients undergoing treatment for gout or their caregivers on the order of a treating healthcare professional. This system should not be used to alter gout treatment by changing any medication schedule or dosage unless specifically instructed by a healthcare professional. This system should only be used with single-use, auto-disabling lancing devices. It should only be used with Nova Max Uric Acid Test Strips and Nova Max Uric Acid Control Solutions. 2. Indication(s) for use: See Intended Use. 3. Special conditions for use statement(s): For prescription use only. The Nova Max Uric Acid Test Strips give correct results when the following limitations are observed: - Elevated levels of tolazamide, L-dopa, and methyl-dopa may falsely decrease measured whole blood uric acid. - Do not share monitor. - Do not reuse! Each Uric Acid Test Strip is for single use only. Use a new Nova Max Uric Acid Test Strip each time you test. - Do not test samples other than fresh capillary whole blood collected from the fingertip. Do not use serum or plasma. - Do not use at altitudes above 15,000 feet (4572 meters) above sea level. - Do not use at temperatures outside 59°F to 104°F (15°C to 40°C). - Do not use when humidity is higher than 90% or lower than 10% as extremes in humidity may cause incorrect results. - Do not use when hematocrit (% of red blood cells) range is outside the acceptable hematocrit range of 20% to 65%. 2 {2} - Dopamine or ascorbic acid (vitamin C) may cause test results to be incorrect (falsely low). - Ibuprofen, for example Motrin, or drugs that contain ibuprofen, may cause test results to be falsely high (up to 13% higher). 4. Special instrument requirements: Nova Max Uric Acid Monitor I. Device Description: The Nova Max Uric Acid Monitoring System uses selective mediated enzymatic action (uricase biosensor) to generate current across the electrodes. The current generated is proportional to the concentration of uric acid in the capillary whole blood sample. The device, which is amperometric, measures the uric acid concentration in the whole blood sample by measuring the amount of current that was generated and flows through the electrodes on the test strips. The Nova Max Uric Acid Monitoring System is comprised of Nova Max Uric Acid Test Strips, a portable handheld Nova Max Uric Acid Monitor, and Nova Max Uric Acid Control Solutions. Monitor Power Supply: The monitor uses a single volt (3V) lithium, non-rechargeable battery. The battery life is approximately 1000 tests. No-Coding System: The user is not required to enter a test strip lot-specific calibration code. Uric Acid Control Solutions are aqueous assayed solutions, containing buffered uric acid, preservatives, FD & C dye, and a viscosity additive. They contain no products of human origin. There are three levels of controls (level 1, 2, and 3). When a control solution sample is applied to the Nova Max Uric Acid Test Strip, the monitor performs a uric acid measurement; the monitor marks the results. The processes of the monitor operation between measuring the control solution sample and measuring a normal patient sample are the same. Safety lancets are provided as an accessory to the Nova Max Uric Acid Monitoring System. They are commercially available single-use, auto disabling sterilized lancing devices. J. Substantial Equivalence Information: 1. Predicate device name(s): URCA Method on the Dimension RxL Max Clinical System {3} 2. Predicate 510(k) number(s): k043546 3. Comparison with predicate: | Item | Nova Max Uric Acid Monitoring System | Predicate: k043546 | | --- | --- | --- | | Intended Use | For the quantitative measurement of uric acid | Same | | Enzyme | Uricase, Peroxidase | Uricase | | Operating Principle | Uric Acid + 2H2O + O2 + uricase → Allantoin + H2O + CO2 Ferrocyanide + H2O2 + Peroxidase → Ferricyanide + H2O Ferricyanide +e → Ferrocyanide (on electrode) | Uric acid + 2H2O + O2 + uricase → Allantoin + H2O + CO2 (Allantoin absorbs at 293 nm) | | Sample type | Capillary whole blood from fingertip | Serum, plasma | | Sample size | 1.2 μL | 17 μL | | Measuring range | 3 - 18 mg/dL | 0 - 20.0 mg/dL | | Quality Control | 3 levels | 2 levels | # K. Standard/Guidance Document Referenced (if applicable): EN 60601-1-2 Electrical Equipment for Measurement, Control and Laboratory use EMC Requirement IEC 61010-1:2010 Safety requirements for electrical equipment for measure control and laboratory use # L. Test Principle: The Nova Max Uric Acid Monitoring System uses the enzymatic conversion of uric acid by uricase to allantoin. This reaction quantitatively produces hydrogen peroxide (equation 1). The hydrogen peroxide then reacts quantitatively with ferrocyanide in the presence of peroxidase forming ferricyanide (equation 2). The current generated at the electrode by the conversion of ferricyanide to ferrocyanide is proportional to the uric acid of the sample (equation 3). {4} Uric acid measurement is based on the following equations: $$ \begin{array}{l} \text{Uric Acid} + \mathrm{O}_2 + 2 \mathrm{H}_2\mathrm{O} \xrightarrow{\text{Uricase}} \text{Allantoin} + \mathrm{CO}_2 + \mathrm{H}_2\mathrm{O}_2 \\ \text{Ferrocyanide} + \mathrm{H}_2\mathrm{O}_2 \xrightarrow{\text{POD(Peroxidase)}} \text{Ferricyanide} + \mathrm{H}_2\mathrm{O} \\ \text{Ferricyanide} \xrightarrow{+e} \text{Ferrocyanide (on electrode)} \\ \end{array} $$ The current generated at the electrode is proportional to the uric acid concentration of the sample. By measuring the generated current, the concentration of the uric acid in the sample is determined. ## M. Performance Characteristics (if/when applicable): ### 1. Analytical performance: #### a. Precision/Reproducibility: A day-to-day precision study was performed by measuring three test strip lots on two meters, twice a day for twenty days using control solutions. The levels of uric acid tested were 5, 10.5, and 16 mg/dL. The total imprecision was calculated (which included test strip lot, meter and day as components of variability): **Total imprecision with control samples** | Control Levels | 5 mg/dL | | 10.5 mg/dL | | 16 mg/dL | | | --- | --- | --- | --- | --- | --- | --- | | Test Strip Lot # | Mean | %CV | Mean | %CV | Mean | %CV | | Lot 1 | 4.88 | 4.2 | 10.63 | 4.4 | 16.06 | 3.9 | | Lot 2 | 4.88 | 4.8 | 10.68 | 4.2 | 15.83 | 3.7 | | Lot 3 | 4.93 | 4.3 | 10.73 | 4.0 | 16.90 | 3.6 | A second precision study was conducted to evaluate within-run precision. Four different whole blood specimens were prepared with levels of uric acid (4.4, 8.8, 11.8 and 17.1 mg/dL). The specimens were tested 10 times on 5 separate meters (n=50). The testing was conducted three times using three separate test strip lots. Each test strip lot was also tested using three different levels of uric acid control solutions (5, 10.5 and 16 mg/dL). Standard deviation was reported for the lowest concentration of uric acid in the control solution and whole blood samples; % CV for all others. {5} Within-run precision with venous whole blood samples | Whole Blood Specimens | | Test Strips Lot 1 (n=50) | Test Strip Lot 2 (n=50) | Test Strip Lot 3 (n=50) | | --- | --- | --- | --- | --- | | 4.4 mg/dL | Mean | 4.5 | 4.6 | 4.3 | | | SD | 0.19 | 0.22 | 0.19 | | 8.8 mg/dL | Mean | 8.7 | 8.6 | 8.5 | | | % CV | 2.7 | 2.9 | 3.5 | | 11.8 mg/dL | Mean | 11.4 | 11.3 | 11.9 | | | % CV | 3.2 | 3.8 | 4.2 | | 17.1 mg/dL | Mean | 16.7 | 17.0 | 16.8 | | | % CV | 4.0 | 3.7 | 3.4 | Within-run precision with control solutions | Control Levels | Test Strip Lot | Lot 1 | Lot 2 | Lot 3 | | --- | --- | --- | --- | --- | | 5 mg/dL (n=50) | Mean (mg/dL) | 4.9 | 4.9 | 5.0 | | | S.D. | 0.20 | 0.19 | 0.18 | | 10.5 mg/dL (n=50) | Mean (mg/dL) | 10.6 | 10.6 | 10.6 | | | % CV | 3.6 | 3.4 | 3.7 | | 16 mg/dL (n=50) | Mean (mg/dL) | 16.0 | 16.3 | 16.3 | | | % CV | 3.7 | 3.4 | 3.2 | b. Linearity/assay reportable range: Linearity was evaluated using spiked venous whole blood samples with nine different uric acid levels (2-3, 3-4, 5-6, 7-8, 9-10,11-12,14-15,16-17,19-21 mg/dL). Each sample was evaluated twice on five separate meters (n=10) and the mean was taken of the 10 separate measurements. The results demonstrated less than 10% deviation from the expected value across the range: | Uric Acid Test Strip Lot | Slope | Intercept | R2 | | --- | --- | --- | --- | | Lot 1 | 0.9866 | 0.2014 | 0.9943 | | Lot 2 | 0.9841 | 0.2079 | 0.9964 | | Lot 3 | 0.9816 | 0.1690 | 0.9957 | c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: Nova Max Uric Acid Monitoring System is traceable to NIST SRM 913B, Uric Acid. {6} 7 # Stability: Control solution: The shelf life stability for the Nova Max Uric Acid Control Solution has been validated for up to 18 months at room temperature, $15 - 30^{\circ}\mathrm{C}$ ($60 - 85^{\circ}\mathrm{F}$) on three lots of control solution. The protocols and acceptance criteria were found to be acceptable. Test Strip: The shelf life stability for the Nova Max Uric Acid Test Strips has been validated for up to 18 months at room temperature, $15 - 30^{\circ}\mathrm{C}$ ($60 - 85^{\circ}\mathrm{F}$) on three lots of test strips. The protocols and acceptance criteria were found to be acceptable. Test Strip Open Vial Stability: The open vial stability for the Nova Max Uric Acid Test Strips has been validated for up to 90 days at room temperature, $15 - 30^{\circ}\mathrm{C}$ ($60 - 85^{\circ}\mathrm{F}$). The protocols and acceptance criteria were found to be acceptable. Control solution open vial stability: The open vial stability for the three levels of Nova Max Uric Acid Control Solution has been validated for up to 90 days at room temperature, $15 - 30^{\circ}\mathrm{C}$ ($60 - 85^{\circ}\mathrm{F}$). The protocols and acceptance criteria were found to be acceptable. # Value Assignment: The value assignment protocol for the quality control solutions was reviewed and found to be acceptable. ## d. Detection limit: The limit of blank (LoB) was established by taking 100 measurements of a blank solution and estimating the LoB non-parametrically as the $95^{\text{th}}$ percentile of the measurement. This yielded a LoB of $0.26 \, \mathrm{mg/dL}$. Four samples with low concentrations of uric acid (4x LoB or $1.04\mathrm{mg / dL}$) were used to estimate the limit of detection (LoD) and the limit of quantitation (LoQ) of the device. The LoD was calculated using the following equation: $\mathrm{LoB} + 1.6494*\mathrm{SD}$. The LoQ was the lowest concentration with a CV less than $20\%$. The results of the detection limits studies are summarized below: | Analyte | LoB | LoD | LoQ | | --- | --- | --- | --- | | Uric Acid | 0.26 mg/dL | 0.54 mg/dL | 1.0 mg/dL | | Analyte | Claimed Measuring Range | | --- | --- | | Uric Acid | 3 – 18 mg/dL | {7} # e. Analytical specificity: To assess potential interference, venous whole blood samples spiked to three uric acid concentration ranges (3-9 mg/dL, 9-15 mg/dL and 15-19 mg/dL) were used. Each of these samples was divided into three pools: control, test pool 1 and test pool 2. The exogenous and endogenous interfering substances were added to the test pools at different concentrations. The percent difference between the test samples and the control sample was calculated. The sponsor defined no significant interference as $\leq$ $10\%$ difference between the test samples and the control samples. No interference was observed with the following compounds at the concentrations listed: | Substance | Concentrations Tested | | --- | --- | | Acetaminophen | 5 and 20 mg/dL | | Ascorbic acid | 0.6 and 3 mg/dL | | Bilirubin | 10 and 20 mg/dL | | Creatinine | 1.2 and 6 mg/dL | | Dopamine | 0.6 and 1 mg/dL | | Ephedrine | 0.3 and 0.9 mg/dL | | Folic acid | 10 and 20 mg/dL | | Glucose | 300 and 900 mg/dL | | Heparin | 19,500 and 39,000 IU/dL | | Hydroxyurea | 15 and 30 mg/dL | | Salicyclic acid | 10 and 20 mg/dL | | Tetracycline hydrochloride | 10 and 30 mg/dL | | Tolbutamide | 15 and 45 mg/dL | | Triglycerides | 750 and 1250 mg/dL | | Vitamin B7 | 10 and 20 mg/dL | | Vitamin B12 | 10 and 20 mg/dL | | Warfarin | 10 and 20 mg/dL | The following compounds and concentrations were found to interfere with the test: L-dopa above $0.4\mathrm{mg / dL}$ produced falsely low values - Methyl-dopa above $1.8\mathrm{mg / dL}$ produced falsely low values - Tolazamide above $14\mathrm{mg / dL}$ produced falsely low values - Ibuprofen above $16\mathrm{mg / dL}$ produced falsely high values The following information is presented in the package insert to describe interferences observed: - Individuals taking dopamine or ascorbic acid may experience falsely low results - Elevated levels of tolazamide, L-dopa, and methyl-dopa may falsely decrease measured whole blood uric acid. {8} - If you are taking Ibuprofen, for example Motrin, or drugs that contain ibuprofen, your test results may be falsely high (up to 13% higher). f. Assay cut-off: Not applicable. 2. Comparison studies: a. Method comparison with predicate device: Described in the clinical studies below in 3c. b. Matrix comparison: Not applicable. 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): User Accuracy Study: A clinical study using laypersons naive to this type of test was conducted using a total of 143 subjects who collected and tested their own fingerstick capillary whole blood samples in singlicate. Lay-users performed the testing without assistance from the healthcare professionals. Lithium heparin plasma samples were then obtained from the users for comparison to the predicate. The results of the testing by the lay-users using the proposed device were compared to the results of the plasma samples using the predicate device. Three different strip lots were used in the testing and each lot of strips was subject to standard shipping and handling conditions prior to the testing. The range of the results in the study was from 3.2 – 17.5 mg/dL uric acid. The results using Deming Regression of the study are summarized in the table below. 9 {9} | | Nova Max-Capillary Fingertip vs. Siemens Dimension RxL Max Venous | | --- | --- | | N | 143 | | Slope | 0.957 | | R² | 0.98 | | Intercept (mg/dL) | 0.137 | # Human Factors Study: A human factors study using 120 laypeople previously diagnosed with gout was conducted in the U.S. to evaluate the Nova Max Uric Acid Monitoring System. The goal of the study was to determine the subjects' ability to use the device. The lay-users were provided the labeling; they used the device and filled out a questionnaire. From the data recorded, $99.2\%$ (119/120) of the subjects were able to successfully perform a capillary fingerstick whole blood measurement and $97.5\%$ (117/120) of the subjects were able to successfully perform a control solution test. The response to the questionnaire indicated that the participants were able to understand the labeling, understand the test result and operate the Nova Max Uric Acid Monitoring System. # 4. Clinical cut-off: Not applicable. # 5. Expected values/Reference range: Nova performed a reference range study to determine reference uric acid levels in capillary whole blood obtained from the fingertip of adult subjects (139 males and 150 females) who were not taking any medications known to affect uric acid levels in the blood, and who did not present with any conditions known to elevate or reduce levels of uric acid in the blood. The central $95\%$ reference interval for uric acid in capillary whole blood obtained from a fingerstick was $3.6 - 7.7 \, \mathrm{mg/dL}$ in healthy males and $2.6 - 6.2 \, \mathrm{mg/dL}$ for healthy females. These upper and lower reference limits show agreement with published ranges of serum uric acid levels in adult populations. # N. Instrument Name: Nova Max Uric Acid Monitor {10} O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes _______ or No ☐ X Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes _______ or No ☐ X 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: There is no sample identification function with this device. Samples are applied directly to the test strip as they are collected. 4. Specimen Sampling and Handling: The uric acid test is intended to be used with capillary whole blood from the finger. The whole blood sample is applied directly to the test strip. 5. Calibration: There is no calibration required for the meter by the user. The meter is automatically coded. 6. Quality Control: Uric Acid Control Solutions are aqueous assayed solutions, containing buffered uric acid, preservatives, FD & C dye, and a viscosity additive. They contain no products of human origin. There are three levels of controls (level 1, 2, and 3). When a control solution sample is applied to the Nova Max Uric Acid Test Strip, the monitor performs a uric acid measurement; the monitor marks the results as a quality 11 {11} control sample. The processes of the monitor operation between measuring the control solution sample and normal patient uric acid sample are same. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above: 1. Sample Volume Study The nominal fill indicated by the labeling of the device is 1.2 µl of capillary whole blood. A study was performed to determine the minimum fill volume of the test strip. Five different meters were tested with three whole blood samples spiked to different uric acid concentrations (5.1, 10.2, and 16.8 mg/dL). Different volumes of whole blood were added to the test strips to determine the minimum volume to trigger the device to take a reading. 0.8, 0.9, 1.0, 1.1, 1.2, 1.3 µl were tested with three different lots of test strips. 100% (90/90) of the test strips triggered a reading at sample volumes ≥ 1.2 µl. 89/90 of the samples triggered readings at 1.1 µl. No test result was released for the remaining 1/90 or for the other volumes tested less than 1.1 µl. These results support the claimed sample volume of 1.2 µl. 2. Altitude Study The effect of altitude was simulated by changing the amount of dissolved oxygen in whole blood with a tonometer to simulate the oxygen concentration in blood at three different altitudes. Two different meters with three venous whole blood samples spiked with uric acid (5.1, 10.2, and 16.8 mg/dL) were used in the study. The result were compared to results obtained using the predicate device. The study demonstrated that the reported uric acid results in whole blood are constant across different pO2 levels and that altitude up 15,000 feet (4572 meters) above sea level did not impact the reported uric acid results. 3. Hematocrit Study: Three different test strip lots were analyzed at five different hematocrit levels (20, 35, 45, 55, and 65%) using five venous whole blood samples spiked with uric acid (3.4, 7.3, 10.8, 14.3, and 18.1 mg/dL) on five different meters. The result were compared to results obtained using the predicate device. The performance of the three lots of test strips demonstrates that the hematocrit levels tested did not affect the performance of the uric acid system. 4. Test System Operating Conditions – humidity and temperature: Three different test strip lots were analyzed at five different temperature and humidity combinations (5 C/10% humidity, 5C/90%, 25 C/50%, 40 C/10% and 40 C/90% humidity) on five different meters using three whole blood samples spiked with uric acid (6.3, 9.9, and 16.8 mg/dL). The result were compared to results obtained using the predicate device. The uric acid control solutions were also evaluated at the five different 12 {12} temperature and humidity concentrations on five different meters. The performance of the device was not significantly affected by the variation in temperature or humidity for either the whole blood samples or the control solutions. 5. Accelerated Bench Testing Using Clorox Germicidal Disposable Wipes: Accelerated cleaning protocols of the monitors were done on four separate devices to evaluate the deterioration of the device due to regular cleaning as indicated in the product labeling. Each monitor was cleaned and disinfected 10,950 times to simulate 10 cycles per day on each monitor for a period of 3 years. None of the four monitors tested showed any deterioration of the housing material, the display screen, the power button and all four devices passed the internal test procedures for functionality of all monitor components including the electronics, display, beeper, test strip port reader and buttons. 6. Disinfection Efficacy/Infection Control Study: The device is intended for single-patient use. Disinfection efficacy studies were performed on the materials comprising the meter by an outside commercial testing laboratory demonstrating complete inactivation of hepatitis B virus (HBV) with the Clorox Healthcare Germicidal Wipes, EPA# 67619-12. The meter passed the evaluation of virus elimination protocol acceptance criteria with the Clorox Healthcare Bleach Germicidal Wipes. 7. Pre and Post Cleaning and Disinfection Precision and Accuracy Study: To evaluate the precision of the four monitors used in the accelerated cleaning protocol above, each monitor took 25 measurements of 5 blood specimens with different uric acid concentrations before and after the cleaning/disinfection cycles. Accuracy was evaluated by measuring five whole blood samples with each of the four meters for five different uric acid concentrations before and after the 10,950 cleaning cycles and comparing the results to the predicate as well as the meters before the cleaning. The 10,950 cleaning and disinfection cycles on the Nova Max did not impact the analytical performance of the monitors. 8. Customer Support Center assistance, call 1-800-681-7390 Monday - Saturday, 9:00 AM - 5:30 PM ET. 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