Scanostics UTI Check Application Test System

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k170118 B. Purpose for Submission: New device C. Measurand: Urinary nitrite and leukocytes D. Type of Test: Qualitative and semi-quantitative urinalysis E. Applicant: Teco Diagnostics F. Proprietary and Established Names: Teco Diagnostics Scanostics UTI Check Application Test System G. Regulatory Information: | Regulation | Product Code | Test Name | Device Class | Panel | | --- | --- | --- | --- | --- | | 21 CFR 864.7675 | LJX | Leukocyte Peroxidase Test | I, meets the limitations of exemption in 21 CFR 864.9 (c)(9) | Hematology | | 21 CFR 862.1510 | JMT | Nitrite (nonquantitative) Test System | I, meets the limitations of exemption in 21 CFR 862.9 (c)(9) | Chemistry | | 21 CFR 862.2900 | KQO | Automated Test System | I | Chemistry | {1} H. Intended Use: 1. Intended use(s): See Indications for use below. 2. Indication(s) for use: The Scanostics UTI Check Application test system consists of the Scanostics UTI Check Application and the URS-2L (UTI) Urine Test Strips. The test system is intended for the qualitative detection of nitrite and leukocytes in urine as an aid in the screening of urinary tract infection (UTI). It is intended for over-the-counter home use only. 3. Special conditions for use statement(s): In vitro diagnostic use only. 4. Special instrument requirements: The representative platform for the application is the iPhone 6 with iOS 9. Compatibility has been validated on both the iPhone 6 and 6S as well as the iPod touch (8th gen) with a minimum iOS requirement of iOS 8. I. Device Description: The Scanostics UTI Check Application test system consists of the Scanostics UTI Check Application, the URS-2L (UTI) Urine Test Strips, and the Scanostics backing card. The URS-2L UTI Test Strips are comprised of two reagent pad areas, which are absorbent material saturated with chemically active substances, then dried and affixed to the plastic strip with double-sided adhesive. The backing card comprises of thirty-two calibration color blocks and 3 black and white alignment squares printed onto a rigid card stock. J. Substantial Equivalence Information: 1. Predicate device name(s): Clinistrip 10SGL 2. Predicate 510(k) number(s): k970250 {2} 3. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Candidate Device | Predicate: Clinistrip 10SGL k970250 | | Intended use | For the detection of nitrite and leukocytes in urine. | Same | | Nitrite test methodology | This test relies on the conversion of nitrate to nitrite by the action of p-arsanilic acid to form a diazonium compound in an acid medium. This compound in turn couples with 1, 2, 3, 4 - tetrahydrobenzo(h) quinoline to produce a pink color. | Same | | Leukocyte test methodology | This test is based on the hydrolysis of an indoxyl ester derivative through the action of leukocyte esterase. The liberated indoxyl ester reacts with a diazonium salt to produce a colored compound (pink to purple). | Same | | Differences | | | | --- | --- | --- | | Item | Candidate Device | Predicate: Clinistrip 10SGL | | Testing parameters | Nitrite and leukocytes | 10 parameters including nitrite and leukocytes | | Special instrument requirements | Apple mobile device with the Scanostics UTI Check App installed. | None | K. Standard/Guidance Document Referenced (if applicable): CLSI-EP7-A2, Interference Testing in Clinical Chemistry, Approved Guideline- $2^{\mathrm{nd}}$ Edition (2005) ISO 14971, Medical Devices- Application for Risk Management to Medical Devices, 2007 L. Test Principle: The Scanostics UTI Check Application measures the color developed in 2 reaction zones (leukocytes and nitrite pads) on the UTI test strip following application of a urine sample. The developed colors are then compared to calibration colors located on the Scanostics {3} backing card and the result for each pad is determined based on the minimum color distance between the developed colors and calibration colors. The Scanostics UTI Check Application instructs the user how to perform a UTI test and uses the built-in smartphone camera to perform color comparison between the test strip and the calibration squares. The application guides the user through the test setup steps and prompts the user to apply the sample to the test strip. The leukocytes test is based on the hydrolysis of an indoxyl ester derivative through the action of leukocyte esterase. The liberated indoxyl ester reacts with a diazonium salt to produce a colored compound (pink to purple). The Nitrite test relies on the conversion of nitrate to nitrite by the action of $p$ -arsanilic acid to form a diazonium compound in an acid medium. This compound in turn couples with 1, 2, 3, 4 - tetrahydrobenzo(h) quinoline to produce a pink color. # M. Performance Characteristics (if/when applicable): # 1. Analytical performance: # a. Precision/Reproducibility: The first precision study was performed in-house with five operators over 10 days using one iPhone 6 device with the App installed. Each day, each operator tested the Scanostics UTI Check application with five urine based controls; negative, trace leukocytes (15 cells/μL, near the clinical decision point), low positive nitrite (0.1 mg/dL, near the clinical decision point), medium leukocytes and nitrite, and high leukocytes and nitrite. Two replicates were obtained per control, so that a total of 100 measurements were collected per control sample. Results are described in the tables below: Leukocyte Results: | Control | Expected Range | % correct (expected range) | Replicates | | --- | --- | --- | --- | | (Negative) | Negative | 100 | 100 | | Medium | Trace to 2+ | 100* | 100 | | High | 1+ to 3+ | 100** | 100 | | Low Positive Leukocytes 15 cells/μL | Trace | 99 | 100 | | Low Positive Nitrite (0.1 mg/dL) | Negative | 100 | 100 | *68% of results for the Medium control were observed as +1; the remaining 32% of results were within +/- one color block. **85% of results for the High control were observed as +2; the remaining 15% of results were within +/- one color block. {4} Nitrite Results: | Control Sample | Expected Value | % correct (expected value) | Replicates | | --- | --- | --- | --- | | Negative | Negative | 100% | 100 | | Medium | Positive | 100% | 100 | | High | Positive | 100% | 100 | | Low Positive Leukocytes (15 cells/μL) | Negative | 100% | 100 | | Low Positive Nitrite (0.1 mg/dL) | Positive | 100% | 100 | In a second precision study, five iPhone 6 devices with the App installed were each tested with five urine based control solutions; negative, trace leukocytes (near the clinical decision point), low positive nitrite (near the clinical decision point), medium leukocytes and nitrite, and high leukocytes and nitrite. 25 replicates were tested for each device with each control solution (Negative, Medium, High, Low Positive Leukocytes (15 cells/ $\mu$ L), and Low Positive Nitrite (0.1 mg/dL). All results were within expected values. b. Linearity/assay reportable range: The lower limit of the device's reportable range is described in section d (detection limit). Device performance across the range is described in section a (precision/reproducibility). c. Traceability, Stability, Expected values (controls, calibrators, or methods): No traceability is claimed. The sponsor claims that the device is stable for 18 months when stored at $15 - 30\mathrm{C}^{\circ}$ The sponsor instructs the user to use the strip immediately after the foil pouch is opened. d. Detection limit: A sensitivity study was performed in-house to evaluate the lower limits of detection of the Scanostics UTI Check application for each analyte. Negative urine was spiked to known concentrations of each analyte and diluted to the analyte concentrations described in the table below. 30 replicates were obtained for each concentration. The limit of detection was defined as the lowest concentration tested where at least $80\%$ of results yielded the trace result for leukocytes or the positive result for nitrite. The results are summarized below: {5} Limit of Detection - Leukocytes: | Leucocyte Concentration | Negative | Trace | Limit of Detection | | --- | --- | --- | --- | | 15 cells/μL | 0% | 100% | | | 11.25 cells/μL | 17% | 83% | * | | 7.5 cells/μL | 80% | 20% | | The lower limit of detection for leukocytes was found to be 11.25 cells/ $\mu \mathrm{L}$ Limit of Detection - Nitrite: | Nitrite Concentration | Negative | Positive | Limit of Detection | | --- | --- | --- | --- | | 0.1 mg/dL | 0% | 100% | | | 0.075 mg/dL | 0% | 100% | | | 0.05 mg/dL | 3% | 97% | | | 0.04 mg/dL | 3% | 97% | * | | 0.035 mg/dL | 27% | 73% | | | 0.030 mg/dL | 73% | 27% | | The lower limit of detection for nitrite was found to be $0.04\mathrm{mg / dL}$ # e. Analytical specificity: The CLSI Guideline EP7-A2: Interference Testing in Clinical Chemistry, Approved Guideline - Second Edition (2005) was referenced in designing the protocol for specificity testing. 31 possible exogenous interferences were added to negative urine, leukocyte positive urine and nitrite positive urine pools and tested using the Scanostics UTI Check Application. First, four pools of urine were prepared; negative urine, low positive leukocyte urine (15 cells/μL), high positive leukocyte urine (500 cells/uL), and low positive nitrite urine (0.1 mg/dL). Stock solutions of the interferents were then added to the negative and positive urine pools. Five replicates were obtained for each pool and the results of the urine pools spiked with interfering agents were compared with the results of the unspiked samples. Where interference was detected, dilutions were made to determine the interference threshold. No interference was observed for the following compounds at the concentrations evaluated below: | Substance | Concentration | Interference Effect | | --- | --- | --- | | Ascorbic Acid | 75 mg/dL | No effect | | Creatine | 10 mg/dL | No effect | | Creatinine | 400 mg/dL | No effect | | Fructose | 100 mg/dL | No effect | | Galactose | 80 mg/dL | No effect | | Hemoglobin | 20 mg/dL | No effect | | Lactose | 10 mg/dL | No effect | {6} | Substance | Concentration | Interference Effect | | --- | --- | --- | | Potassium Chloride | 1500 mg/dL | No effect | | Riboflavin | 10 mg/L | No effect | | Sodium Bicarbonate | 1500 mg/dL | No effect | | Sodium Chloride | 6000 mg/dL | No effect | | Sodium Phosphate | 500 mg/dL | No effect | | Urea | 4000 mg/dL | No effect | | Uric acid | 150 mg/dL | No effect | | IgG | 25 mg/dL | No effect | | Ammonium Chloride | 200 mg/dL | No effect | | Glycine | 450 mg/dL | No effect | | Lithium Acetoacetate | 60 mg/dL | No effect | | Sodium Acetate | 25 mg/dL | No effect | | Sodium Nitrate | 10 mg/dL | No effect | | Theophylline | 100 mg/L | No effect | For the following compounds, interference was observed as described at the concentrations tested below for either leukocytes (LEU) or nitrite (NIT): | Substance | Maximum Concentration Not Affecting Test | Interference Effect | | --- | --- | --- | | Albumin | 200 mg/dL | False negative results observed for Trace LEU samples at albumin > 200 mg/dL | | Bilirubin | 4 mg/dL | False negative results for Large LEU samples at bilirubin > 4 mg/dL | | Calcium Chloride | 200 mg/dL | False negative results observed for Trace LEU samples at calcium chloride > 200 mg/dL | | Glucose | 1500 mg/dL | False negative results observed for Trace and Large LEU samples at calcium chloride > 200 mg/dL | | Oxalic Acid | 35 mg/dL | False negative results observed for Trace LEU samples at oxalic acid > 35 mg/dL | | Sodium Nitrite | 0 mg/dL | False positive results for NIT samples at sodium nitrite > 0.04 mg/dL | | Blood | 0.01% | False positive results for Trace LEU samples at blood at > 0.1%; false positive results for NIT | {7} 8 | Substance | Maximum Concentration Not Affecting Test | Interference Effect | | --- | --- | --- | | | | samples at blood > 0.01%. | | Citric Acid | 62.5 mg/dL | False negative results observed for Trace LEU samples at citric acid > 62.5 mg/dL | | Phenazopyridine | 3 mg/dL | False positive results for NIT samples at phenazopyridine > 3 mg/dL | The possible interference of certain endogenous analytes commonly tested in urine on Leukocyte and Nitrite was tested with protocols following the recommendations in CLSI Guideline EP7-A2: Interference Testing in Clinical Chemistry, Approved Guideline – Second Edition (2005). Each possible interfering substance was tested at three different concentrations in 10 replicates. Each analyte was first tested at a specific concentration without the interfering substance present, and then again with the interfering substance present. The results are summarized below: Effect of Nitrite on Leukocytes: | Nitrite Concentration (mg/dL) | Leukocyte Concentration (cells/μL) Expected | | | | | --- | --- | --- | --- | --- | | | Negative (0) | Trace (15) | Small (70) | Moderate (125) | | Positive (0.1) | Negative | Trace | Small | Moderate | | Positive ++ (10) | Negative | Trace | Small | Moderate | The sponsor claims that nitrite does not affect the leukocyte results. Effect of Leukocytes on Nitrite: | Leukocyte concentration (cells/μL) | Nitrite Concentration (mg/dL) Expected | | | | | --- | --- | --- | --- | --- | | | Negative (0) | Positive (0.1) | Positive (1.0) | Positive (10) | | Small (70) | Negative | Positive | Positive ++ | Positive ++ | | Moderate (125) | Negative | Positive | Positive ++ | Positive ++ | The sponsor claims that leukocytes do not affect the nitrite results. {8} Effect of pH on Leukocytes: | pH | Leukocyte Concentration (cells/μL) Expected | | | | | --- | --- | --- | --- | --- | | | Negative (0) | Trace (15) | Small (70) | Moderate (125) | | 5.0 | Negative | Trace | Small | 9/10 Moderate 1/10 Small | | 6.5 | Negative | Trace | Small | Moderate | | 8.0 | Negative | Trace | Small | 9/10 Moderate 1/10 Small | The sponsor claims that pH does not affect the leukocyte test. Effect of pH on Nitrite: | pH | Nitrite Concentration (mg/dL) Expected | | | | | --- | --- | --- | --- | --- | | | Negative (0) | Positive (0.1) | Positive (1.0) | Positive (10) | | 5.0 | Negative | Positive | Positive ++ | Positive ++ | | 6.5 | Negative | Positive | Positive ++ | Positive ++ | | 8.0 | Negative | Positive | Positive ++ | Positive ++ | The sponsor claims that pH does not affect the nitrite test. Effect of Specific Gravity (SG) on Leukocytes: | Specific Gravity | Leukocyte Concentration (cells/μL) Expected | | | | | --- | --- | --- | --- | --- | | | Negative (0) | Trace (15) | Small (70) | Moderate (125) | | 1.005 | Negative | Trace | Small | Moderate | | 1.015 | Negative | Trace | Small | 9/10 Moderate 1/10 Large | | 1.030 | Negative | 6/10 Trace 4/10 Negative | 2/10 Small 8/10 Trace | 6/10 Small 4/10 Trace | The sponsor claims that SG causes negative interference for leukocyte results at $\mathrm{SG} \geq 1.030$ . Effect of Specific Gravity on Nitrite: | Specific Gravity | Nitrite Concentration (mg/dL) Expected | | | | | --- | --- | --- | --- | --- | | | Negative (0) | Positive (0.1) | Positive (1.0) | Positive (10) | | 1.005 | Negative | Positive | Positive ++ | Positive ++ | | 1.015 | Negative | Positive | Positive ++ | Positive ++ | | 1.030 | Negative | Positive | Positive ++ | Positive ++ | The sponsor claims that SG does not affect the nitrite test. To address the observed interferences, the labeling indicates that dehydration (high {9} SG), antibiotics, blood, and dye-containing drugs (such as Pyridium, Azo Gantrisin, and Azo Gantanol), as well as albumin, bilirubin, calcium chloride, citric acid, glucose, and oxalic acid may interfere with results. f. Assay cut-off: See detection limit, above. 2. Comparison studies: a. Method comparison with predicate device: Three sites were selected to perform the comparison studies. 159 lay users were recruited to test the Scanostics UTI Check application test system. Laypersons performed one test with the Scanostics UTI Check application using midstream urine collection and then collected a sample of their urine for comparison testing by healthcare professionals (HCPs). HCPs then performed the test using the predicate method. In order to evaluate an adequate number of leukocyte and nitrite positive samples, 25 additional users tested their own midstream samples as well as four additional blinded, unaltered urine samples, for a total of 125 additional samples. All samples were also tested by an HCP using the predicate method. Additionally, 14 positive samples were prepared by spiking negative urine with esterase and with sodium nitrite. Each sample was masked and given to one lay user (naïve to the test method) for testing. A total of 298 samples were tested by 184 lay users. The results obtained by the lay users using the candidate device compared to the results obtained by the HCPs using the predicate device are summarized below: 10 {10} Results from 184 lay users testing their own unaltered samples– Leukocytes: | Predicate result Scanosics Result | Large (3+) | Moderate (2+) | Small (1+) | Trace | Negative | Total | | --- | --- | --- | --- | --- | --- | --- | | Large (3+) | 7 | 1 | | | | 8 | | Moderate (2+) | 2 | 6 | 1 | | | 9 | | Small (1+) | | | 12 | 4 | | 16 | | Trace | | | 1 | 22 | 11 | 34 | | Negative | | | | 2 | 115 | 117 | | Total | 9 | 7 | 14 | 28 | 126 | 184 | | % Agreement (Exact Match) | 77.8 | 85.7 | 85.7 | 78.6 | 91.3 | 88.0% | | % Agreement (+/- Color Block) | 100% | 100% | 100% | 100% | 100% | 100.0% | Results from 184 lay users testing their own unaltered samples– Nitrite: | Predicate Result Scanosics Result | Positive | Negative | Overall | | --- | --- | --- | --- | | Positive | 8 | 2 | 10 | | Negative | | 174 | 174 | | e | 8 | 176 | 184 | | % Agreement (Exact Match) | 100% | 98.9% | 98.9% | | % Agreement (+/- Color Block) | 100% | 100% | 100% | {11} Results from all samples– Leukocytes: | Predicate Result Scanosics Result | Large (3+) | Moderate (2+) | Small (1+) | Trace | Negative | Overall | | --- | --- | --- | --- | --- | --- | --- | | Large (3+) | 16 | 2 | | | | 18 | | Moderate (2+) | 2 | 19 | 2 | | | 23 | | Small (1+) | | | 23 | 4 | | 27 | | Trace | | | 1 | 48 | 19 | 68 | | Negative | | | | 2 | 160 | 162 | | Total | 18 | 21 | 26 | 54 | 179 | 298 | | % Agreement (Exact Match) | 88.9% | 90.5% | 88.5% | 88.9% | 89.4% | 89.3% | | % Agreement (+/- 1 Color Block) | 100% | 100% | 100% | 100% | 100% | 100% | Results from all samples – Nitrite: | Predicate Result Scanosics Result | Positive | Negative | Overall | | --- | --- | --- | --- | | Positive | 69 | 4 | 73 | | Negative | | 225 | 225 | | Total | 69 | 229 | 298 | | % Agreement (Exact Match) | 100% | 98.8% | 98.7% | | % Agreement (+/- Color Block) | 100% | 100% | 100% | b. Matrix comparison: Not applicable. This device is intended to be used only with urine samples from a midstream collection. 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): {12} 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Urine from normal healthy subjects should contain no leukocytes or nitrite. The following information is provided in the labeling: | Leukocyte Result | Nitrite Result | Meaning of Your Result | | --- | --- | --- | | Negative (-) | Negative (-) | No sign of UTI detected. Consult a physician or health professional if you still have symptoms. There are some cases of UTI that the test may not detect. | | | Positive (+) | Results suggest a sign of UTI. Consult a physician or health professional immediately. | | Trace (+/-) | Negative (-) | Results suggest additional testing is required. Consult a physician or healthcare professional if you have symptoms. If not, test again the following day using a new strip. If you get another trace Leukocyte result or if you have symptoms, consult a physician or health professional. | | | Positive (+) | Results suggest a sign of UTI. Consult a physician or health professional immediately. | | Positive (+,++,+++) | Negative (-) | Results suggest a sign of UTI. Consult a physician or health professional immediately. | | | Positive (+) | Results suggest a sign of UTI. Consult a physician or health professional immediately. | # N. Instrument Name: The representative platform for the application is the iPhone 6 with iOS 9. Compatibility has been validated on both the iPhone 6 and 6S as well as the iPod touch (8th gen) with a minimum iOS requirement of iOS 8. {13} O. System Descriptions: 1. Modes of Operation: Smartphone image capture, analysis Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? ☑ Yes ☐ X or No Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? ☑ Yes ☐ X or No 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: ☑ Yes ☐ X or No The sponsor has classified their software as a Moderate level of concern. Documentation provided in this submission adequately addresses requirements for this level of concern. 3. Specimen Identification: There is no sample identification function with these devices. Samples are applied directly to the urinalysis strips as they are collected. 4. Specimen Sampling and Handling: The device is intended to be used with a freshly collected urine sample (midstream collection). The App instructs the user to image the test strip (to obtain a test result) no more than two minutes after sample application. 5. Calibration: Color coded backing card serves to reference the color interpretation of the strip, to normalize for lighting conditions. 6. Quality Control: Scanostics UTI Check performs two quality control checks on your device’s optics during image processing with a positive and negative control on the backing card. 14 {14} 15 P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above: 1. Dip time study: A dip time study was performed using low positive samples (near clinical decision points) and negative control solutions, including nitrite and leukocyte samples of 15 cells/μL and nitrite samples at 0.1 mg/dL. Test strips were dipped in control samples for 2, 4, 6, 8, 10, 20, and 30 seconds prior to imaging by the App to determine the impact of dipping time on reported results. This study indicated that dipping times between two and 30 seconds did not impact results. 2. Assay time study: An assay time study was performed using positive and negative control solutions, including nitrite and leukocyte samples of 15 cells/μL and nitrite samples at 0.1 mg/dL. In this study, test strips were imaged by the App at 30 second intervals between two and five minutes after sample application. This study indicated that assay times between 2:00 and 2:30 did not did not impact results, and a positive bias (an increase in results of +1 color block) is observed in the leukocyte test at 3:00. Based on these results, a timer is included in the App that instructs the user to image the test strip two minutes after wetting the strip, and will alert the user if the image of the strip has not been captured within three minutes after strip wetting (instructing the user to discard the test strip and start again). 3. Humidity Study: Stability studies were performed at 15 and 30 C° and 20%, 50%, and 70% relative humidity using positive and negative control solutions, including nitrite and leukocyte samples of 15 cells/μL and nitrite samples at 0.1 mg/dL. The sponsor evaluated 20%, 50%, and 70% relative humidity at 30 C°, and evaluated 50% relative humidity at 15 C°. The sponsor determined that samples were stable for 4 hours at the temperature and humidity conditions tested. 4. Lighting conditions: The sponsor evaluated the performance of the device in different lighting conditions (levels ranging from 100 to 500 lux) and demonstrated that the device works as expected in these lighting conditions. The labeling indicates that testing should be performed in a well-lit area. The App warns the user if there are shadows detected. 5. The App can also detect if the strip is misaligned and will warn the user when the strip is not properly aligned. 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.