K Number
K141289
Manufacturer
Date Cleared
2015-07-24

(431 days)

Product Code
Regulation Number
862.1340
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The TC-Thunderbolt Automated Urine Analyzer System is an in vitto diagnostic device used to automate the urine chemistry analysis using TC-Thunderbolt URS-10 strips. It produces semi-quantitative results of glucose, protein, pH, bilirubin, blood, ketone, urobilinogen, nitrite, specific gravity and leukocytes in urine. TC-Thunderbolt URS-10 strips are intended for use only with TC-Thunderbolt Automated Urine Analyzer System, they are not intended for manual visual reading. This device is for clinical laboratory use only. This device is not for Point of Care Use. These measurements are used to aid in the diagnosis of metabolic disorders, kidney function anomalies, urinary tract infections and liver function.

Device Description

The proposed device is an automated urine chemistry analyzer system intended for use only with TC-Thunderbolt URS-10 strips for the measurement of ten urine chemistry analytes from the chemistry strip. The system consists of the TC-Thunderbolt Automated Urine Analyzer and the TC-Thunderbolt URS-10 strips.

AI/ML Overview

This document describes the performance of the TC-Thunderbolt Automated Urine Analyzer System, an in vitro diagnostic device for semi-quantitative analysis of urine chemistry. The studies presented focus on the analytical performance of the device and its associated test strips (TC-Thunderbolt URS-10 strips) rather than human-in-the-loop performance with an AI. Therefore, sections related to human reader improvement with AI assistance (MRMC studies) and expert consensus in the typical sense for AI model ground truth are not directly applicable to this type of device submission.

Here's a breakdown of the requested information based on the provided text, focusing on the device's analytical performance:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implied by the results of the precision and method comparison studies, generally aiming for high agreement with either the expected control values or a predicate device. The tables below summarize the reported device performance for selected analytes from the precision (within-run and run-to-run) and method comparison studies.

Precision Study Acceptance Criteria & Performance (Within-Run & Run-to-Run for Urine Controls):

The acceptance criteria for precision studies are generally for high exact match agreement and 100% agreement within +/- one color block.

AnalyteStudy TypeTarget LevelAcceptance Criteria (Exact Match)Reported Performance (% Exact Match)Acceptance Criteria (+/- Color Block)Reported Performance (% +/- Color Block)
GlucoseWithin Run500 mg/dLHigh Agreement (e.g.,>95%)96.67%100%100%
Within Run100 mg/dLHigh Agreement (e.g.,>95%)96.67%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to Run500 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to Run100 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
BilirubinWithin RunModerateHigh Agreement (e.g.,>95%)100%100%100%
Within RunSmallHigh Agreement (e.g.,>95%)100%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to RunModerateHigh Agreement (e.g.,>95%)100%100%100%
Run to RunSmallHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
KetoneWithin Run40 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Within Run40 mg/dLHigh Agreement (e.g.,>95%)98.83%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to Run40 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to Run40 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Specific GravityWithin Run1.015High Agreement (e.g.,>95%)100%100%100%
Within Run1.015High Agreement (e.g.,>95%)95%100%100%
Within Run1.005High Agreement (e.g.,>95%)96.67%100%100%
Run to Run1.015High Agreement (e.g.,>95%)98.83%100%100%
Run to Run1.015High Agreement (e.g.,>95%)93.34%100%100%
Run to Run1.005High Agreement (e.g.,>95%)100%100%100%
BloodWithin RunModerateHigh Agreement (e.g.,>95%)98.34%100%100%
Within RunTraceHigh Agreement (e.g.,>95%)100%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to RunModerateHigh Agreement (e.g.,>95%)100%100%100%
Run to RunTraceHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
NitriteWithin RunPositiveHigh Agreement (e.g.,>95%)100%100%100%
Within RunPositiveHigh Agreement (e.g.,>95%)100%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to RunPositiveHigh Agreement (e.g.,>95%)100%100%100%
Run to RunPositiveHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
ProteinWithin Run300 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to Run300 mg/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
UrobilinogenWithin Run8 EU/dLHigh Agreement (e.g.,>95%)100%100%100%
Within Run0.2 EU/dLHigh Agreement (e.g.,>95%)100%100%100%
Within Run0.2 EU/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to Run8 EU/dLHigh Agreement (e.g.,>95%)98.83%100%100%
Run to Run0.2 EU/dLHigh Agreement (e.g.,>95%)100%100%100%
Run to Run0.2 EU/dLHigh Agreement (e.g.,>95%)100%100%100%
LeukocyteWithin RunModerateHigh Agreement (e.g.,>95%)100%100%100%
Within RunSmallHigh Agreement (e.g.,>95%)100%100%100%
Within RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
Run to RunModerateHigh Agreement (e.g.,>95%)100%100%100%
Run to RunSmallHigh Agreement (e.g.,>95%)96.67%100%100%
Run to RunNegativeHigh Agreement (e.g.,>95%)100%100%100%
pHWithin Run7.5High Agreement (e.g.,>95%)100%100%100%
Within Run7.5High Agreement (e.g.,>95%)100%100%100%
Within Run6.5High Agreement (e.g.,>95%)96.67%100%100%
Run to Run7.5High Agreement (e.g.,>95%)100%100%100%
Run to Run7.5High Agreement (e.g.,>95%)100%100%100%
Run to Run6.5High Agreement (e.g.,>95%)100%100%100%

Method Comparison Study Acceptance Criteria & Performance (vs. Predicate Device):

The acceptance criteria for method comparison studies are generally for high overall agreement, with a specific note for SG.

AnalyteAcceptance Criteria (Overall Exact Match)Reported Overall Exact MatchAcceptance Criteria (Overall +/- Color Block)Reported Overall +/- Color Block
GlucoseHigh Agreement (e.g., >95%)98.36%High Agreement (e.g., 100%)100%
BilirubinHigh Agreement (e.g., >95%)99.59%High Agreement (e.g., 100%)100%
KetoneHigh Agreement (e.g., >95%)97.74%High Agreement (e.g., 100%)100%
Specific GravityHigh Agreement (e.g., >75%)79.88%+/- 0.005 (note)99.18%
BloodHigh Agreement (e.g., >95%)95.48%High Agreement (e.g., 100%)100%
ProteinHigh Agreement (e.g., >95%)97.95%High Agreement (e.g., 100%)100%
UrobilinogenHigh Agreement (e.g., >95%)95.69%High Agreement (e.g., 100%)100%
pHHigh Agreement (e.g., >85%)86.45%High Agreement (e.g., >99%)99.59%
NitriteHigh Agreement (e.g., >99%)99.79%High Agreement (e.g., 100%)100%
LeukocyteHigh Agreement (e.g., >95%)96.71%High Agreement (e.g., 100%)100%

2. Sample Size Used for the Test Set and Data Provenance

Precision Study (Test Set):
For Within Run precision: 60 strips per control level (20 replicates x 1 day x 3 operators/strip lots) were tested. There were 3 control levels (I, II, III).
For Run to Run precision: 60 strips per control level (2 replicates x 2 runs x 5 days x 3 operators/strip lots) were tested. There were 3 control levels (I, II, III).
Data Provenance: Not explicitly stated for all samples, but the "Method Comparison Study Summary" states: "This comparison study testing was performed at Teco Diagnostics, Anaheim CA in United States." It also mentions "The urine samples for analysis in these method comparison studies were provided by external clinical sites." This implies a prospective data collection for the method comparison, and likely also for the precision studies, as real-time control solutions were used.

Method Comparison Study (Test Set):
A total of 487 urine samples were used for the method comparison study.
Data Provenance: The study was performed at Teco Diagnostics, Anaheim, CA, United States. Samples were collected from external clinical sites. These could be considered a mix of retrospective and prospective, as some samples might have been collected specifically for the study (prospective), and others could have been existing samples (retrospective), but the description implies a prospective approach to sample collection and testing for the study. Spiked samples were also prepared.

Sensitivity/Cutoff Point Determination Study & Linearity Study (Test Set):
For Sensitivity: 21 data points for each level (7 strips x 3 operators/strip lots). This study used spiked urine samples.
For Linearity: 21 measurements for every sample tested (7 strips x 3 operators/strip lots). This study used negative urine and spiked negative urine.
Data Provenance: Performed at Teco Diagnostics, Anaheim, CA, United States. Samples were negative urine, with many spiked to achieve various concentrations.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

For this type of in vitro diagnostic device, "ground truth" is typically established by:

  • Reference materials/control solutions: For precision studies, commercially available urine control solutions with confirmed target analyte concentrations were used.
  • Comparative method (Predicate Device or Reference Method): For method comparison, the predicate device (Uritek-720+ Urine Analyzer) served as the comparative method against which the new device's performance was evaluated.
  • Known concentrations: For sensitivity and linearity studies, samples were prepared by spiking known concentrations of analytes into negative urine. For pH, a pH meter confirmed results, and for Specific Gravity, a clinical, handheld refractometer confirmed values.

Therefore, the ground truth is established by analytical reference methods and known chemical concentrations, rather than human expert reads of images. There is no mention of human experts establishing ground truth in the context of image interpretation or reading. The studies mentioned involve operators performing tests, but their role is to execute the protocol and collect data, not to adjudicate ground truth. The number of operators (3) is mentioned for precision and sensitivity/linearity studies, indicating consistency checks across different users of the device.

4. Adjudication Method for the Test Set

Adjudication as typically understood in the context of human reader disagreement for AI models is not directly applicable here. The "ground truth" for these analytical tests is based on the known concentrations of controls, the results from a predicate device, or measurements by reference instruments (pH meter, refractometer). Discrepancies in device readings are analyzed as agreement percentages (exact match and +/- color block) against these pre-established analytical references, rather than being arbitrated by human experts.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not performed. This submission is for an automated in vitro diagnostic device (urine analyzer) that produces semi-quantitative results by measuring chemical reactions on test strips. It is not an AI-assisted diagnostic imaging device that involves human readers interpreting images. Therefore, the concept of human readers improving with or without AI assistance is not relevant to this submission.

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

Yes, the studies are essentially standalone performance evaluations of the automated device (TC-Thunderbolt Automated Urine Analyzer System). While operators conduct the tests, the output is generated by the instrument's sensing and processing of the chemical reactions on the strips. The tables presented show the performance of the device itself (e.g., % agreement with controls or predicate device), representing its standalone analytical capability.

7. The Type of Ground Truth Used

The types of ground truth used are:

  • Defined Control Solutions/Reference Materials: For precision studies, commercially available urine control solutions with certified analyte concentrations were used.
  • Predicate Device Gold Standard: For method comparison, the Uritek-720+ Urine Analyzer (the predicate device) served as the reference against which the new device was compared.
  • Known Chemical Concentrations: For sensitivity/cutoff point determination and linearity studies, samples were prepared by spiking urine with precise, known concentrations of analytes.
  • Reference Instruments: For pH, a pH meter was used as the ground truth. For specific gravity, a clinical, handheld refractometer was used as the ground truth.

8. The Sample Size for the Training Set

This document only describes analytical performance studies for a medical device submitted for 510(k) clearance, which demonstrates substantial equivalence to a predicate device. It does not provide information about a "training set" in the context of machine learning. The device's operation is based on established chemical principles and optical measurement, not on a machine learning model that requires a "training set."

9. How the Ground Truth for the Training Set Was Established

Since there is no mention of a machine learning model or a "training set" in the context of AI development, this question is not applicable. The device relies on chemical reactions and optical measurement, for which the underlying scientific principles and performance are validated through the analytical studies described.

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, arranged in a way that they appear to be connected or overlapping.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 24, 2015

TECO DIAGNOSTICS AQUIL MERCHANT RESEARCH SCIENTIST 1268 NORTH LAKEVIEW AVE. ANAHEIM CA 92807

Re: K141289

Trade/Device Name: TC-Thunderbolt Automated Urine Analyzer System Regulation Number: 21 CFR 862.1340 Regulation Name: Urinary glucose (nonquantitative) test system Regulatory Class: II Product Code: JIL, JIO, KQO, LJX, JRE, CEN, JMT, JIR, JIN, CDM, JJB Dated: July 17, 2015 Received: July 20, 2015

Dear Mr. Merchant:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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510(k) Summary

Applicant:

510(k) Number: K141289 Teco Diagnostics 1268 N. Lakeview Avenue Anaheim, CA 92807

Aquil Merchant, M.S., Research Scientist Tel: 714.463.1111 | Fax: 714.463.1169 Email: amerchant@tecodiag.com | Web: http://www.tecodiag.com Date: 07/24/2015

4.1) TC-Thunderbolt Automated Urine Analyzer System:

A) Proprietary and Established Names:

Proprietary Names: TC-Thunderbolt Automated Urine Analyzer System

Common Names: Automated Urine Analyzer, Urine Test System (non-quantitative). The system consists of the TC-Thunderbolt Automated Urine Analyzer and the TC-Thunderbolt URS-10 strips.

Regulation sectionCodeTestClassification
21 CFR § 862.1340JILUrinary Glucose (nonquantitative) Test SystemII
21 CFR § 864.6550JIOOccult Blood TestII
21 CFR § 862.2900KQOAutomated Urinalysis SystemI
21 CFR § 864.7675LJXLeukocyte Peroxidase TestI
21 CFR § 862.2800JRERefractometer for clinical useI
21 CFR § 862.1550CENUrinary pH (nonquantitative) Test SystemI
21 CFR § 862.1510JMTNitrite (nonquantitative) Test SystemI
21 CFR § 862.1645JIRUrinary Protein or Albumin (nonquantitative) TestSystemI
21 CFR § 862.1435JINKetones (nonquantitative) Test SystemI
21 CFR § 862.1785CDMUrinary Urobilinogen (nonquantitative) Test SystemI
21 CFR § 862.1115JJBUrinary Bilirubin and its conjugates (nonquantitative) Test SystemI

4.2) Regulatory Information:

4.3) Indication for Use:

The TC-Thunderbolt Automated Urine Analyzer System is an in vitto diagnostic device used to automate the urine chemistry analysis using TC-Thunderbolt URS-10 strips. It produces semi-quantitative results of glucose, protein, pH, bilirubin, blood, ketone, urobilinogen, nitrite, specific gravity and leukocytes in urine. TC-Thunderbolt URS-10 strips are intended for use only with TC-Thunderbolt Automated Urine Analyzer System, they are not intended for manual visual reading. This device is for clinical laboratory use only. This device is not for Point of Care Use. These measurements are used to aid in the diagnosis of metabolic disorders, kidney function anomalies, urinary tract infections and liver function.

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4.4) Predicate Device:

Uritek-720+ Urine Analyzer for the use with Teco Diagnostic's URS-10 strips (K051526).

4.5) Description of the proposed device:

The proposed device is an automated urine chemistry analyzer system intended for use only with TC-Thunderbolt URS-10 strips for the measurement of ten urine chemistry analytes from the chemistry strip. The system consists of the TC-Thunderbolt Automated Urine Analyzer and the TC-Thunderbolt URS-10 strips.

DescriptionProposedPredicate
DeviceTC-Thunderbolt AutomatedAnalyzer SystemUritek-720+ Analyzer
Intended UseAutomated Urine Chemistry Analyzer usedfor in vitro measurement of glucose,protein, pH, bilirubin, blood, ketone,urobilinogen, nitrite, specific gravity andleukocytes in urine.Same
DesignSame as predicateUses proven chemical testmethod protocol for the intendeduse determinations of all 10parameters
DesignSame as predicateUses the principle of lightreflection to determine the colorintensity on reagent strip testarea
DesignSame as predicateUses testing technology of acold light source, integratingsphere and modularizedblocking systematical designwhich enhances the stability ofthe optical system
DesignThe test module uses the principle of light-reflection to determine the changes in papercolor, conduct a digital analysis on thecentral portion most uniform in color of thepaperMeasures the color intensity byirradiating the white light anddetecting the reflectance on theurine pad with an integratedsphere photo-detector

4.6) TC-Thunderbolt Automated Urine Analyzer System v/s Uritek-720+ Analyzer:

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Testing PatternThe test module uses automatic sample-suction, strip advance, and sample-application technologies instead of manualoperations to facilitate urinalysis. Transferof urine sample takes place via a sample-suction needle and pipe which extracts andapplies the sample to the test stripThe test strip needs to be dippedin the test tube containing urinesample manually. Dry the stripon an absorbent piece of paperand place it on the test table.
SafetyThe device has been certified to complywith the latest applicable safety standardswhich includes EN 61010-1:2010 for LVDand EN 61010-2-101: 2002 for IVDThe device has been certified tocomply with the latest applicablesafety standards which includesEN 61010-1:2010 for LVD andEN 61010-2-101: 2002 for IVD
ElectromagneticCompatibilityThe proposed device has been tested andcertified to EN 61326-1:2006 EMCrequirements-general, EN 61326-2-6:2006EMC requirements-particular requirementsfor IVD medical equipment, EN 61000-3-2:2006 + A1:2009 + A2: 2009 and EN61000-3-3:2008The device has been tested andcertified to EN 61000-4-2, EN61000-4-4, EN 61000-4-5 andEN 61000-4-11
Chemistry StripsThe TC-Thunderbolt Automated UrineAnalyzer System is intended for use onlywith TC-Thunderbolt URS-10 stripsThe Uritek-720+ analyzer isintended for use only with TecoDiagnostic's URS 10 strips
DescriptionTC-Thunderbolt Automated Urine Analyzer SystemTeco Diagnostic's URS-10 Strips
Intended SpecimenUrineSame
Materials ProvidedPlastic strips affixed with reagent padsSame
Dimension110mm (length) x 5mm (width)108mm (length) x 5mm (width)
Glucose MethodologyBased on a double sequential enzyme reaction. One enzyme, glucose oxidase, catalyzes the reaction in which glucose is oxidized to produce gluconic acid and hydrogen peroxide. A second enzyme, peroxidase, catalyzes the reaction of hydrogen peroxide with potassium iodide chromogen in which the chromogen is oxidized to different colors ranging from blue-green to greenish-brown through brown and dark brown.Same
Bilirubin MethodologyBased on the coupling of bilirubin with a diazotized dichioroaniline in a strongly acid medium. Varying bilirubin levels will produce light tan to reddish brown color proportional to its concentration in urine.Same
Ketone MethodologyBased on the reaction of acetoacetic acid with sodium nitroprusside in a strongly basic medium. The colors range from beige or buff-pink color for a "Negative" reading to pink and pink-purple for a "Positive" reading.Same
Specific Gravity MethodologyBased on the apparent pKa change of certain pretreated polyelectrolytes in relation to the ionic concentration. In the presence of an indicator, the colors range from dark blue or blue-green in urine of low ionic concentration to green and yellow-green in urine of higher ionic concentration.Same
Blood MethodologyBased on the pseudoperoxidase action of hemoglobin and erythrocytes which catalyzes the reaction of 3,3', 5, 5 '-tetramethyl-benzidine and buffered organic peroxide. The resulting colors range from orange to yellow-green and dark green. Very high blood concentration may cause the color development to continue to dark blue.Same
pH MethodologyBased on the well-known double pH indicator method, where bromothymol blue and methyl red give distinguishable colors over the pH range of 5-9. The colors range from red-orange to yellowSame
ProteinMethodologyBased on the protein error-of-indicator principle.At a constant pH, the development of any greencolor is due to the presence of protein. Colorsrange from yellow for a "Negative" reaction toyellow-green and green to blue-green for a"Positive" reaction.Same
UrobilinogenMethodologyBased on a modified Ehrlich reaction in which p-diethylaminobenzaldehydereactswithurobilinogen in a strongly acid medium. Colorsrange from light pink to bright magenta.Same
NitriteMethodologyThis test depends on the conversion of nitrate tonitrite by the action of Gram-negative bacteria inthe urine. The nitrite reacts with p-arsanilic acidto from a diazonium compound in an acidmedium. The diazoniumn compound in turncouples with 1, 2, 3, 4- tetrahydrobenzo (h)quinolin to produce a pink color.Same
LeukocyteMethodologyBased on the action of esterase present inleukocytes, which catalyzes the hydrolysis of anindoxyl ester derivative. The indoxyl esterliberated reacts with a diazoniumn salt to producea beige-pink to purple color.Same

The TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ analyzer share the same technological characteristics including the testing parameters, print out, calibration method, and power requirements. The most notable difference is in their respective testing patterns, wherein TC-Thunderbolt Automated Urine Analyzer System uses automatic sample-suction, strip advance, and sample-application technologies and for the predicate the test strip needs to be dipped in urine sample and placed on the test table manually. In addition to this, they also differ in their display, user interface, entered parameter (user ID), dimensions and weight. These differences do not have any effect on the results of the devices since the color development and reflectance values are measured after one minute.

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4.7) TC-Thunderbolt Automated Urine Analyzer System v/s Teco Diagnostic's URS-10 Strips:

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The TC-Thunderbolt URS-10 Strips and Teco Diagnostic's URS-10 strips share the same characteristics including Glucose, Bilirubin, Ketone, Specific Gravity, Blood, pH, Protein, Urobilinogen, Nitrite and Leukocyte methodologies. The differences between the TC-Thunderbolt URS-10 Strips and Teco Diagnostic's URS-10 strips could be the length of the strip, paper of reagent pad and black plastic pad. The TC-Thunderbolt URS-10 strips are 2mm longer in length and have a black plastic pad at the end which is meant only for alignment purpose in the TC-Thunderbolt Automated Urine Analyzer System. However these differences do not have any effect on the results or operations of the devices.

4.8) Test Principle:

Glucose: This test is based on a double sequential enzyme reaction. One enzyme, glucose oxidase, catalyzes the reaction in which glucose is oxidized to produce gluconic acid and hydrogen peroxide. A second enzyme, peroxidase, catalyzes the reaction of hydrogen peroxide with potassium iodide chromogen in which the chromogen is oxidized to different colors ranging from blue-green to greenishbrown through brown and dark brown.

Bilirubin: This test is based on the coupling of bilirubin with a diazotized dichioroaniline in a strongly acid medium. Varying bilirubin levels will produce light tan to reddish brown color proportional to its concentration in urine.

Ketone: This test is based on t reaction of acetoacetic acid with sodium n basic medium. The colors range from beige or buff-pink color for a "Negative" reading to pinkpurple for a "Positive" reading.

Specific Gravity: This test is based on the apparent pKa change of certai relation to the ionic concentration. In the presence of an indicator, the colors range from dark blue or

{8}------------------------------------------------

blue-green in urine of low ionic concentration to green and yellow-green in urine of higher ionic concentration.

Blood: This test is based on the pseudoperoxidase action of hemoglobin and erythrocytes which catalyzes the reaction of 3,3', 5, 5 '-tetramethyl-benzidine and buffered organic peroxide. The resulting colors range from orange to yellow-green and dark green. Very high blood concentration may cause the color development to continue to dark blue.

pH: This test is based on the well-known double pH indicator method, where bromothymol blue and methyl red give distinguishable colors over the pH range of 5-9. The colors range to yellow and yellow-green to blue-green.

Protein: This test is based on the protein error-of-indicator principle. At a constant pH, the development of any green color is due to the presence of protein. Colors range from yellow for a "Negative" reaction to yellow-green and green to blue-green for a "Positive" reaction.

Urobilinogen: This test is based on a modified Ehrlich reaction in which p-diethylaminobenzaldehyde reacts with urobilinogen in a strongly acid medium. Colors range from light pink to bright magenta.

Nitrite: This test depends on the conversion of nitrate to nitrite by the action of Gram-negative bacteria in the urine. The nitrite reacts with p-arsanilic acid to from a diazonium compound in an acid medium. The diazoniumn compound in turn couples with 1, 2, 3, 4- tetrahydrobenzo(h) quinolin to produce a pink color.

Leukocytes: This test is based on the action of esterase present in leukocytes, which catalyzes the hydrolysis of an indoxyl ester derivative. The indoxyl ester liberated reacts with a diazoniumn salt to produce a beige-pink to purple color.

4.9) Analytical Performance Studies

A) Precision Study Summary:

  • Within Run:
    Repeatability (within run and day-to-day) precision of the TC-Thunderbolt Automated Urine Analyzer System was evaluated using commercially available urine control solutions at Level I (High analyte concentration), Level II (Low analyte concentration) and Level III (Negative). The package insert and certificate of analysis of these control solutions confirmed the specific target analyte concentration in each level. 20 replicate assays of each level (negative, and high positive) were analyzed on TC-Thunderbolt Automated Urine Analyzer with three lots of TC-Thunderbolt URS-10 strips by three operators. A total of 60 strips were used for each level control solution tested (20 strips x 1 day x 3 operators/strip lots = 60 tests per control). The results from the Within Run Precision study are summarized below:

AnalyteLevelExactMatchAgreement% Agreement(Exact Match)+/- ColorBlockAgreement% Agreement(+/- ColorBlock)N
Glucose500 mg/dL58/6096.6760/6010060
BilirubinModerate60/6010060/6010060
Ketone40 mg/dL60/6010060/6010060

Urine Control Level I

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Specific Gravity1.01560/6010060/6010060
BloodModerate59/6098.3460/6010060
NitritePositive60/6010060/6010060
Protein300 mg/dL60/6010060/6010060
Urobilinogen8 EU/dL60/6010060/6010060
LeukocyteModerate60/6010060/6010060
pH7.560/6010060/6010060

Urine Control Level II

AnalyteLevelExactMatchAgreement%Agreement(Exact Match)+/- ColorBlockAgreement%Agreement(+/- ColorBlock)N
Glucose100 mg/dL58/6096.6760/6010060
BilirubinSmall60/6010060/6010060
Ketone40 mg/dL59/6098.8360/6010060
Specific Gravity1.01557/609560/6010060
BloodTrace59/6010060/6010060
NitritePositive60/6010060/6010060
ProteinNegative60/6010060/6010060
Urobilinogen0.2 EU/dL60/6010060/6010060
LeukocyteSmall60/6010060/6010060
pH7.560/6010060/6010060

Urine Control Level III

AnalyteLevelExactMatchAgreement% Agreement(Exact Match)+/- ColorBlockAgreement% Agreement(+/- ColorBlock)N
GlucoseNegative60/6010060/6010060
BilirubinNegative60/6010060/6010060
KetoneNegative59/6010060/6010060
Specific Gravity1.00558/6096.6760/6010060
BloodNegative59/6010060/6010060
NitriteNegative60/6010060/6010060
ProteinNegative60/6010060/6010060
Urobilinogen0.2 EU/dL60/6010060/6010060
LeukocyteNegative60/6010060/6010060
pH6.558/6096.6760/6010060

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> Run to Run:

TC-Thunderbolt Automated Urine Analyzer was evaluated by testing each control level (negative, low positive, and high positive) by three operators with three lots of TC-Thunderbolt URS-10 strips in two replicate assays for 2 non- consecutive runs/day over 5 days. Run 1 and Run 2 were separated by atleast 1 hour. A total of 60 strips were used for each level control solution tested (2 strips x 2 run x 5 days x 3 operators/ strip lots = 60 tests per control). The results from the Run to Run Precision study are summarized below:

Urine Control Level I

AnalyteLevelExactMatchAgreement% Agreement(Exact Match)+/- ColorBlockAgreement%Agreement(+/- ColorBlock)N
Glucose500 mg/dL60/6010060/6010060
BilirubinModerate60/6010060/6010060
Ketone40 mg/dL60/6010060/6010060
Specific Gravity1.01559/6098.8360/6010060
BloodModerate59/6010060/6010060
NitritePositive60/6010060/6010060
Protein300 mg/dL60/6010060/6010060
Urobilinogen8 EU/dL59/6098.8360/6010060
LeukocyteModerate60/6010060/6010060
pH7.560/6010060/6010060

Urine Control Level II

AnalyteLevelExactMatchAgreement% Agreement(Exact Match)+/- ColorBlockAgreement% Agreement(+/- ColorBlock)N
Glucose100 mg/dL60/6010060/6010060
BilirubinSmall60/6010060/6010060
Ketone40 mg/dL60/6010060/6010060
Specific Gravity1.01556/6093.3460/6010060
BloodTrace59/6010060/6010060
NitritePositive60/6010060/6010060
ProteinNegative60/6010060/6010060
Urobilinogen0.2 EU/dL60/6010060/6010060
LeukocyteSmall58/6096.6760/6010060
pH7.560/6010060/6010060

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Urine Control Level III

AnalyteLevelExactMatchAgreement% Agreement(Exact Match)+/- ColorBlockAgreement% Agreement(+/- ColorBlock)N
GlucoseNegative60/6010060/6010060
BilirubinNegative60/6010060/6010060
KetoneNegative60/6010060/6010060
Specific Gravity1.00560/6010060/6010060
BloodNegative60/6010060/6010060
NitriteNegative60/6010060/6010060
ProteinNegative60/6010060/6010060
Urobilinogen0.2 EU/dL60/6010060/6010060
LeukocyteNegative60/6010060/6010060
pH6.560/6010060/6010060

B) Method Comparison Study Summary:

This comparison study testing was performed at Teco Diagnostics, Anaheim CA in United States. The urine samples for analysis in these method comparison studies were provided by external clinical sites. Samples were collected within 4 hours of testing if maintained at room temperature or were stored for up to 8 hours prior to testing if maintained at 2-8°C. In order to obtain a desired range of abnormal values a pool of negative urine samples were spiked to elevated level with the analytes to be evaluated. These spiked samples represent 10% of the total samples tested. For each chemistry analyte, the values obtained for the individual urine samples were referred to the respective cut-off values for each system to discriminate between the negative (normal) and positive (abnormal) findings, if applicable. The data was represented in concordance charts showing percent exact match agreement and percent agreement within 1 color block.

Glucose
ThunderboltUritek-720+1000500250100NegOverall
100011
500194
2503221
1004
Neg423
Total1122265423487
% Agreement (Exact Match)100.0086.3684.6280.00100.0098.36
% Agreement (+/- Color Block)100.00100.00100.00100.00100.00100.00

Glucose concentration levels compared at a 98.36% overall exact match and a 100% overall agreement +/- one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

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BilirubinUritek-720+3+2+1+NegOverall
Thunderbolt
3+6
2+7
1+40
Neg2432
Total6742432487
% Agreement (Exact Match)100.00100.0095.24100.0099.59
% Agreement (+/- Color Block)100.00100.00100.00100.00100.00

Bilirubin concentration levels compared at a 99.59% overall exact match and a 100% overall agreement +/- one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

Ketone
Uritek-720+804015TRANegOverall
Thunderbolt806
40103
153252
TRA2141
Neg421
Total6133016422487
% Agreement (Exact Match)100.0076.9283.3387.5099.7697.74
% Agreement (+/- Color Block)100.00100.00100.00100.00100.00100.00

Ketone concentration levels compared at a 97.74% overall exact match and a 100% overall agreement +/one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

Specific Gravity
Uritek-720+Thunderbolt>1.0301.0251.0201.0151.010<1.005Overall
>1.03091
1.025311812
1.0205444
1.015710132
1.01030685
<1.00522449
Total12124631379556487
% Agreement (Exact Match)75.0095.1669.8473.7271.5887.5079.88
% Agreement (+/- Color Block)100.00100.00100.0098.54100.0096.4399.18

Specific Gravity concentration levels compared at a 79.88% overall exact match and a 99.18% overall agreement +/- one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer. * The Acceptance Criteria for SG is +/- 0.005.

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Blood
Uritek-720+Thunderbolt3+2+1+TRANegOverall
3+133
2+1456
1+4205
TRA171
Neg2370
Total14522624371487
% Agreement (Exact Match)92.8686.5476.9270.8399.7395.48
% Agreement (+/- Color Block)100.00100.00100.00100.00100.00100.00

Blood concentration levels compared at a 95.48% overall exact match and a 100% overall agreement +/one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

Protein
ThunderboltUritek-720+>30010030TRANegOverall
>300403
100332
3017
TRA320
Neg1368
Total43352021368487
% Agreement (Exact Match)93.0291.4385.0095.24100.0097.95
% Agreement (+/- Color Block)100.00100.00100.00100.00100.00100.00

Protein concentration levels compared at a 97.95% overall exact match and a 100% overall agreement +/one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

Urobilinogen
ThunderboltUritek-720+>8.04210.2Overall
>8.0101
4.01664
2.01271
1.03113
0.2332
Total11683132345487
% Agreement (Exact Match)90.9197.0687.1096.8896.2395.69
% Agreement (+/- Color Block)100.00100.00100.00100.00100.00100.00

Urobilinogen concentration levels compared at a 95.69% overall exact match and a 100% overall agreement +/- one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

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pH
ThunderboltUritek-720+8.587.57.06.56.05.0Overall
8.510
8.012
7.511141
7.035921
6.539433
6.06418
5.0171
Total101211466979989487
% Agreement (Exact Match)10010097.3789.3996.9164.6579.7886.45
% Agreement (+/- Color Block)100100100.00100.0098.9798.99100.0099.59

pH concentration levels compared at an 86.45% overall exact match and a 99.59% overall agreement +/one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

NitriteUritek-720++-Overall
Thunderbolt+70
-1416
Total71416373
% Agreement (Exact Match)98.59100.0099.79
% Agreement (+/- Color Block)100.00100.00100.00

Nitrite concentration levels compared at a 99.79% overall exact match and a 100% overall agreement +/one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

Leukocyte
ThunderboltUritek-720+3+2+1+TRANegOverall
3+12
2+1174
1+5275
TRA115
Neg400
Total13223220400487
% Agreement (Exact Match)92.3177.2784.3875.00100.0096.71
% Agreement (+/- Color Block)100.00100.0096.88100.00100.00100.00

Leukocyte concentration levels compared at a 96.71% overall exact match and a 100% overall agreement +/- one color block match between the TC-Thunderbolt Automated Urine Analyzer System and Uritek-720+ Analyzer.

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C) Sensitivity/ Cutoff Point Determination Study Summary

A Sensitivity Study

Sensitivity Study was performed to determine the cutoff point concentration at which each analyte on the TC-Thunderbolt URS-10 strip changed from negative to the positive color blocks. Samples were prepared by spiking the specified analyte concentration into negative urine with a minimum of 4 levels across the measuring range for each color block. Each pool was then analyzed in replicates of 7 by 3 operators on each of the 3 individual strip lots (7 strips x 3 operators/ strip lots), for a total of 21 data points for each level. The cutoff point determination study for each color block for each analyte is defined as the lowest concentration at which >55% of the test results are positive.

Results:

The cut-off values and percentage sensitivity for each color block for individual analyte is summarized and demonstrated in the table below:

AnalyteColor BlockCut-off Concentration% Positive Results
Glucose100 mg/dL75 mg/dL90%
250 mg/dL212.5 mg/dL85%
500 mg/dL437.5 mg/dL85%
1000 mg/dL875 mg/dL85%
BilirubinSmall0.375 mg/dL57%
Moderate1 mg/dL100%
Large2.5 mg/dL57%
KetoneTrace3.75 mg/dL95%
15 mg/dL10 mg/dL55%
40 mg/dL27.5 mg/dL55%
80 mg/dL60 mg/dL95%
BloodTrace0.023 mg/dL61%
Small0.064 mg/dL76%
Moderate0.199 mg/dL90%
Large0.628 mg/dL90%
ProteinTrace11.25 mg/dL75%
30 mg/dL26.25 mg/dL85%
100 mg/dL82.5 mg/dL95%
300 mg/dL200 mg/dL85%
2000 mg/dL1150 mg/dL70%
NitritePositive0.1 mg/dL55%
LeukocyteTrace15 ca cells/µL100%
Small56.25 ca cells/µL95%
Moderate97.5 ca cells/µL60%

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Large406.25 ca cells/µL55%
Urobilinogen0.2 mg/dL0.2 mg/dL100%
1.0 mg/dL0.8 mg/dL71%
2.0 mg/dL2.0 mg/dL90%
4.0 mg/dL3.5 mg/dL55%
8.0 mg/dL7.0 mg/dL85%
pH5.05.0
6.06.095%
6.56.595%
7.07.095%
7.57.595%
8.08.0100%
8.58.5100%
SG1.0051.005100%
1.0101.010100%
1.0151.015100%
1.0201.020100%
1.0251.025100%
1.0301.030100%

The results for specific analyte concentration at each color block are shown below:

ConcentrationTestedPercentage Agreement at Each Color Block
Negative100 mg/dL250 mg/dL500 mg/dL1000 mg/dL
GLUCOSE25 mg/dL100%0%0%0%0%
50 mg/dL100%0%0%0%0%
75 mg/dL10%90%0%0%0%
100 mg/dL0%100%0%0%0%
137.5 mg/dL0%100%0%0%0%
175 mg/dL0%100%0%0%0%
212.5 mg/dL0%15%85%0%0%
250 mg/dL0%0%100%0%0%

{17}------------------------------------------------

312.5 mg/dL0%0%100%0%0%
375 mg/dL0%0%100%0%0%
437.5 mg/dL0%0%15%85%0%
500 mg/dL0%0%0%100%0%
625 mg/dL0%0%0%100%0%
750 mg/dL0%0%0%60%40%
875 mg/dL0%0%0%15%85%
1000 mg/dL0%0%0%0%100%
ConcentrationTestedPercentage Agreement at Each Color Block
NegativeSmallModerateLarge
0.125 mg/dL100%0%0%0%
0.25 mg/dL100%0%0%0%
0.375 mg/dL43%57%0%0%
0.5 mg/dL0%100%0%0%
BILIRUBIN0.625 mg/dL0%100%0%0%
0.75 mg/dL0%100%0%0%
0.875 mg/dL0%71%29%0%
1 mg/dL0%0%100%0%
1.5 mg/dL0%0%100%0%
2 mg/dL0%0%100%0%
2.5 mg/dL0%0%43%57%
3 mg/dL0%0%0%100%
ConcentrationTestedPercentage Agreement at Each Color Block
NegativeTrace15 mg/dL40 mg/dL80 mg/dL
KETONE1.25 mg/dL100%0%0%0%0%
2.5 mg/dL85%15%0%0%0%
3.75 mg/dL5%95%0%0%0%

{18}------------------------------------------------

5 mg/dL0%100%0%0%0%
7.5 mg/dL0%100%0%0%0%
10 mg/dL0%45%55%0%0%
12.5 mg/dL0%10%90%0%0%
15 mg/dL0%0%100%0%0%
21.5 mg/dL0%0%90%10%0%
27.5 mg/dL0%0%45%55%0%
33.75 mg/dL0%0%0%100%0%
40 mg/dL0%0%0%100%0%
50 mg/dL0%0%0%60%40%
60 mg/dL0%0%0%5%95%
70 mg/dL0%0%0%0%100%
80 mg/dL0%0%0%0%100%
ConcentrationTestedPercentage Agreement at Each Color Block
NegativeTraceSmallModerateLarge
BLOOD0.008 mg/dL90%10%0%0%0%
0.015 mg/dL81%19%0%0%0%
0.023 mg/dL29%61%0%0%0%
0.03 mg/dL0%100%0%0%0%
0.043 mg/dL0%100%0%0%0%
0.053 mg/dL0%90%10%0%0%
0.064 mg/dL0%24%76%0%0%
0.075 mg/dL0%0%100%0%0%
0.116 mg/dL0%0%100%0%0%
0.158 mg/dL0%0%100%0%0%
0.199 mg/dL0%0%10%90%0%
0.24 mg/dL0%0%0%100%0%
0.368 mg/dL0%0%0%100%0%

{19}------------------------------------------------

0.495 mg/dL0%0%0%100%0%
0.628 mg/dL0%0%0%10%90%
0.75 mg/dL0%0%0%0%100%
ConcentrationTestedPercentage Agreement at Each Color Block
NegativeTrace30mg/dL100mg/dL300mg/dL2000mg/dL
3.75 mg/dL100%0%0%0%0%0%
7.5 mg/dL55%45%0%0%0%0%
11.25 mg/dL25%75%0%0%0%0%
15 mg/dL0%100%0%0%0%0%
18.75 mg/dL0%90%10%0%0%0%
22.5 mg/dL0%20%80%0%0%0%
PROTEIN26.25 mg/dL0%15%85%0%0%0%
30 mg/dL0%0%100%0%0%0%
47.5 mg/dL0%0%100%0%0%0%
65 mg/dL0%0%5%95%0%0%
82.5 mg/dL0%0%5%95%0%0%
100 mg/dL0%0%0%100%0%0%
150 mg/dL0%0%0%80%20%0%
200 mg/dL0%0%0%15%85%0%
250 mg/dL0%0%0%5%95%0%
300 mg/dL0%0%0%0%100%0%
725 mg/dL0%0%0%0%55%45%
1150 mg/dL0%0%0%0%30%70%
1575 mg/dL0%0%0%0%10%90%
2000 mg/dL0%0%0%0%0%100%

{20}------------------------------------------------

ConcentrationTested (cacells/µL)Percentage Agreement at Each Color Block
NegativeTraceSmallModerateLarge
LEUKOCYTES3.75100%0%0%0%0%
7.5100%0%0%0%0%
11.2595%5%0%0%0%
150%100%0%0%0%
28.750%95%5%0%0%
42.50%80%20%0%0%
56.250%5%95%0%0%
700%0%100%0%0%
83.750%0%100%0%0%
97.50%0%40%60%0%
111.250%0%0%100%0%
1250%0%0%100%0%
218.750%0%0%100%0%
312.50%0%0%100%0%
406.250%0%0%45%55%
5000%0%0%0%100%
Concentration testedPercentage Agreement at Each Color Block
NegativePositive
NITRITE0.025 mg/dL100%0%
0.05 mg/dL100%0%
0.075 mg/dL100%0%
0.1 mg/dL45%55%
ConcentrationTested (mg/dL)Percentage Agreement at Each Color Block
UROBILINOGEN0.212.04.08.0

{21}------------------------------------------------

0.2100%0%0%0%0%
0.4100%0%0%0%0%
0.6100%0%0%0%0%
0.829%71%0%0%0%
1.00%100%0%0%0%
1.250%100%0%0%0%
1.50%90%0%0%0%
1.750%62%28%0%0%
2.00%10%90%0%0%
2.50%0%100%0%0%
3.00%0%100%0%0%
3.50%0%45%55%0%
4.00%0%0%100%0%
5.00%0%0%100%0%
6.00%0%0%80%20%
7.00%0%0%15%85%
8.00%0%0%0%100%
ConcentrationTestedPercentage Agreement at Each Color Block
5.06.06.57.07.58.08.5
pH5.095%5%0%0%0%0%0%
6.05%95%0%0%0%0%0%
6.50%0%95%0%0%0%0%
7.00%0%5%95%0%0%0%
7.50%0%0%5%95%0%0%
8.00%0%0%0%5%100%0%
8.50%0%0%0%0%5%100%
ConcentrationTestedPercentage Agreement at Each Color Block
SG1.0051.0101.0151.0201.0251.030

{22}------------------------------------------------

1.000100%0%0%0%0%0%
1.005100%0%0%0%0%0%
1.0100%100%0%0%0%0%
1.0150%0%100%0%0%0%
1.0200%0%0%100%0%0%
1.0250%0%0%0%100%0%
1.0300%0%0%0%0%100%

D) Linearity Study/ Assay Reportable Range Study Summary:

The linear range of TC-Thunderbolt Automated Urine Analyzer was evaluated by measuring negative urine and negative urine spiked with known increasing concentrations of analytes relative to each color block covering the entire measuring range of each analyte present on the TC-Thunderbolt URS-10 strip. Sample measurement was performed in replicates of 7 by 3 operators on each of 3 individual strip lots (7 strips x 3 operators/ strip lots), for a total of 21 measurements for every sample tested. A pH meter was used to confirm the pH results. The specific gravity values were confirmed by a clinical, handheld refractometer. A specific gravity reading of 1.000 was obtained from distilled water. Specific gravity measurements were performed in replicates of 7 by 3 operators on each of 3 individual strip lots (7 strips x 3 operators/ strip lots), for a total of 21 measurements for every sample tested. Results:

The linear range of the TC-Thunderbolt Automated Urine Analyzer is summarized in the table below:

AnalyteTC-Thunderbolt Output BlockMeasuring Range
GlucoseNegative0.0 - 75 mg/dL
100 mg/dL75 - 212.5 mg/dL
250 mg/dL212.5 - 437.5 mg/dL
500 mg/dL437.5 - 875 mg/dL
1000 mg/dL> 875 mg/dL
BilirubinNegative0.0 - 0.375 mg/dL
Small0.375 - 1.0 mg/dL
Moderate1.0 - 2.5 mg/dL
Large> 2.5 mg/dL
KetoneNegative0.0 - 3.75 mg/dL
Trace3.75 - 10.0 mg/dL
15 mg/dL10.0 - 27.5 mg/dL
40 mg/dL27.5 - 60.0 mg/dL
80 mg/dL> 60.0 mg/dL
BloodNegative0.0 - 0.023 mg/dL
Trace0.023 - 0.064 mg/dL
Small0.064 - 0.199 mg/dL
Moderate0.199 - 0.628 mg/dL
Large> 0.628 mg/dL
Negative0.0 - 11.25 mg/dL
Trace11.25 - 26.25 mg/dL
Protein30 mg/dL26.25 - 82.5 mg/dL
100 mg/dL82.5 - 200 mg/dL
300 mg/dL200 - 1150 mg/dL
2000 mg/dL> 1150 mg/dL
NitriteNegative0.0 - 0.1 mg/dL
Positive> 0.1 mg/dL
LeukocyteNegative0.0 - 15 ca cells/µL
Trace15 - 56.25 ca cells/µL
Small56.25 - 97.5 ca cells/µL
Moderate97.5 - 406.25 ca cells/µL
Large> 406.25 ca cells/µL
Urobilinogen0.2 mg/dL0.2 - 0.6 mg/dL
1.0 mg/dL0.8 - 1.5 mg/dL
2.0 mg/dL2.0 - 3.0 mg/dL
4.0 mg/dL3.5 - 6.0 mg/dL
8.0 mg/dL7.0 - 8.0 mg/dL
pH5.05.0
6.06.0
6.56.5
7.07.0
7.57.5
8.08.0
8.58.5
SG1.0051.005
1.0101.010
1.0151.015
1.0201.020
1.0251.025
1.0301.030

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E) Analytical Specificity and Interference

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Interfering substance studies were performed to assess the interfering effect of various substances on the TC-Thunderbolt URS-10 strips used on the TC-Thunderbolt Automated Urine Analyzer. Urine sample pools were prepared at 2 concentrations for each urine chemistry analyte; negative and positive. The negative sample pools had no analyte present while the positive sample pools were prepared by spiking each analyte into negative urine at the concentrations listed below:

AnalyteConcentrations to be Tested
NegativePositiveUnit
Glucose0100mg/dL
Protein030mg/dL
Bilirubin00.5mg/dL
Urobilinogen02mg/dL
pH6.07.0-
Blood00.24mg/dL
Ketone015mg/dL
Nitrite00.10mg/dL
Leukocytes0125ca Cells/µL

Concentration of Samples Tested

Each urine sample was tested with 3 replicates using TC-Thunderbolt Urine Analyzer System and a mean result was calculated. The mean result from samples with no interfering substance was compared against the mean result of the sample spiked with the interfering substance at the stated concentration. Interference was defined as a change in output of ± 1 color blocks between spiked control sample. For pH, interference was defined as a change of ± 2 color blocks between the spiked and unspiked control sample.

The concentrations of the potential interfering substances that did not have any influence on the test results are listed below:

Potential Interfering SubstanceHighest Concentration of substance testedwhich demonstrated no Interference
Ascorbic Acid10 mg/dL
Ammonium Chloride400 mg/dL
Albumin300 mg/dL
Bilirubin4 mg/dL
Calcium Chloride80 mg/dL
Citric Acid65 mg/dL
Creatinine600 mg/dL
D (+) Glucose500 mg/dL
Glycine900 mg/dL
Hemoglobin0.3 mg/dL
Potassium Chloride1000 mg/dL
Sodium Chloride2000 mg/dL
Oxalic Acid20 mg/dL
Sodium Nitrate10 mg/dL
Sodium Nitrite0.5 mg/dL
Sodium Phosphate1000 mg/dL
Urea3000 mg/dL
D (+) Galactose300 mg/dL

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Tetracycline100 mg/dL
-------------------------

The following table shows the substances which did interfere with one or more of the TC-Thunderbolt URS-10 analytes. Results are expressed as the lowest concentration of interfering substance that exhibited interference and the resulting change in output of color block.

AnalyteConcentration of Substance at which Interferencewas observedChange in Color blockOutput
GlucoseAscorbic Acid ≥ 30 mg/dL-1
ProteinHemoglobin ≥ 50 mg/dL, D(+) Glucose ≥ 2000mg/dL+1, -1
BilirubinAscorbic Acid ≥ 30 mg/dL, MESNA ≥ 50 mg/dL,Sodium Nitrite ≥ 2 mg/dL, Sodium Nitrate ≥ 10mg/dL, D(+) Glucose ≥ 2000 mg/dL-1
Urobilinogen----
BloodAlbumin ≥ 1000 mg/dL, Ascorbic Acid ≥ 30 mg/dL+1, -1
NitriteD(+) Glucose ≥ 2000 mg/dL-1
LeukocytesD(+) Glucose ≥ 2000 mg/dL, Ascorbic Acid ≥ 30mg/dL-1
KetoneMESNA ≥ 50 mg/dL,+3
pHAcetoacetate ≥ 60 mg/dL, Oxalic Acid ≥ mg/dL,Citric Acid ≥ 130 mg/dl+1, -1, -1

Based on the results of this testing the sponsor has included the effects from above interfering substances in the labeling as limitations of procedure.

4.10) Shelf Life Studies:

A) Accelerated Stability Study Summary

Accelerated study was performed on closed bottles of TC-Thunderbolt URS-10 strips as a means of assessing the shelf-life of the closed product, which is verified in real time studies. This study involves testing the device once per week periodically, for the duration of the study using Urine Control Solutions Levels I, II and III. TC-Thunderbolt URS-10 bottles used in the Stressed Study will have passed Quality Control inspection and stored at 37°C ± 2°C.

Acceptance Criteria:

The TC-Thunderbolt URS-10 strips must pass Quality Control testing for ≥ 90 days to confirm the closed bottle shelf life of two (2) years at room temperature (15-30°C) with 20-30% humidity.

Results:

Three lots of TC-Thunderbolt URS-10 strips all passed Quality Control testing for 91 days at 37°C ± 2°C. The expected shelf life of the TC-Thunderbolt URS-10 strips is 28 months based on the Accelerated Stability Study Test Results.

B) Real-time Stability Study Summary:

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A real time, temperature and humidity stability study is currently being performed on closed bottles of TC-Thunderbolt URS-10 strips to validate the claims stated in the Stress Stability Studies. This study involves testing the TC-Thunderbolt URS-10 strips using Urine Control Solutions Levels I, II and III for every six (6) months from the manufactured date, until 18 months. After the TC-Thunderbolt URS-10 strips has passed 18 months, test every three (3) months until the product fails or until 28 months. Three (3) lots of TC-Thunderbolt URS-10 strips used in the Real Time Shelf Life Study will have passed Quality Control inspection and are being kept at room temperature (15-30°C) and 20-30% humidity.

Acceptance Criteria: The product must pass Quality Control testing in real-time through its expiration date in the conditions that the product will be stored: closed bottle, room temperature (15-30°C)

Result:

This study is currently on-going. The three lots of TC-Thunderbolt URS-10 strips have passed the 12 months Quality Control testing and we plan to continue testing until 28 months.

C) Open-vial Stability Study Summary:

Open-vial Study was performed on opened bottles (broken seal) of TC-Thunderbolt URS-10 strips as a means of assessing the shelf-life of the opened bottle product once the seal is broken. This study involves testing the device once per week periodically, for the duration of the study using Urine Control Solutions Levels I, II and III. TC-Thunderbolt URS-10 bottles used in the Open-vial Study will have passed Quality Control inspection and are opened (seals broken) and stored at room temperature (15-30°C) and 20-30% humidity.

Acceptance Criteria:

The TC-Thunderbolt URS-10 strips must pass Quality Control testing for ≥ 90 days to confirm the opened bottle shelf life of 3 months at room temperature (15-30°C) with 20-30% humidity.

Result:

Three lots of Open Vial TC-Thunderbolt URS-10 strips all passed Quality Control testing for 91 days at 15-30°C. The expected shelf life of the Open Vial TC-Thunderbolt URS-10 strips is 90 days based on the Open Vial Stability Study Test Results.

4.11) Conclusion:

The performance characteristics of the TC-Thunderbolt Automated Urine Analyzer System were verified by method comparison, precision, sensitivity and cutoff point determination, linearity/ assay reportable range, analytical specificity and interference, shelf life and stress studies. Testing results indicate that the TC-Thunderbolt Automated Urine Analyzer System perform satisfactorily when used appropriately, as outlined in the package insert.

§ 862.1340 Urinary glucose (nonquantitative) test system.

(a)
Identification. A urinary glucose (nonquantitative) test system is a device intended to measure glucosuria (glucose in urine). Urinary glucose (nonquantitative) measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, hypoglycemia, and hyperglycemia.(b)
Classification. Class II.