AUTION ELEVEN Semi-Automated Urinalysis System

K160062 · Arkray, Inc. · JIL · Oct 7, 2016 · Clinical Chemistry

Device Facts

• Record ID: K160062
• Device Name: AUTION ELEVEN Semi-Automated Urinalysis System
• Applicant: Arkray, Inc.
• Product Code: JIL · Clinical Chemistry
• Decision Date: Oct 7, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1340
• Device Class: Class 2

Intended Use

The AUTION ELEVEN Semi-Automated Urinalysis System provides a qualitative and semi-quantitative measurements for glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity and color tone in urine specimens. The system is intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.

Device Story

The AUTION ELEVEN Semi-Automated Urinalysis System is a semi-automated urine chemistry analyzer used in clinical laboratories by professional staff. The system consists of the AE-4022 analyzer and AUTION Sticks 10EA test strips. The user dips the test strip into a urine sample and places it on the analyzer; the instrument automatically transports the strip to the photometric section. The device uses four light-emitting diodes to measure the reflectance of the reagent pads at two wavelengths per analyte (except blood, which uses one). It also measures a blank pad to correct for urine color tone. The system calculates qualitative and semi-quantitative results based on reflectance values. An optional barcode reader allows for patient ID entry. The device provides rapid screening results to assist healthcare providers in clinical decision-making regarding patient health status.

Clinical Evidence

No clinical trials were performed. Substantial equivalence was established through bench testing, including precision/reproducibility studies (N=120-240 replicates), linearity/reportable range verification, analytical specificity (interference testing), and method comparison studies against the predicate device (N=2000+ samples for most analytes). Results showed high concordance with the predicate, with overall exact agreement ranging from 81% to 99.5% and within +/- 1 color block agreement at 99-100%.

Technological Characteristics

System uses colorimetric reflectometry with 4 LED wavelengths (red, green, blue, infrared). Reagent strips contain 10 pads. Dimensions: 210(w) x 328(d) x 164(h) mm. Power: 100-240 VAC, 50/60 Hz with 12 VDC adapter. Connectivity: RS-232C/Ethernet. Software-controlled with barcode reader support. Analyte detection via chemical reaction-induced color change.

Indications for Use

Indicated for in vitro diagnostic screening of urine specimens in clinical laboratories to provide qualitative and semi-quantitative measurements of glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity, and color tone.

Regulatory Classification

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.

Predicate Devices

• AUTION MAX AX-4030 Urinalysis System (k093098)

Reference Devices

• AUTION JET AJ-4270 Urine Analyzer (k030600)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the seal for the Department of Health & Human Services - USA. The seal is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the seal is a stylized image of three human profiles facing to the right, stacked one in front of the other.

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

October 7, 2016

ARKRAY, INC. NAVEEN THURAMALLA VICE PRESIDENT, REGULATORY AFFAIRS 5182 76TH STREET EDINA MN 55439

Re: K160062

Trade/Device Name: AUTION ELEVEN Semi-Automated Urinalysis System Regulation Number: 21 CFR 862.1340 Regulation Name: Urinary glucose (nonquantitative) test system Regulatory Class: II Product Code: JIL, JIO, KQO, CDM, CEN, JIN, JJR, JJB, JMT, LJX, JRE Dated: August 29, 2016 Received: August 30, 2016

Dear Naveen Thuramalla:

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.

{1}------------------------------------------------

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 [phone] or [phone] 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 [phone] or [phone] or at its Internet address

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

Sincerely yours.

Courtney H. Lias -S

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

{2}------------------------------------------------

#### Indications for Use

510(k) Number (if known) k160062

Device Name

AUTION ELEVEN Semi-Automated Urinalysis System

Indications for Use (Describe)

The AUTION ELEVEN Semi-Automated Urinalysis System provides a qualitative and semi-quantitative measurements for glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity and color tone in urine specimens. The system is intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.

The AUTION ELEVEN Semi-Automated Urinalysis System consists of the following:

- · AUTION ELEVEN model AE-4022 Urine Analyzer (device component)
- · AUTION Sticks 10EA Test Strips (reagent component)

| Type of Use (Select one or both, as applicable) |
|-------------------------------------------------|
|-------------------------------------------------|

Research Use Only (21 CFR 201.3 Subject to Review)

Over-The-Counter Use Only (21 CFR 201.3 Subject to Review)

> Prescription Use (Part 21 CFR 801 Subpart D)

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

#### CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

# 510(k) Summary

This 510(k) Summary of the AUTION ELEVEN Semi-Automated Urinalysis System is submitted in compliance of 21 CFR 807.92 for the purposes of safety and effectiveness.

| 510(k) Number: | k160062 |
|-----------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Date Prepared: | October 06, 2016 |
| Establishment: | ARKRAY Inc.<br>Yousuien-Nai<br>59 Gansuin-Cho, Kamigyo-Ku<br>Kyoto 602-0008, Japan<br>Establishment Registration Number: 9611444 |
| Submitter: | ARKRAY, Inc.<br>57 Nishiaketa-Cho, Higashi-Kujo, Minami-Ku<br>Kyoto 601-8045, Japan<br>Telephone: [phone]<br>Fax: [phone]<br><br>Official US Agent: Tom Speikers<br>ARKRAY Factory USA, Inc.<br>VP, Regulatory Affairs and Quality Systems<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail] |
| Contact Person: | Naveen Thuramalla<br>ARKRAY Factory USA, Inc.<br>Vice President, Regulatory Affairs<br>Phone: (cell): 202-738-8303<br>Email: [e-mail] |

{4}------------------------------------------------

#### Device Name

| Trade Name: | AUTION ELEVEN Semi-Automated Urinalysis System |
|----------------|------------------------------------------------|
| Common Name: | Automated Urinalysis System |
| 510(k) Number: | k160062 |

| Regulation:<br>21 CFR<br>Section | Product<br>Code | Classification | Description |
|----------------------------------|-----------------|----------------|-------------------------------------------------------------|
| 862.1340 | JIL | Class II | Glucose (Urinary, Non-Quantitative) |
| 864.6550 | JIO | Class II | Blood, Occult, Colorimetric, In Urine |
| 862.2900 | KQO | Class I | Automated Urinalysis System |
| 862.1785 | CDM | Class I | Urobilinogen (Urinary Non-Quant.) |
| 862.1550 | CEN | Class I | pH (Urinary, Non-Quant.) |
| 862.1435 | JIN | Class I | Ketones (Urinary, Non-Quant.) |
| 862.1645 | JIR | Class I | Protein or Albumin (Urinary, Non-<br>Quant.) |
| 862.1115 | JJB | Class I | Urinary Bilirubin & Its Conjugates<br>(Urinary, Non-Quant.) |
| 862.1510 | JMT | Class I | Nitrite (Urinary, Non-Quant.) |
| 864.7675 | LJX | Class I | Test, Urine Leukocyte |
| 862.2800 | JRE | Class I | Specific Gravity |

#### Table 1: Regulatory Information

## Predicate Devices

AUTION MAX AX-4030 Urinalysis System (K093098)

{5}------------------------------------------------

## Intended Use

The AUTION ELEVEN Semi-Automated Urinalysis System provides a qualitative and semi-quantitative measurements for glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity and color tone in urine specimens. The system is intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.

The AUTION ELEVEN Semi-Automated Urinalysis System consists of the following:

- AUTION ELEVEN model AE-4022 urine analyzer (device component) ●
- AUTION Sticks 10EA test strips (reagent component) ●

### Device Description

The AUTION ELEVEN Semi-Automated Urinalysis System provides a qualitative and semi-quantitative measurement for glucose, protein, bilirubin, urobilinogen, pH, blood, ketones, nitrites, leukocytes, specific gravity and color tone. The system is intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The AUTION ELEVEN Semi-Automated Urinalysis System consists of AUTION ELEVEN model AE-4022 urine analyzer and AUTION Sticks 10EA test strips.

The AUTION sticks 10EA consist of a plastic strip containing 10 pads impregnated with chemicals specific for the determination of a particular analyte. The chemical reaction with the urine results in a color change which is measured by the AUTION ELEVEN AE-4022 device, resulting in a display and print out indicating analyte concentration. The AUTION ELEVEN technology provides fast results that can be used along with other diagnostic information to rule out certain disease states and to determine if microscopic analysis is needed.

The semi-automated nature of the device requires the user to dip an AUTION Stick 10EA test strip into a patient urine specimen and place it on the instrument. The instrument processes the test strip, allowing 60 seconds for the chemical reactions to occur on the test strip reagent pads. After 60 seconds, the device measures the amount of reflectance generated from each reagent pad and converts the reflectance measurements to qualitative and semi-quantitative results for physician use.

{6}------------------------------------------------

# Substantial Equivalence

| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
|----|--------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 1 | Proprietary<br>Name | AUTION MAX | AUTION<br>ELEVEN | N/A |
| 2 | 510(k) Number | K093098 (2009) | K160062 | N/A |
| 3 | Class | Class II (Blood and Glucose<br>analytes raise system to<br>Class II / 510(k) required) | Class II (Blood<br>and Glucose<br>analytes raise<br>system to Class II /<br>510(k) required) | SAME |
| 4 | Data Type | Qualitative, Semi-<br>Quantitative | Qualitative, Semi-<br>Quantitative | SAME |
| 5 | Location | Clinical Laboratory | Clinical<br>Laboratory | SAME |
| 6 | Medical<br>Device/IVD | Medical Device/IVD | Medical<br>Device/IVD | SAME |
| 7 | Specimen | Human Urine | Human Urine | SAME |
| 8 | Analytes | Glucose<br>Protein<br>Bilirubin<br>Urobilinogen<br>pH<br>Blood<br>Ketones<br>Nitrite<br>Leukocyte<br>Specific Gravity | Glucose<br>Protein<br>Bilirubin<br>Urobilinogen<br>pH<br>Blood<br>Ketones<br>Nitrite<br>Leukocyte<br>Specific Gravity | SAME |
| 9 | Color Tone<br>Detection | 23 color tones using 3<br>wavelengths (red, green and<br>blue); executed by a color<br>tone unit with a different<br>calculation | 23 color tones<br>using 4<br>wavelengths (red,<br>green, blue,<br>infrared); executed<br>by the optical unit | Testing<br>demonstrates<br>color tone<br>detection. |
| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
| 10 | Color Tone<br>correction | Calculation to mitigate urine<br>color interference | Calculation to<br>mitigate urine<br>color interference | Testing shows<br>color does not<br>inhibit results. |
| 11 | Abnormal<br>Color Marker<br>(!)<br>(ketone,<br>urobilinogen,<br>bilirubin) | Calculations based on<br>wavelengths 430nm, 500nm,<br>565nm, and 635nm | Calculations based<br>on wavelengths<br>430nm, 500nm,<br>565nm, and 635nm | Same formula<br>comparing the<br>analyte pad<br>reflectance<br>ratio of 2<br>colors divided<br>by the<br>reference pad<br>reflectance<br>ratio of the<br>same 2 colors. |
| 12 | Turbidity/<br>Clarity | Determines turbidity | Does not<br>determine<br>turbidity. Option<br>available for user<br>to enter level of<br>clarity per<br>laboratory<br>professional<br>education. | Device does<br>not determine<br>this optional<br>parameter. |
| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
| 13 | Reagent Test<br>Strips | AUTION Sticks 9EB:<br>(1) No specific gravity<br>reagent pad (uses<br>Refractometer);<br>(2) Uses blank pad for<br>correction due to urine<br>color; different calculation<br>(3) Has black marker for<br>model distinction by device | AUTION<br>Sticks10EA:<br>(1) Has specific<br>gravity reagent<br>pad;<br>(2) Uses blank pad<br>for correction due<br>to urine color;<br>(3) Has black<br>marker for model<br>distinction by<br>device | SAME as<br>AUTION<br>MAX for all<br>reagent pads<br>except<br>specific<br>gravity.<br>SAME<br>chemical<br>reactions, as<br>AUTION<br>MAX.<br>AUTION<br>ELEVEN was<br>compared to<br>AUTION<br>MAX for 9<br>analytes, as<br>the more<br>recent<br>predicate, and<br>was compared<br>to AUTION<br>JET<br>(k030600) for<br>specific<br>gravity only. |
| 14 | Quality Control<br>Solution | Commercial urine analyzer<br>Control Solution | Commercial urine<br>analyzer Control<br>Solution | SAME |
| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
| 15 | Check Strips –<br>for quality<br>control of<br>device optical<br>unit's light<br>intensity | AUTION Check Strips<br>(provided with device) | AUTION Check<br>Strips (provided<br>with device) | SAME |
| 16 | Method of<br>device<br>chemistry<br>determination | Colorimetric Reflectometry<br>of reagent chemical reaction<br>with analyte for all analytes<br>*except Refractometry for<br>specific gravity | Colorimetric<br>Reflectometry of<br>reagent chemical<br>reaction with<br>analyte for all<br>analytes | SAME as<br>AUTION<br>MAX for all<br>reagent pads<br>except<br>specific<br>gravity.<br>SAME as<br>AUTION JET<br>(k030600) for<br>specific<br>gravity. |
| 17 | Barcode<br>Reader<br>Possible/Not<br>Required | Yes | Yes | SAME |
| 18 | Urine mixed<br>for<br>homogeneity | By hand and aspirator | By hand | Clinical<br>Testing shows<br>that AUTION |
| 19 | Urine applied<br>to reagent pad | Automatic pipette-applied | Hand-dipped for 2<br>seconds | MAX and<br>AUTION |
| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
| 20 | Timing<br>between urine<br>application and<br>determination | Automatic | Controlled by<br>Human<br>count/sound<br>alarms +<br>automation | ELEVEN<br>devices<br>perform<br>similarly and<br>there is no<br>additional<br>effect on<br>safety and<br>effectiveness. |
| 21 | Timing of<br>reagent<br>reaction | Approximately 60 seconds | Approximately 60<br>seconds | SAME |
| 22 | Result<br>determination | Automatic | Automatic | SAME |
| 23 | Rank Table | Includes Qualitative and<br>Semi-Quantitative Ranks | Includes<br>Qualitative and<br>Semi-Quantitative<br>Ranks; Semi-<br>Quantitative ranks<br>match Qualitative<br>ranks in number | SAME; All<br>Semi-<br>Quantitative<br>ranks within<br>the respective<br>Qualitative<br>rank are<br>combined.<br>The ranks<br>align with<br>predicate<br>Qualitative<br>ranks and<br>their<br>respective<br>Semi-<br>Quantitative<br>concentration<br>limits<br>although only<br>1 Semi- |
| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
| | | | | Quantitative<br>concentration<br>reference is<br>provided<br>where therefor a<br>predicate<br>Semi-<br>Quantitative<br>rank. |
| 24 | Software-<br>Controlled | Yes | Yes | SAME |
| 25 | Printed Data<br>Report | Yes | Yes | SAME |
| 26 | Measurement<br>Wavelengths<br>for Analytes | Dual wavelength<br>measurement using 565,<br>635, 760 nm (Except blood,<br>which uses only 635 nm) | Dual wavelength<br>measurement<br>using 565, 635,<br>760 nm (Except<br>blood, which uses<br>only 635 nm) | SAME |
| 27 | Processing<br>Speed | 225 samples/hr | 514 samples/hr | Result<br>determination<br>time remains<br>the same, so<br>no difference<br>in technology<br>or chemistry<br>– just<br>throughput. |
| 28 | Memory<br>Capacity | 2500 tests | 520 tests | Testing for<br>electronic<br>safety and<br>compatibility. |
| 29 | Crystal (LC)<br>Display | Yes | Yes | |
| 30 | Built-in printer | Yes | Yes | |
| 31 | External output | RS-232C/Ethernet | RS-232C/Ethernet | |
| # | Element of<br>Comparison | AUTION MAX AX-4030<br>(Predicate) | Claimed<br>Substantial<br>Equivalent<br>Device, AUTION<br>ELEVEN<br>Semi-Automated<br>Urinalysis System | AUTION<br>ELEVEN<br>Comparison |
| 32 | Barcode<br>Specifications | NW-7, CODE39, code 128,<br>ITF;<br>On unit | NW-7, CODE39,<br>code 128, ITF;<br>hand held type | |
| 33 | Voltage Supply | 100-240 VAC, 50/60 Hz | 100-240 VAC,<br>50/60 Hz; use<br>adapter 12 VDC<br>3A | |
| 34 | Dimensions<br>(mm) | 530 (w) x 530(d) x 530 (h) | 210 (w) x 328 (d)<br>x 164 (h) | N/A |
| 35 | Linearity | Yes | Yes | SAME |
| 36 | Sensitivity | Yes | Yes | SAME |
| 37 | Interfering<br>Substances | Yes | Yes | SAME |
| 38 | Detection<br>Limit/<br>Specificity | Yes | Yes | SAME |
| 39 | Accuracy by<br>Comparison | Yes | Yes | SAME |
| 40 | Precision | Yes | Yes | SAME |
| 41 | Color Tone<br>Detection | Yes | Yes | SAME |
| 42 | Color Tone<br>Correction | Yes | Yes | SAME |
| 43 | Electrical<br>Safety | Yes | Yes | Slight<br>differences |
| 44 | Radiofrequency | Yes | Yes | per |
| 45 | Electrical<br>Compatibility | Yes | Yes | specifications.<br>Testing |
| 46 | Device<br>Software | Yes | Yes | ensures safety<br>and efficacy. |
| 47 | Stability-<br>Closed Bottle | Yes | Yes | SAME |
| 48 | Stability-Open<br>Bottle | Yes | Yes | SAME |

### Table 2: Substantial Equivalence

{7}------------------------------------------------

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

{9}------------------------------------------------

{10}------------------------------------------------

{11}------------------------------------------------

{12}------------------------------------------------

{13}------------------------------------------------

### Standards Referenced

Clinical and Laboratory Standards Institute. (2014). EP05-A3 Vol 34 No.13 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Ed.

Clinical and Laboratory Standards Institute. (2003). EP06-A Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

Clinical and Laboratory Standards Institute. (2005). EP07-A2 Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition.

Clinical and Laboratory Standards Institute. (2010). EP09-A2-IR Vol. 30 No. 17 Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Second Edition.

Clinical and Laboratory Standards Institute. (2009). GP-16-A2 21 No.19 Urinalysis: Approved Guideline - Third Edition.

Clinical and Laboratory Standards Institute. (2012). EP17-A2 Vol 32 No.8 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition.

{14}------------------------------------------------

## Test Principle

The AUTION ELEVEN Semi-Automated Urinalysis System device model AE-4022 uses 4 LED wavelengths to accurately read AUTION 10EA Stick test strips which are impregnated with chemicals to induce the reactions shown below upon contact with particular analytes in urine. Three (3) of the wavelengths read the analyte interaction while the fourth wavelength is used for color tone detection and correction.

Glucose: Glucose oxidase reaction. GOD → Gluconic acid + H₂O₂ Glucose POD H2O2 + 4-AAP + 1-Naphthol-3,6-disulfonic acid > Quinone imine dye (purple color) oxidation Protein: Protein-error reaction. Protein + pH indicator _ acid > pH indicator changes to a cyan color Bilirubin: Azo-coupling reaction. acid 2-Methyl-5-nitroaniline + Sodium nitrite Diazonium salt diazo reaction acid Bilirubin + Diazonium salt Azo dye (reddish brown color) coupling reaction Urobilinogen: Azo-coupling reaction. acid Urobilinogen + Diazonium salt > Azo dye (reddish brown color) coupling reaction pH: pH indicator. ► ► mixed pH indicator shows range of colors H+ + mixed pH indicator covering the urinary pH range (yellow - cyan color) Specific Gravity: Cation extraction. cation extraction Cation + D-2-EHPA + pH indicator color reaction of pH indicator (cyan - yellow color) Blood: Activity measurement of pseudoperoxidase in hemoglobin. hemoglobin > H2O + Cumene + Oxidation dye (cyan color) CHP + TMBZ pseudoperoxidase action Ketones: Legal reaction. alkaline Ketones + Sodium nitroprusside > Ketones complex (purple color) Nitrite: Griess reaction. acid Nitrite + Sulfanilamide -> Diazo-compound + NEDA-2HCl acid Azo dye (pink color) coupling reaction Leukocytes: Measurement of leukocyte esterase activity. TAI esterase from leukocytes - Indoxyl + MMB -______________________________________________________________________________________________________________________________________________________________________________ hydrolysis

{15}------------------------------------------------

## Performance Characteristics

Bench testing and clinical testing were done in order to verify that the above differences are minor in nature and do not affect the overall performance, safety, or effectiveness of the proposed device compared to the predicate device.

### Precision Results

Each analyte was tested at 3 clinical sites using 3 operators on 3 devices for a minimum of 20 days. Three (3) levels of quality controls were used to attain results at negative, midlevel positive and high-positive analyte ranges. Two (2) levels of commercial controls were used to obtain the 3 levels, using dilutions and spiking materials as needed to obtain the highest and mid-level controls for testing of all the analyte ranks.

| | Table 3: Precision Results | |
|--|----------------------------|--|
| | | |

| | Repeatability | | Reproducibility | |
|---------------------|------------------|---------------------------|------------------|---------------------------|
| Analyte | Exact match<br>% | +/- 1<br>Color Block<br>% | Exact match<br>% | +/- 1<br>Color Block<br>% |
| Glucose | 98% | 100% | 99% | 100% |
| Protein | 100% | 100% | 100% | 100% |
| Bilirubin | 99% | 100% | 99% | 100% |
| Urobilinogen | 99% | 100% | 100% | 100% |
| pH | 98% | 100% | 99% | 100% |
| Specific<br>gravity | 96% | 100% | 97% | 100% |
| Blood | 99% | 100% | 100% | 100% |
| Ketones | 100% | 100% | 100% | 100% |
| Nitrite | 100% | 100% | 100% | 100% |
| Leukocytes | 100% | 100% | 100% | 100% |

{16}------------------------------------------------

### Comparison Study Results

A Method Comparison study was performed at 3 sites to compare the AUTION ELEVEN Semi-Automated Urinalysis System against 2 commercially available urinalysis predicates, 1 semi-automated urine analyzer was used for specific gravity comparison and one fully-automated urine analyzer was used to compare all the rest of the analytes.

Each site collected urine patient samples from their clinical laboratory or obtained them from nearby hospitals. Urine samples were collected and refrigerated within 2 hours of collection, for up to 24 hours of refrigeration prior to clinical study testing. For inclusion into the study, the samples collected had to be positive for at least one of the chemistry analytes present on the AUTION Stick 10EA urinalysis strip

Data from each site was combined for the analysis. Accuracy (percent agreement) results are shown below.

| Analyte | Number of<br>samples | Percent<br>Positive<br>Samples | Exact<br>Agreement<br>with Predicate | 95% CI | Agreement<br>within ± 1<br>color block |
|------------------|----------------------|--------------------------------|--------------------------------------|-------------|----------------------------------------|
| Glucose | 2199 | 16% | 98% | 97.5 - 98.6 | 100% |
| Protein | 563 | 56% | 86% | 83.2 - 89.1 | 100% |
| Bilirubin | 2323 | 8% | 100% | 99.1 - 99.7 | 100% |
| Urobilinogen | 2308 | 12% | 98% | 94.7 - 96.4 | 100% |
| pH | 2307 | 100% | 89% | 88.3 - 90.9 | 100% |
| Specific Gravity | 548 | 100% | 81% | 77.9 - 84.6 | 99% |
| Blood | 548 | 45% | 92% | 89.2 - 94 | 100% |
| Ketones | 2221 | 28% | 96% | 95.1 - 96.8 | 100% |
| Nitrite | 2209 | 6% | 99% | 99.6 - 98.8 | 100% |
| Leukocyte | 548 | 40% | 92% | 89 - 93.8 | 100% |

#### Table 4: Method Comparison Results

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

# Interfering Substances

#### Table 5: Interferent Results

| Analyte | Interferent | Concentration | Result |
|------------------|------------------------------------------|---------------|-------------------------------------------------|
| Glucose | Ascorbic acid | >50 mg/dL | False negative<br>(-2 to -3 color block change) |
| Glucose | pH | <pH4 | False positive<br>(+2 color block change) |
| Protein | Hemoglobin | >20 mg/dL | False positive<br>(+2 color block change) |
| Bilirubin | Urobilinogen | >8 mg/dL | False positive<br>(+1 color block change) |
| Urobilinogen | Bilirubin | >3 mg/dL | False positive<br>(+1 color block change) |
| pH | | N/A | |
| Specific Gravity | pH | <pH4 | Elevated<br>(+2 color block change) |
| | Albumin | >300 mg/dL | Elevated<br>(+2 color block change) |
| | Ammonium chloride | >200 mg/dL | Elevated<br>(+2 color block change) |
| Blood | Substances such as<br>MESNA that contain | >50 mg/dL | False negative<br>(-3 color block change) |
| Ketones | Substances such as<br>MESNA that contain | >5 mg/dL | False positive<br>(+2 to +5 color block change) |
| Nitrite | | N/A | |
| Leukocytes | Glucose | >200 mg/dL | False negative<br>(-2 color block change) |
| | Albumin | >300 mg/dL | False negative<br>(-2 color block change) |
| | pH | <pH4 | False negative<br>(-2 color block change) |

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

### Detection Limits/Sensitivity Results

Listed below are thresholds by which the analyte concentration/level is met for the higher rank at least 50% of the time.

Table 6: Detection Limits

| Analyte | Qualitative<br>Rank | Semi-<br>Quantitative<br>Rank | Actual<br>Concentration | Percent in<br>Rank | Units |
|--------------|---------------------|-------------------------------|-------------------------|--------------------|-------|
| Glucose | - | NEG | 0 | 100% | mg/dL |
| | ± | 30 | 30 | 100% | mg/dL |
| | 1+ | 70 | 60 | 100% | mg/dL |
| | 2+ | 150 | 125 | 100% | mg/dL |
| | 3+ | 300 | 250 | 100% | mg/dL |
| | 4+ | 1000 | 750 | 87% | mg/dL |
| Protein | - | NEG | 0 | 100% | mg/dL |
| | ± | 10 | 10 | 100% | mg/dL |
| | 1+ | 30 | 25 | 63% | mg/dL |
| | 2+ | 100 | 85 | 100% | mg/dL |
| | 3+ | 300 | 250 | 100% | mg/dL |
| | 4+ | 1000 | 800 | 97% | mg/dL |
| Bilirubin | - | NEG | 0 | 100% | mg/dL |
| | 1+ | 0.5 | 0.5 | 50% | mg/dL |
| | 2+ | 2 | 1.9 | 53% | mg/dL |
| | 3+ | 6 | 5.3 | 87% | mg/dL |
| 4+ | 14 | 12 | 100% | mg/dL | |
| Urobilinogen | NORM | NORM | 0 | 100% | mg/dL |
| | 1+ | 2 | 2.0 | 100% | mg/dL |
| | 2+ | 4 | 3.5 | 50% | mg/dL |
| | 3+ | 8 | 6.5 | 100% | mg/dL |
| 4+ | 16 | 14 | 100% | mg/dL | |
| pH | N/A | 5.0 | 5.0 | 100% | N/A |
| | | 5.5 | 5.3 | 100% | |
| | | 6.0 | 5.8 | 100% | |
| | | 6.5 | 6.3 | 87% | |
| | | 7.0 | 6.8 | 100% | |
| | | 7.5 | 7.3 | 87% | |
| | | 8.0 | 7.8 | 97% | |
| | | 8.5 | 8.3 | 50% | |
| | | 9.0 | 8.9 | 50% | |

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

| Analyte | Qualitative<br>Rank | Semi-<br>Quantitative<br>Rank | Actual<br>Concentration | Percent in<br>Rank | Units |
|---------------------|---------------------|-------------------------------|--------------------------------|--------------------|--------------------|
| Specific<br>Gravity | N/A | < 1.005 | 1.005 | 100% | N/A |
| | | 1.010 | 1.008 | 60% | |
| | | 1.015 | 1.013 | 90% | |
| | | 1.020 | 1.019 | 100% | |
| | | 1.025 | 1.023 | 97% | |
| | | >1.030 | 1.028 | 83% | |
| Blood | - | NEG | 0 | 100%…