← Product Code [JIL](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JIL) · K052525

# CYBOW 11 SERIES REAGENT STRIPS FOR URINALYSIS (K052525)

_DFI Co., Ltd. · JIL · Mar 29, 2006 · Clinical Chemistry · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JIL/K052525

## Device Facts

- **Applicant:** DFI Co., Ltd.
- **Product Code:** [JIL](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JIL.md)
- **Decision Date:** Mar 29, 2006
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.1340
- **Device Class:** Class 2
- **Review Panel:** Clinical Chemistry

## Indications for Use

CYBOW 11 Reagent Strips are for the rapid visual determination of urobilinogen, glucose, bilirubin, ketones (acetoacetic acid), specific gravity, blood, pH, protein, nitrite, leukocytes and ascorbic acid in urine.

## Device Story

CYBOW 11 Series Reagent Strips are dip-and-read test strips for in vitro diagnostic use. The device consists of multiple chemically reactive pads on a plastic strip. The operator dips the strip into a urine sample and visually compares the color of each pad to a color chart provided on the vial label. The device provides qualitative or semi-quantitative results for 11 analytes: urobilinogen, glucose, bilirubin, ketones, specific gravity, blood, pH, protein, nitrite, leukocytes, and ascorbic acid. These results assist clinicians in assessing carbohydrate metabolism, kidney and liver function, acid-base balance, and urinary tract infections. The device is intended for professional use in point-of-care or laboratory settings.

## Clinical Evidence

No clinical data provided; bench testing only.

## Technological Characteristics

Reagent strip for urinalysis; colorimetric chemical reaction principle; visual readout; single-use; professional use only.

## Regulatory 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.

## Submission Summary (Full Text)

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>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k052525

B. Purpose for Submission:
Clearance to market CYBOW 11 Series Reagent Strips for Urinalysis

C. Measurand:
Urobilinogen, bilirubin and its conjugates, ketones (acetoacetic acid), blood, glucose, protein, nitrite, leukocytes, glucose, specific gravity, pH, and ascorbic acid in urine.

D. Type of Test:
Qualitative and semi-quantitative urine tests

E. Applicant:
DFI Co., Ltd.

F. Proprietary and Established Names:
CYBOW 11 Series Reagent Strips for Urinalysis

G. Regulatory Information:

1. Regulation section:
21 CFR §864.6550: Occult blood test.
21 CFR §862.1340: Urinary glucose (nonquantitative) test system.
21 CFR §862.1785: Urinary urobilinogen (nonquantitative) test system.
21 CFR §862.1115: Urinary bilirubin and its conjugates (nonquantitative) test system.
21 CFR §862.1435: Ketones (nonquantitative) test system.
21 CFR §862.1645: Urinary protein or albumin (nonquantitative) test system.
21 CFR §862.1510: Nitrite (nonquantitative) test system.
21 CFR §864.7675: Leukocyte peroxidase test.
21 CFR §862.1550: Urinary pH (nonquantitative) test system.
21 CFR §862.1095: Ascorbic acid test system.

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2. Classification:

Class II

3. Product code:

Occult blood test - JIO
Urinary glucose (nonquantitative) test system - JIL
Urinary urobilinogen (nonquantitative) test system - CDM
Urinary bilirubin and its conjugates (nonquantitative) test system - JJB
Ketones (non-quantitative) test system - JIN
Urinary protein or albumin (non-quantitative) test system - JIR
Nitrite (non-quantitative) test system - JMT
Leukocyte peroxidase test - LJX
Urinary pH (nonquantitative) - CEN
Ascorbic acid test system - JMA

4. Panel:

Chemistry (75)
Hematology (82)

H. Intended Use:

1. Intended use(s):

CYBOW 11 Reagent Strips are for the rapid visual determination of urobilinogen, glucose, bilirubin, ketones (acetoacetic acid), specific gravity, blood, pH, protein, nitrite, leukocytes and ascorbic acid in urine.

2. Indication(s) for use:

CYBOW 11 Reagent Strips are for single use in professional near-patient (point of-care) and centralized laboratory locations. The strips are intended for use in screening at-risk patients to assist diagnosis in the following areas:

- Kidney function
- Urinary tract infections
- Carbohydrate metabolism (e.g. diabetes mellitus)
- Liver function
- Acid-base balance
- Urine concentration

The results can be used along with other diagnostic information to rule out certain disease states and to determine if microscopic analysis is needed. The test is to be read visually.

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3. Special conditions for use statement(s):

For prescription use only

4. Special instrument requirements:

Not applicable to this device.

I. Device Description:

CYBOW Reagent Strips are dip-and-read test strips for In Vitro Diagnostic Use only for testing analytes in urine. Test result may provide information regarding the status of carbohydrate metabolism, kidney and liver function, acid-base balance, and urinary tract infection. It is measured by comparison of test paper attached to a plastic strip to a color chart printed on the vial label.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Bayer Corporation MULTISTIX 10SG Reagent Strips

2. Predicate 510(k) number(s):

k852611

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Specimen | Urine | Same  |
|  Intended Use Audience | Professional use | Same  |
|  Test results | Color comparison | Color comparison  |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP6-A: "Evaluation of Linearity of Quantitative Measurement Procedures: A Statistical Approach"; Approved Guideline, 2003

CLSI EP09-A2: "Method Comparison and Bias Estimation Using Patient Samples"; Approved Guideline, 2002

CLSI EP12-A: "User Protocol for Evaluation of Qualitative Test Performance"; Approved Guideline, 2002

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ISO 2895-1: “Sampling Procedures for Inspection by Attributes - Part 1: Sampling Schemes Indexed by Acceptance Quality Limit (AQL) for Lot-by-Lot Inspection-Second Edition”

L. Test Principle:

The device is composed of multiple chemically reactive spots separate from each other on a plastic strip. Read-out is accomplished by visually matching the position and color of an exposed spot to a color coded chart provided with the device.

For the detection of urobilinogen, the device employs a modified Ehrlich’s reaction. Urobilinogen reacts with Ehrlich’s reagent to form a red-colored compound. Color changes from light orange-pink to dark pink.

For the detection of glucose, the device employs glucose oxidase to catalyze the oxidation of glucose to form hydrogen peroxide. The hydrogen peroxide thus formed then oxidizes a chromogen on the reaction pad by the action of peroxidase.

For the detection of bilirubin, diazonium salts in an acidic matrix on the strip undergo an azo-coupling reaction with bilirubin to form an azodye. The spot color changes from light tan to beige or light pink.

The device uses Legal’s test-nitroprusside reaction for the detection of ketones. Acetoacetic acid in an alkaline medium reacts with nitroferricyanide to produce a color change from beige to purple.

The device uses a correlation between the concentration of ionic species and the sample’s specific gravity to report an estimated specific gravity. Ionic solutes present in the urine release protons from a polyelectrolyte. The released protons decrease the pH on that strip spot and produce a color change in bromothymol blue from blue-green to yellow-green.

To detect blood, the device exploits the pseudo-peroxidase activity of the haem moiety of hemoglobin and myoglobin. A chromogen is oxidized by a hydroperoxide in the presence of haem and changes color from yellow to blue.

The device employs a combination of methyl red and bromothymol blue indicators to give distinct color changes from orange to green to blue (pH 5.0 to 9.0).

To qualitatively estimate protein concentration, the device uses the “error of indicators” principle. Proteins interact with an ionizable electrolyte driving the release of protons which in turn interact with a spectator indicator. The color change in the indicator is correlated with the protein concentration.

The device detects nitrite through a reaction of the nitrite with an aromatic amine. The resulting diazo compound reacts with another aromatic to form a pink compound.

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One location on the strip contains an indoxyl ester and diazonium salt. Leukocytes contain an esterase that hydrolyzes the indoxyl ester. The liberated compound reacts with the diazonium salt on the strip to generate a purple compound. The concentration of leukocytes is correlated with a color change from beige to violet.

The ascorbic acid test uses the decolorization of Tillmann's reagent. The presence of ascorbic acid causes the color of the test field to change from gray-blue to yellow.

## M. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

#### a. Precision/Reproducibility:

Within-run and Within-day precisions were determined at the manufacture's site, using level 1 and level 2 urinalysis controls.

Reproducibility testing was done in accordance with CLSI EP12-A "User Protocol for Evaluation of Qualitative Test Performance". Two clinical pathologists were employed as readers for the precision testing.

For within-run precision testing, twenty replicates were run on each of two levels of liquid urine controls. Each of the twenty replicates was assayed consecutively, using strips obtained from each of 3 lots of vial. For within-day precision testing, two levels were analyzed in duplicate, one a day, for 20 days using strips obtained from 3 lots of vials. Percentage agreements were calculated using the concentrations specified in the control labeling and the concentration ranges specified for the strip.

The results of the within-day testing:

|   | Negative Control |   |   |   |   | Positive Control  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Analyte | Expected Result | Lot 10205 | Lot 10721 | Lot 20108 | Total Agreement | Expected Result | Lot 10205 | Lot 10721 | Lot 20108 | Total Agreement  |
|  Urobilinogen | Negative | 20/20 | 20/20 | 59/60 | 59/60 (98.3%) | 4 mg/dl | 19/20 | 19/20 | 18/20 | 56/60 (93.3%)  |
|  Glucose | Negative | 20/20 | 20/20 | 20/20 | 60/60 (100%) | 1000 mg/dl | 19/20 | 19/20 | 20/20 | 58/60 (96.6%)  |
|  Bilirubin | Negative | 19/20 | 20/20 | 19/20 | 58/60 (96.7%) | +++ | 17/20 | 17/20 | 18/20 | 52/60 (86.7%)  |
|  Ketones (acetoacetic acid) | Negative | 20/20 | 20/20 | 20/20 | 60/60 (100%) | 40 mg/dl | 20/20 | 17/20 | 19/20 | 56/60 (93.3%)  |
|  Specific Gravity | 1.020 | 17/20 | 18/20 | 19/20 | 54/60 (90%) | 1.020 | 17/20 | 18/20 | 17/20 | 52/60 (86.7%)  |
|  Blood | Negative | 19/20 | 20/20 | 20/20 | 59/60 (98.3%) | 250 RBC/ul | 19/20 | 20/20 | 19/20 | 58/60 (96.6%)  |
|  pH | 6 | 18/20 | 20/20 | 19/20 | 57/60 (95%) | 7 | 17/20 | 17/20 | 18/20 | 52/60 (86.7%)  |

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The results of the within-run testing:

|   | Negative Control |   |   |   |   | Positive Control  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Analyte | Result | Lot 10205 | Lot 10721 | Lot 20108 | Total Agreement | Expected Result | Lot 10205 | Lot 10721 | Lot 20108 | Total Agreement  |
|  Protein | Negative | 20/20 | 20/20 | 19/20 | 59/60 (98.3%) | 100 mg/dl | 19/20 | 20/20 | 19/20 | 58/60 (96.7%)  |
|  Nitrite | Negative | 20/20 | 19/20 | 20/20 | 59/60 (98.3%) | Positive | 20/20 | 20/20 | 20/20 | 60/60 (100%)  |
|  Leukocytes | Negative | 20/20 | 20/20 | 20/20 | 60/60 (100%) | 75 WBC/ul | 18/20 | 19/20 | 17/20 | 54/60 (90.0%)  |
|  Ascorbic | Negative | 20/20 | 20/20 | 20/20 | 60/60 (100%) | Negative | 20/20 | 20/20 | 20/20 | 60/60 (100%)  |

b. Linearity/assay reportable range:

The company assessed the range of the device by repeated testing with urine containing known concentrations of the measured analytes.

Samples of the candidate device were randomly selected from routine production following ISO 2895-1: "Sampling procedures for inspection by attribute-sampling scheme indexed by acceptances quality limit (AQL) by lot-to-lot inspection". Strips were selected from three manufacturing lots.

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Test material was created by spiking analytes into negative urine or by serial dilution with negative urine of a known high concentration of an analyte in urine. Test material was adjusted to match the mid-point of a concentration range for a particular color block on the strip – if a particular color indicated a concentration of $2 - 4\mathrm{mg / dL}$, the test urine was adjusted to $3\mathrm{mg / dL}$.

Three pathologists independently read each of the three lots of test strips. Tests were done 10 times at each test concentration with 3 different product lots. Sample application was done according to the device's product insert. Color comparisons were made against the color chart that accompanies the product.

The company illustrated the performance of their device by presenting the results of these tests as a scoring matrix. The results of this testing is summarized below.

For urobilinogen, the company demonstrated:

Applied Concentration, mg/dL

|   |  | 0.1 | 1 | 2 | 4 | 8  |
| --- | --- | --- | --- | --- | --- | --- |
|  Concentration reported by Strip, mg/dL | 8 | 0 | 0 | 0 | 1 | 28  |
|   |  4 | 0 | 0 | 2 | 25 | 2  |
|   |  2 | 0 | 1 | 26 | 3 | 0  |
|   |  1 | 0 | 29 | 2 | 1 | 0  |
|   |  0.1 | 30 | 0 | 0 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30 | 30 | 30  |

For glucose, the company demonstrated:

Applied Concentration, mg/dL

|   |  | Neg. | 100 | 250 | 500 | 1000  |
| --- | --- | --- | --- | --- | --- | --- |
|  Concentration reported by Strip, mg/dL | 1000 | 0 | 0 | 0 | 2 | 26  |
|   |  500 | 0 | 0 | 2 | 27 | 4  |
|   |  250 | 0 | 1 | 27 | 1 | 0  |
|   |  100 | 0 | 29 | 1 | 0 | 0  |
|   |  Neg. | 30 | 0 | 0 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30 | 30 | 30  |

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For bilirubin, the company demonstrated:

|   | Neg. | + | ++ | +++  |
| --- | --- | --- | --- | --- |
|  +++ | 0 | 0 | 3 | 29  |
|  ++ | 0 | 4 | 27 | 1  |
|  + | 0 | 25 | 0 | 0  |
|  Neg. | 30 | 1 | 0 | 0  |
|  Total Number of samples applied at concentration | 30 | 30 | 30 | 30  |

For ketones, the company demonstrated:

|   | Applied Concentration, mg/dL  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |   |  Neg. | 5 | 15 | 40 | 100  |
|  Concentration reported by Strip, mg/dL | 100 | 0 | 0 | 0 | 2 | 28  |
|   |  40 | 0 | 0 | 1 | 25 | 2  |
|   |  15 | 0 | 0 | 28 | 3 | 0  |
|   |  5 | 0 | 29 | 1 | 0 | 0  |
|   |  Neg. | 30 | 1 | 0 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30 | 30 | 30  |

For the specific gravity, the company demonstrated:

|   | Applied Specific Gravity  |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  1.000 | 1.005 | 1.010 | 1.015 | 1.020 | 1.025 | 1.030  |
|  Specific gravity reported by Strip | 1.030 | 0 | 0 | 0 | 0 | 0 | 2 | 29  |
|   |  1.025 | 0 | 0 | 0 | 0 | 4 | 26 | 1  |
|   |  1.020 | 0 | 0 | 0 | 1 | 24 | 2 | 0  |
|   |  1.015 | 0 | 0 | 1 | 26 | 2 | 0 | 0  |
|   |  1.010 | 0 | 2 | 26 | 3 | 0 | 0 | 0  |
|   |  1.005 | 0 | 28 | 3 | 0 | 0 | 0 | 0  |
|   |  1.000 | 30 | 0 | 0 | 0 | 0 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30 | 30 | 30 | 30 | 30  |

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For hemolyzed blood, the company demonstrated:

Applied RBC/  $\mu$ l

|   |  | Neg. | 10 RBC/μl | 50 RBC/μl | 250 RBC/μl  |
| --- | --- | --- | --- | --- | --- |
|  RBC/μl reported by Strip | 250 |  |  |  |   |
|   |  RBC/μl | 0 | 0 | 3 | 30  |
|   |  50 |  |  |  |   |
|   |  RBC/μl | 0 | 3 | 26 | 0  |
|   |  10 |  |  |  |   |
|  Total Number of samples applied at concentration | RBC/μl | 0 | 27 | 1 | 0  |
|   |  Neg. | 30 | 0 | 0 | 0  |
|   |  | 30 | 30 | 30 | 30  |

For non-hemolyzed blood, the company demonstrated:

|   |  | Applied Non-hemolyzed blood  |   |   |
| --- | --- | --- | --- | --- |
|   |  | Neg. | + | ++  |
|  Non-hemolyzed blood reported by Strip | ++ | 0 | 4 | 27  |
|   |  + | 0 | 26 | 3  |
|   |  Neg. | 30 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30  |

For pH, the company demonstrated:

|  pH reported by Strip | Applied pH  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |  5 | 6 | 6.5 | 7 | 8 | 9  |
|   |  9 | 0 | 0 | 0 | 1 | 29  |
|   |  8 | 0 | 0 | 0 | 2 | 28  |
|   |  7 | 0 | 0 | 3 | 28 | 1  |
|   |  6.5 | 0 | 0 | 23 | 0 | 0  |
|   |  6 | 1 | 26 | 4 | 0 | 0  |
|   |  5 | 29 | 4 | 0 | 0 | 0  |
|  Total Number of samples applied at concentration | 30 | 30 | 30 | 30 | 30 | 30  |

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For protein, the company demonstrated:

|   |  | Applied protein, mg/dL  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  | Neg. | 15 | 30 | 100 | 300 | 1000  |
|  Protein reported by Strip, mg/dL | 1000 | 0 | 0 | 0 | 0 | 1 | 29  |
|   |  300 | 0 | 0 | 0 | 2 | 28 | 1  |
|   |  100 | 0 | 0 | 3 | 28 | 1 | 0  |
|   |  30 | 0 | 0 | 23 | 0 | 0 | 0  |
|   |  15 | 1 | 26 | 4 | 0 | 0 | 0  |
|   |  Neg. | 29 | 4 | 0 | 0 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30 | 30 | 30 | 30  |

For nitrite, the company demonstrated:

|   |  | Applied nitrite  |   |   |
| --- | --- | --- | --- | --- |
|   |  | Neg. | Tr. | Pos.  |
|  Nitrite reported by Strip | Pos. | 0 | 1 | 30  |
|   |  Tr. | 1 | 28 | 0  |
|   |  Neg. | 29 | 1 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30  |

For leukocytes, the company demonstrated:

|  Applied leukocytes/μl  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |  | Neg. | 25 Leu/μl | 75 Leu/μl | 500 Leu/μl  |
|  Lue/μl reported by Strip | 500 Leu/μl | 0 | 0 | 1 | 29  |
|   |  75 Leu/μl | 0 | 1 | 26 | 1  |
|   |  25 Leu/μl | 0 | 25 | 3 | 0  |
|   |  Neg. | 30 | 4 | 0 | 0  |
|   |  Total Number of samples applied at concentration | 30 | 30 | 30 | 30  |

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For ascorbic acid, the company demonstrated:

|   |  | Applied ascorbic acid  |   |   |
| --- | --- | --- | --- | --- |
|   |  | 20 | 40 |   |
|   |  | Neg. | mg/dL | mg/dL  |
|  Ascorbic acid reported by Strip | 40 mg/dL | 0 | 4 | 27  |
|   |  20 mg/dL | 0 | 26 | 3  |
|   |  Neg. | 30 | 0 | 0  |
|  Total Number of samples applied at concentration |   | 30 | 30 | 30  |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The company used a combination of real-time and accelerated aging studies to demonstrate their claimed shelf life. The company used samples taken from three different manufacturing lots in assessing their shelf life.

The company conducted real time aging studies to empirically determine the shelf life of their device. Bottles from each manufacturing lot were stored in an environmental chamber at temperatures ranging from  $2 - 30^{\circ}\mathrm{C}$ . The relative humidity was set to less than  $30\%$ . Strips were withdrawn monthly and tested with negative and spiked positive urine samples. The company demonstrated that the performance of their device did not change over the course of this 2 year storage test.

In addition, the company conducted accelerated aging studies at storage temperatures of  $40^{\circ}\mathrm{C}$ ,  $50^{\circ}\mathrm{C}$ , and  $60^{\circ}\mathrm{C}$ . Data supplied by company demonstrated that the strips could be stored at  $60^{\circ}\mathrm{C}$  for 3 weeks without a change in performance. Strips could be stored at  $50^{\circ}\mathrm{C}$  for 4 weeks and  $40^{\circ}\mathrm{C}$  for 6 weeks without a change in performance.

The company conducted tests at room temperature and high relative humidity to quantify the impact of ambient water vapor. Strips stored at less than  $50\%$  relative humidity did not demonstrate a change in performance over a 2 year period.

The data provided by the company supports their claim that the CYBOW 11 Reagent strips for Urinalysis are stable for 24 months when stored between  $15 - 30^{\circ}\mathrm{C}$  and a relative humidity of less than  $50\%$ .

d. Detection limit:

The company demonstrated their detection limit by challenging the concentration cutoff with samples adjusted to concentrations  $20\%$  above and  $20\%$  below the cutoff concentration specified for the analyte. The company

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conducted this study using 20 strips from each of 3 lots for a total of 60 measurements at each concentration.

For urobilinogen, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 58 | 0 | 0  |
|  Positive | 2 | 60 | 60  |
|  Percent Correct | 96.7% | 100% | 100%  |
|  Cutoff Used | 2 Ehrlich units/dL  |   |   |

For glucose, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 57 | 1 |   |
|  Positive | 3 | 59 | 60  |
|  Percent Correct | 95% | 98.3% | 100%  |
|  Cutoff Used | 50 mg/dL  |   |   |

For bilirubin, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 59 | 0 | 0  |
|  Positive | 1 | 60 | 60  |
|  Percent Correct | 98.3% | 100% | 100%  |
|  Cutoff Used | 0.5 mg/dL  |   |   |

For ketones, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 57 | 0 | 0  |
|  Positive | 3 | 60 | 60  |
|  Percent Correct | 95% | 100% | 100%  |
|  Cutoff Used | 5 mg/dL  |   |   |

For hemolyzed blood, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 52 | 1 | 0  |
|  Positive | 8 | 59 | 60  |
|  Percent Correct | 86.7% | 98.3% | 100%  |
|  Cutoff Used | 10 RBC/μL  |   |   |

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For non-hemolyzed blood, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 50 | 2 | 0  |
|  Positive | 10 | 58 | 60  |
|  Percent Correct | 83.3% | 96.7% | 100%  |
|  Cutoff Used | 10 RBC/μL  |   |   |

For protein, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 42 | 8 | 0  |
|  Positive | 18 | 52 | 60  |
|  Percent Correct | 70.0% | 86.7% | 100%  |
|  Cutoff Used | 12 mg/dL  |   |   |

For nitrite, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 55 | 0 | 0  |
|  Positive | 5 | 60 | 60  |
|  Percent Correct | 91.7% | 100% | 100%  |
|  Cutoff Used | 0.05 mg/dL  |   |   |

For leukocytes, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 41 | 5 | 0  |
|  Positive | 19 | 55 | 60  |
|  Percent Correct | 68.3% | 91.7% | 100%  |
|  Cutoff Used | 23 WBC/μL  |   |   |

For ascorbic acid, the company demonstrated:

|  Sample | 0.8*Cutoff Conc. | Cutoff Conc. | 1.2*Cutoff Conc.  |
| --- | --- | --- | --- |
|  Normal | 58 | 0 | 0  |
|  Positive | 2 | 60 | 60  |
|  Percent Correct | 96.7% | 100% | 100%  |
|  Cutoff Used | 20 mg/dL  |   |   |

e. Analytical specificity:

The company conducted tests using analytes suspected of interfering with their device. Fresh negative urine was spiked with the analyte of interest and the interfering analyte. The company documented the impact of the interfering analyte in their product insert. A summary of the company's findings:

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|  Test | Interfering Analyte | Impact on test  |
| --- | --- | --- |
|  Urobilinogen | p-amino salicylic acid | False positive  |
|   |  Azo gantrinsin | Test inoperative – unable to read  |
|  Glucose | High specific gravity (>1.2) | False negative  |
|   |  High pH (>8.5) | False negative  |
|   |  Ascorbic acid (>40 mg/dL) | False negative  |
|   |  Elevated ketones (>40 mg/dL) | False negative  |
|  Bilirubin | Selenium | False positive  |
|   |  Pyrindum (drug metabolite) | False positive  |
|   |  Indoxyl sulfate | Test inoperative – unable to read  |
|   |  Therapeutic dyes | False positive  |
|  Ketones | Colored contaminates | False positive  |
|   | L-dopa and metabolites | False positive  |
|   |  High specific gravity (>1.025) | False positive  |
|   |  Low pH | False positive  |
|   |  Phenosulfonphthalein(>0.05 mg/dL) | False positive  |
|  Blood (hemolyzed and non-hemolyzed) | Microbial peroxidase | False positive  |
|   |  Ascorbic acid (>40 mg/dL) | False negative  |
|  Specific Gravity | Elevated proteins (>300 mg/dL) | High specific gravity not indicative of high urine electrolytes  |
|   | Buffered alkaline samples (pH > 8.5) | Low reported specific gravity  |
|   | Buffered acidic samples (pH < 5) | Low reported specific gravity  |
|  pH | Cross-contamination from adjacent reagent pads | Low reported pH  |
|  Protein | Turbidity/ Lipemic samples | Test inoperative – unable to read  |
|   |  High pH (>9) | False positive  |
|  Nitrite |   |   |
|   |  Ascorbic acid | False negative  |
|  Leukocyte | High glucose (>1000 mg/dL) | Low reported WBC/μL  |
|   |  High albumin (>1000 mg/dL) | Low reported WBC/μL  |
|   | Formaldehyde (>5%) | Low reported WBC/μL  |
|   | Oxalic acid (>50 mg/dL) | Low reported WBC/μL  |
|   | Oxidizing agents (permanganate) | Low reported WBC/μL  |

# f. Assay cut-off:

Not applicable for devices of this type. The performance of the device around

{14}

the "not present"/"present" cutoff is discussed under d) Detection Limit above.

# 2. Comparison studies:

# a. Method comparison with predicate device:

The company conducted a method comparison of the submitted device to the legally marketed predicate, the Bayer Multistix 10 SG. Using fresh negative and spiked urine samples, 3 pathologists recorded the results of measurements on 300 samples made with the proposed device and to those made with the Bayer predicate. Strips from 3 manufacturing lots of the propose device were used in the comparison. Measurements were made according to the respective product inserts.

For the specific gravity, the company the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device | 1.030 | 0 | 0 | 0 | 0 | 0 | 0 | 50  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  1.025 | 0 | 0 | 0 | 0 | 10 | 54 | 18  |
|   |  1.020 | 0 | 0 | 0 | 8 | 56 | 0 | 0  |
|   |  1.015 | 0 | 0 | 15 | 48 | 1 | 0 | 0  |
|   |  1.010 | 0 | 0 | 33 | 1 | 0 | 0 | 0  |
|   |  1.005 | 0 | 6 | 0 | 0 | 0 | 0 | 0  |
|   |  1.000 | 0 | 0 | 0 | 0 | 0 | 0 | 0  |
|   |  SG | 1.000 | 1.005 | 1.010 | 1.015 | 1.020 | 1.025 | 1.030  |
|   | Predicate Device  |   |   |   |   |   |   |   |

For pH, the company the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device | 9 | 0 | 0 | 0 | 0 | 3 | 2 | 7  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  8 | 0 | 0 | 0 | 0 | 15 | 8 | 3  |
|   |  7 | 0 | 0 | 2 | 43 | 3 | 2 | 1  |
|   |  6.5 | 2 | 5 | 21 | 12 | 0 | 0 | 0  |
|   |  6 | 12 | 84 | 17 | 2 | 0 | 0 | 0  |
|   |  5 | 47 | 9 | 0 | 0 | 0 | 0 | 0  |
|   |  pH | 5 | 6 | 6.5 | 7 | 7.5 | 8 | 8.5  |
|   | Predicate Device  |   |   |   |   |   |   |   |

{15}

For urobilinogen, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (mg/dL) | 8 | 0 | 0 | 0 | 3 | 55  |
| --- | --- | --- | --- | --- | --- | --- |
|   |  4 | 0 | 0 | 3 | 53 | 4  |
|   |  2 | 0 | 3 | 54 | 3 | 1  |
|   |  1 | 0 | 53 | 3 | 1 | 0  |
|   |  0.1 | 60 | 4 | 0 | 0 | 0  |
|   |  Uro | 0.1 | 1 | 2 | 4 | 8  |
|   |   | Predicate Device (mg/dL)  |   |   |   |   |

For glucose, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (mg/dL) | >1000 | 0 | 0 | 1 | 3 | 33 | 19  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  500 | 0 | 0 | 3 | 54 | 5 | 1  |
|   |  250 | 0 | 4 | 53 | 2 | 2 | 0  |
|   |  100 | 0 | 54 | 3 | 1 | 0 | 0  |
|   |  Negative | 60 | 2 | 0 | 0 | 0 | 0  |
|   |  Glucose | Negative | 100 | 250 | 500 | 1000 | 2000  |
|   | Predicate Device (mg/dL)  |   |   |   |   |   |   |

For urinary bilirubin, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device | 3+ | 0 | 2 | 2 | 72  |
| --- | --- | --- | --- | --- | --- |
|   |  2+ | 0 | 4 | 71 | 3  |
|   |  1+ | 4 | 70 | 5 | 5  |
|   |  Negative | 56 | 4 | 2 | 0  |
|   |  Bilirubin | Negative | 1+ | 2+ | 3+  |
|   | Predicate Device  |   |   |   |   |

For urinary ketones, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (mg/dL) | >100 | 0 | 0 | 1 | 3 | 34 | 18  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  40 | 0 | 0 | 2 | 50 | 4 | 2  |
|   |  15 | 0 | 4 | 52 | 4 | 2 | 0  |
|   |  5 | 2 | 51 | 4 | 3 | 0 | 0  |
|   |  Negative | 58 | 5 | 1 | 0 | 0 | 0  |
|   |  Ketones | Negative | 5 | 15 | 40 | 80 | 160  |
|   | Predicate Device (mg/dL)  |   |   |   |   |   |   |

{16}

For hemolyzed urinary blood, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (RBC/μl) | 250 | 0 | 0 | 0 | 5 | 43  |
| --- | --- | --- | --- | --- | --- | --- |
|   |  50 | 0 | 0 | 5 | 41 | 5  |
|   |  10 | 4 | 45 | 45 | 4 | 2  |
|   |  Negative | 56 | 5 | 0 | 0 | 0  |
|   |  Hemolyzed Blood | Negative | 10 | 25 | 80 | 250  |
|   | Predicate device (RBC/μl)  |   |   |   |   |   |

For non-hemolyzed blood in the urine, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (RBC/μl) | 80 | 0 | 1 | 17  |
| --- | --- | --- | --- | --- |
|   |  10 | 4 | 17 | 3  |
|   |  Negative | 56 | 2 | 0  |
|   |  Non-hemolyzed blood | Negative | 10 | 80  |
|   | Predicate device (RBC/μl)  |   |   |   |

For urinary protein, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (mg/dL) | 1000 | 0 | 0 | 0 | 0 | 2 | 18  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  300 | 0 | 0 | 0 | 3 | 35 | 2  |
|   |  100 | 0 | 0 | 1 | 55 | 3 | 0  |
|   |  30 | 0 | 3 | 54 | 2 | 0 | 0  |
|   |  15 | 3 | 53 | 4 | 0 | 0 | 0  |
|   |  Negative | 57 | 4 | 1 | 0 | 0 | 0  |
|   |  Protein | Negative | 15 | 30 | 100 | 300 | 1000  |
|   |   | Predicate device (mg/dL)  |   |   |   |   |   |

For nitrite, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device | Positive | 0 | 11 | 95  |
| --- | --- | --- | --- | --- |
|   |  +/- | 0 | 87 | 5  |
|   |  Negative | 100 | 2 | 0  |
|   |  Nitrite | Negative | +/- | Positive  |
|   | Predicate device  |   |   |   |

For leukocytes in the urine, the company demonstrated the following correlation between the proposed and predicate device:

|  Proposed Device (Leu/μL) | 500 | 0 | 0 | 3 | 4 | 55  |
| --- | --- | --- | --- | --- | --- | --- |
|   |  75 | 0 | 3 | 54 | 54 | 3  |
|   |  25 | 2 | 44 | 2 | 2 | 2  |
|   |  Negative | 58 | 13 | 1 | 0 | 0  |
|   |  Leukocytes | Negative | 15 | 70 | 125 | 500  |
|   | Predicate device (Leu/μL)  |   |   |   |   |   |

{17}

b. Matrix comparison:

The CYBOW 11 Reagent Strips for Urinalysis are only for use with urine.

# 3. Clinical studies:

a. Clinical Sensitivity:

Not applicable for a device of this type.

b. Clinical specificity:

Not applicable for a device of this type.

c. Other clinical supportive data (when a. and b. are not applicable):

The company demonstrated the equivalence of their proposed device to their predicate using patient samples analyzed in the environment in which the device will be used. The company undertook a clinical comparison of the device to the predicate at 2 hospitals' clinical laboratories. A total of 909 patient samples were compared over 30 days.

The clinical comparison followed CLSI EP9A "Method Comparison and Bias Estimation Using Patient Samples". In the study, the company used 3 different manufacturing lots for the proposed device and 3 different lots of strips from the cleared, on-market predicate.

Fresh urine samples obtained during routine processing at the medical facility were analyzed within 4 hours of collection. The fresh urine samples were detergent-free and were not centrifuged or spiked. Strip readings were conducted by laboratory personnel according to the respective device instructions.

For urobilinogen, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device (mg/dL) | 8 | 0 | 0 | 0 | 3 | 6  |
| --- | --- | --- | --- | --- | --- | --- |
|   |  4 | 4 | 0 | 2 | 16 | 5  |
|   |  2 | 9 | 6 | 17 | 4 | 2  |
|   |  1 | 10 | 22 | 6 | 1 | 0  |
|   |  Normal | 771 | 24 | 1 | 0 | 0  |
|   |  Urobilinogen | Normal | 1 | 2 | 4 | 8  |
|   | Predicate Device (mg/dL)  |   |   |   |   |   |

For glucose, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

{18}

|  Proposed Device (mg/dL) | 1000 | 0 | 0 | 2 | 6 | 36 | 34  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  500 | 0 | 1 | 15 | 40 | 2 | 3  |
|   |  250 | 1 | 14 | 59 | 6 | 0 | 0  |
|   |  100 | 23 | 53 | 7 | 5 | 0 | 0  |
|   |  Negative | 575 | 24 | 3 | 0 | 0 | 0  |
|   |  Glucose | Negative | 100 | 250 | 500 | 1000 | 2000  |
|   |  Predicate Device (mg/dL)  |   |   |   |   |   |   |

For bilirubin, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device (mg/dL) | 3+ | 0 | 1 | 4 | 21  |
| --- | --- | --- | --- | --- | --- |
|   |  2+ | 0 | 4 | 24 | 3  |
|   |  1+ | 30 | 29 | 10 | 7  |
|   |  Negative | 750 | 21 | 5 | 0  |
|   |  Bilirubin | Negative | 1+ | 2+ | 3+  |
|   | Predicate Device (mg/dL)  |   |   |   |   |

For urinary ketones, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device (mg/dL) | >100 | 0 | 0 | 0 | 3 | 33 | 0  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  40 | 0 | 0 | 4 | 47 | 9 | 0  |
|   |  15 | 7 | 8 | 32 | 10 | 4 | 0  |
|   |  5 | 17 | 45 | 8 | 2 | 0 | 0  |
|   |  Negative | 658 | 20 | 2 | 0 | 0 | 0  |
|   |  Ketones | Negative | 5 | 15 | 40 | 80 | 160  |
|   | Predicate Device (mg/dL)  |   |   |   |   |   |   |

For specific gravity, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device | 1.030 | 0 | 0 | 0 | 0 | 11 | 33 | 62  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  1.025 | 0 | 0 | 0 | 16 | 37 | 63 | 13  |
|   |  1.020 | 0 | 0 | 20 | 62 | 91 | 30 | 9  |
|   |  1.015 | 0 | 11 | 49 | 102 | 42 | 3 | 0  |
|   |  1.010 | 4 | 58 | 83 | 9 | 2 | 0 | 0  |
|   |  1.005 | 6 | 56 | 16 | 4 | 0 | 0 | 0  |
|   |  1.000 | 14 | 4 | 0 | 0 | 0 | 0 | 0  |
|   |  SG | 1.000 | 1.005 | 1.010 | 1.015 | 1.020 | 1.025 | 1.030  |
|   | Predicate Device  |   |   |   |   |   |   |   |

For urinary blood, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

{19}

|  Proposed Device (RBC/μl) | 250 | 0 | 0 | 7 | 18 | 128  |
| --- | --- | --- | --- | --- | --- | --- |
|   |  50 | 3 | 22 | 28 | 120 | 20  |
|   |  10 | 12 | 98 | 101 | 26 | 8  |
|   |  Negative | 280 | 28 | 9 | 1 | 0  |
|   |  Hemolyzed Blood | Negative | 10 | 25 | 80 | 250  |
|   | Predicate device (RBC/μl)  |   |   |   |   |   |

For urinary pH, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 9  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  8 | 0 | 0 | 0 | 12 | 21 | 67 | 10  |
|   |  7 | 0 | 2 | 15 | 110 | 92 | 16 | 0  |
|   |  6.5 | 5 | 21 | 75 | 32 | 7 | 2 | 0  |
|   |  6 | 61 | 159 | 37 | 7 | 1 | 0 | 0  |
|   |  5 | 92 | 50 | 6 | 0 | 0 | 0 | 0  |
|   |  pH | 5 | 6 | 6.5 | 7 | 7.5 | 8 | 8.5  |
|   | Predicate Device  |   |   |   |   |   |   |   |

For urinary protein, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device (mg/dL) | 4+ | 0 | 0 | 0 | 0 | 2 | 18  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  3+ | 0 | 0 | 0 | 3 | 35 | 2  |
|   |  2+ | 0 | 0 | 1 | 55 | 3 | 0  |
|   |  1+ | 0 | 3 | 54 | 2 | 0 | 0  |
|   |  +/- | 3 | 53 | 4 | 0 | 0 | 0  |
|   |  Negative | 57 | 4 | 1 | 0 | 0 | 0  |
|   |  Protein | Negative | +/- | 1+ | 2+ | 3+ | 4+  |
|   | Predicate device (mg/dL)  |   |   |   |   |   |   |

For urinary nitrite, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

|  Proposed Device | Positive | 6 | 4 | 108  |
| --- | --- | --- | --- | --- |
|   |  +/- | 10 | 43 | 8  |
|   |  Negative | 711 | 10 | 9  |
|   |  Nitrite | Negative | +/- | Positive  |
|   | Predicate device  |   |   |   |

For urinary leukocytes, the company demonstrated the following correlation between the proposed and predicate device using patient samples in a clinical lab setting:

{20}

|  Proposed Device (Leu/μL) | 500 | 1 | 0 | 2 | 10 | 100  |
| --- | --- | --- | --- | --- | --- | --- |
|   |  75 | 9 | 6 | 95 | 79 | 20  |
|   |  25 | 3 | 66 | 21 | 24 | 5  |
|   |  Negative | 378 | 79 | 10 | 0 | 0  |
|   |  Leukocytes | Negative | 15 | 70 | 125 | 500  |
|   | Predicate device (Leu/μL)  |   |   |   |   |   |

# 4. Clinical cut-off:

Not applicable for a device of this type.

# 5. Expected values/Reference range:

The company indicated the following published reference ranges for their analytes:

Urobilinogen: 0.1 to 1.0 Ehrlich unit /dL

Glucose:  $&lt; 100\mathrm{mg / dL}$

Bilirubin:  $&lt;$  Trace

Ketones:  $0\mathrm{mg / dL}$  in urine with this test

pH: 5 - 9.

Blood:  $&lt; 3$  RBC/μL

Specific Gravity (SG): 1.001 to 1.035.

Protein:  $&lt; 20\mathrm{mg / dL}$

Nitrite:  $0\mathrm{mg / dL}$

Leukocyte: Negative

Ascorbic acid: urinary output of  $20 - 30\mathrm{mg / day}$

# N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

# O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

---

**Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JIL/K052525](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/JIL/K052525)

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