Healgen URS Test Strips

K231045 · Healgen Scientific,, LLC · LJX · Jun 16, 2023 · Hematology

Device Facts

• Record ID: K231045
• Device Name: Healgen URS Test Strips
• Applicant: Healgen Scientific,, LLC
• Product Code: LJX · Hematology
• Decision Date: Jun 16, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7675
• Device Class: Class 1

Indications for Use

The Healgen URS Test Strips are for the qualitative detection of Leukocytes (white blood cells) and nitrite in urine as an aid in the screening of a Urinary Tract infection (UTI). It is intended for over-the-counter home use only.

Device Story

Healgen URS Test Strips are in vitro diagnostic devices for qualitative detection of leukocytes and nitrite in human urine. The device consists of two color-reactive pads on a strip. Principle of operation: leukocyte esterase hydrolyzes an indoxyl ester derivative, which reacts with a diazonium salt to produce a pink-to-purple color; nitrite is converted to a diazonium compound via p-arsanilic acid in an acid medium, which then couples with 1,2,3,4-tetrahydrobenzo(h)quinoline to produce a pink color. The user dips the strip in urine and visually compares the resulting pad colors against a provided color chart. Used in home settings by patients for UTI screening. Results assist users in identifying the need for further clinical evaluation. Benefits include rapid, accessible, and convenient preliminary screening for UTI symptoms.

Clinical Evidence

Clinical evidence consists of a lay-user study (n=150) comparing self-testing results to healthcare professional results. The study demonstrated 100% agreement for positive/negative results between lay users and professionals. Exact match agreement for color blocks ranged from 88.5% to 98.3%. Analytical performance included LOD verification (15 cells/µL for leukocytes; 0.05 mg/dL for nitrite), precision studies (100% agreement across 45 replicates), and interference testing against 20 substances. No clinical prospective/retrospective trials were required.

Technological Characteristics

In vitro diagnostic test strips with two reagent pads. Leukocyte detection via hydrolysis of indoxyl ester derivative; nitrite detection via p-arsanilic acid/diazonium coupling. Dimensions/form factor: strip with color pads. Connectivity: none (standalone). Storage: 15-30°C. Stability: 24 months shelf-life; 1-hour open-pouch stability. Traceability: Nitrite to NIST SRM 8040; Leukocyte to commercial solution.

Indications for Use

Indicated for individuals with symptoms of a urinary tract infection (UTI) for the qualitative detection of leukocytes and nitrite in urine as a screening aid.

Regulatory Classification

Identification

A leukocyte peroxidase test is a device used to distinguish certain myeloid cells derived from the bone marrow, i.e., neutrophils, eosinophils, and monocytes, from lymphoid cells of the lymphatic system and erythroid cells of the red blood cell series on the basis of their peroxidase activity as evidenced by staining. The results of this test are used in the differential diagnosis of the leukemias.

Predicate Devices

• Teco Diagnostics Uti Detection Strips (K100024)

Submission Summary (Full Text)

{0}

FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K231045

B Applicant

Healgen Scientific LLC

C Proprietary and Established Names

Healgen URS Test Strips

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| JMT | Class I, meets the limitations of exemptions in 21 CFR 862.9 (c)(9) | 21 CFR 862.1510 - Nitrite (nonquantitative) test system | CH - Clinical Chemistry |
| LJX | Class I, meets the limitations of exemptions in 21 CFR 864.9 (c)(9) | 21 CFR 864.7675 - Leukocyte Peroxidase Test | HE - Hematology |

## II Submission/Device Overview:

A Purpose for Submission:

New device

B Measurand:

Urinary nitrite and leukocytes

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

{1}

C Type of Test:

Qualitative and semi-quantitative urinalysis

III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

The Healgen URS Test Strips are for the qualitative detection of Leukocytes (white blood cells) and nitrite in urine as an aid in the screening of a Urinary Tract infection (UTI). It is intended for over-the-counter home use only.

C Special Conditions for Use Statement(s):

OTC - Over The Counter

D Special Instrument Requirements:

Not Applicable

IV Device/System Characteristics:

A Device Description:

Healgen URS Test Strips are an in vitro diagnostic device that use reagents for qualitative detection of leukocyte and nitrite in urine.

The device is composed of two-color pads aligned on a strip. One pad is employed for testing leukocyte and the other for nitrite by visually reading the color change of the pad and comparing with the corresponding blocks on a color chart.

B Principle of Operation:

The Healgen URS Test Strips measure the color developed in 2 reaction zones (leukocytes and nitrite pads) on the test strips following application of a urine sample. The developed colors are then compared to calibration colors located on the Healgen color chart card and the result for each pad is determined based on the minimum color distance between the developed colors and calibration colors.

The leukocytes test uses the hydrolysis of an indoxyl ester derivative through the action of leukocyte esterase. The liberated indoxyl ester reacts with a diazonium salt to produce a colored compound (pink to purple).

K231045 - Page 2 of 9

{2}

The nitrite test uses the conversion of nitrate to nitrite by the action of p-arsanilic acid to form a diazonium compound in an acid medium. This compound then couples with 1, 2, 3, 4-tetrahydrobenzo (h) quinoline to produce a pink color.

V Substantial Equivalence Information:

A Predicate Device Name(s):

Teco Diagnostics Uti Detection Strips

B Predicate 510(k) Number(s):

K100024

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K231045 | K100024 |
| --- | --- | --- |
| Device Trade Name | Healgen URS Test Strips | Teco Diagnostics UTI Test Strips |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For the detection of nitrite and leukocytes in urine. | Same |
| Nitrite test methodology | By conversion of nitrate to nitrite using the action of p-arsanilic acid to form a diazonium compound in an acid medium. This compound then couples with 1, 2, 3, 4 - tetrahydrobenzo(h) quinoline to produce a pink color. | Same |
| Leukocyte test methodology | By hydrolysis of an indoxyl ester derivative through the action of leukocyte esterase. The liberated indoxyl ester reacts with a diazonium salt to produce a colored compound (pink to purple). | Same |
| Specimen type | Human urine | Same |

K231045 - Page 3 of 9

{3}

K231045 - Page 4 of 9

| Device & Predicate Device(s): | K231045 | K100024 |
| --- | --- | --- |
| Testing parameters | Nitrite and leukocytes | Same |
| Conditions for use | Over-the-Counter | Same |
| General Device Characteristic Differences | | |
| Interference substances | Ascorbic Acid >100 mg/dL
No interferences observed for Phenazopyridine at 30 mg/dL or Riboflavin at 50 mg/dL | Ascorbic Acid > 30 mg/dL
Phenazopyridine > 5 mg/dL
Riboflavin > 10 mg/dL |

VI Standards/Guidance Documents Referenced:

None were referenced.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

The precision study on the URS Test Strips was performed at three (3) clinical sites with two (2) operators at each site. The evaluation included three (3) replicate assays over five (5) days with the midstream method. A total of forty-five (45) assays results on each of eight levels of control were obtained. All sample concentrations were masked. Three lots of the device were used with each level of control. The obtained results are listed in the following tables:

| Control | Analyte | Concentration | Expected Value | N | % Agreement with Expected results |
| --- | --- | --- | --- | --- | --- |
| Control 1 | Leukocyte | 0 cells/μL | Negative | 45 | 100 |
| | Nitrite | 0 mg/dL | Negative | 45 | 100 |
| Control 2 | Leukocyte | 15 cells/μL | Trace (15) | 45 | 100 |
| | Nitrite | 0 mg/dL | Negative | 45 | 100 |
| Control 3 | Leukocyte | 70 cells/μL | Small (70) | 45 | 100 |
| | Nitrite | 0 mg/dL | Negative | 45 | 100 |
| Control 4 | Leukocyte | 125 cells/μL | Moderate (125) | 45 | 100 |
| | Nitrite | 0 mg/dL | Negative | 45 | 100 |
| Control 5 | Leukocyte | 500 cells/μL | Large (500) | 45 | 100 |
| | Nitrite | 0 mg/dL | Negative | 45 | 100 |

{4}

| Control | Analyte | Concentration | Expected Value | N | % Agreement with Expected results |
| --- | --- | --- | --- | --- | --- |
| Control 6 | Leukocyte | 0 cells/μL | Negative | 45 | 100 |
| | Nitrite | 0.1 mg/dL | Positive | 45 | 100 |
| Control 7 | Leukocyte | 0 cells/μL | Negative | 45 | 100 |
| | Nitrite | 0.3 mg/dL | Positive | 45 | 100 |
| Control 8 | Leukocyte | 70 cells/μL | Small (70) | 45 | 100 |
| | Nitrite | 0.1 mg/dL | Positive | 45 | 100 |

2. Linearity:

Not Applicable.

3. Analytical Specificity/Interference:

Potentially interfering substances were added to negative urine or urine with different leukocyte and nitrite concentrations. These samples were tested with three lots of the Healgen URS Test Strips by three different operators (one operator per lot). The following substances showed no interference with the tests at the specified concentrations.

| Substances | Testing Concentration (mg/dL) |
| --- | --- |
| Albumin | 1000 |
| Ammonium Chloride | 400 |
| Ascorbic Acid | 100 |
| Bilirubin | 10 |
| Ciprofloxacin | 1 |
| Creatinine | 600 |
| Fructose | 18 |
| Galactose | 15 |
| Glucose | 500 |
| Glycine | 900 |
| Hemoglobin | 100 |
| Lactose | 29 |
| Oxalic Acid | 1 |
| Phenazopyridine | 30 |
| Phenolphthalein | 4 |
| Potassium Chloride | 1200 |
| Riboflavin | 50 |
| Sodium Nitrate | 10 |
| Sodium Nitrite* | 10 |
| Sodium Phosphate | 1000 |
| Sulfamethoxazole | 40 |
| Theophylline | 4 |
| Urea | 4000 |

* This interference is tested for Leukocyte results only.

K231045 - Page 5 of 9

{5}

High glucose levels (≥1000 mg/dL) and high ascorbic acid (≥150 mg/dL) may decrease leukocyte readings. High ascorbic acid (≥150 mg/dL) may cause a false negative nitrite reading.

To investigate the effect of urine specific gravity and urine pH, urine samples with specific gravity ranging from 1.000 to 1.035 and urine samples with pH ranging from pH of 5 to 9 were tested at different leukocyte and nitrite concentrations. The test results show that pH >8.0 may cause false positive leukocyte readings, and specific gravity ≥1.035 may cause false negative leukocyte readings. There is no effect of both pH and specific gravity on nitrite testing.

To address the observed interference, the labeling indicates that dehydration (high specific gravity), high glucose, and high vitamin C (ascorbic acid) may interfere with results. The labeling also describes that urine with abnormal color (e.g., bright yellow or green) should not be tested.

## Sample Carryover

A sample carryover study was performed. Three (3) lots of test strips were used for testing. The study was performed by dipping the test strip into the sample and holding the test strip vertically upward or downward for 10 seconds to allow the sample flow from one pad to the other pad (e.g., run-over for the leucocyte pad to the nitrite pad with a sample with a high concentration of leukocyte and a normal concentration of nitrite and runover for the nitrite to the leukocyte pad with a sample with a high concentration of nitrite and a normal concentration of leukocyte). Testing was also repeated in the other direction. The study demonstrated that carryover (run-over) does not impact the test results.

## 4. Assay Reportable Range:

The results of the analytical studies support the following measurement ranges:

| Analyte | Measurement range |
| --- | --- |
| Leukocytes | qualitative: Negative, Trace, +, ++, +++
semi-quantitative: Negative, 15, 70, 125, 500 (cells/μL) |
| Nitrite | qualitative: Negative, Positive |

## 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

### Traceability

The nitrite test is traceable to NIST SRM 8040 and the leukocyte pad is traceable to a commercially available solution.

### Stability

The sponsor provided information to support that the device is stable for 24 months when stored at 2-30 °C based on real-time stability studies. The package insert recommends that users store the strips at 15-30°C (59-86°F).

K231045 - Page 6 of 9

{6}

The sponsor instructs the user to use the test strip immediately after the foil pouch is opened based on the results of the open-pouch stability study that demonstrated an open-pouch stability of 1 hour.

# 6. Detection Limit:

See Assay cutoff section below.

# 7. Assay Cut-Off:

A sensitivity study was performed to evaluate the lower limits of detection for each analyte on the URS Test Strips. Urine samples were spiked to known concentrations of each analyte. These samples were then diluted to the lowest positive concentrations that are indicated on the color chart. Each sample was tested in duplicate (2) with three (3) device lots by five (5) different operators. The sponsor defined the LOD as the concentration of analyte that produces positive URS Test Strip results approximately $50\%$ of the time. The results support the claim that the sensitivity of the leukocyte test is 15 cells/ $\mu \mathrm{L}$ and the sensitivity of the nitrite test is $0.05\mathrm{mg / dL}$ .

| Leucocyte Concentration (cells/μL) | Negative | Positive | Limit of Detection |
| --- | --- | --- | --- |
| 30 | 0 | 30 | 100% |
| 15 | 0 | 30 | 100% |
| 10 | 16 | 14 | 47% |
| 5 | 28 | 2 | 7% |
| 3 | 30 | 0 | 0 |
| Nitrite Concentration (mg/dL) | Negative | Positive | Limit of Detection |
| --- | --- | --- | --- |
| 0.1 | 0 | 30 | 100% |
| 0.08 | 0 | 30 | 100% |
| 0.06 | 5 | 25 | 83% |
| 0.05 | 15 | 15 | 50% |
| 0.04 | 30 | 0 | 0 |

The sponsor provided studies to support the recommended wetting time (1-2 seconds) and the recommended reading time (2 minutes).

# B Comparison Studies:

# 1. Lay User study:

Three (3) sites were selected to perform the lay-user studies. One hundred fifty (150) lay users with UTI symptoms were recruited to test their own urine sample using the Healgen URS Test Strips. Laypersons performed one test with the Healgen URS Test Strips according to the product insert and then collected a sample of their urine for comparison testing by

K231045 - Page 7 of 9

{7}

healthcare professionals using the predicate device. The results obtained by the lay users using the Healgen URS Test Strips compared to the results obtained by the healthcare professionals using the predicate device are summarized below.

Results from 150 subjects testing their own urine samples using the midstream collection method for leukocytes:

| Predicate HCP Lay User | Large (3+) | Moderate (2+) | Small (1+) | Trace | Negative | Total |
| --- | --- | --- | --- | --- | --- | --- |
| Large (3+) | 10 | 0 | 0 | 0 | 0 | 10 |
| Moderate (2+) | 1 | 23 | 0 | 0 | 0 | 24 |
| Small (1+) | 0 | 2 | 26 | 1 | 0 | 29 |
| Trace | 0 | 0 | 3 | 23 | 1 | 27 |
| Negative | 0 | 0 | 0 | 2 | 58 | 60 |
| Total | 11 | 25 | 29 | 26 | 59 | 150 |
| % Agreement (Exact Match) | 90.9 | 92 | 89.7 | 88.5 | 98.3 | |
| % Agreement (+/- Color Block) | 100 | 100 | 100 | 100 | 100 | |

Results from 150 subjects testing their own urine samples using the midstream collection method for nitrite:

| Predicate HCP Lay User | Positive | Negative | Total |
| --- | --- | --- | --- |
| Positive | 32 | 0 | 32 |
| Negative | 0 | 118 | 118 |
| Total | 32 | 118 | 150 |
| % Agreement (Exact Match) | 100 | 100 | |

2. Matrix Comparison:

Not Applicable. This device is intended to be used for urine samples using the midstream collection method.

C Clinical Studies:

1. Clinical Sensitivity:

Not Applicable.

K231045 - Page 8 of 9

{8}

2. Clinical Specificity:

Not Applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

Not Applicable.

D Clinical Cut-Off:

Not Applicable.

E Expected Values/Reference Range:

The following information is provided in the labeling:

| TEST STRIP RESULTS | | RECOMMENDATIONS |
| --- | --- | --- |
| Leukocytes (LEU) | Nitrite (NIT) | |
| Negative | Negative | No sign of UTI detected. However, if you still have symptoms, consult your physician; there are some cases of UTI that the test may not detect. |
| Trace | Negative | Results suggest additional testing is required. Test again the following day with a new strip. If you have symptoms or if you get another trace leukocyte result, consult your physician. |
| Negative or Trace | Positive | Results suggest a sign of a UTI. Consult your physician immediately. |
| Positive +,++,+++ | Positive | Results suggest a sign of a UTI. Consult your physician immediately. |
| Positive +,++,+++ | Negative | Results suggest a sign of a UTI. Repeat the test next time you urinate using a new test strip. Make sure to wash the genital area first. If LEU is still positive, consult your physician. |

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

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

K231045 - Page 9 of 9