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 Description

Healgen URS Test Strips are in vitro diagnostic test devices 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.

AI/ML Overview

The document describes the performance of the Healgen URS Test Strips for the qualitative detection of Leukocytes and Nitrite in urine to aid in UTI screening for over-the-counter home use.

Here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" for each performance characteristic in a formal table. However, it presents various study results that implicitly serve as an indication of meeting performance expectations for a Class I device intended for OTC use. The implied acceptance is based on the presented results demonstrating sufficient sensitivity, precision, and user-friendability.

Here's a table summarizing the reported device performance for key characteristics:

Performance Characteristic	Analyte	Reported Device Performance
Limit of Detection (LOD)	Leukocyte	LOD verified at 15 cells/uL (100% detection at 30 and 15 cells/uL, 47% at 10 cells/uL, 7% at 5 cells/uL).
	Nitrite	LOD verified at 0.05 mg/dL (100% detection at 0.1 and 0.08 mg/dL, 83% at 0.06 mg/dL, 50% at 0.05 mg/dL).
Precision/Reproducibility	Leukocyte	100% agreement with expected results across Negative, Trace (15 cells/uL), Small (70 cells/uL), Moderate (125 cells/uL), and Large (500 cells/uL) controls (N=45 for each control level).
	Nitrite	100% agreement with positive results for 0.1 mg/dL and 0.3 mg/dL controls (N=45 for each control level).
Analytical Specificity	Leukocyte	No interference from various substances (Albumin, Ammonium Chloride, Bilirubin, Ciprofloxacin, Creatinine, Fructose, Galactose, Glycine, Hemoglobin, Lactose, Oxalic Acid, Phenazopyridine, Phenolphthalein, Potassium Chloride, Riboflavin, Sodium Nitrate, Sodium Nitrite, Sodium Phosphate, Sulfamethoxazole, Theophylline, Urea) at specified concentrations. Potential interference: High glucose (≥1000 mg/dL), high ascorbic acid (≥150 mg/dL) may decrease readings. pH >8.0 may cause false positive readings. Specific gravity >1.035 may cause false negative readings.
	Nitrite	No interference from various substances (same list as Leukocyte). Potential interference: High ascorbic acid (≥150 mg/dL) may cause false negative readings. No effect of pH or specific gravity on nitrite testing.
Stability	Both	Stable for 24 months at 2-30℃ based on real-time stability studies.
Lay-user Study (Method Comparison)	Leukocyte	+% Agreement (Exact Match): Large (90.9%), Moderate (92%), Small (89.7%), Trace (88.5%), Negative (98.3%). +% Agreement (+/- Color Block): 100% for all levels.
	Nitrite	+% Agreement (Exact Match): 100% for both Positive and Negative, with 100% overall agreement.
Lay-user Instruction Survey	Instructions	All lay users indicated that the device instructions can be easily followed. Flesch-Kincaid reading analysis showed a reading grade level less than 7.

2. Sample size used for the test set and the data provenance

Test Set Sample Sizes:
- Sensitivity Study (LOD): 30 samples/tests per concentration for each analyte (Leukocyte and Nitrite). Each sample was tested in duplicates.
- Precision/Reproducibility Study: 45 assays results for each of eight levels of control (total 3 lots x 3 sites x 2 operators x 5 days x 1 rep/day = 90 tests per control, though results are reported as N=45 for each control).
- Analytical Specificity: Not explicitly stated as a single test set size, but multiple urine samples (negative urine spiked with interfering substances) were tested with three device lots by three different operators for each substance.
- Lay-user Studies: 150 lay users with UTI symptoms.
Data Provenance: The document does not explicitly state the country of origin for the data. However, for the precision study, it mentions "three clinical sites," implying clinical data from a real-world setting. The lay-user study involved recruitment of "150 lay users with UTI symptoms," suggesting prospective collection of real-world user data. The sensitivity and analytical specificity studies appear to be laboratory-based. It is not specified if any data was retrospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

LOD and Precision Studies: "Known concentrations" for spiked samples and "expected ranges/values" for controls are used as ground truth. The expertise involved in preparing these precisely calibrated samples and controls is implied but not explicitly detailed (e.g., analytical chemists, laboratory technicians). Operators are mentioned (5 for LOD, 2 at each of 3 sites for precision), but their role is to perform the tests, not establish ground truth.
Analytical Specificity: Ground truth is established by "negative urine with different leukocyte and nitrite concentrations" which were likely precisely prepared laboratory samples.
Lay-user Studies: The "comparison testing by healthcare professionals" served as the ground truth. The number and qualifications of these healthcare professionals are not specified beyond the general term "healthcare professionals."

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

The document does not describe a formal adjudication method (like 2+1 or 3+1) for resolving discrepancies in the test results.
For the lay-user study, the comparison is made between the layperson's results and the results obtained by healthcare professionals, implying the healthcare professional's result is the definitive ground truth for comparison.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not done. This device is a test strip for visual interpretation by lay-users, not an AI-assisted diagnostic device evaluated by professional readers. The study focuses on direct comparison of lay-user performance to healthcare professional results for the test strip itself, not on the impact of AI assistance on human readers.

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

No, this device is not an algorithm. It is a visual assay (colorimetric test strip) that requires human interpretation. Therefore, a standalone algorithm-only performance study is not applicable. The "standalone" performance here refers to the device's inherent chemical reaction and color development, which is then interpreted by a human.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

LOD, Precision, Analytical Specificity: Ground truth was established using known concentrations of spiked analytes in urine samples and control materials, presumably confirmed by established laboratory methods and validated reagents.
Lay-user Study: Ground truth was established by results obtained by healthcare professionals using the same test strips. This implies the healthcare professionals' interpretation served as the 'expert' reference. It's not explicitly stated whether these healthcare professionals confirmed results with a gold standard like culture or microscopic analysis, or if their reading of the strip was considered the definitive truth for the purpose of the study.

8. The sample size for the training set

The document describes performance studies for the Healgen URS Test Strips, which are a chemical assay (test strips) with visual interpretation. This is not a machine learning or AI-based device that typically requires a "training set." Therefore, the concept of a training set size is not applicable here.

9. How the ground truth for the training set was established

As stated above, this is not an AI/ML device, so there is no training set or ground truth establishment for a training set in the context of machine learning. The studies described are for analytical and lay-user performance of a diagnostic test strip.

Summary

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June 16, 2023

Healgen Scientific LLC % Joe Shia Director LSI International Inc. 504 East Diamond Ave., Suite I Gaithersburg, MD 20877

Re: K231045

Trade/Device Name: Healgen URS Test Strips Regulation Number: 21 CFR 862.1510 Regulation Name: Nitrite (Non-Quantitative) Test System Regulatory Class: Class I (meets the limitations of exemptions in 862.9(c)(9)) Product Code: JMT, LJX Dated: April 7, 2023 Received: April 12, 2023

Dear Joe Shia:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see

https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

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Paula Caposino, Ph.D. Acting Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K231045

Device Name Healgen URS Test Strips

Indications for Use (Describe)

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

| | Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) SUMMARY K231045

1.	Date:	June 15, 2023
2.	Submitter:	Healgen Scientific LLC5213 Maple StreetBellaire, TX77401
3.	Contact person:	Joe ShiaLSI International Inc.504 East Diamond Ave., Suite IGaithersburg, MD 20878Telephone: 240-505-7880Fax: 301-916-6213Email: shiajl@yahoo.com

1. Device Name: Healgen URS Test Strips

Classification: Class I (meets the limitations of exemptions in 862.9(c)(9))

Product Code	CFR #	Panel
LJX	21 CFR § 864.7675, Leukocyte Peroxidase Test System	Hematology
JMT	21 CFR § 862.1510, Nitrite Test System	Chemistry

1. Predicate Devices: K100024 Teco Diagnostics UTI Test Strips
1. Intended Use:

1. Device Description:
  Healgen URS Test Strips are in vitro diagnostic test devices for qualitative detection of leukocyte and nitrite in urine.

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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.

Item	Device	Predicate – K100024
Indication(s)for use	For the detection of nitrite andleukocytes in urine.	Same
Nitrite testmethodology	By conversion of nitrate to nitrite usingthe action of p-arsanilic acid to form a diazoniumcompound in an acid medium. Thiscompound then couples with 1, 2, 3, 4-tetrahydrobenzo( h ) quinoline to producea pink color.	Same
Leukocyte testmethodology	By hydrolysis of an indoxyl esterderivative through the action ofleukocyte esterase. The liberatedindoxyl ester reacts with a diazoniumsalt to produce a colored compound(pink to purple).	Same
SpecimenType	Human urine	Same
Testingparameters	Nitrite and leukocytes	Same
Conditions forUse	Over-the-Counter	Same
Test ReadTime	2 minutes for both nitrite and leukocytes	2 minutes for leukocytes1 minute for nitrite

1. Substantial Equivalence Information

9. Test Principle

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 is using the hydrolysis of an indoxy] 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).

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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.

10. Performance Characteristics

1. 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 duplicates with three device lots by five different operators.

Leukocyte 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	Negative	Positive	Limit of Detection
(mg/dL)
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

LOD values of 15 cells/uL and 0.05 mg/dL are verified for Leukocyte and nitrite respectively.

2. Precision/Reproducibility

The precision study on the URS Test Strips was performed at three clinical sites with two operators at each site. The evaluation included three replicate assays over five days. A total of forty-five assays results on each of eight levels of control were obtained. All sample concentrations were masked.

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Three lots of the device were used with each level of control. The obtained results are listed in the following tables.

Leukocyte Results:

Control	ExpectedRange	N	% AgreementwithExpected Results
Negative	Negative	45	100
Trace	15	45	100
Small	70	45	100
Moderate	125	45	100
Large	500	45	100

Nitrite Results:

Control Sample	ExpectedValue	N	% AgreementwithExpected Results
0.1 mg/dL	Positive	45	100%
0.3 mg/dL	Positive	45	100%

Leukocyte and Nitrite Results:

Control Sample		ExpectedValue	N	% AgreementwithExpectedResults
Leukocyte	Small	70	45	100%
Nitrite	0.1 mg/dL	Positive	45	100%

1. Analytical specificity
  Potentially interfering substances were added to negative urine with different leukocyte and nitrite concentrations. These samples were tested with three lots of the Healgen URS Test Strips by three different operators. The following substances showed no interference with the tests at the specified concentrations. 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.

Substances	Testing Concentration (mg/dL)
Albumin	1000
Ammonium Chloride	400
Ascorbic Acid	100
Bilirubin	10
Ciprofloxacin	1

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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.

To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 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.

4. Stability

The devices are stable at 2-30℃ for 24 months based on real-time stability studies.

1. Method Comparison and Lay-user Studies
  Three sites were selected to perform the lay-user studies. 150 lay users with UTI symptoms were recruited to test her/his 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 healthcare professionals.

The results obtained by the lay users compared to the results obtained by the healthcare professionals are summarized below:

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Predicate Results byHealth Professionals
LaypersonResults	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

Predicate Results by HealthProfessionals	Positive	Negative	Overall
Layperson Results
Positive	32	0	32
Negative	0	118	118
Total	32	118	150
% Agreement (Exact Match)	100	100

Lay-users were also given surveys on the ease of understanding the package insert instructions. All lay users indicated that the device instructions can be easily followed. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7.

1. Clinical Studies
  Not applicable.

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11. Conclusion

Based on the test principle and performance characteristics of the device including LOD, precision, interference, method comparison and lay-user studies of the devices, it's concluded that Healgen URS Test Strips is substantially equivalent to the predicate.

Regulation Number and Section

§ 864.7675 Leukocyte peroxidase test.

(a)
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.(b)
Classification. Class I (general controls). This device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.