The Healgen® Accurate Fentanyl Rapid Test Dip Card (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only preliminary result. A more specific alternative chemical must be used to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Evaluate preliminary positive results carefully.

The Healgen® Accurate Fentanyl Rapid Test Strip (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only preliminary result. A more specific alternative chemical must be used to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Evaluate preliminary positive results carefully.

The Healgen® Accurate Fentanyl Rapid Test Cassette (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only preliminary result. A more specific alternative chemical must be used to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Evaluate preliminary positive results carefully.

The Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (CC-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

The Healgen® Accurate Rapid Fentanyl Test Strip (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (C-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

The Healge® Accurate Rapid Fentanyl Test Cassette (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (C-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

Device Description

The Healgen® Accurate Fentanyl Tests are immunoassays intended for the qualitative detection of fentanyl in human urine. Each Healgen® Accurate Fentanyl Test consists of a Test Device in format of Cassette or Dip Card or Strip, and a package insert. Each Test Device is sealed with sachets of desiccant in an aluminum pouch.

AI/ML Overview

The document provided is a 510(k) summary for a urine drug test for Fentanyl. It details the performance characteristics of the Healgen® Accurate Fentanyl Rapid Test Dip Card (Urine), Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine), Healgen® Accurate Fentanyl Rapid Test Strip (Urine), Healgen® Accurate Rapid Fentanyl Test Strip (Urine), Healgen® Accurate Fentanyl Rapid Test Cassette (Urine), and Healgen® Accurate Rapid Fentanyl Test Cassette (Urine).

This document describes a medical device (rapid diagnostic test), not an AI/ML algorithm or software as a medical device (SaMD). Therefore, many of the requested criteria related to AI/ML studies (e.g., number of experts for ground truth, adjudication methods, MRMC studies, training set size/ground truth) are not applicable.

However, I can extract the relevant information regarding the device's acceptance criteria and the studies performed to demonstrate its performance.

Here's the breakdown of the acceptance criteria and the study that proves the device meets them, focusing on what is applicable to a rapid diagnostic test:

Acceptance Criteria and Reported Device Performance

For rapid diagnostic tests like this one, "acceptance criteria" are typically defined by performance characteristics such as precision (accuracy at and around the cutoff), specificity (no cross-reactivity with other substances), interference (no effect from common urine constituents), and comparison to a gold standard method. The document presents data to demonstrate these characteristics.

1. Table of Acceptance Criteria and the Reported Device Performance (Summary of Key Performance)

The document implicitly defines the acceptance criteria through the presented performance data, showing that the device consistently performs as expected at and around the cutoff concentration of 1.0 ng/mL for fentanyl.

Performance Metric	Acceptance Criteria (Implicit from Study Design)	Reported Device Performance (Cassette, Dip Card, Strip formats show similar performance, so a representative example or combined summary is given)
Precision (Accuracy at specific concentrations vs. cutoff)	- Expected 100% negative results for concentrations below cutoff. - Expected 100% positive results for concentrations above cutoff. - Mixed results expected at cutoff (ideally close to 50% positive/negative).	Cassette Example (across 3 lots, 60 tests per lot/concentration) -100% to -50% cut off: 60-/0+ (100% Negative) -25% cut off: 58-60 negative, 0-3 positive (e.g., Lot 2: 58-/2+, Lot 1: 60-/0+, Lot 3: 59-/1+) Cut off: Mixed results (e.g., Lot 1: 38+/22-, Lot 2: 33+/27-, Lot 3: 36+/24-) +25% to +100% cut off: 60+/0- (100% Positive) (Similar performance observed for Dip Card and Strip formats)
Specificity (Cross-reactivity)	No significant interference from tested compounds at physiological/therapeutic concentrations, or clear cross-reactivity profiles are established.	Fentanyl Analogs/Metabolites: - Cyclopropyl fentanyl: 1 ng/mL (100% cross-reactivity) - Acetyl fentanyl: 1 ng/mL (100% cross-reactivity) - Acrylfentanyl: 0.9 ng/mL (111.11% cross-reactivity) - 4-Fluoro-isobutyrylfentanyl: 5 ng/mL (20% cross-reactivity) - Norfentanyl: 30,000 ng/mL (0.003% cross-reactivity) (Extensive list of other non-fentanyl compounds tested at 100 µg/mL showed no cross-reactivity)
Interference	No interference from common endogenous or exogenous substances in urine.	No interference from a wide range of compounds (e.g., acetaminophen, albumin, glucose, ethanol, common drugs) at specified concentrations.
Effect of Urine Specific Gravity & pH	Performance should remain accurate across a range of urine specific gravity and pH values.	All samples (spiked at -50% and +50% Cut-Off levels) tested correctly across ranges of specific gravity (1.000 to 1.035) and pH (4 to 9).
Method Comparison with LC/MS	High concordance with GC/MS (or LC/MS) as the gold standard, especially for samples far from the cutoff. Discrepancies primarily expected around the cutoff.	Cassette Example (80 clinical samples per operator): - 7 Negative, 19 Low Negative: 100% agreement with LC/MS. - Near Cutoff Negative (LC/MS < 1.0 ng/mL): 11-12 Negative, 2-3 Positive (total 14 samples) - Near Cutoff Positive (LC/MS > 1.0 ng/mL): 20-21 Positive, 2-3 Negative (total 23 samples) - 17 High Positive: 100% agreement with LC/MS. (Similar results for Dip Card and Strip formats. Discordant results are concentrated around the cutoff as expected for qualitative tests.)
Lay-User Performance (For OTC products)	High percentage of correct results by untrained lay users following package insert instructions.	Cassette Example (140 lay persons total, 20 samples each concentration): -100% to -25% Cutoff: 100% correct negative results. +25% to +75% Cutoff: 100% correct positive results. (Exceptions for Dip Card: 1 false positive at -25% Cutoff, resulting in 95% correct. Strip: 100% correct across all positive/negative points.)

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

Precision Studies:
- Sample Size: For each of the nine concentrations tested (from -100% cutoff to +100% cutoff), 60 tests were performed per device lot. With 3 lots, this implies 180 tests per concentration per device format (Cassette, Dip Card, Strip). Total for precision studies: 9 concentrations * 60 tests/concentration/lot * 3 lots * 3 formats = 4860 tests.
- Data Provenance: Samples were prepared by spiking fentanyl into negative samples. Concentrations were confirmed by LC/MS. The document does not specify the country of origin, but generally, these types of lab studies for FDA submissions are conducted domestically or in compliant international facilities. These are prospective experiments.
Specificity and Interference Studies:
- Sample Size: "Three batches of each device" were used. The number of individual tests on each substance is not explicitly stated, but it's implied that sufficient replicates were performed to draw conclusions.
- Data Provenance: Substances were added to drug-free urine and target drug fentanyl urine. These are prospective lab experiments.
Method Comparison Studies (Clinical Samples):
- Sample Size: 80 "unaltered clinical samples" were used for each device format (Cassette, Dip Card, Strip). These 80 samples were split into categories: 7 Negative (0 ng/mL), 19 Low Negative, 14 Near Cutoff Negative, 23 Near Cutoff Positive, and 17 High Positive. Each sample was tested by three different operators.
- Data Provenance: "unaltered clinical samples." The document does not specify the country of origin, but implies real-world urine specimens. It is a retrospective evaluation against a confirmed gold standard.
Lay-User Study:
- Sample Size: 140 lay persons participated for each device format (Cassette, Dip Card, Strip). Each participant received 1 blind-labeled sample. The samples themselves were prepared with different fentanyl concentrations, with 20 samples per concentration level.
- Data Provenance: Urine samples were prepared by spiking fentanyl into drug-free pooled urine specimens. Concentrations were confirmed by LC/MS. This is a prospective study involving human subjects (lay users).

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

The ground truth for all performance studies (precision, specificity, interference, method comparison, lay-user study) was established by LC/MS (Liquid Chromatography-Mass Spectrometry) or GC/MS (Gas Chromatography-Mass Spectrometry). These are established analytical chemistry methods considered the "gold standard" for confirming drug concentrations in toxicology.
While these methods require expert chemists/toxicologists to operate and interpret, the document does not specify the "number of experts" or their "qualifications" in the same way one would for clinical image interpretation, as the ground truth is obtained from an analytical instrument, not human interpretation of a test. The results from LC/MS are quantitative and definitive.

4. Adjudication Method for the Test Set

For the analytical performance and method comparison studies, the rapid test results (positive/negative) were directly compared to the quantitative LC/MS results.
For the method comparison study, the results of three different operators were compared for each sample. The tables present the agreement of each operator's reading with the LC/MS result. Discordant results are explicitly listed for each operator involved. There is no mention of an "adjudication method" in the sense of a committee for final decision-making, as the LC/MS result serves as the definitive reference.

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

Not Applicable. This is a rapid diagnostic test (an in-vitro diagnostic device), not an AI/ML SaMD that assists human readers. No MRMC comparative effectiveness study was done for AI assistance, as AI is not part of this device.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

Not Applicable. This is a rapid diagnostic test, interpreted visually by a human (either a trained operator or a lay user). There is no "algorithm" component in this device in the sense of an AI/ML model for standalone performance evaluation. The "test" itself is the standalone device performance when read correctly by a human.

7. The Type of Ground Truth Used

The primary ground truth used throughout the studies was LC/MS (Liquid Chromatography-Mass Spectrometry) or GC/MS (Gas Chromatography-Mass Spectrometry) results. These are highly accurate, quantitative analytical methods for identifying and quantifying substances in a sample.

8. The Sample Size for the Training Set

Not Applicable. This device is a rapid immunoassay test, not an AI/ML algorithm that requires a "training set" in the computational learning sense. The device's "training" would be its manufacturing process and quality control.

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

Not Applicable. As there is no AI/ML training set, this question is not relevant to this device.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.

Healgen Scientific LLC % Joe Shia Director LSI International Inc 504E Diamond Ave., Suite H Gaithersburg, Maryland 20877

Re: K240949

Trade/Device Name: Healgen® Accurate Fentany] Rapid Test Dip Card (Urine); Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine); Healgen® Accurate Fentanyl Rapid Test Strip (Urine); Healgen® Accurate Rapid Fentanyl Test Strip (Urine); Healgen® Accurate Fentanyl Rapid Test Cassette (Urine); Healgen® Accurate Rapid Fentanyl Test Cassette (Urine)

Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: NGL Dated: April 6, 2024 Received: April 8, 2024

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 (the 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 available 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

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Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 mediation-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,

Digitally signed by Joseph A. Kotarek -S

Joseph A. Kotarek -S Date: 2024.05.10 20:14:02 -04'00'

Joseph Kotarek Branch Chief for Toxicology

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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) K240949

Device Name

Healgen® Accurate Fentanyl Rapid Test Dip Card (Urine); Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine) Healgen® Accurate Fentanyl Rapid Test Strip (Urine); Healgen® Accurate Rapid Fentanyl Test Strip (Urine) Healgen® Accurate Fentanyl Rapid Test Cassette (Urine); Healgen® Accurate Rapid Fentanyl Test Cassette (Urine)

Indications for Use (Describe)

The Healgen® Accurate Fentanyl Rapid Test Dip Card (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only preliminary result. A more specific alternative chemical must be used to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Evaluate preliminary positive results carefully.

The Healgen® Accurate Fentanyl Rapid Test Strip (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

The Healgen® Accurate Fentanyl Rapid Test Cassette (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

The Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (CC-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

The Healgen® Accurate Rapid Fentanyl Test Strip (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only a preliminary result. A more specific alternative chemical must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (C-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

The Healge® Accurate Rapid Fentanyl Test Cassette (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (C-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(k) SUMMARY K240949

May 9, 2024 1. Date: Healgen Scientific LLC. 2. Submitter: 3818 Fuqua Street Houston, TX 77047 3. Contact person: Joe Shia LSI International Inc. 504E Diamond Ave., Suite H Gaithersburg, MD 20877 Telephone: 240-505-7880 Email: shiajl@yahoo.com 4. Device Names: Healgen® Accurate Fentanyl Rapid Test Dip Card (Urine) Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine) Healgen® Accurate Fentanyl Rapid Test Strip (Urine) Healgen® Accurate Rapid Fentanyl Test Strip (Urine) Healgen® Accurate Fentanyl Rapid Test Cassette (Urine) Healgen® Accurate Rapid Fentanyl Test Cassette (Urine)

Product Code	Classification	Regulation Section	Panel
NGL	II	21 CFR § 862.3650Opiate Test System	Toxicology (91)

5. Predicate Devices:

AllTest Fentanyl Urine Test Cassette (K233417)

1. Indications for Use
  The Healgen® Accurate Fentanyl Rapid Test Dip Card (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. This test provides only preliminary result. A more specific alternative chemical must be used to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Evaluate preliminary positive results carefully.

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The Healgen® Accurate Rapid Fentanyl Test Dip Card (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (GC-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem massspectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

The Healgen® Accurate Rapid Fentanyl Test Strip (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (GC-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem massspectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

The Healgen® Accurate Rapid Fentanyl Test Cassette (Urine) is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL.

This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (GC-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem massspectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

1. Device Description
  The Healgen® Accurate Fentanyl Tests are immunoassays intended for the qualitative detection of fentanyl in human urine. Each Healgen® Accurate Fentanyl Test consists of a Test Device in format of Cassette or Dip Card or Strip, and a package insert. Each Test Device is sealed with sachets of desiccant in an aluminum pouch.
1. Substantial Equivalence Information
  A summary comparison of features of the Healgen® Accurate Fentanyl Test and the predicate devices is provided in following table.

Item	Device	Predicate – K233417
Indication(s)for Use	For the qualitative determination offentanyl in human urine.	Same
Calibrator and Cut-OffValues	Fentanyl (FTY)1 ng/ml	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same

Table 1: Features Comparison of Healgen® Accurate Fentanyl Test and the Predicate Device

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Specimen Type	Human Urine	Same
Intended Use	For OTC use	Same
Configurations	Cassette, Dip Card, Strip	Cassette
Storage	4-30°C	Same

1. Test Principle
  The Healgen® Accurate Fentanyl Tests are immunoassays based on the principle of competitive binding.

During testing, a urine specimen migrates upward by capillary action. Fentanyl, if present in the urine specimen below 1 ng/mL, will not saturate the binding sites of antibody-coated particles in the test device. The antibody-coated particles will then be captured by immobilized fentanyl conjugate and a visible colored line will show up in the test line region. The colored line will not form in the test line region if the fentanyl level exceeds 1 ng/mL because it will saturate all the binding sites of anti-fentanyl antibodies.

To serve as a procedural control, a colored line will always appear at the control line region indicating that proper volume of specimen has been added and membrane wicking has occurred.

10. Performance Characteristics

1. Analytical Performance
- a. Precision

Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cut off, +25% cut off, +50% cut off, +75% cut off and +100% cut off. These samples were prepared by spiking fentanyl in negative samples. Each fentanyl concentration was confirmed by LC/MS. All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing. For each concentration, tests were performed two tests per day for 10 days per device lot in a randomized order.

LotNumber	-100%cut off	-75%cut off	-50%cut off	-25%cutoff	cut off	+25%cut off	+50%cut off	+75%cut off	+100%cut off
Lot 1	60-/0+	60-/0+	60-/0+	60-/0+	38+/22-	60+/0-	60+/0-	60+/0-	60+/0-
Lot 2	60-/0+	60-/0+	60-/0+	58-/2+	33+/27-	60+/0-	60+/0-	60+/0-	60+/0-
Lot 3	60-/0+	60-/0+	60-/0+	59-/1+	36+/24-	60+/0-	60+/0-	60+/0-	60+/0-

Dip Card

Lot Number	-100% cut off	-75% cut off	-50% cut off	-25% cutoff	+25% cut off	+50% cut off	+75% cut off	+100% cut off
Lot 1	60-/0+	60-/0+	60-/0+	58-/2+	36+/24-	60+/0-	60+/0-	60+/0-
Lot 2	60-/0+	60-/0+	60-/0+	60-/0+	38+/22-	60+/0-	60+/0-	60+/0-
Lot 3	60-/0+	60-/0+	60-/0+	59-/1+	33+/27-	60+/0-	60+/0-	60+/0-

Strip

LotNumber	-100%cut off	-75%cut off	-50%cut off	-25%cutoff	cut off	+25%cut off	+50%cut off	+75%cut off	+100%cut off
Lot 1	60-/0+	60-/0+	60-/0+	57-/3+	34+/26-	60+/0-	60+/0-	60+/0-	60+/0-
Lot 2	60-/0+	60-/0+	60-/0+	60-/0+	35+/25-	60+/0-	60+/0-	60+/0-	60+/0-
Lot 3	60-/0+	60-/0+	60-/0+	60-/0+	38+/22-	60+/0-	60+/0-	60+/0-	60+/0-

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c. Stability
The devices are stable at 36-86F for 24 months based on the real-time stability study.

d. Interference

Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drug fentanyl urine with concentrations at 50% below and 50% above Cut-Off levels. These urine samples were tested using three batches of each device. Compounds that showed no interference at a concentration of 100µg/mL or specified concentrations are summarized in the following tables.

Acetaminophen	Doxepin	Nortriptyline
Acetone (1000 mg/dL)	Ecgonine methyl ester	Noscapine
Acetophenetidin	Ephedrine	O-Hydroxyhippuric acid
Acetylsalicylic acid	Erythromycin	Octopamine
Albumin (100 mg/dL)	Ethanol (1%)	Oxalic acid (100 mg/dL)
Albuterol	Fenoprofen	Oxazepam
Aminopyrine	Fluphenazine	Oxolinic acid
Amitriptyline	Furosemide	Oxymetazoline
Amobarbital	Galactose (10 mg/dL)	Papaverine
Amoxicillin	Gamma globulin (500 mg/dL)	Penicillin G
Ampicillin	Gentisic acid	Perphenazine
Apomorphine	Glucose (3000 mg/dL)	Phencyclidine
Ascorbic Acid	Hemoglobin	Phenelzine
Aspartame	Hydralazine	Phenobarbital
Atropine	Hydrochlorothiazide	Prednisone
Benzilic acid	Hydrocortisone	Propoxyphene
Benzoic acid	Hydroxytyramine	Propranolol
Benzoylecgonine	Ibuprofen	Pseudoephedrine
Bilirubin	Imipramine	Quinine
Boric acid (1% w/v)	Isoproterenol	Ranitidine
Bupropion	Isoxsuprine	Riboflavin (10 mg/dL)
Caffeine	Ketamine	Salicylic acid
Carbamazepine	Ketoprofen	Secobarbital
Chloral hydrate	Labetalol	Serotonin (5-hydroxytyramine)
Chloramphenicol	Lidocaine	Sulfamethazine
Chlorothiazide	Loperamide	Sulindac
Chlorpromazine	Maprotiline	Tetrahydrocortisone 3-(β-Dglucuronide)
Cholesterol	Meperidine	Tetrahydrocortisone 3-acetate
Clomipramine	Meprobamate	Tetrahydrozoline
Clonidine	Methapyrilene	Thiamine
Cortisone	Methaqualone	Thioridazine
Cotinine	Methoxyphenamine	Triamterene
Creatinine	Metronidazole (300 µg/mL)	Trifluoperazine
Cyclobenzaprine	N-Acetylprocainamide	Trimethoprim
Deoxycorticosterone	NaCl (4000 mg/dL)	Tyramine
Desipramine	Nalidixic acid	Urea (2000 mg/dL)
Dextromethorphan	Naloxone	Uric acid
Diclofenac	Naltrexone	Valproic acid (250 µg/mL)
Diflunisal	Naproxen	Venlafaxine
Digoxin	Niacinamide	Verapamil
Diphenhydramine	Nicotine	Zomepirac
DL-Tryptophan	Nifedipine	ß-Estradiol
DL-Tyrosine	Norethindrone

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

e.Specificity

To test specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of device. The lowest concentration that caused a positive result for each compound are listed below. There are no differences in the test results for different device format.

Fentanyl (Cutoff=1ng/mL)	Minimumconcentration requiredto obtain a positiveresult (ng/mL)	% Cross-Reactivity
Norfentanyl	30,000	0.003%
Carfentanil	8,000	0.013%
Sufentanil	50,000	0.002%
Cyclopropyl fentanyl	1	100%
Furanyl Fentanyl	10	10%
Para-fluorobutyryl fentanyl	10	10%
4-Fluoro-isobutyrylfentanyl	5	20%
O-Fluorofentanyl	10	10%
2'-Fluoro ortho-Fluorofenyanyl	10	10%
Valeryl Fentanyl	5	20%
(±) β-hydroxythiofentanyl	3	33.33%
Tetrahydrofuranyl fentanyl	1.56	64.10%
2-Thiofuranyl fentanyl	5	20%
Methoxyacetyl fentanyl	1.56	64.10%
4-methoxybutyryl fentanyl (para)	20	5%
N-methyl norfentanyl	20,000	0.005%
3',4'-dimethoxy Fentanyl	125	0.8%
Acetyl-α-methyl fentanyl	62.5	1.6%
4'-methyl acetyl fentanyl	125	0.8%
Benzyl fentanyl	125	0.8%
Meta-methoxy Furanyl fentanyl	100	1%
α-methyl fentanyl	62.5	1.6%
Para-fluoro fentanyl	1	100%
Ocfentanil	5	20%
Isobutyryl fentanyl	2.5	40%
Butyryl fentanyl	3	33.33%
Acetyl fentanyl	1	100%
Acrylfentanyl	0.9	111.11%
Risperidone	50,000	0.002%
9-Hydroxyrisperidone	10,000	0.01%
(±)-3-cis-methyl fentanyl	50	2%
Despropionyl fentanyl (4-ANPP)	7000	0.014%

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

ω-1-Hydroxyfentanyl	50,000	0.002%
Acetyl norfentanyl	>100 µg/mL	<0.001%
Norcarfentanil	>100 µg/mL	<0.001%
Remifentanil	>100 µg/mL	<0.001%
Alfentanil	>100 µg/mL	<0.001%

The following opioids compounds were tested at a concentration of 100ug/mL. Negative results were obtained for all these compounds. There is no cross-reactivity for these compounds using the Healgen® Accurate Fentanyl Tests of all three device formats.

6-Acetyl morphine	Naltrexone
Amphetamine	Norbuprenorphine
Buprenorphine	Norcodeine
Buprenorphineglucuronide	Norketamine
Codeine	Normeperidine
Dextromethorphan	Normorphine
Dihydrocodeine	Noroxycodone
EDDP	Oxycodone
EMDP	Oxymorphone
Fluoxetine	Pentazocine (Talwin)
Heroin	Pipamperone
Hydrocodone	Risperidone
Hydromorphone	Tapentadol
Ketamine	Thioridazine
Levorphanol	Tilidine
Meperidine	Tramadol
Methadone	Tramadol-O-Desmethyl
Morphine	Tramadol-N-Desmethyl
Morphine-3-glucuronide	Trazodone
Naloxone

f. Effect of Urine Specific Gravity and Urine pH

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 4 to 9 were spiked with target fentanyl at 50% below and 50% above Cut-Off levels. These samples were tested using three lots of device. Results were all positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off. There are no differences in the test results for different device format.

2. Comparison Studies

Method comparison studies for the Healgen® Accurate Fentanyl Test were performed using three different lots of the device. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were blind labeled and compared to LC/MS results are presented in the tables below.

Cassette

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

		Negative	LowNegative byLC/MS(less than-50%)	Near CutoffNegative byLC/MS(Between-50% andcutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator1	Positive	0	0	3	21	17
	Negative	7	19	11	2	0
Operator2	Positive	0	0	2	21	17
	Negative	7	19	12	2	0
Operator3	Positive	0	0	2	20	17
	Negative	7	19	12	3	0

Discordant Results

Operator	Sample ID	LC/MS Result (ng/mL)	Rapid Test Result
Operator 1, 3	FENM128	0.928	Positive
Operator 1, 2	FENM148	0.946	Positive
Operator 2	FENM107	0.863	Positive
Operator 1, 3	FENM156	0.983	Positive
Operator 1, 3	FENM132	1.016	Negative
Operator 2, 3	FENM129	1.085	Negative
Operator 1	FENM171	1.094	Negative
Operator 2, 3	FENM120	1.119	Negative

Dip Card

		Negative	LowNegative byLC/MS(less than-50%)	Near CutoffNegative byLC/MS(Between-50% andcutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator1	Positive	0	0	3	22	17
	Negative	7	19	11	1	0
Operator2	Positive	0	0	4	21	17
	Negative	7	19	10	2	0
Operator3	Positive	0	0	1	19	17
	Negative	7	19	13	4	0

Discordant Results

Operator	Sample ID	LC/MS Result (ng/mL)	Rapid Test Result
Operator 2	FENM028	0.817	Positive
Operator 3	FENM010	0.829	Positive
Operator 1	FENM022	0.863	Positive
Operator 1, 2	FENM050	0.928	Positive

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

Operator 2	FENM014	0.946	Positive
Operator 1, 2	FENM013	0.983	Positive
Operator 1, 2, 3	FENM021	1.016	Negative
Operator 3	FENM045	1.085	Negative
Operator 2	FENM054	1.094	Negative
Operator 3	FENM041	1.119	Negative
Operator 3	FENM026	1.121	Negative

Strip

		Negative	LowNegative byLC/MS(less than-50%)	Near CutoffNegative byLC/MS(Between-50% andcutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator1	Positive	0	0	2	22	17
	Negative	7	19	12	1	0
Operator2	Positive	0	0	3	21	17
	Negative	7	19	11	2	0
Operator3	Positive	0	0	1	21	17
	Negative	7	19	13	2	0

Discordant Results

Operator	Sample ID	LC/MS Result (ng/mL)	Rapid Test Result
Operator 2	FENM450	0.829	Positive
Operator 2	FENM478	0.863	Positive
Operator 1	FENM413	0.928	Positive
Operator 2	FENM442	0.946	Positive
Operator 1, 3	FENM414	0.983	Positive
Operator 1	FENM426	1.016	Negative
Operator 2, 3	FENM449	1.085	Negative
Operator 3	FENM454	1.094	Negative
Operator 2	FENM430	1.119	Negative

3. Lay-user study

A lay user study was performed at three intended user sites with 140 lay persons for each device format. They had diverse educational and professional backgrounds and ranged in age from 18 to >50 years. Urine samples were prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cut-off by spiking fentanyl into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:

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

Cassette

ันมมั่น และ	Numberofsamples	Fentanyl Concentrationby LC/MS(ng/mL)	Lay person results		The
% of Cutoff			No. ofPositive	No. ofNegative	percentage ofcorrect results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	0.252	0	20	100
-50% Cutoff	20	0.506	0	20	100
-25% Cutoff	20	0.735	0	20	100
+25% Cutoff	20	1.241	20	0	100
+50% Cutoff	20	1.492	20	0	100
+75% Cutoff	20	1.727	20	0	100
Dip Card
	Number	Fentanyl Concentration	Lay person results		The
% of Cutoff	of	by LC/MS	No. of	No. of	percentage of
	samples	(ng/mL)	Positive	Negative	correct results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	0.252	0	20	100
-50% Cutoff	20	0.506	0	20	100
-25% Cutoff	20	0.735	l	19	તેર
+25% Cutoff	20	1.241	20	0	100
+50% Cutoff	20	1.492	20	0	100
+75% Cutoff	20	1.727	20	0	100
Strip
	Number	Fentanyl Concentration	Lay person results		The
% of Cutoff	of	by LC/MS			percentage of
	samples	(ng/mL)	No. ofPositive	No. of	correct results
				Negative	(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	0.252	0	20	100
-50% Cutoff	20	0.506	0	20	100
-25% Cutoff	20	0.735	0	20	100
+25% Cutoff	20	1.241	20	0	100
+50% Cutoff	20	1.492	20	0	100
+75% Cutoff	20	1.727	20	0	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.

4. Clinical Studies

Not applicable.

11. Conclusion

Based on the test principle and acceptable performance characteristics including precision, cut-off, interference, specificity, method comparison and Lay-user studies of the devices, it's concluded a substantial equivalence decision.

Regulation Number and Section

§ 862.3650 Opiate test system.

(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).