Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel; Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel

K241969 · Qingdao Hightop Biotech Co., Ltd. · NGL · Aug 14, 2024 · Clinical Toxicology

Device Facts

• Record ID: K241969
• Device Name: Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel; Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel
• Applicant: Qingdao Hightop Biotech Co., Ltd.
• Product Code: NGL · Clinical Toxicology
• Decision Date: Aug 14, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Indications for Use

Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl and norfentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below: Analyte Cut-off Level Fentanyl (FYL) 1ng/mL Norfentanyl (NFYL) 5ng/mL The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL. It is intended for OTC use. The test provides only a preliminary test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl and norfentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below: Analyte Calibrator Cut-off Level Fentanyl (FYL) Fentanyl 1ng/mL Norfentanyl (NFYL) Norfentanyl 5ng/mL The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL. The test panel provides only a preliminary test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. The test panel is not intended to distinguish between prescription use or abuse of fentanyl. Clinical consideration and professional judgment should be applied to the test result, particularly in evaluating a preliminary positive result.

Device Story

Lateral flow immunochromatographic assay; detects fentanyl (1 ng/mL) and norfentanyl (5 ng/mL) in human urine. Principle: competitive binding; urine migrates via capillary action; target drugs below cutoff allow antibody-coated particles to bind immobilized drug conjugate, forming visible colored line; drug levels exceeding cutoff saturate binding sites, preventing line formation. Procedural control line confirms proper wicking. Used in home settings by lay users; OTC availability. Results provide preliminary screening; requires professional confirmatory testing (GC/MS or LC/MS). Clinical decision-making relies on professional judgment following preliminary positive results.

Clinical Evidence

Bench testing only. Precision/reproducibility studies conducted over 10 days with three operators using spiked urine samples. Analytical specificity and cross-reactivity evaluated against numerous compounds. Method comparison study performed with 80 clinical samples compared to LC/MS. Lay-user study (n=140) demonstrated high accuracy (95-100%) across various concentrations relative to cut-offs. No clinical sensitivity/specificity studies required for this assay type.

Technological Characteristics

Lateral flow immunochromatographic assay; competitive binding principle. Form factor: test panel. Storage: 2-30°C. No electronic components, energy source, or software algorithms. Qualitative visual readout.

Indications for Use

Indicated for qualitative detection of fentanyl and norfentanyl in human urine for OTC home use or professional use. Intended for preliminary screening; requires confirmatory testing via GC/MS or LC/MS. Not intended to distinguish between prescription use and abuse.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• AllTest Fentanyl Urine Test Cassette (K233417)

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K241969

B Applicant

Qingdao HIGHTOP Biotech Co., Ltd.

C Proprietary and Established Names

Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel; Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| NGL | Class II | 21 CFR 862.3650 - Opiate Test System | TX - Clinical Toxicology |

## II Submission/Device Overview:

A Purpose for Submission:

New Device

B Measurand:

Fentanyl and Norfentanyl

C Type of Test:

lateral flow immunochromatographic assay

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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K241969 - Page 2 of 13

# III Intended Use/Indications for Use:

## A Intended Use(s):

See Indications for Use below.

## B Indication(s) for Use:

Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl and norfentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:

Analyte Cut-off Level

Fentanyl (FYL) 1ng/mL

Norfentanyl (NFYL) 5ng/mL

The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL. It is intended for OTC use.

The test provides only a preliminary test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.

Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl and norfentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:

Analyte Calibrator Cut-off Level

Fentanyl (FYL) Fentanyl 1ng/mL

Norfentanyl (NFYL) Norfentanyl 5ng/mL

The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL.

The test panel provides only a preliminary test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.

The test panel is not intended to distinguish between prescription use or abuse of fentanyl. Clinical consideration and professional judgment should be applied to the test result, particularly in evaluating a preliminary positive result.

## C Special Conditions for Use Statement(s):

OTC - Over The Counter

## D Special Instrument Requirements:

Not applicable

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# IV Device/System Characteristics:

# A Device Description:

The Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel and Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel are immunoassays intended for the qualitative detection of fentanyl and norfentanyl in human urine. Each Hightop® fentanyl/norfentanyl urine test device consists of a Test Panel and a package insert. Each Test Panel is sealed with sachets of desiccant in an aluminum pouch.

# B Principle of Operation:

These devices are rapid lateral flow immunoassays. To perform the test, the user will pull off the cap on the device and activate the test by dipping the sample pads into human urine sample for 5-10 seconds. Urine sample will be absorbed by the sample pad and move up to the conjugate pad that contains anti-drug antibody colloidal gold conjugates. The urine sample will continue to move up to the nitrocellulose membrane where drug protein is coated onto the Test Region. If there is no drug present or the drug concentration in the specimen is below cutoff level, the red colloidal gold conjugate will bind to the drug conjugate at the Test Region, to form a visible band which indicated a negative result. If there is drug present in the specimen at above cutoff level, the drug will bind to the limited antibodies on colloidal gold, leaving no antibody available for binding to the drug conjugates on membrane. Thus, the absences of a test line band present at Test Region indicates a presumptive positive result for that drug.

The Control Region is to indicate that the test has performed properly and should appear regardless of the presence of the drug. This is a built-in internal control of the device. If control line does not appear, the test result is invalid.

# V Substantial Equivalence Information:

# A Predicate Device Name(s):

AllTest Fentanyl Urine Test Cassette

# B Predicate 510(k) Number(s):

K233417

# C Comparison with Predicate(s):

| Device & Predicate Device(s): | K241969 | K233417 |
| --- | --- | --- |
| Device Trade Name | Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel | AllTest Fentanyl Urine Test Cassette |
| General Device | | |

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| Characteristic Similarities | | |
| --- | --- | --- |
| Intended Use/Indications For Use | For the qualitative determination of fentanyl in human urine. | Same |
| Methodology | Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry. | Same |
| Specimen Type | Urine | Same |
| General Device Characteristic Differences | | |
| Calibrator and Cut-Off Values | Fentanyl (FTY) 1 ng/ml
Norfentanyl (NFTY) 5 ng/ml | Fentanyl (FTY) 1 ng/ml |
| Configuration | Panel | Cassette |

VI Standards/Guidance Documents Referenced:

Not applicable.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

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 for each target drug. These samples were prepared by spiking fentanyl or norfentanyl in negative urine samples. Each fentanyl or norfentanyl 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. Three operators tested blinded urine samples over a 10-day period in randomized order with six tests per day per concentration per lot per operator (6 replicate per day per lot x 9 concentrations) for a total of 54 tests per day per operator.

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Fentanyl

| Lot Number | -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+ | 40+/20- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 38+/22- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 38+/22- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |

Norfentanyl

| Lot Number | -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+ | 58-/2+ | 35+/25- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 58-/2+ | 32+/28- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 33+/27- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |

2. Linearity:

Not applicable. These devices are intended for qualitative use only.

3. Analytical Specificity/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 | Ecgonine methyl ester | Oxolinic acid |
| --- | --- | --- |
| Acetone (1000 mg/dL) | Ephedrine | Oxymetazoline |
| Acetophenetidin | Erythromycin | Papaverine |
| Acetylsalicylic acid | Estradiol | Penicillin G |
| Albumin (100 mg/dL) | Estrone | Perphenazine |
| Albuterol | Ethanol (1%) | Phencyclidine |
| 7-Aminonitrazepam | Fenfluramine | Phenelzine |
| Amitriptyline | Fenofibrate | Phenobarbital |
| Amlodipine besylate | Fenoprofen | Phentermine |
| Amobarbital | Fluphenazine | Phenylethylamine |
| Amoxicillin | Fotemustine | Prednisone |
| Ampicillin | Furosemide | Promazine |
| Apomorphine | Galactose | Promethazine |
| Ascorbic acid | γ-Globulin (500 mg/dL) | Propoxyphene |
| Aspartame | Gemfibrozil | Propranolol |
| Aspirin | Gentisic acid | Pseudoephedrine |
| Atropine | Glucose (3000 mg/dL) | Pyridoxine |

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| Baclofen | Guaiacolglyceryl ether | Pyrilamine |
| --- | --- | --- |
| Benzilic acid | Hemoglobin | Pyrogallol |
| Benzocaine | Hexobarbital | Quinidine |
| Benzoic acid | Hydralazine | Quinine |
| Benzoylecgonine | Hydrochlorothiazide | Quinolinic Acid |
| Benzylpiperazine | Hydrocortisone | Ranitidine |
| Bilirubin | Hydroxybutyric Acid | Riboflavin |
| Boric Acid (1%) | Ibuprofen | Salicylic acid |
| Bromo-2,5,Dimethoxyphenethylamine | Imipramine | Secobarbital |
| Bupropion | Isoproterenol | Serotonin |
| Caffeine | Isoxsuprine (10 µg/mL) | Sodium Azide |
| Carbamazepine | Ketoprofen | Sulfamethazine |
| Carisoprodol | Labetalol | Sulindac |
| Cetirizine | Lamotrigine | Tetracycline |
| Chloral hydrate | Lidocaine | Tetrahydrocortisone3-(β-Dglucuronide) |
| Chloramphenicol | Lisinopril | Tetrahydrocortisone 3-acetate |
| Chlordiazepoxide | Loperamide | Tetrahydrozoline |
| Chlorothiazide | Loratidine | Thiamine |
| Chlorpheniramine | Maprotiline | Triamterene |
| Chlorpromazine | Meperidine | Trifluoperazine |
| Cholesterol | Meprobamate | Trifluoromethylphenyl-piperazine |
| Clofibrate | Methapyrilene | Trimethoprim |
| Clomipramine | Methaqualone | Tryptamine |
| Clonidine | Methoxyphenamine | Tyramine |
| Cortisone | Methylphenidate | Urea (2000 mg/dL) |
| Cotinine | Metoprolol | Uric acid |
| Creatine Hydrate | Metronidazole | Valproic acid (250 µg/mL) |
| Creatinine | N-Acetylprocainamide | Venlafaxine |
| Cyclobenzaprine | N-desmethyl Tapentadol | Verapamil |
| γ-Cyclodextrin | Nacl (4000 mg/dL) | Zolpidem |
| Cyproheptadine | Nalidixic acid | Zomepirac |
| Demoxepam | Naproxen | 7-Aminoflunitrazepam |
| Deoxycorticosterone | Niacinamide | Metformin |
| Desipramine | Nicotine | Norpeudopephedrine |
| Diclofenac | Nicotinic Acid | Oxazepam Glucuronide |
| Diflunisal | Nifedipine | Lorazepam Glucuronide |
| Digoxin | Norethindrone | LSD |
| Dimethyl-aminoantipyrine | Norpropoxyphene | THC |
| Diphenhydramine | Nortriptyline | L-thyroxine |
| Diphenylhydantoin | Noscapine | Dextromethorphan |
| DL-Tryptophan | O-Hydroxyhippuric acid | Ketamine |
| DL-Tyrosine | Octopamine | Thioridazine |

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| Dopamine (Hydroxytyramine) | Oxalic acid (100mg/dL) | |
| --- | --- | --- |
| Doxepin | Oxazepam | |

## Specificity

To test specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of the device. The lowest concentration that caused a positive result for each compound are listed below. If no cross reactivity was observed the highest concentration tested is shown.

| Fentanyl (Cutoff=1ng/mL) | Minimum concentration required to obtain a positive result (ng/mL) | % Cross-Reactivity |
| --- | --- | --- |
| Fentanyl | 1 | 100 |
| Norfentanyl | >100000 | <0.001 |
| 4-Fluoro-isobutyryl fentanyl | 200 | 0.5 |
| 9-Hydroxy Risperidone | 10000 | 0.01 |
| Acetyl fentanyl | 5 | 20 |
| Acetyl Norfentanyl | >100000 | <0.001 |
| (±)-β-hydroxythiofentanyl | 25 | 4 |
| Acryl fentanyl | 5 | 20 |
| Alfentanil | 10000 | 0.01 |
| Butyryl fentanyl | 10 | 10 |
| Carfentanil | 10 | 10 |
| (±)-cis-3-methylfentanyl | 1000 | 0.1 |
| Despropionyl fentanyl (4-ANPP) | 10000 | 0.01 |
| Furanyl Fentanyl | 20 | 5 |
| Isobutyryl Fentanyl | 50 | 2 |
| Labetalol Hydrochloride | >100000 | <0.001 |
| MT-45 | 10000 | 0.01 |
| Norcarfentanil | >20000 | <0.005 |
| Ocfentanil | 1000 | 0.1 |
| Para-fluorobutyryl Fentanyl (PFBF) | 20 | 5 |
| Para-fluoro Fentanyl | 20 | 5 |
| Remifentanil | >20000 | <0.005 |
| Risperidone | 1000 | 0.1 |
| Sufentanil | 1000 | 0.1 |
| Thienyl Fentanyl | 1000 | 0.1 |
| Trans-d, I 3-Methylfentanyl | 1000 | 0.1 |
| Trazodone | 1000 | 0.1 |
| U-47700 | >100000 | <0.001 |

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| Fentanyl (Cutoff=1ng/mL) | Minimum concentration required to obtain a positive result (ng/mL) | % Cross-Reactivity |
| --- | --- | --- |
| Valeryl fentanyl | 50 | 2 |
| ω-1-Hydroxyfentanyl | >20000 | <0.005 |
| Norfentanyl (Cutoff=5ng/mL) | Minimum concentration required to obtain a positive result | %Cross-Reactivity |
| --- | --- | --- |
| Norfentanyl | 5 | 100 |
| Fentanyl | 9 | 55.6 |
| 4-Fluoro-isobutyryl fentanyl | >20,000 | <0.025 |
| 9-Hydroxy Risperidone | 10,000 | 0.05 |
| Acetyl fentanyl | 150 | 3.3 |
| Acetyl Norfentanyl | 200 | 2.5 |
| (±)-β-hydroxythiofentanyl | 20 | 25 |
| Acryl fentanyl | 50 | 10 |
| Alfentanil | 1,000 | 0.5 |
| Butyryl fentanyl | 10 | 50 |
| Carfentanil | 10,000 | 0.05 |
| (±)-cis-3-methylfentanyl | 50 | 10 |
| Despropionyl fentanyl (4-ANPP) | >20,000 | <0.025 |
| Furanyl Fentanyl | 50 | 10 |
| Isobutyryl Fentanyl | 1,000 | 0.5 |
| Labetalol Hydrochloride | >100,000 | <0.005 |
| MT-45 | 5,000 | 0.1 |
| Norcarfentanil | >20,000 | <0.025 |
| Ocfentanil | 500 | 1 |
| Para-fluorobutyryl Fentanyl (PFBF) | 20 | 25 |
| Para-fluoro Fentanyl | 10 | 50 |
| Remifentanil | 10,000 | 0.05 |
| Risperidone | 1,000 | 0.5 |
| Sufentanil | 1000 | 0.5 |
| Thienyl Fentanyl | 50 | 10 |
| Trans-d, I 3-Methylfentanyl | 50 | 10 |
| Trazodone | 10,000 | 0.05 |
| U-47700 | >100,000 | <0.005 |
| Valeryl fentanyl | >20,000 | <0.025 |
| ω-1-Hydroxyfentanyl | >20,000 | <0.025 |

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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 Hightop® Device.

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

## Effect of Urine Specific Gravity and Urine pH

To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.000, 1.003, 1.006, 1.009, 1.011, 1.014, 1.017, 1.02, 1.023, 1.027, 1.031, and 1.035 specific gravity or urine samples with pH 4, 5, 6, 7, 8, and 9 were spiked with targets fentanyl and norfentanyl 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-Offs and all negative for samples at and below -50% Cut-Offs.

## Read Time Study

Fentanyl and Norfentanyl Standards with concentrations of -50% cutoff, +50% cutoff, and drug free urine were tested using three lots of the device and read at 10 time points (i.e. 3rd, 4th, 5th, 10th, 15th, 20th, 25th, 30th, 35th, 40th minutes) by three different operators according to procedures in the product insert. All the results were consistent with the required reading time at 5 minutes and not more than 10 minutes.

## 4. Assay Reportable Range:

Characterization of how the device performs analytically around the claimed cutoff concentration appears in the precision section VII.A.1 above.

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

All drug calibrators of the device are traceable to available commercial reference materials.

6. Detection Limit:

Characterization of how the device performs at low concentrations appears in the precision section VII.A.1 above.

7. Assay Cut-Off:

Characterization of how the device performs analytically around the claimed cutoff concentration appears in the precision section VII.A.1 above.

B Comparison Studies:

1. Method Comparison with Predicate Device:

Method comparison studies for 1 lot of the Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel were performed by three different operators. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were blind labeled and compared to LC/MS results. The results are presented in the tables below.

Fentanyl

| | | Negative | Low Negative by LC/MS (less than -50%) | Near Cutoff Negative by LC/MS (Between -50% and cutoff) | Near Cutoff Positive by LC/MS (Between the cutoff and +50%) | High Positive by LC/MS (greater than +50%) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator 1 | Positive | 0 | 0 | 2 | 19 | 20 |
| | Negative | 10 | 13 | 15 | 1 | 0 |
| Operator 2 | Positive | 0 | 0 | 2 | 19 | 20 |
| | Negative | 10 | 13 | 15 | 1 | 0 |
| Operator 3 | Positive | 0 | 0 | 1 | 19 | 20 |
| | Negative | 10 | 13 | 16 | 1 | 0 |

Discordant Results

| Operator | Sample ID | LC/MS Result (ng/mL) | Rapid Test Result |
| --- | --- | --- | --- |
| Operator 1, 3 | SE086 & SE156 | 0.7880 | Positive |

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| Operator | Sample ID | LC/MS Result (ng/mL) | Rapid Test Result |
| --- | --- | --- | --- |
| Operator 1, 2 | SE052 &SE169 | 0.7912 | Positive |
| Operator 1 | SE031 | 1.0078 | Negative |
| Operator 2 | SE110 | 0.7874 | Positive |
| Operator 2 | SE182 | 1.0282 | Negative |
| Operator 3 | SE240 | 1.0811 | Negative |

Norfentanyl

| | | Negative | Low Negative by LC/MS (less than -50%) | Near Cutoff Negative by LC/MS (Between -50% and cutoff) | Near Cutoff Positive by LC/MS (Between the cutoff and +50%) | High Positive by LC/MS (greater than +50%) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator 1 | Positive | 0 | 0 | 1 | 19 | 20 |
| | Negative | 10 | 13 | 16 | 1 | 0 |
| Operator 2 | Positive | 0 | 0 | 2 | 18 | 20 |
| | Negative | 10 | 13 | 15 | 2 | 0 |
| Operator 3 | Positive | 0 | 0 | 1 | 19 | 20 |
| | Negative | 10 | 13 | 16 | 1 | 0 |

Discordant Results

| Operator | Sample ID | LC/MS Result (ng/mL) | Rapid Test Result |
| --- | --- | --- | --- |
| Operator 1, 2 | SF133 & SF107 | 4.6743 | Positive |
| Operator 1 | SF016 | 5.1608 | Negative |
| Operator 2, 3 | SF201 & SF219 | 4.1946 | Positive |
| Operator 2 | SF231 | 5.1303 | Negative |
| Operator 2, 3 | SF088 & SF221 | 5.0744 | Negative |

2. Matrix Comparison:

Not applicable. These devices are for use with urine samples only.

C Clinical Studies:

1. Clinical Sensitivity:

Not applicable.

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2. Clinical Specificity:

Not applicable.

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

A lay user study was performed at three testing sites representative of intended use sites with 140 lay users. The lay users had diverse educational and professional backgrounds and ranged in age from 18 to &gt;50 years. Three lots of the device were used in the study. Urine samples were prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cut-offs by spiking drug(s) 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:

| % of Cutoff | Number of samples | Fentanyl Concentration by LC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100.0% |
| -75% Cutoff | 20 | 0.24 | 0 | 20 | 100.0% |
| -50% Cutoff | 20 | 0.47 | 0 | 20 | 100.0% |
| -25% Cutoff | 20 | 0.72 | 0 | 20 | 100.0% |
| +25% Cutoff | 20 | 1.21 | 20 | 0 | 100.0% |
| +50% Cutoff | 20 | 1.50 | 20 | 0 | 100.0% |
| +75% Cutoff | 20 | 1.81 | 20 | 0 | 100.0% |
| % of Cutoff | Number of samples | Norfentanyl Concentration by LC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100.0% |
| -75% Cutoff | 20 | 1.33 | 0 | 20 | 100.0% |
| -50% Cutoff | 20 | 2.63 | 0 | 20 | 100.0% |
| -25% Cutoff | 20 | 4.06 | 1 | 19 | 95.0% |
| +25% Cutoff | 20 | 6.03 | 20 | 0 | 100.0% |
| +50% Cutoff | 20 | 7.29 | 20 | 0 | 100.0% |
| +75% Cutoff | 20 | 9.08 | 20 | 0 | 100.0% |

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

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Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7.

**D Clinical Cut-Off:**
Not applicable.

**E Expected Values/Reference Range:**
Not applicable.

**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.

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