Labcorp Fentanyl Urine Visual Test

{0} FDA U.S. FOOD &amp; DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K252684 B Applicant MEDTOX Diagnostics, Inc. C Proprietary and Established Names Labcorp Fentanyl Urine Visual Test D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | DJG | Class II | 21 CFR 862.3650 - Opiate Test System | TX - Clinical Toxicology | ## II Submission/Device Overview: A Purpose for Submission: New device B Measurand: Norfentanyl C Type of Test: Qualitative ## III Intended Use/Indications for Use: A Intended Use(s): See Indications for Use below. B Indication(s) for Use: Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} The Labcorp Fentanyl Urine Visual Test is a lateral flow competitive immunoassay for the rapid qualitative detection of norfentanyl (fentanyl metabolite) in human urine at a cutoff of 5 ng/mL. It is intended for prescription use. For in vitro diagnostic use only. This test provides only a preliminary result. Clinical consideration and professional judgment must be applied to any drug test result, particularly in evaluating a preliminary positive result. To confirm preliminary positive results, a more specific analytical method must be used. Gas Chromatography-Mass Spectrometry (GC-MS), Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS), and High Performance Liquid Chromatography (HPLC) are the preferred confirmatory methods. ## C Special Conditions for Use Statement(s): Rx - For Prescription Use Only ## D Special Instrument Requirements: This 510(k) premarket submission for the Labcorp Fentanyl Urine Visual Test assay only. ## IV Device/System Characteristics: ### A Device Description: The Labcorp Fentanyl Urine Visual Test is a lateral flow competitive immunoassay for the rapid qualitative detection of Norfentanyl (nFEN), the primary urinary metabolite of Fentanyl, in human urine at concentrations above 5 ng/mL. It is intended for prescription use. The single-use, in vitro diagnostic device is available in a cassette format with a disposable dropper provided for sample transfer. The Labcorp Fentanyl Urine Visual Test contains a test strip that gives a qualitative result for presence of Norfentanyl in human urine. The test is read visually and has labeling with instructions for interpreting test results. ### B Principle of Operation: The Labcorp Fentanyl Urine Visual Test uses lateral flow immunoassay technology in which a modified drug (drug-protein conjugate) completes with drug that may be present in the urine. The colorless drug-protein conjugate is applied to the membrane of the test strip at the test line position. The colored drug-specific antibody-colloidal gold is applied to the sample pad of the test strip. When urine is transferred onto the sample pad it dissolves and migrates the colored antibody-colloidal gold across the strip membrane. If drug is not present or is below the cutoff, the drug-specific antibodies will bind to the conjugate line on the membrane and the colloidal gold will form a visible line, which indicates a negative result. If drug is present in the urine, the drug-specific antibodies will bind to the drug in solution and bypass the conjugate on the membrane and no line will form, which indicates a preliminary positive result. A visible control line should form in the control line position regardless of whether drug is present to indicate that the test has been performed properly. K252684 - Page 2 of 11 {2} V Substantial Equivalence Information: A Predicate Device Name(s): Chemtrue® Drug Screen Fentanyl/Tramadol Cup Test, Chemtrue® Drug Screen Fentanyl/Tramadol Dip Card Test, Chemtrue® Multi-Panel Drug Screen Cup Test, Chemtrue® Multi-Panel Drug Screen Dip Card Test B Predicate 510(k) Number(s): K232736 C Comparison with Predicate(s): | Device & Predicate Device(s): | K252684 | K232736 | | --- | --- | --- | | Device Trade Name | Labcorp Fentanyl Urine Visual Test | Chemtrue® Drug Screen Fentanyl Cup/Dip Card Tests | | General Device Characteristic Similarities | | | | Indications For Use | Qualitative detection of norfentanyl in human urine at a cut-off of 5 ng/mL | Same | | General Device Characteristic Differences | | | | Test Device Format | Cassette | Cup/Dip Card | VI Standards/Guidance Documents Referenced: CLSI EP07 3rd Edition - Interference Testing in Clinical Chemistry VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: These studies were carried out using urine samples containing norfentanyl (nFEN) spiked into a drug-free urine pool with LC-MS/MS confirmed concentrations of 0%, 25%, 50%, 75%, 100%, 125%, 150%, and 200% of the test cutoff. These samples were prepared in a blind randomized panel in triplicate and evaluated by 3 in-house operators over 5 days using 3 different lots. Each result was visually interpreted at 10 minutes. Results are summarized below: | Test | Concentration Tested | Lot 1 Neg/Pos | Lot 2 Neg/Pos | Lot 3 Neg/Pos | Total Neg/Pos | | --- | --- | --- | --- | --- | --- | | nFEN | Negative | 45/0 | 45/0 | 45/0 | 135/0 | K252684 - Page 3 of 11 {3} K252684 - Page 4 of 11 | Test | Concentration Tested | Lot 1 Neg/Pos | Lot 2 Neg/Pos | Lot 3 Neg/Pos | Total Neg/Pos | | --- | --- | --- | --- | --- | --- | | | 25% of Cutoff | 45/0 | 45/0 | 45/0 | 135/0 | | | 50% of Cutoff | 45/0 | 45/0 | 45/0 | 135/0 | | | 75% of Cutoff | 40/5 | 35/10 | 31/14 | 106/29 | | | Cutoff | 20/25 | 22/23 | 18/27 | 60/75 | | | 125% of Cutoff | 3/24 | 8/37 | 3/42 | 14/121 | | | 150% of Cutoff | 0/45 | 0/45 | 0/45 | 0/135 | | | 200% of Cutoff | 0/45 | 0/45 | 0/45 | 0/135 | 2. **Linearity:** Not applicable because this device is intended for qualitative use only for detection of norfentanyl in human urine at concentrations above 5 ng/mL. 3. **Analytical Specificity/Interference:** Interference and cross-reactivity studies were conducted based upon recommendations in the Clinical and Laboratory Standards Institute (CLSI) Guideline EP05-A3: Evaluation of Precision of Quantitative Measurement Methods. Test concentrations were determined using medically relevant calculations based on maximum daily doses, urinary excretion percentages, and minimum urine volumes. At least 9 professional laboratory operators performed visual readings. For each drug and cutoff, specificity was evaluated by spiking various concentrations of similarly structured drug compounds into drug-free urine. Results are expressed as a minimum concentration of metabolite or compound required to produce a response approximately equivalent to the cutoff concentration of the assay. The percent cross reactivity of those compounds is listed below (if no cross reactivity was observed, the highest concentration tested is shown as &lt;1%): | Compound | Concentration | % Cross-Reactivity | | --- | --- | --- | | Norfentanyl (nFEN) (Norfentanyl, 5 ng/mL) | | | | Parent drug: Fentanyl | 7.5 ng/mL | 67% | | Fentanyl/Norfentanyl analog cross-reactants | | | | 3-Methylfentanyl | 150 ng/mL | 3% | | 4-Fluoro-Isobutyryl Fentanyl | 15 ng/mL | 33% | | 4’-Methylacetyl Fentanyl (para-Methacetyl Fentanyl) | 750 ng/mL | 1% | | Acetyl Fentanyl | 5 ng/mL | 100% | | Acetyl Norfentanyl | 50 ng/mL | 10% | | Acryl Fentanyl | 10 ng/mL | 50% | | Alfentanil | 2,500 ng/mL | < 1% | | Butyryl Fentanyl | 10 ng/mL | 50% | | Cis-DL-3-Methylfentanyl | 100 ng/mL | 5% | | Cyclopropyl Fentanyl | 10 ng/mL | 50% | {4} Interference from endogenous compounds and non-structurally related exogenous compounds using samples containing drugs at 50% of cutoff and 150% of cutoff urine samples. Each compound and urine sample were tested by running at least 5 replicates and 3 lots. The following endogenous compounds showed no interference at the concentrations listed: | Endogenous Compound | Concentration (ng/mL) | Endogenous Compound | Concentration (ng/mL) | | --- | --- | --- | --- | | Acetone | 10,000,000 | Glucose | 30,000,000 | | Albumin, Human | 5,000,000 | Hemoglobin, Human | 3,000,000 | | Ascorbic Acid | 5,000,000 | Niacinamide | 100,000 | | Atropine | 100,000 | Nicotinic Acid | 100,000 | | Beta-Hydroxybutyric Acid | 100,000 | Octopamine | 150,000 | | Bilirubin | 20,000 | Oxalic Acid | 100,000 | | Biotin | 100,000 | Potassium Chloride | 10,000,000 | | Calcium Chloride | 3,000,000 | Pyridoxine | 90,000 | | Cholesterol | 100,000 | Quinolinic Acid | 100,000 | | Creatine Hydrate | 100,000 | Riboflavin | 75,000 | | Creatinine | 5,000,000 | Sodium Chloride | 10,000,000 | | Deoxycorticosterone | 100,000 | Thiamine | 100,000 | | Dopamine (3-Hydroxytyramine) | 100,000 | Tryptamine | 100,000 | | Ethanol | 10,000,000 | Tyramine | 100,000 | | Galactose | 100,000 | Urea | 60,000,000 | | Gamma Globulin | 5,000,000 | Uric Acid | 100,000 | | Cyclopropyl Norfentanyl | 7.5 ng/mL | 67% | | --- | --- | --- | | Fluorocyclopropyl Fentanyl (para-Fluorocyclopropyl Fentanyl) | 15 ng/mL | 33% | | Furanyl Fentanyl | 25 ng/mL | 20% | | Furanyl Norfentanyl | 7.5 ng/mL | 67% | | (±) β-Hydroxythiofentanyl | 10 ng/mL | 50% | | Isobutyryl Fentanyl | 7.5 ng/mL | 67% | | Isobutyryl Norfentanyl | 5 ng/mL | 100% | | Methoxyacetylfentanyl (MAF) | 15 ng/mL | 33% | | N-Benzylfuranyl Norfentanyl | 50 ng/mL | 10% | | N-Benzyl-Para-Fluoro Norfentanyl | 25 ng/mL | 20% | | Octfentanil | 500 ng/mL | 1% | | Para-Fluoro-Butyryl Fentanyl (p-FBF) | 75 ng/mL | 7% | | Para-Fluorofentanyl | 10 ng/mL | 50% | | Phenylacetyl Fentanyl | 7.5 ng/mL | 67% | | Remifentanil | 100 ng/mL | 5% | | THF Fentanyl (THFF) | 35 ng/mL | 14% | | Thienyl Fentanyl | 15 ng/mL | 33% | | Trans-DL-3-Methylfentanyl | 10 ng/mL | 50% | | Valeryl Fentanyl | 50 ng/mL | 10% | K252684 - Page 5 of 11 {5} The following non-structurally related compounds showed no interference at the concentrations listed: | Common Drug | Concentration (ng/mL) | Common Drug | Concentration (ng/mL) | | --- | --- | --- | --- | | 1-(3-Trifluoromethylphenyl)-piperazine | 100,000 | Isotonitazene | 10,000 | | 11-Hydroxy- 9-THC | 10,000 | Ketamine | 100,000 | | 11-Nor-9-carboxy- 9-THC | 10,000 | Labetalol | 1,800,000 | | 4-Bromo-2,5, Dimethoxyphenethylamine | 100,000 | Lamotrigine | 100,000 | | 6-Acetylmorphine (6-MAM) | 100,000 | Lansoprazole | 100,000 | | 7-Aminoclonazepam | 100,000 | L-Cotinine | 100,000 | | 7-Aminoflunitrazepam | 100,000 | L-Erythromycin | 100,000 | | 7-Aminonitrazepam | 10,000 | Levonorgestrel | 100,000 | | Acetaminophen | 2,900,000 | Levorphanol | 100,000 | | Acetylsalicylic Acid | 100,000 | Levothyroxine (L-Thyroxine) | 100,000 | | AH-7921 (Doxylam) | 10,000 | Lisinopril | 100,000 | | AH-8529 | 100,000 | L-Methamphetamine | 100,000 | | AH-8533 | 100,000 | Loperamide | 100,000 | | Albuterol | 100,000 | Loratadine | 100,000 | | Allopurinol | 100,000 | Lorazepam | 100,000 | | Alprazolam | 100,000 | Losartan | 100,000 | | Aminopyrine (4-Dimethylaminoantipyrine) | 100,000 | Lurasidone | 10,000 | | Amlodipine Besylate | 100,000 | Lysergic Acid Diethylamide (LSD) | 10,000 | | Amoxicillin | 2,600,000 | Maprotiline | 100,000 | | Ampicillin | 100,000 | Meperidine | 100,000 | | Apixaban | 100,000 | Meprobamate | 100,000 | | Apomorphine | 100,000 | Metformin | 2,900,000 | | Aspartame | 100,000 | Methadone | 100,000 | | Atenolol | 200,000 | Methapyrilene | 100,000 | | Atorvastatin | 100,000 | Methylphenidate | 100,000 | | Baclofen | 100,000 | Metonitazene | 10,000 | | Benzocaine | 100,000 | Metoprolol | 550,000 | | Benzoic Acid | 100,000 | Mitragynine | 100,000 | | Benzoylecgonine | 100,000 | Morphine | 300,000 | | Benzylpiperazine | 10,000 | Morphine-3-glucuronide | 10,000 | | Brompheniramine | 100,000 | Nalidixic Acid | 100,000 | | Buprenorphine | 100,000 | Naloxegol | 100,000 | K252684 - Page 6 of 11 {6} K252684 - Page 7 of 11 | Common Drug | Concentration (ng/mL) | Common Drug | Concentration (ng/mL) | | --- | --- | --- | --- | | Bupropion | 100,000 | Naloxone | 100,000 | | Caffeine | 1,200,000 | Naltrexone | 100,000 | | Cannabidiol | 100,000 | Naproxen | 1,800,000 | | Carbamazepine | 100,000 | N-Desmethylapentadol | 10,000 | | Carisoprodol | 100,000 | Nifedipine | 100,000 | | Carvedilol | 100,000 | Norbuprenorphine | 100,000 | | Cetirizine | 100,000 | Norcodeine | 100,000 | | Chloramphenicol | 100,000 | Nordiazepam | 100,000 | | Chlorcyclizine | 100,000 | Norethindrone | 100,000 | | Chlordiazepoxide | 100,000 | Norketamine | 100,000 | | Chlorpheniramine | 100,000 | Normeperidine | 100,000 | | Chlorpromazine | 15,000 | Normorphine | 10,000 | | Cimetidine | 1,800,000 | Noroxycodone | 100,000 | | Citalopram | 100,000 | Norpropoxyphene | 100,000 | | Clofibrate | 100,000 | Norpseudoephedrine (Cathine) | 100,000 | | Clomipramine | 100,000 | Noscapine | 100,000 | | Clonazepam | 100,000 | Omeprazole | 100,000 | | Clonidine | 100,000 | Oxazepam | 100,000 | | Clopidogrel | 200,000 | Oxazepam Glucuronide | 1,000 | | Codeine | 120,000 | Oxycodone | 100,000 | | Cortisone | 100,000 | Oxymetazoline | 100,000 | | Cyclobenzaprine | 100,000 | Oxymorphone | 100,000 | | Cyclodextrin-r | 100,000 | Pantoprazole | 100,000 | | Cyproheptadine | 100,000 | Papaverine | 100,000 | | DL-Isoproterenol | 100,000 | Penicillin-G (Benzylpenicillin) | 100,000 | | D-Amphetamine | 350,000 | Pentazocine | 35,000 | | Demoxepam | 100,000 | Perospirone | 10,000 | | Dextromethorphan | 100,000 | Phenelzine | 100,000 | | Diclofenac | 200,000 | Pheniramine | 100,000 | | Difunisal | 100,000 | Phentermine | 100,000 | | Dihydrocodeine | 100,000 | Phenylephrine | 100,000 | | Diphenhydramine | 100,000 | Phenylethylamine | 100,000 | | Diphenylhydantoin (Phenytoin) | 100,000 | Pravastatin | 100,000 | | D-Methamphetamine | 100,000 | Prednisone | 100,000 | | Doxylamine | 100,000 | Promazine | 100,000 | | D-Pseudoephedrine | 250,000 | Promethazine | 100,000 | | Duloxetine | 150,000 | Propoxyphene | 10,000 | {7} | Common Drug | Concentration (ng/mL) | Common Drug | Concentration (ng/mL) | | --- | --- | --- | --- | | EDDP (Methadone metabolite) | 100,000 | Propranolol | 700,000 | | Ephedrine | 100,000 | Propylhexedrine | 50,000 | | Ergocalciferol | 100,000 | Pyrilamine | 150,000 | | Escitalopram | 100,000 | Pyrogallol | 100,000 | | Esomeprazole Mg hydrate | 250,000 | Ranitidine | 150,000 | | Estrone | 100,000 | Rosuvastatin | 100,000 | | Ethinyl Estradiol | 100,000 | Salicylic Acid | 1,000,000 | | Famotidine | 1,000,000 | Sertindole | 10,000 | | Fenfluramine | 100,000 | Sertraline | 30,000 | | Fenofibrate | 100,000 | Simvastatin | 100,000 | | Fexofenadine | 75,000 | Sodium Azide | 100,000 | | Fluoxetine | 100,000 | Sulfamethazine | 100,000 | | Fluticasone | 100,000 | Sulindac | 100,000 | | Furosemide | 500,000 | Tamsulosin | 100,000 | | Gabapentin | 4,500,000 | Temazepam | 100,000 | | Gemfibrozil | 100,000 | Tetracycline | 100,000 | | Gentisic Acid | 100,000 | Tetrahydrozoline | 100,000 | | Glipizide | 100,000 | Thioridazine | 100,000 | | Guaifenesin | 100,000 | Tianeptine | 100,000 | | Heroin (Diacetylmorphine) | 100,000 | Tramadol | 450,000 | | Hexobarbital | 10,000 | Trazodone | 10,000 | | Hydralazine | 100,000 | Trifluoperazine | 100,000 | | Hydrochlorothiazide | 150,000 | Venlafaxine | 100,000 | | Hydrocodone | 100,000 | Xylazine | 100,000 | | Hydrocortisone | 100,000 | Ziprasidone | 100,000 | | Hydromorphone | 100,000 | Zolpidem | 100,000 | | Ibuprofen | 2,700,000 | Zolpidem Tartrate | 100,000 | | Insulin | 100,000 | | | Positive interference was observed for the following compounds when tested at concentrations above those listed in the table above: Pentazocine and Fexofenadine. Negative interference was observed for the following compounds when tested at concentrations above those listed in the table above: Baclofen, Chlorpromazine, Fexofenadine Propranolol, Sertraline, Potassium Chloride, Pyridoxine. The following Norfentanyl analogs were also observed to cause negative interference above those listed in the table below: Carfentanil, MT-45, 4-Methoxybutyryl Fentanyl, and U-4770. K252684 - Page 8 of 11 {8} The following non-structurally related compounds showed interference and/or cross reactivity at the concentrations listed: | Non-Fentanyl Cross Reactive Compounds | | | | --- | --- | --- | | Compound | Concentration | % Cross Reactivity | | Fluphenazine | Positive at 50,000 ng/mL | < 1% | | Perphenazine | Positive at 75,000 ng/mL | < 1% | | Quinidine | Positive at 25,000 ng/mL | < 1% | | Quinine | Positive at 50,000 ng/mL | < 1% | | Risperidone | Positive at 2,500 ng/mL | < 1% | | Risperidone Metabolite: 9-Hydroxyrisperidone | Positive at 2,500 ng/mL | < 1% | | Non-reactive Fentanyl/Norfentanyl analogs | | | | --- | --- | --- | | Compound | Concentration | % Cross Reactivity | | Carfentanil | Negative at 500 ng/mL | N/A | | Despropionylfentanyl (4-ANPP) | Negative at 1,000 ng/mL | N/A | | MT-45 | Negative at 3,500 ng/mL | N/A | | 4-Methoxybutyryl Fentanyl | Negative at 5,000 ng/mL | N/A | | Norcarfentanil | Negative at 1,000 ng/mL | N/A | | Sufentanil | Negative at 1,000 ng/mL | N/A | | U-47700 | Negative at 5,000 ng/mL | N/A | pH study: To evaluate the effect of pH value on the test results, urine controls at 50% and 150% of the cutoff value was used. Each control level was adjusted by either 6N NaOH solution or 6N HCl to pH levels of 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0 and 9.0. A total of 5 replicates per sample were tested. Specific gravity study: To evaluate the effect of specific gravity, urine controls at 50% and 150% of the cutoff values were mixed and pooled as needed to obtain specific gravities of 1.001, 1.004, 1.010, 1.014, 1.020, 1.025, and 1.030. A total of 5 replicates per sample were tested. The results demonstrated that pH and specific gravity do not affect the results from the device at the conditions tested. 4. Assay Reportable Range: Not applicable because this device is intended for qualitative use only for detection of norfentanyl in human urine at concentrations above 5 ng/mL. 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. K252684 - Page 9 of 11 {9} 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: The sponsor performed a method comparison study comparing the performance of the test strips to the LC/MS reference method. A total of 40 samples that did not contain norfentanyl (or fentanyl) and 47 samples containing varying concentrations of norfentanyl (and fentanyl), including 7 below the test cutoff, were assayed on 3 lots using a different operator for each lot and run in a random order over 3 days. The results are summarized below: | Fentanyl Test (nFEN) (5 ng/mL Cutoff) | Concentration by LC-MS/MS (ng/mL) | | | | | | | --- | --- | --- | --- | --- | --- | --- | | | | No Drug Present | Low Negative (<50% of cutoff) | Near Cutoff Negative (50% - 100% of cutoff) | Near Cutoff Positive (100% - 150% of cutoff) | True Positive (>150% of cutoff) | | Lot 1 | Positive | 0 | 0 | 3 | 4 | 36 | | | Negative | 40 | 3 | 1 | 0 | 0 | | Lot 2 | Positive | 0 | 0 | 3 | 4 | 36 | | | Negative | 40 | 3 | 1 | 0 | 0 | | Lot 3 | Positive | 0 | 0 | 3 | 4 | 36 | | | Negative | 40 | 3 | 1 | 0 | 0 | Three near cutoff negative clinical samples produced positive discordant results with all three strip lots. Discordant results are summarized below: | Fentanyl Test (nFEN) Result | LC-MS/MS Norfentanyl (ng/mL) | | --- | --- | | Positive (+) | 4.76 | | Positive (+) | 3.86 | | Positive (+) | 3.34 | 2. Matrix Comparison: Not applicable. This device is for use with urine samples only. C Clinical Studies: 1. Clinical Sensitivity: Not applicable. 2. Clinical Specificity: Not applicable. K252684 - Page 10 of 11 {10} 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable. D. Clinical Cut-Off: Not applicable. E. Expected Values/Reference Range: Not applicable. VIII. Proposed Labeling: The labeling does support the finding of substantial equivalence for this device. IX. Conclusion: The submitted information in this premarket notification is complete and does support a substantial equivalence decision. K252684 - Page 11 of 11