CLUNGENE Fentanyl Home Test Cassette; CLUNGENE Fentanyl Test Cassette

{0} FDA U.S. FOOD &amp; DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY ## I Background Information: A 510(k) Number K242802 B Applicant Hangzhou Clongene Biotech Co., Ltd. C Proprietary and Established Names CLUNGENE Fentanyl Home Test Cassette; CLUNGENE Fentanyl Test Cassette 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 C Type of Test: Qualitative competitive binding lateral flow immunochromatographic assay ## III Intended Use/Indications for Use: A Intended Use(s): Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} See Indications for Use below. ## B Indication(s) for Use: The CLUNGENE Fentanyl Home Test Cassette is competitive binding, lateral flow immunochromatographic assay for the qualitative detection of Fentanyl in human urine at the cut off 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 analytical result. Gas Chromatography-Mass Spectrometry (GC/MS) or Liquid Chromatography-Mass Spectrometry (LC/MS) is the preferred confirmatory method. Evaluate preliminary positive results carefully. The CLUNGENE Fentanyl Test Cassette is competitive binding, lateral flow immunochromatographic assay for the qualitative detection of Fentanyl in human urine at the cut off 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 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. ## C Special Conditions for Use Statement(s): OTC - Over The Counter ## D Special Instrument Requirements: Not applicable ## IV Device/System Characteristics: ### A Device Description: The CLUNGENE Fentanyl Tests are immunoassays intended for the qualitative detection of fentanyl in human urine. Each CLUNGENE Fentanyl Test device consists of a Test Cassette, a Dropper and a package insert. Each Test Cassette is sealed with sachets of desiccant in an aluminum pouch. ### B Principle of Operation: The CLUNGENE Fentanyl Test Cassette detects Fentanyl through visual interpretation of color development on the device. Drug conjugates are immobilized on the test region of the membrane. During testing, the specimen reacts with antibodies conjugated to colored particles and precoated on the sample pad. The mixture then migrates through the membrane by capillary action, and interacts with reagents on the membrane. If there are insufficient drug molecules in the specimen, the antibody-colored particle conjugate will bind to the drug conjugates, forming a colored band at the test region of the membrane. Therefore, a colored band appears in the test region when the urine is negative for the drug. If drug molecules are present in the urine above the cut-off concentration of the test, they compete with the immobilized drug conjugate on the test region for limited antibody binding sites. This will prevent attachment of the antibody-colored particle conjugate to the test region. Therefore, the absence of a colored band at the test region indicates a positive result. The appearance of a colored band at the control region serves K242802 - Page 2 of 9 {2} as a procedural control, indicating that the proper volume of specimen has been added and membrane wicking has occurred. 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): | K242802 | K233417 | | --- | --- | --- | | Device Trade Name | CLUNGENE Fentanyl Test Cassette | AllTest Fentanyl Urine Test Cassette | | General Device Characteristic Similarities | | | | Indications for Use | For the qualitative determination of fentanyl in human urine | Same | | Calibrator and Cut-Off Values | Fentanyl (FTY) 1 ng/ml | Same | | Methodology | Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry | Same | | Type of Test | Qualitative | Same | | Specimen Type | Human Urine | Same | | Configurations | Cassette | Same | | Storage | 4-30°C | Same | | General Device Characteristic Differences | | | | Cross Reactivity | Percent Cross Reactivity (Carfentanil 2%) | Percent Cross Reactivity (Carfentanil 50%) | VI Standards/Guidance Documents Referenced: Not applicable K242802 - Page 3 of 9 {3} VII Performance Characteristics (if/when applicable): ## A Analytical Performance: ### 1. Precision/Reproducibility: A precision study was carried out at one site 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, where the fentanyl cut-off concentration was 1 ng/mL. Samples with concentration of -100% cut-off were drug-free urine samples. Other samples were prepared by spiking fentanyl in negative samples, and the study was randomized and blinded. 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. Samples were tested by three operators using three different lots at two runs per day per operator for 10 days in a randomized order. Eighteen tests per day per concentration (3 operators x 3 lots x 2 runs) were tested for a total of 162 tests per day. There is a total of 60 tests per lot per concentration. | Lot Number | -100% cut off | -75% cut off | -50% cut off | -25% cut off | cut off | +25% cut off | +50% cut off | +75% cut off | +100% cut off | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 58-/2+ | 33-/27+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 26-/34+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 58-/2+ | 32-/28+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | ### 2. Linearity: Not applicable, this device is intended for qualitative use only. ### 3. Analytical Specificity/Interference: #### Cross-Reactivity: To test specificity, similarly structured drug metabolites and other components that are likely to interfere in urine samples were added to the drug-free urine samples at different concentrations and tested using three lots of the device by three different operators. Results are expressed as a minimum concentration of metabolite or compound required to produce positive response (ng/mL). The percent cross reactivity of those compounds (calculated by dividing the cutoff concentration by the minimum concentration required to obtain a positive result and then multiplying by 100%) and lowest concentration that caused a positive result for each compound are listed below. | Fentanyl (Cutoff = 1 ng/mL) | Minimum concentration required to obtain a positive result (ng/mL) | % Cross-Reactivity | | --- | --- | --- | | Acetyl fentanyl | 1 | 100% | | Acrylfentanyl | 1 | 100% | | Isobutyryl fentanyl | 2.5 | 40% | K242802 - Page 4 of 9 {4} The following structurally unrelated opioid compounds were tested at a concentration of 100 $\mu \mathrm{g} / \mathrm{mL}$. Three device lots were used to test each sample, and each operator used one lot. Negative results were obtained for all these compounds. | 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 | Risperidone | | Ketamine | Tapentadol | | Levorphanol | Thioridazine | | Meperidine | Tilidine | | Methadone | Tramadol | | Morphine | Tramadol-O- Desmethyl | | Morphine-3-glucuronide | Tramadol-N- Desmethyl | | Ocfentanil | 5 | 20% | | --- | --- | --- | | Butyryl fentanyl | 5 | 20% | | Furanyl fentanyl | 10 | 10% | | Valeryl fentanyl | 5 | 20% | | (±)-β-hydroxythiofentanyl | 2.5 | 40% | | 4-Fluoro-isobutyrylfentanyl | 10 | 10% | | Para-fluorobutyryl fentanyl | 5 | 20% | | Para-fluoro fentanyl | 2.5 | 40% | | Carfentanil | 50 | 2% | | Sufentanil | 25 | 4% | | Alfentanil | 7,500 | 0.01% | | Ω-1-Hydroxy fentanyl | 2,500 | 0.04% | | (±)-3-cis-methyl fentanyl | 75 | 1.33% | | Despropionyl fentanyl (4-ANPP) | 2,000 | 0.05% | | β-hydroxyfentanyl | 100 | 1% | | Thiofentanyl | 50 | 2% | | Cyclopropyl Fentanyl | 10 | 10% | | Trazodone | 1,000 | 0.1% | | Remifentanil | >100,000 | <0.001% | | Norcarfentanil | >100,000 | <0.001% | | Norfentanyl | >100,000 | <0.001% | | Acetyl norfentanyl | >100,000 | <0.001% | K242802 - Page 5 of 9 {5} # Interference: Potential endogenous and exogenous interfering substances commonly found in human urine 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 lots of each device, with tests performed for compounds at a concentration of $100\mathrm{ug / mL}$ or other specified concentration. No compounds showed any interference. Refer to the table below for the compounds tested at a concentration of $100\mu \mathrm{g / mL}$ or other specified concentration. | Acetaminophen | Erythromycin | Octopamine | | --- | --- | --- | | Acetone (1000 mg/dL) | Ethanol (1%) | O-Hydroxyhippuric acid | | Acetophenetidin | Fenofibrate | Olanzapine | | Acetylsalicylic acid | Fenoprofen | Omeprazole | | Acyclovir | Fluphenazine | Oxalic acid (100 mg/dL) | | Albumin (100mg/dL) | Furosemide | Oxazepam | | Albuterol | Galactose (10 mg/dL) | Oxolinic acid | | Aminopyrine | Gamma globulin (500 mg/dL) | Oxymetazoline | | Amitriptyline | Gatifloxacin | Papaverine | | Amobarbital | Gentisic acid | Penicillin G | | Amoxicillin | Glibenclamide | Perphenazine | | Ampicillin | Gliclazide | Phencyclidine | | Apomorphine | Glucose (3000 mg/dL) | Phenelzine | | Ascorbic acid | Hemoglobin | Phenobarbital | | Aspartame | Hydralazine | Prednisone | | Atropine | Hydrochlorothiazide | Procaine | | Benzilic acid | Hydrocortisone | Promethazine | | Benzoic acid | Hydroxytyramine | Propoxyphene (50 mg/dL) | | Benzoylecgonine | Ibuprofen | Propranolol | | Bilirubin | Imipramine | Propylthiouracil | | Boric acid (1%) | Isoproterenol | Pseudoephedrine | | Bupropion | Isoxsuprine | Quinine | | Caffeine | Ketamine | Ranitidine | | Captopril | Ketoprofen | Ribavirin | | Carbamazepine | Labetalol | Riboflavin (10 mg/dL) | | Chloral hydrate | Levonorgestrel | Rifampicin | | Chloramphenicol | Lidocaine | Salicylic acid | | Chlorothiazide | Loperamide | Secobarbital | | Chlorpheniramine | Maprotiline | Serotonin (5-Hydroxytyramine) | | Chlorpromazine | MDMA | Simvastatin | | Cholesterol | Meperidine | Sulfamethazine | | Clarithromycin | Meprobamate | Sulindac | | Clomipramine | Methamphetamine | Tetrahydrocortisone 3-(β-Dglucuronide) | | Clonidine | Methapyrilene | Tetrahydrocortisone 3-acetate | | Cortisone | Methaqualone | Tetrahydrozoline | | Cotinine | Methoxyphenamine | Theophylline | | Creatinine | Metoprolol tartrate | Thiamine | K242802 - Page 6 of 9 {6} | Cyclobenzaprine | Metronidazole (300 μg/mL) | Thioridazine | | --- | --- | --- | | Deoxycorticosterone | Mifepristone | Triamterene | | Desipramine | Montelukast sodium | Trifluoperazine | | Dextromethorphan | N-Acetylprocainamide | Trimethoprim | | Diazepam | NaCl (4000 mg/dL) | Tyramine | | Diclofenac | Nalidixic acid | Urea (2000 mg/dL) | | Diflunisal | Naloxone | Uric acid | | Digoxin | Naltrexone | Valproic acid (250 μg/mL) | | Diphenhydramine | Naproxen | Venlafaxine | | DL-Tryptophan | Niacinamide | Verapamil | | DL-Tyrosine | Nicotine | Zomepirac | | Doxepin | Nifedipine | β-Estradiol | | Ecgonine methyl ester | Norethindrone | Δ9-THC | | Ephedrine | Nortriptyline | / | | Epinephrine hydrochloride | Noscapine | / | **Effect of Urine Density and pH Value:** To evaluate the effect of urine density and urine pH value on the accuracy of test measurements, urine samples with 1.000, 1.003, 1.008, 1.014, 1.018, 1.020, 1.022, 1.025, 1.028, 1.030, 1.032, and 1.035 specific gravity and urine samples with pH of 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0 were spiked with target fentanyl at 50% below and 50% above cut-off levels. These samples were tested using three lots of the device and one operator per lot. Results were all positive for samples at and above +50% cut-off and all negative for samples at and below -50% cut-off. 4. **Assay Reportable Range:** Not applicable 5. **Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):** **Traceability:** The assay is traceable to a commercially available standard from Cerilliant Corp. 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 at low concentrations appears in the precision section VII.A.1. above. B **Comparison Studies:** 1. **Method Comparison with LC-MS/MS method:** K242802 - Page 7 of 9 {7} A randomized and blinded method comparison study was conducted at one testing site by three operators between the CLUNGENE Fentanyl Test Cassette and LC-MS/MS method using only one device lot. Clinical samples tested included a total of 80 urine samples (40 negative and 40 positive) obtained from a hospital laboratory. The samples were blinded and compared to LC/MS results. Sample concentrations of fentanyl were confirmed by LC-MS/MS and ranged from drug-free, &lt; -50% Cut-off (low positive), between -50% Cutoff and the cutoff (near cut-off negative), between cutoff and +50% (near cut-off positive), and &gt; +50% Cut-off (high positive), with fentanyl cut-off of 1 ng/mL. The results are summarized in the tables below. | | | 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 | 21 | 18 | | | Negative | 10 | 16 | 13 | 1 | 0 | | Operator 2 | Positive | 0 | 0 | 1 | 20 | 18 | | | Negative | 10 | 16 | 13 | 2 | 0 | | Operator 3 | Positive | 0 | 0 | 1 | 20 | 18 | | | Negative | 10 | 16 | 13 | 2 | 0 | Discordant Results | Operator | Sample ID | LC/MS Result (ng/mL) | Rapid Test Result | | --- | --- | --- | --- | | Operator 1 | FYL57 | 0.953 | Positive | | Operator 2 | FYL66 | 0.987 | Positive | | Operator 3 | FYL66 | 0.987 | Positive | | Operator 1 | FYL38 | 1.073 | Negative | | Operator 2 | FYL19 | 1.083 | Negative | | Operator 2 | FYL55 | 1.004 | Negative | | Operator 3 | FYL24 | 1.073 | Negative | | Operator 3 | FYL55 | 1.004 | Negative | 2. Matrix Comparison: Not applicable. These devices are for use with urine samples only. C Clinical Studies: 1. Clinical Sensitivity: Not applicable 2. Clinical Specificity: Not applicable K242802 - Page 8 of 9 {8} K242802 - Page 9 of 9 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Lay User Study: A lay user study was performed at three sites representative of intended use settings with 140 lay persons and three device lots. The lay users had diverse educational and professional backgrounds and ranged in age from 19 to &gt;50 years. Urine samples were prepared at -100%, +/-75%, +/-50%, and +/-25% of the fentanyl cut-off by spiking fentanyl into 6 drug free-pooled urine sample pools. Drug-free urine samples were also used in the study. The drug concentrations of the samples were confirmed by LC/MS. Each sample was further aliquoted into 20 individual containers (total 140 aliquots), blind-labeled and randomized. All 140 aliquots were distributed to the three testing sites, where each participant was provided with the package insert, 1 blind labeled sample and a device. Each participant tested the sample with the device, and the results are summarized below. | % of Cutoff by LC/MS | Number of samples | Drug 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 | 0.23 | 0 | 20 | 100.0% | | -50% Cutoff | 20 | 0.53 | 0 | 20 | 100.0% | | -25% Cutoff | 20 | 0.75 | 1 | 19 | 95% | | +25% Cutoff | 20 | 1.20 | 20 | 0 | 100.0% | | +50% Cutoff | 20 | 1.46 | 20 | 0 | 100.0% | | +75% Cutoff | 20 | 1.77 | 20 | 0 | 100.0% | Each participant was given a questionnaire to evaluate ease of understanding the instructions for use and device use. The questionnaire focused on personal information, product information, test procedures, and test results by the lay user. A Flesch-Kincaid Grade reading analysis was also performed on the package insert and resulted in a reading score of Grade 7 Level. 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.