GenPrime Snap-Top Split Key Cup

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k140655 B. Purpose for Submission: Addition of Barbiturates, Benzodiazepine, and Cocaine analytes to the Split Key Cup component of a previously cleared device system (k130082). C. Measurand: Barbiturates, Benzodiazepine, Cocaine D. Type of Test: Qualitative immunochromatographic assay E. Applicant: GenPrime Incorporated F. Proprietary and Established Names Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse (DOA) Reader System G. Regulatory Information: | Product | Classificatie | Regulation Section | Panel | | --- | --- | --- | --- | | DIS | Class II | 21 CFR 862.3150 Barbiturate test system | 91 (Toxicology) | | JXM | Class II | 21 CFR 862.3170 Benzodiazepine test system | 91 (Toxicology) | | DIO | Class II | 21 CFR 862.3250 Cocaine and cocaine metabolite test system | 91 (Toxicology) | {1} H. Intended Use: 1. Intended Use(s): See Indications for use below. 2. Indication(s) for use: The Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse (DOA) Reader System is for in vitro diagnostic use and is intended for prescription use in laboratories, point-of-care, and workplaces by trained users. The test is not intended for over-the-counter use. The test cannot be read visually and must be used with the GenPrime DOA Reader. The Snap-Top Split Key Cup qualitatively detects drug classes in human urine at the cut-off concentrations shown below: | Test | Calibrated to | Cut-off | | --- | --- | --- | | Amphetamines | d-Amphetamine | 500 ng/mL | | Barbiturates | Secobarbital | 300 ng/mL | | Benzodiazepines | Oxazepam | 300 ng/mL | | Cocaine | Benzoylecgonine | 150 ng/mL | | Methamphetamine | d-Methamphetamine | 500 ng/mL | | Methadone | Methadone | 300 ng/mL | | Morphine | Morphine | 300 ng/mL | | Opiates 2000 | Morphine | 2000 ng/mL | | Oxycodone | Oxycodone | 100 ng/mL | | Phencyclidine | Phencyclidine | 25 ng/mL | | Marijuana | Delta-9-THC-COOH | 50 ng/mL | Configurations of the Snap-Top Split Key cup may consist of any combination of the above listed drug analytes. The Snap-Top Split Key Cup provides only a preliminary analytical result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography / mass spectrometry (GC/MS), high performance liquid chromatography (HPLC) or liquid chromatography / tandem mass spectrometry (LC/MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained. {2} 3. Special conditions for use statement(s): For in vitro diagnostic prescription use in laboratories, point-of-care, and workplace sites 4. Special instrument requirements: The GenPrime DOA Reader I. Device Description: The Snap-Top Split Key Cup (Snap-Top SK Cup) is a rapid, single use, disposable immunochromatographic test for the qualitative detection of drugs of abuse in human urine. The device consists of a test card with drug strips integrated into a urine cup with a partition that requires a key activation step to disperse urine into the cup for testing to begin. The Snap-Top Split Key Cup is intended for use solely with the GenPrime Drugs of Abuse Reader System. J. Substantial Equivalence Information: 1. Predicate device names(s) Profile-V MEDTOXScan Drugs of Abuse Test System 2. Predicate K number(s): k080635 3. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Candidate Device | Predicate (k080635) | | Intended Use | Same | Qualitative and preliminary detection of drugs in human urine using an instrument reader | | Methodology | Same | Lateral flow immunochromatographic | | Type of assay | Same | Qualitative | | Cutoff Values for Cocaine(COC) | Same | COC = 150 ng | {3} | Differences | | | | --- | --- | --- | | Item | Candidate | Predicate | | Detection Method | Measures density of visible lines against background on single-use test device | Measures reflectance of visible lines on single use test cassette | | Cutoff Values for Barbiturates(BAR)and Benzodiazepine (BZO) | BAR = 300 ng BZO = 300 ng | BAR = 200 ng BZO = 150 ng | # K. Standard/Guidance Document Referenced (if applicable): - ISO 14971:2007 Second Addition: Medical devices-Application of risk management to medical devices - IEC 62304 First edition 2006-05, Medical device software - Software life cycle processes - AAMI/ANSI/IEC 60601-1-2:2007, Medical electrical equipment - Part 1-2: General Requirements for Basic Safety and Essential Performance - Collateral Standard: Electromagnetic Compatibility - Requirements and Tests - UL 60950-1, $1^{\text{st}}$ Edition, 2006-07-07 Information Technology Equipment - Safety - Part 1: General Requirements - CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance # L. Test Principle: The Snap-Top SK Cup measures density of visible lines against background to produce a preliminary positive or negative result for single-use, immunochromatographic drug tests. Each drug strip of the cup consists of: (1) a purple colored pad containing mouse monoclonal anti-drug antibodies conjugated with colloidal gold and rabbit IgG antibodies conjugated with colloidal gold that are hydrated and solubilized by urine samples for transport through the test strip, and (2) a nitrocellulose membrane strip containing Test lines and a Control line. The Test line is coated with drug-protein conjugate and the Control line is coated with goat anti-rabbit IgG antibodies. During analysis, an image of the drug test strip is captured and the software algorithm determines from the image whether the presence or absence of colored test lines is associated with a preliminary positive or negative result for each analyte. The software also confirms the validity of the results by verifying the presence of control lines. {4} M. Performance Characteristics (if/when applicable): The performance testing described herein is for the BAR, BZO and COC analytes only. The analytes amphetamine, methadone, methamphetamine, morphine, opiate, phencyclidine (PCP) and cannabinoid were previously cleared under k130082 and the performance of those analytes is described in k130082. 1. Analytical performance: a. Precision/Reproducibility: The precision studies were performed with the Snap-Top SK Cup at three sites representative of laboratory, workplace, and POC settings with an intended use operator at each site. The operators performed the tests following the instructions for use. Precision studies were performed with the target analytes at 0%, 25%, 50%, 75%, 125%, 150%, 175%, and 200% of the cutoff during a 20 working day period using solutions containing drug concentrations confirmed by GC/MS. The identity of the samples was masked from the operator. Performance was evaluated for each drug analyte by testing each drug at the stated concentration using a minimum of 15 tests per operator. Results for all sites are shown in the tables below. Note that for the Barbiturates analyte, testing was not performed at the 200% cut-off level for Lot 2 due to a test device shipping error. Information is provided for this analyte at this cut-off level for the other two device lots evaluated. Barbiturates | ALL LOTS COMBINED | | | | | | | --- | --- | --- | --- | --- | --- | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 45 | 45 | 0 | 100% | | 25% | 75 | 45 | 45 | 0 | 100% | | 50% | 150 | 46 | 46 | 0 | 100% | | 75% | 225 | 45 | 39 | 6 | 86.7% | | 125% | 375 | 45 | 0 | 45 | 100% | | 150% | 450 | 45 | 0 | 45 | 100% | | 175% | 525 | 45 | 0 | 45 | 100% | | 200% | 600 | 46 | 0 | 46 | 100% | | LOT 1 | | | | | | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 75 | 15 | 15 | 0 | 100% | | 50% | 150 | 15 | 15 | 0 | 100% | {5} 6 | 75% | 225 | 15 | 15 | 0 | 100% | | --- | --- | --- | --- | --- | --- | | 125% | 375 | 15 | 0 | 15 | 100% | | 150% | 450 | 15 | 0 | 15 | 100% | | 175% | 525 | 15 | 0 | 15 | 100% | | 200% | 600 | 15 | 0 | 15 | 100% | <h2>LOT 2</h2> | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | --- | --- | --- | --- | --- | --- | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 75 | 15 | 15 | 0 | 100% | | 50% | 150 | 16 | 16 | 0 | 100% | | 75% | 225 | 15 | 10 | 5 | 66.7% | | 125% | 375 | 14 | 0 | 14 | 100% | | 150% | 450 | 15 | 0 | 15 | 100% | | 175% | 525 | 14 | 0 | 14 | 100% | <h2>LOT 3</h2> | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | --- | --- | --- | --- | --- | --- | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 75 | 15 | 15 | 0 | 100% | | 50% | 150 | 15 | 15 | 0 | 100% | | 75% | 225 | 15 | 14 | 1 | 93.3% | | 125% | 375 | 16 | 0 | 16 | 100% | | 150% | 450 | 15 | 0 | 15 | 100% | | 175% | 525 | 16 | 0 | 16 | 100% | | 200% | 600 | 31 | 0 | 31 | 100% | ## Benzodiazepines | ALL LOTS COMBINED | | | | | | | --- | --- | --- | --- | --- | --- | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 45 | 45 | 0 | 100% | | 25% | 75 | 50 | 50 | 0 | 100% | | 50% | 150 | 50 | 48 | 2 | 96.0% | | 75% | 225 | 50 | 29 | 21 | 58.0% | | 125% | 375 | 50 | 2 | 48 | 96.0% | | 150% | 450 | 49 | 0 | 49 | 100% | | 175% | 525 | 49 | 0 | 49 | 100% | | 200% | 600 | 49 | 0 | 49 | 100% | <h2>LOT 1</h2> {6} 7 | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | --- | --- | --- | --- | --- | --- | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 75 | 15 | 15 | 0 | 100% | | 50% | 150 | 15 | 14 | 1 | 93.3% | | 75% | 225 | 15 | 7 | 8 | 46.7% | | 125% | 375 | 15 | 0 | 15 | 100% | | 150% | 450 | 15 | 0 | 15 | 100% | | 175% | 525 | 15 | 0 | 15 | 100% | | 200% | 600 | 15 | 0 | 15 | 100% | | LOT 2 | | | | | | | --- | --- | --- | --- | --- | --- | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 10 | 10 | 0 | 100% | | 25% | 75 | 16 | 16 | 0 | 100% | | 50% | 150 | 15 | 15 | 0 | 100% | | 75% | 225 | 15 | 14 | 1 | 93.3% | | 125% | 375 | 15 | 0 | 15 | 100% | | 150% | 450 | 15 | 0 | 15 | 100% | | 175% | 525 | 15 | 0 | 15 | 100% | | 200% | 600 | 15 | 0 | 15 | 100% | | LOT 3 | | | | | | | --- | --- | --- | --- | --- | --- | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 20 | 20 | 0 | 100% | | 25% | 75 | 19 | 19 | 0 | 100% | | 50% | 150 | 20 | 19 | 1 | 95.0% | | 75% | 225 | 20 | 8 | 12 | 40.0% | | 125% | 375 | 20 | 2 | 18 | 90.0% | | 150% | 450 | 19 | 0 | 19 | 100% | | 175% | 525 | 19 | 0 | 19 | 100% | | 200% | 600 | 19 | 0 | 19 | 100% | ## Cocaine | ALL LOTS COMBINED | | | | | | | --- | --- | --- | --- | --- | --- | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 45 | 45 | 0 | 100% | | 25% | 75 | 45 | 45 | 0 | 100% | | 50% | 150 | 46 | 46 | 0 | 100% | | 75% | 225 | 45 | 28 | 17 | 62.2% | {7} | 125% | 375 | 45 | 1 | 44 | 97.8% | | --- | --- | --- | --- | --- | --- | | 150% | 450 | 46 | 0 | 46 | 100% | | 175% | 525 | 46 | 0 | 46 | 100% | | 200% | 600 | 47 | 0 | 47 | 100% | | LOT 1 | | | | | | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 37.5 | 15 | 15 | 0 | 100% | | 50% | 75 | 15 | 15 | 0 | 100% | | 75% | 112.5 | 15 | 10 | 5 | 66.7% | | 125% | 187.5 | 15 | 0 | 15 | 100% | | 150% | 225 | 15 | 0 | 15 | 100% | | 175% | 262.5 | 15 | 0 | 15 | 100% | | 200% | 300 | 15 | 0 | 15 | 100% | | LOT 2 | | | | | | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 37.5 | 15 | 15 | 0 | 100% | | 50% | 75 | 15 | 15 | 0 | 100% | | 75% | 112.5 | 15 | 11 | 4 | 66.7% | | 125% | 187.5 | 15 | 1 | 14 | 100% | | 150% | 225 | 15 | 0 | 15 | 100% | | 175% | 262.5 | 15 | 0 | 15 | 100% | | 200% | 300 | 18 | 0 | 18 | 100% | | LOT 3 | | | | | | | % of Cutoff | ng/mL | N | #NEG | #POS | Precision | | NEG | 0 | 15 | 15 | 0 | 100% | | 25% | 37.5 | 15 | 15 | 0 | 100% | | 50% | 75 | 16 | 16 | 0 | 100% | | 75% | 112.5 | 15 | 7 | 8 | 46.7% | | 125% | 187.5 | 15 | 0 | 15 | 100% | | 150% | 225 | 16 | 0 | 16 | 100% | | 175% | 262.5 | 16 | 0 | 16 | 100% | | 200% | 300 | 14 | 0 | 14 | 100% | b. Linearity/assay reportable range: Not applicable; the device is intended for qualitative use. {8} c. Traceability, Stability, Expected values (controls, calibrators, or methods): External control standards are not supplied with this device. The sponsor states that specific external quality control products must be used with the device system. The quality control products were previously cleared under k121122. Stability: The sponsor’s stability protocols and acceptance criteria were reviewed and found acceptable. The information supports that the Snap-Top SK Cup unopened stability is 12 months. Stability testing is ongoing. d. Detection limit: Analytical performance of the device around the cutoff is described in Section M.1.a. (Precision/Reproducibility) above. e. Analytical specificity: Analytical specificity studies were performed with the Snap-Top SK Cup to determine whether drugs and drug metabolites within the same class of drugs or with similar molecular structures cross- react in the test system. Reference standards for the various metabolites and compounds were prepared at 100 µg/mL in pooled negative human urine samples. Compounds that tested positive were serially diluted until a negative result was observed. Results shown are expressed as the minimum concentration producing a positive result in the indicated assay. A list of these compounds and their level of cross reactivity is shown below. | Related Compound or Cross-Reactant | Result | % Cross Reactive | | --- | --- | --- | | Barbiturate (BAR) (Secobarbital) (300 ng/mL) | | | | Butabarbital | Positive at 75 ng/mL | 400% | | Butethal | Positive at 250 ng/mL | 120% | | Pentobarbital | Positive at 300 ng/mL | 100% | | Phenobarbital | Positive at 250 ng/mL | 120% | | Aprobarbital | Positive at 200 ng/mL | 150% | | Barbital | Positive at 250 ng/mL | 120% | | Alphenal | Positive at 600 ng/mL | 50% | | Amobarbital | Positive at 850 ng/mL | 35% | | Cyclopentobarbital | Positive at 600 ng/mL | 50% | | Allobarbital | Positive at 1000 ng/mL | 30% | {9} | Butalbital | Positive at 5000 ng/mL | 6% | | --- | --- | --- | | Mephobarbital | Positive at 50000 ng/mL | 1% | | Barbituric Acid | Negative at 100000 ng/mL | N/A | | Glutethimide | Negative at 100000 ng/mL | N/A | | Hexobarbital | Negative at 100000 ng/mL | N/A | | Phenytoin (diphenylhydantoin) | Negative at 100000 ng/mL | N/A | | Thiopental | Negative at 100000 ng/mL | N/A | | Benzodiazepines (BZO) (Oxazepam) (300 ng/mL) | | | | Temazepam glucuronide | Positive at 50 ng/mL | 600% | | Clobazam | Positive at 98 ng/mL | 306% | | N-Desmethylflunitrazepam | Positive at 100 ng/mL | 300% | | Nitrazepam | Positive at 100 ng/mL | 300% | | Oxazepam glucuronide | Positive at 100 ng/mL | 300% | | Temazepam | Positive at 125 ng/mL | 240% | | RS-Lorazepam glucuronide | Positive at 150 ng/mL | 200% | | Diazepam | Positive at 195 ng/mL | 154% | | Flunitrazepam | Positive at 195 ng/mL | 154% | | Clorazepate | Positive at 200 ng/mL | 150% | | Alprazolam | Positive at 250 ng/mL | 120% | | Desalkylflurazepam | Positive at 390 ng/mL | 77% | | Nordiazepam | Positive at 390 ng/mL | 77% | | Clonazaepam | Positive at 400 ng/mL | 75% | | Bromazepam | Positive at 1000 ng/mL | 30% | | Estazolam | Positive at 1250 ng/mL | 24% | | α-hydroxyalprazolam | Positive at 1262 ng/mL | 24% | | Lorazepam (d,l) | Positive at 1500 ng/mL | 20% | | Triazolam | Positive at 2500 ng/mL | 12% | | Chlordiazepoxide | Positive at 3125 ng/mL | 10% | | N-Desmethylchlordiazepoxide | Positive at 6250 ng/mL | 5% | | Midazolam | Positive at 12500 ng/mL | 2% | | Triazolam, 1-hydroxy | Positive at 50000 ng/mL | N/A | | 7-Aminoclonazepam | Negative at 100000 ng/mL | N/A | | 7-Aminoflunitrazepam | Negative at 100000 ng/mL | N/A | | Flurazepam | Negative at 100000 ng/mL | N/A | {10} 11 | Cocaine (COC) (Benzoylecgonine) 150 ng/mL | | | | --- | --- | --- | | Cocaethylene | Positive at 9325 ng/mL | 2% | | Cocaine | Positive at 2000 ng/mL | 8% | | Ecgonine | Positive at 30000 ng/mL | 1% | | Ecgonine Methyl Ester | Negative at 100000 ng/mL | N/A | ## Prescription Drugs Drug free urine samples were spiked with BAR, BZO, and COC concentrations that were at 50% (negative) and 150% (positive) of cutoff. Concentrations of 100,000 ng/mL of structurally-unrelated compounds were then added to the preparation and assayed using the Snap-Top SK Cup. None of the following compounds affected the expected results: | N-Acetylprocainamide | Fenoprofen | Niacinamide | Sulfamethazine | | --- | --- | --- | --- | | Amoxicillin | Furosemide | Nifedipine | Sulindac | | Ampicillin | Hydralazine | Noscapine | Tetracycline | | l-Ascorbic Acid | Hydrochlorothiazide | Oxolinic acid | Tetrahydrocortisone 3-acetate | | Atropine | Hydrocortisone | Oxymetazoline | Tetrahydrozoline | | Chlorothiazide* | o-Hydroxyhippuric acid | Papaverine | Thiamine | | Chlorpromazine | Ketamine | Penicillin-G | Thioridazine | | Clonidine | Ketoprofen | Perphenazine | Tolbutamide | | l-Cotinine | Labetalol | Phenelzine | Triamterene | | Cortisone | Loperamide | Prednisone | Trifluoperazine | | Diclofenac | Meprobamate | d,l-Propranolol | Trimethoprim | | Diflunisal | Methoxyphenamine | Quinine | d,l-Tryptophan | | Digoxin | Methylphenidate | Quinidine | Verapamil | | Diphenhydramine | Nalidixic acid | Serotonin | Zomepirac | | Erythromycin | | | | ## pH and Specific Gravity The Snap-Top SK Cup was assayed with pH values of 3.0, 4.0, 7.0 and 9.0. The pH samples were fortified with drug concentrations at 50% (negative) and 150% (positive) of cutoff for BAR, BZO, and COC. Each sample was assayed in triplicate. All pH samples gave negative results at the 50% of cutoff level for each drug, and all gave positive results at the 150% of cutoff level for each drug. The Snap-Top SK Cup was assayed in triplicate with samples with specific gravity {11} values of 1.003, 1.015 and 1.030. The specific gravity samples were fortified with drug concentrations as described above for pH. All specific gravity samples gave negative results at the 50% of cutoff level for each drug, and all gave positive results at the 150% of cutoff level for each drug. ## Structurally-unrelated Drug free urine samples were spiked with BAR, BZO, and COC concentrations that were at 50% (negative) and 150% (positive) of cutoff. Concentrations of 100,000 ng/mL of structurally-unrelated compounds were then added to the preparation and assayed using the Snap-Top SK Cup. None of the following compounds affected the expected results: acetylsalicylic acid, acetaminophen, bropheniramine maleate, caffeine, carbamazepine, chlorpheniramine, cocaine, dextromethorphan, doxylamine, ibuprofen, morphine, phenobarbital, phenytoin (diphenylhydantoin), d-pseudoephedrine, salicylic acid. The labeling states that there is the possibility that other substances and/or factors not listed above may interfere with the test and cause false results. ## f. Assay cut-off: Analytical performance of the device around the cutoff is described in Section M.1.a. (Precision/Reproducibility) above. ## 2. Comparison studies: a. Method comparison with predicate device: The accuracy of the Snap-Top SK Cup was evaluated at three sites representative of laboratory, workplace, and POC settings with blind coded clinical urine samples that contained varying concentrations of drugs as determined by GC/MS or LC/MS/MS. Results summaries are provided below, for all sites combined: | | | Negative Urine | Near Cutoff Negative by GC/MS (Between - 50% and the cutoff) | Near Cutoff Positive by GC/MS (Between the cutoff and +50%) | High Positive by GC/MS (greater than +50%) | % Total Agreement with GCMS | | --- | --- | --- | --- | --- | --- | --- | | Barbiturates | Positive Results | 0 | 2 | 4 | 36 | 97.8 | | | Negative Results | 45 | 3 | 0 | 0 | | | Benzodiazepines | Positive | 0 | 2 | 4 | 36 | 97.6 | {12} 13 Summary of discordant results shown in the table above: | Sample Numbers | Drug Test | Cutoff value (ng/mL) | Result (POS/NEG) | Drug/Metabolite GC/MS value (ng/mL) | | | --- | --- | --- | --- | --- | --- | | | | | | Drug /Metabolite | GC/MS value (ng/ml) | | 86 | BAR | 300 | POS | Butalbital | 4788 | | 88 | BAR | 300 | POS | Phenobarbital | 160 | | 39 | BZO | 300 | POS | Oxazepam | 271 | | 42 | BZO | 300 | POS | Oxazepam | 235 | b. Lay user study: Not applicable. The assay is intended for prescription use. b. Matrix comparison: Not applicable. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Not applicable. {13} 4. Clinical cut-off Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence determination. 14