Immunalysis Benzoylecgonine Urine Enzyme Immunoassay, Immunalysis Benzoylecgonine Urine Calibrators, Immunalysis Benzoylecgonine Urine Control Set

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k150925 B. Purpose for Submission: New device C. Measurand: Benzoylecgonine D. Type of Test: Qualitative and semi-quantitative homogeneous enzyme immunoassay E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Immunalysis Benzoylecgonine Urine Calibrators Immunalysis Benzoylecgonine Urine Control Set G. Regulatory Information: | Product Code | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | DIO – Cocaine and cocaine metabolite test system | Class II | 21 CFR §862.3250 | 91 – Toxicology | | DLJ – Clinical Toxicology Calibrator | Class II | 21 CFR §862.3200 | 91 – Toxicology | | LAS – Clinical Toxicology Control Material | Class I, reserved | 21 CFR §862.3280 | 91 – Toxicology | {1} H. Intended Use: 1. Intended use(s): See Indication(s) for use below. 2. Indication(s) for use: Immunalysis Benzoylecgonine Urine Enzyme Immunoassay The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150 ng/mL and 300 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzoylecgonine. This in-vitro device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures. The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. Immunalysis Benzoylecgonine Urine Calibrators The Immunalysis Benzoylecgonine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calibrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers. Immunalysis Benzoylecgonine Urine Control Set The Immunalysis Benzoylecgonine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analyte currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers 3. Special conditions for use statement(s): For prescription use only. 4. Special instrument requirements: {2} Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit contains two reagents, which are provided as ready-to-use: - Antibody/Substrate Reagent (RA) – This reagent contains polyclonal sheep antibodies to benzoylecgonine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. - Enzyme Conjugate Reagent (RE) – This reagent contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with benzoylecgonine in Tris buffer with Sodium Azide as a preservative. The Immunalysis Benzoylecgonine Urine Calibrators and the Immunalysis Benzoylecgonine Urine Control Sets are sold as individual bottles and are liquid and ready-to-use. The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. Each calibrator and control level contains a known concentration of Benzoylecgonine spiked into the negative calibrator matrix. J. Substantial Equivalence Information: 1. Predicate device name(s): Randox Cocaine Metabolite Assay Randox Multidrug Calibrator Set Randox Multidrug Controls, Level 1 and 2 2. Predicate 510(k) number(s): k113751 3. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Candidate Devices | Predicate – k113751 | | Intended Use | Same | For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine | | Test Principle | Same | Homogeneous Enzyme Immunoassay | {3} | Similarities | | | | --- | --- | --- | | Item | Candidate Devices | Predicate – k113751 | | Cutoff | 150 and 300 ng/mL | 300 ng/mL | | Reagent Form | Same | Liquid Ready-to-Use Two Reagent Assay | | Reagent Storage | Same | 2 – 8° C | | Calibrator Levels | Same | Five levels at 0, 150, 300, 500, and 1000 ng/mL | | Control and Calibrator Storage | Same | 2 – 8° C | | Differences | | | | --- | --- | --- | | Item | Candidate Devices | Predicate – k113751 | | Antibody | Polyclonal sheep antibody to benzoylecgonine | Mouse monoclonal antibodies to benzoylecgonine | | Control Levels | Four levels at 112.5, 187.5, 225, and 375 ng/mL | Two levels at 225 and 375 ng/mL | # K. Standard/Guidance Document Referenced (if applicable): - CLSI EP5-A2, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline—Second Edition - CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline—Second Edition # L. Test Principle: The assay is based on the competition of benzoylecgonine labeled enzyme glucose-6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine sample and enzyme activity. The enzyme G6PDH activity is determined at $340\mathrm{nm}$ spectrophotometrically by the conversion of NAD to NADH. # M. Performance Characteristics (if/when applicable): # 1. Analytical performance: a. Precision/Reproducibility: A precision/cutoff characterization study was performed for 20 days, 2 runs per day {4} in duplicate (N=80) on drug-free negative urine samples spiked with benzoylecgonine to concentrations of ±25%, ±50%, ±75%, and ±100% of each cutoff, as well as a zero concentration sample. The benzoylecgonine concentrations in spiked samples were confirmed by mass spectrometry. The results of the study are summarized below: | Qualitative Analysis (for 150 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Neg / 0 Pos | | 37.5 | -75% | 80 | 80 Neg / 0 Pos | | 75 | -50% | 80 | 80 Neg / 0 Pos | | 112.5 | -25% | 80 | 80 Neg / 0 Pos | | 150 | Cutoff | 80 | 36 Neg / 44 Pos | | 187.5 | +25% | 80 | 80 Pos / 0 Neg | | 225 | +50% | 80 | 80 Pos / 0 Neg | | 262.5 | +75% | 80 | 80 Pos / 0 Neg | | 300 | +100% | 80 | 80 Pos / 0 Neg | | Qualitative Analysis (for 300 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Neg / 0 Pos | | 75 | -75% | 80 | 80 Neg / 0 Pos | | 150 | -50% | 80 | 80 Neg / 0 Pos | | 225 | -25% | 80 | 80 Neg / 0 Pos | | 300 | Cutoff | 80 | 37 Neg / 43 Pos | | 375 | +25% | 80 | 80 Pos / 0 Neg | | 450 | +50% | 80 | 80 Pos / 0 Neg | | 525 | +75% | 80 | 80 Pos / 0 Neg | | 600 | +100% | 80 | 80 Pos / 0 Neg | | Semi-quantitative Analysis (for 150 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Neg / 0 Pos | | 37.5 | -75% | 80 | 80 Neg / 0 Pos | | 75 | -50% | 80 | 80 Neg / 0 Pos | | 112.5 | -25% | 80 | 80 Neg / 0 Pos | | 150 | Cutoff | 80 | 25 Neg / 55 Pos | | 187.5 | +25% | 80 | 80 Pos / 0 Neg | | 225 | +50% | 80 | 80 Pos / 0 Neg | | 262.5 | +75% | 80 | 80 Pos / 0 Neg | | 300 | +100% | 80 | 80 Pos / 0 Neg | {5} | Semi-quantitative Analysis (for 300 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Neg / 0 Pos | | 75 | -75% | 80 | 80 Neg / 0 Pos | | 150 | -50% | 80 | 80 Neg / 0 Pos | | 225 | -25% | 80 | 80 Neg / 0 Pos | | 300 | Cutoff | 80 | 24 Neg / 56 Pos | | 375 | +25% | 80 | 80 Pos / 0 Neg | | 450 | +50% | 80 | 80 Pos / 0 Neg | | 525 | +75% | 80 | 80 Pos / 0 Neg | | 600 | +100% | 80 | 80 Pos / 0 Neg | b. Linearity/assay reportable range: A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of benzoylecgonine and generating serial dilutions to achieve concentrations ranging from 100 ng/mL to 1100 ng/mL. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: | Linearity/Recovery | | | | --- | --- | --- | | Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) | | 100 | 98.9 | 98.9 | | 150 | 162.9 | 108.6 | | 200 | 194.7 | 97.4 | | 300 | 304.5 | 101.5 | | 400 | 419.7 | 104.9 | | 500 | 489.9 | 98.0 | | 600 | 602.8 | 100.5 | | 700 | 736.4 | 105.2 | | 800 | 803.1 | 100.4 | | 900 | 946.0 | 105.1 | | 1000 | 996.0 | 99.6 | | 1100 | 1003.1 | 91.2 | c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability The analyte in the calibrator and controls is traceable to a commercially available standard solution. The standard is certified material with the concentration verified by GC-MS or LC/MS-MS. This standard is diluted with the proper calibrator buffer to make the calibrator and controls to the desired concentrations. The concentrations are confirmed by Gas Chromatography/Mass Spectrometry Analysis (GC/MS) and/or {6} Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS). ## Value Assignment/Expected Values The Negative Calibrator is a processed, drug free urine matrix. The standard is compared to a reference negative standard to ensure that it is free of analyte. A value is assigned when the test is within the acceptable range. The non-zero calibrators and the controls are prepared by spiking known concentrations of benzoylecgonine into the negative calibrator matrix. The concentrations are confirmed by GC/MS or LC/MS/MS. If any of the analytes are out of the acceptable range, then the calibrator or control is adjusted and re-tested. Values are assigned to the calibrator or control once the GC/MS or LC/MS/MS results are within the acceptable range. ## Stability A closed-vial accelerated stability study and an onboard, open vial stability study were conducted for the calibrators and controls. Real-time stability studies are ongoing. All stability protocols were reviewed and found to be acceptable. These studies support the closed vial stability claim of one year and the opened vial stability claim of 28 days when calibrators and controls are stored at 2-8°C. d. Detection limit: Not applicable. e. Analytical specificity: ## Structurally related compounds The sponsor performed studies at both claimed cutoffs in both qualitative and semi-quantitative modes to evaluate the cross-reactivity of compounds that are structurally related to benzoylecgonine. Results are summarized below: | Structurally Related Compounds at 150 ng/mL cutoff | | | | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | Cross-reactivity (%) | | Benzoylecgonine | 150 | 100 | | Cocaine | 100,000 | 0.15 | | Ecgonine | 59,000 | 0.25 | | Ecgonine Methyl Ester | 100,000 | <0.15 | {7} 8 | Structurally Related Compounds at 300 ng/mL cutoff | | | | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | Cross-reactivity (%) | | Benzoylecgonine | 150 | 100 | | Cocaine | 100,000 | <0.15 | | Ecgonine | 100,000 | <0.15 | | Ecgonine Methyl Ester | 100,000 | <0.15 | ## Non-structurally related compounds Potential interference from non-structurally related drugs and metabolites was evaluated in the qualitative and semi-quantitative modes by spiking these compounds into drug free urine containing benzoylecgonine at $\pm 25\%$ of the $150~\mathrm{ng/mL}$ cutoff (112.5 ng/mL and 187.5 ng/mL) and $\pm 25\%$ of the $300~\mathrm{ng/mL}$ cutoff (225 ng/mL and 375 ng/mL). The results were the same for the qualitative and semi-quantitative modes and are summarized below: | Structurally Unrelated Compounds (for 150 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | -25% Cutoff | +25% Cutoff | | | | Result | Result | | 4-Bromo-2,5,Dimethoxyphenethylamine | 100,000 | Negative | Positive | | 6-Acetylcodeine | 100,000 | Negative | Positive | | 6-Acetylmorphine | 100,000 | Negative | Positive | | 7-Aminoclonazepam | 100,000 | Negative | Positive | | 7-Aminoflunitrazepam | 100,000 | Negative | Positive | | 7-Aminonitrazepam | 100,000 | Negative | Positive | | 11-hydroxy-delta-9-THC | 100,000 | Negative | Positive | | 11-nor-9 carboxy-delta-THC | 100,000 | Negative | Positive | | Acetaminophen | 500,000 | Negative | Positive | | Acetylsalicylic Acid | 500,000 | Negative | Positive | | Alprazolam | 100,000 | Negative | Positive | | Amitriptyline | 100,000 | Negative | Positive | | Amobarbital | 100,000 | Negative | Positive | | S-(+ ) Amphetamine | 100,000 | Negative | Positive | | Benzylpiperazine | 100,000 | Negative | Positive | | Bromazepam | 100,000 | Negative | Positive | | Buprenorphine | 100,000 | Negative | Positive | | Bupropion | 100,000 | Negative | Positive | | Butabarbital | 100,000 | Negative | Positive | | Butalbital | 100,000 | Negative | Positive | | Caffeine | 500,000 | Negative | Positive | {8} | Cannabidiol | 100,000 | Negative | Positive | | --- | --- | --- | --- | | Cannabinol | 100,000 | Negative | Positive | | Carbamazepine | 100,000 | Negative | Positive | | Carisoprodol | 100,000 | Negative | Positive | | Chlordiazepoxide | 100,000 | Negative | Positive | | Chlorpromazine | 100,000 | Negative | Positive | | cis-Tramadol | 100,000 | Negative | Positive | | Clobazam | 100,000 | Negative | Positive | | Clomipramine | 100,000 | Negative | Positive | | Clonazepam | 100,000 | Negative | Positive | | Clozapine | 100,000 | Negative | Positive | | Codeine | 100,000 | Negative | Positive | | Cotinine | 100,000 | Negative | Positive | | Cyclobenzaprine | 100,000 | Negative | Positive | | Dehydronorketamine | 100,000 | Negative | Positive | | Delta-9-THC | 100,000 | Negative | Positive | | Demoxepam | 100,000 | Negative | Positive | | Desakylflurazepam | 100,000 | Negative | Positive | | Desipramine | 100,000 | Negative | Positive | | Dextromethorphan | 100,000 | Negative | Positive | | Diazepam | 100,000 | Negative | Positive | | Digoxin | 100,000 | Negative | Positive | | Dihydrocodeine | 100,000 | Negative | Positive | | Diphenhydramine | 500,000 | Negative | Positive | | Doxepin | 100,000 | Negative | Positive | | EDDP | 100,000 | Negative | Positive | | 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive | | 1S,2R(+)-Ephedrine | 100,000 | Negative | Positive | | Ethyl β-D-glucuronide | 100,000 | Negative | Positive | | Ethylmorphine | 100,000 | Negative | Positive | | Fenfluramine | 100,000 | Negative | Positive | | Fentanyl | 100,000 | Negative | Positive | | Flunitrazepam | 100,000 | Negative | Positive | | Fluoxetine | 100,000 | Negative | Positive | | Flurazepam | 100,000 | Negative | Positive | | Haloperidol | 100,000 | Negative | Positive | | Heroin | 100,000 | Negative | Positive | | Hexobarbital | 100,000 | Negative | Positive | | Hydrocodone | 100,000 | Negative | Positive | | Hydromorphone | 100,000 | Negative | Positive | | Ibuprofen | 500,000 | Negative | Positive | | Imipramine | 100,000 | Negative | Positive | | Ketamine | 100,000 | Negative | Positive | | Lamotrignine | 100,000 | Negative | Positive | | Levorphanol Tartrate | 100,000 | Negative | Positive | | Lidocaine | 100,000 | Negative | Positive | 9 {9} | Lorazepam | 100,000 | Negative | Positive | | --- | --- | --- | --- | | Lorazepam Glucuronide | 50,000 | Negative | Positive | | Lormetazepam | 100,000 | Negative | Positive | | LSD | 100,000 | Negative | Positive | | Maprotiline | 100,000 | Negative | Positive | | MDA | 100,000 | Negative | Positive | | MDEA | 100,000 | Negative | Positive | | MDMA | 100,000 | Negative | Positive | | Meperidine | 100,000 | Negative | Positive | | Meprobamate | 100,000 | Negative | Positive | | Methadone | 100,000 | Negative | Positive | | Methamphetamine | 100,000 | Negative | Positive | | Methaquolone | 100,000 | Negative | Positive | | Methoxetamine | 100,000 | Negative | Positive | | Methylone | 100,000 | Negative | Positive | | Methylphenidate | 100,000 | Negative | Positive | | Midazolam | 100,000 | Negative | Positive | | Morphine | 100,000 | Negative | Positive | | Morphine 3-D-glucuronide | 100,000 | Negative | Positive | | Morphine 6-D-glucuronide | 50,000 | Negative | Positive | | Nalorphine | 100,000 | Negative | Positive | | Naloxone | 100,000 | Negative | Positive | | Naltrexone | 100,000 | Negative | Positive | | Naproxen | 100,000 | Negative | Positive | | N-desmethyltentadol | 100,000 | Negative | Positive | | Nitrazepam | 100,000 | Negative | Positive | | Norbuprenorphine | 50,000 | Negative | Positive | | Norcodeine | 100,000 | Negative | Positive | | Nordiazepam | 100,000 | Negative | Positive | | Norketamine | 100,000 | Negative | Positive | | Normorphine | 100,000 | Negative | Positive | | Norproxyphene | 100,000 | Negative | Positive | | Norpseudoephedrine | 100,000 | Negative | Positive | | Nortriptyline | 100,000 | Negative | Positive | | Olanzapine | 100,000 | Negative | Positive | | Oxazepam | 100,000 | Negative | Positive | | Oxycodone | 100,000 | Negative | Positive | | Oxymorphone | 100,000 | Negative | Positive | | PCP | 100,000 | Negative | Positive | | Pentazocine | 100,000 | Negative | Positive | | Pentobarbital | 100,000 | Negative | Positive | | Phenobarbital | 100,000 | Negative | Positive | | Phentermine | 100,000 | Negative | Positive | | Phenylephedrine | 100,000 | Negative | Positive | | Phenylpropanolamine | 100,000 | Negative | Positive | | Phenytoin | 100,000 | Negative | Positive | 10 {10} | Structurally Unrelated Compounds (for 300 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | -25% Cutoff | +25% Cutoff | | | | Result | Result | | 4-Bromo-2,5,Dimethoxyphenethylamine | 100,000 | Negative | Positive | | 6-Acetylcodeine | 100,000 | Negative | Positive | | 6-Acetylmorphine | 100,000 | Negative | Positive | | 7-Aminoclonazepam | 100,000 | Negative | Positive | | 7-Aminoflunitrazepam | 100,000 | Negative | Positive | | 7-Aminonitrazepam | 100,000 | Negative | Positive | | 11-hydroxy-delta-9-THC | 100,000 | Negative | Positive | | 11-nor-9 carboxy-delta-THC | 100,000 | Negative | Positive | | Acetaminophen | 500,000 | Negative | Positive | | Acetylsalicylic Acid | 500,000 | Negative | Positive | | Alprazolam | 100,000 | Negative | Positive | | Amitriptyline | 100,000 | Negative | Positive | | Amobarbital | 100,000 | Negative | Positive | | S-(+)-Amphetamine | 100,000 | Negative | Positive | | Benzylpiperazine | 100,000 | Negative | Positive | | Citalopram | 100,000 | Negative | Positive | | Citalopram | 100,000 | Negative | Positive | | Citalopram | 100,000 | Negative | Positive | | Citalopram | 100,000 | Negative | Positive | {11} | Bromazepam | 100,000 | Negative | Positive | | --- | --- | --- | --- | | Buprenorphine | 100,000 | Negative | Positive | | Bupropion | 100,000 | Negative | Positive | | Butabarbital | 100,000 | Negative | Positive | | Butalbital | 100,000 | Negative | Positive | | Caffeine | 500,000 | Negative | Positive | | Cannabidiol | 100,000 | Negative | Positive | | Cannabinol | 100,000 | Negative | Positive | | Carbamazepine | 100,000 | Negative | Positive | | Carisoprodol | 100,000 | Negative | Positive | | Chlordiazepoxide | 100,000 | Negative | Positive | | Chlorpromazine | 100,000 | Negative | Positive | | cis-Tramadol | 100,000 | Negative | Positive | | Clobazam | 100,000 | Negative | Positive | | Clomipramine | 100,000 | Negative | Positive | | Clonazepam | 100,000 | Negative | Positive | | Clozapine | 100,000 | Negative | Positive | | Codeine | 100,000 | Negative | Positive | | Cotinine | 100,000 | Negative | Positive | | Cyclobenzaprine | 100,000 | Negative | Positive | | Dehydronorketamine | 100,000 | Negative | Positive | | Delta-9-THC | 100,000 | Negative | Positive | | Demoxepam | 100,000 | Negative | Positive | | Desakylflurazepam | 100,000 | Negative | Positive | | Desipramine | 100,000 | Negative | Positive | | Dextromethorphan | 100,000 | Negative | Positive | | Diazepam | 100,000 | Negative | Positive | | Digoxin | 100,000 | Negative | Positive | | Dihydrocodeine | 100,000 | Negative | Positive | | Diphenhydramine | 500,000 | Negative | Positive | | Doxepin | 100,000 | Negative | Positive | | EDDP | 100,000 | Negative | Positive | | 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive | | 1S,2R(+)-Ephedrine | 100,000 | Negative | Positive | | Ethyl β-D-glucuronide | 100,000 | Negative | Positive | | Ethylmorphine | 100,000 | Negative | Positive | | Fenfluramine | 100,000 | Negative | Positive | | Fentanyl | 100,000 | Negative | Positive | | Flunitrazepam | 100,000 | Negative | Positive | | Fluoxetine | 100,000 | Negative | Positive | | Flurazepam | 100,000 | Negative | Positive | | Haloperidol | 100,000 | Negative | Positive | | Heroin | 100,000 | Negative | Positive | | Hexobarbital | 100,000 | Negative | Positive | | Hydrocodone | 100,000 | Negative | Positive | | Hydromorphone | 100,000 | Negative | Positive | 12 {12} | Ibuprofen | 500,000 | Negative | Positive | | --- | --- | --- | --- | | Imipramine | 100,000 | Negative | Positive | | Ketamine | 100,000 | Negative | Positive | | Lamotrigine | 100,000 | Negative | Positive | | Levorphanol Tartrate | 100,000 | Negative | Positive | | Lidocaine | 100,000 | Negative | Positive | | Lorazepam | 100,000 | Negative | Positive | | Lorazepam Glucuronide | 50,000 | Negative | Positive | | Lormetazepam | 100,000 | Negative | Positive | | LSD | 100,000 | Negative | Positive | | Maprotiline | 100,000 | Negative | Positive | | MDA | 100,000 | Negative | Positive | | MDEA | 100,000 | Negative | Positive | | MDMA | 100,000 | Negative | Positive | | Meperidine | 100,000 | Negative | Positive | | Meprobamate | 100,000 | Negative | Positive | | Methadone | 100,000 | Negative | Positive | | Methamphetamine | 100,000 | Negative | Positive | | Methaquolone | 100,000 | Negative | Positive | | Methoxetamine | 100,000 | Negative | Positive | | Methylone | 100,000 | Negative | Positive | | Methylphenidate | 100,000 | Negative | Positive | | Midazolam | 100,000 | Negative | Positive | | Morphine | 100,000 | Negative | Positive | | Morphine 3-D-glucuronide | 100,000 | Negative | Positive | | Morphine 6-D-glucuronide | 50,000 | Negative | Positive | | Nalorphine | 100,000 | Negative | Positive | | Naloxone | 100,000 | Negative | Positive | | Naltrexone | 100,000 | Negative | Positive | | Naproxen | 100,000 | Negative | Positive | | N-desmethyltentadol | 100,000 | Negative | Positive | | Nitrazepam | 100,000 | Negative | Positive | | Norbuprenorphine | 50,000 | Negative | Positive | | Norcodeine | 100,000 | Negative | Positive | | Nordiazepam | 100,000 | Negative | Positive | | Norketamine | 100,000 | Negative | Positive | | Normorphine | 100,000 | Negative | Positive | | Norproxyphene | 100,000 | Negative | Positive | | Norpseudoephedrine | 100,000 | Negative | Positive | | Nortriptyline | 100,000 | Negative | Positive | | Olanzapine | 100,000 | Negative | Positive | | Oxazepam | 100,000 | Negative | Positive | | Oxycodone | 100,000 | Negative | Positive | | Oxymorphone | 100,000 | Negative | Positive | | PCP | 100,000 | Negative | Positive | | Pentazocine | 100,000 | Negative | Positive | 13 {13} | Pentobarbital | 100,000 | Negative | Positive | | --- | --- | --- | --- | | Phenobarbital | 100,000 | Negative | Positive | | Phentermine | 100,000 | Negative | Positive | | Phenylephedrine | 100,000 | Negative | Positive | | Phenylpropanolamine | 100,000 | Negative | Positive | | Phenytoin | 100,000 | Negative | Positive | | PMA | 100,000 | Negative | Positive | | Prazepam | 100,000 | Negative | Positive | | Propoxyphene | 100,000 | Negative | Positive | | Propranolol | 100,000 | Negative | Positive | | Protriptyline | 100,000 | Negative | Positive | | R,R(-)-Pseudoephedrine | 100,000 | Negative | Positive | | S,S(+)-Pseudoephedrine | 100,000 | Negative | Positive | | Ranitidine | 100,000 | Negative | Positive | | Ritalinic Acid | 100,000 | Negative | Positive | | Salicylic Acid | 100,000 | Negative | Positive | | Secobarbital | 100,000 | Negative | Positive | | Sertraline | 100,000 | Negative | Positive | | Sufentanil Citrate | 50,000 | Negative | Positive | | Tapentadol | 100,000 | Negative | Positive | | Temazepam | 100,000 | Negative | Positive | | Theophylline | 100,000 | Negative | Positive | | Thioridazine | 100,000 | Negative | Positive | | Trazodone | 100,000 | Negative | Positive | | Triazolam | 100,000 | Negative | Positive | | Trifluoromethylphenyl-piperazine | 100,000 | Negative | Positive | | Trimipramine | 100,000 | Negative | Positive | | Venlafaxine | 100,000 | Negative | Positive | | Verapamil | 100,000 | Negative | Positive | | Zolpidem Tartrate | 100,000 | Negative | Positive | # Endogenous compounds Potential interference from endogenous compounds was evaluated in the qualitative and semi-quantitative modes by spiking these compounds into drug free urine containing benzoylecgonine at $\pm 25\%$ of the $150~\mathrm{ng / mL}$ cutoff (112.5 ng/mL and $187.5~\mathrm{ng / mL}$ ) and $\pm 25\%$ of the $300~\mathrm{ng / mL}$ cutoff (225 ng/mL and $375~\mathrm{ng / mL}$ ). The results were the same for the qualitative and semi-quantitative modes and are summarized below: {14} | Endogenous Compounds (for 150 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Compound | Concentration Tested | -25% Cutoff | +25% Cutoff | | Acetone | 1.0 g/dL | Negative | Positive | | Ascorbic Acid | 1.5 g/dL | Negative | Positive | | Bilirubin | 0.002 g/dL | Negative | Positive | | Creatinine | 0.5 g/dL | Negative | Positive | | Ethanol | 1.0 g/dL | Negative | Positive | | Galactose | 0.01 g/dL | Negative | Positive | | γ-Globulin | 0.5 g/dL | Negative | Positive | | Glucose | 2.0 g/dL | Negative | Positive | | Hemoglobin | 0.300 g/dL | Negative | Positive | | Human Serum Albumin | 0.5 g/dL | Negative | Positive | | Oxalic Acid | 0.1 g/dL | Negative | Positive | | Riboflavin | 0.0075 g/dL | Negative | Positive | | Sodium Azide | 1% w/v | Negative | Positive | | Sodium Chloride | 6.0 g/dL | Negative | Positive | | Sodium Fluoride | 1% w/v | Negative | Positive | | Urea | 6.0 g/dL | Negative | Positive | | Endogenous Compounds (for 300 ng/mL cutoff) | | | | | --- | --- | --- | --- | | Compound | Concentration Tested | -25% Cutoff | +25% Cutoff | | Acetone | 1.0 g/dL | Negative | Positive | | Ascorbic Acid | 1.5 g/dL | Negative | Positive | | Bilirubin | 0.002 g/dL | Negative | Positive | | Creatinine | 0.5 g/dL | Negative | Positive | | Ethanol | 1.0 g/dL | Negative | Positive | | Galactose | 0.01 g/dL | Negative | Positive | | γ-Globulin | 0.5 g/dL | Negative | Positive | | Glucose | 2.0 g/dL | Negative | Positive | | Hemoglobin | 0.300 g/dL | Negative | Positive | | Human Serum Albumin | 0.5 g/dL | Negative | Positive | | Oxalic Acid | 0.1 g/dL | Negative | Positive | | Riboflavin | 0.0075 g/dL | Negative | Positive | | Sodium Azide | 1% w/v | Negative | Positive | | Sodium Chloride | 6.0 g/dL | Negative | Positive | | Sodium Fluoride | 1% w/v | Negative | Positive | | Urea | 6.0 g/dL | Negative | Positive | Boric Acid was also evaluated. Boric Acid at a concentration of $1\%$ w/v was found to cause false negative results at $+25\%$ of the 150 and $300\mathrm{ng / mL}$ cutoffs in both the qualitative and semiquantitative modes and the following statement is provided in the limitations section of the labeling: "Boric Acid is not recommended as a preservative for urine. {15} 16 # pH and Specific Gravity To evaluate potential interference from the pH of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine pH values (3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0). All test samples were prepared in drug free urine containing benzoylecgonine at ± 25% of the 150 ng/mL cutoff (112.5 ng/mL and 187.5 ng/mL) and ± 25% of the 300 ng/mL cutoff (225 ng/mL and 375 ng/mL). No positive or negative interference was observed at urine pH values ranging from 3.0 to 11.0 for each test mode. To evaluate potential interference from the specific gravity of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine specific gravity values (1.000, 1.002, 1.005, 1.010, 1.015, 1.020, 1.025 and 1.030). All test samples were prepared in drug free urine containing benzoylecgonine at ± 25% of the 150 ng/mL cutoff (112.5 ng/mL and 187.5 ng/mL) and ± 25% of the 300 ng/mL cutoff (225 ng/mL and 375 ng/mL). No positive or negative interference was observed at urine specific gravity values ranging from 1.000 to 1.030 for each test mode. ## f. Assay cut-off: Characterization of how the device performs analytically around the claimed cutoff concentrations of 150 ng/mL and 300 ng/mL is described in the precision section, M.1.a. above. ## 2. Comparison studies: ### a. Method comparison with predicate device: Eighty unaltered urine samples from clinical testing laboratories were analyzed for benzoylecgonine by the candidate device on the Beckman Coulter AU400e clinical chemistry analyzer and with LC/MS. Results were obtained in both qualitative and semi-quantitative modes and are summarized below: | (150 ng/mL Cutoff - Qualitative) | | | | | | --- | --- | --- | --- | --- | | | (<50% cutoff) | (-50% to cutoff) | (cutoff to +50%) | (>50% cutoff) | | Positive | 0 | 1* | 4 | 36 | | Negative | 36 | 3 | 0 | 0 | | Discordant Result Summary* | | | --- | --- | | Qualitative Result | LC/MS Concentration (ng/mL) | | Positive | 124 | {16} | (300 ng/mL Cutoff – Qualitative) | | | | | | --- | --- | --- | --- | --- | | | (<50% cutoff) | (-50% to cutoff) | (cutoff to +50%) | (>50% cutoff) | | Positive | 0 | 0 | 4 | 36 | | Negative | 36 | 4 | 0 | 0 | | (150 ng/mL Cutoff – Semi-quantitative) | | | | | | --- | --- | --- | --- | --- | | Candidate Device Results | | | | | | | (<50% cutoff) | (-50% to cutoff) | (cutoff to +50%) | (>50% cutoff) | | Positive | 0 | 1* | 4 | 36 | | Negative | 36 | 3 | 0 | 0 | | Discordant Result Summary* | | | --- | --- | | Semi-quantitative Result | LC/MS Concentration | | Positive | 124 | | (300 ng/mL Cutoff – Semi-quantitative) | | | | | | --- | --- | --- | --- | --- | | Candidate Device Results | | | | | | | (<50% cutoff) | (-50% to cutoff) | (cutoff to +50%) | (>50% cutoff) | | Positive | 0 | 0 | 4 | 36 | | Negative | 36 | 4 | 0 | 0 | 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. {17} 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 decision. 18