Immunalysis Opiates Urine Enzyme Immunoassay, Immunalysis Opiates Urine Calibrators 300, Immunalysis Opiates Urine Calibrators 2000, Immunalysis Multi-Drug Controls

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k143502 B. Purpose for Submission: New device C. Measurand: Opiates D. Type of Test: Qualitative and semi-quantitative homogeneous enzyme immunoassay E. Applicant: Immunalysis Corporation F. Proprietary and Established Names: Immunalysis Opiates Enzyme Immunoassay Immunalysis Opiates Urine Calibrators 300 Immunalysis Opiates Urine Calibrators 2000 Immunalysis Multi-Drug Controls G. Regulatory Information: | Product Code | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | DJG – Opiate Test System | II | 862.3650 | 91 – Toxicology | | DLJ– Clinical Toxicology Calibrator | II | 862.3200 | 91 – Toxicology | | DIF – Clinical Toxicology Control Material | I, reserved | 862.3280 | 91 – Toxicology | H. Intended Use: 1. Intended use(s): See Indication(s) for use below. {1} 2. Indication(s) for use: The Immunalysis Opiates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 300ng/mL and 2000ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of opiates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Morphine. This in-vitro diagnostic 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 Opiates 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. The Immunalysis Opiates Urine Calibrators 300 are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Morphine. The Immunalysis Opiates Urine Calibrators 300 consists of 4 levels, with Level 1 containing 100ng/mL, Level 2 containing 300ng/mL, Level 3 containing 500ng/mL and Level 4 containing 1000ng/mL of morphine. The calibrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers. The Immunalysis Multi-Drug Controls are intended for in vitro diagnostic use to monitor the performance of assays for the analytes currently listed in the package insert: Benzoylecgonine, Methadone, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam for Immunalysis Multi-Drug Controls 1 and Benzoylecgonine, Methamphetamine and Morphine for Immunalysis Multi-Drug Controls 2. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers. The Immunalysis Opiates Urine Calibrators 2000 are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Morphine. The Immunalysis Opiates Urine Calibrators 2000 consists of 4 levels, with Level 1 containing 1000ng/mL, Level 2 containing 2000ng/mL, Level 3 containing 4000ng/mL and Level 4 containing 6000ng/mL of morphine. The calibrators 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. {2} 4. Special instrument requirements: Performance data was obtained using the Beckman AU400e clinical chemistry analyzer. I. Device Description: The Immunalysis Opiates Urine Enzyme Immunoassay Kit contains two reagents, which are provided as ready-to-use: - Antibody/Substrate Reagent (RA) – This reagent contains monoclonal antibodies to morphine, 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 morphine in Tris buffer with Sodium Azide as a preservative. The Immunalysis Opiates Urine Calibrators 300, the Immunalysis Opiates Urine Calibrators 2000, and the Immunalysis Multi-Drug Controls 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 a specific drug analyte spiked into the negative calibrator matrix (see tables below). | Immunalysis Opiates Urine Calibrators 300 | | | | | | --- | --- | --- | --- | --- | | Analyte | Level 1 | Level 2 | Level 3 | Level 4 | | Morphine | 100 ng/mL | 300 ng/mL | 500 ng/mL | 1000 ng/mL | | Immunalysis Opiates Urine Calibrators 2000 | | | | | | Analyte | Level 1 | Level 2 | Level 3 | Level 4 | | Morphine | 1000 ng/mL | 2000 ng/mL | 4000 ng/mL | 6000 ng/mL | | Immunalysis Multi-Drug Controls 1 | | | | --- | --- | --- | | Analyte | LOW Control 1 | HIGH Control 1 | | Benzoylecgonine | 112.5 ng/mL | 187.5 ng/mL | | Methadone | 225 ng/mL | 375 ng/mL | | Methamphetamine | 375 ng/mL | 625 ng/mL | | Morphine | 225 ng/mL | 375 ng/mL | | PCP | 19 ng/mL | 31 ng/mL | | Secobarbital | 150 ng/mL | 250 ng/mL | | Oxazepam | 150 ng/mL | 250 ng/mL | | Immunalysis Multi-Drug Controls 2 | | | | --- | --- | --- | | Analyte | LOW Control 2 | HIGH Control 2 | | Benzoylecgonine | 225 ng/mL | 375 ng/mL | | Methamphetamine | 750 ng/mL | 1250 ng/mL | | Morphine | 1500 ng/mL | 2500 ng/mL | {3} J. Substantial Equivalence Information: 1. Predicate device name(s): DRI DAU Opiate Assay LZI Multiple Analyte Urine Drugs of Abuse Calibrators and Controls 2. Predicate 510(k) number(s): k011150 k051088 3. Comparison with predicate: | Opiates Assay | | | | --- | --- | --- | | Item | Immunalysis Opiates Urine EIA | DAU Opiate Assay k011150 | | Intended Use | For the qualitative and semi-quantitative determination of the presence of opiates in human urine at a cutoff of 300 ng/mL and 2000 ng/mL | Same | | Type of Product | Analytical Reagents | Same | | Measured Analytes | Opiates | Same | | Test Matrix | Urine | Same | | Cutoff Levels | 300 ng/mL and 2000 ng/mL of Morphine | Same | | Test System | Homogeneous Enzyme Immunoassay (EIA) | Same | | Materials | Antibody/Substrate Reagents and Enzyme Labeled Conjugate | Same | | Mass Spectroscopy Confirmation | Required for preliminary positive analytical results | Same | | Antibody | Monoclonal antibody to Opiates | Same | | Storage | 2-8°C until expiration date | Same | {4} | Calibrators | | | | --- | --- | --- | | Item | Immunalysis Opiates Urine Calibrators 300 and 2000 | LZI Multiple Analytes Calibrators and Controls k051088 | | Analytes | Morphine | Benzoylecgonine, d-methamphetamine, methadone, morphine, oxazepam, secobarbital, phencyclidine, propxyphene | | Matrix | Processed, drug-free synthetic urine | Same | | Calibrator Levels | 5 levels (Negative, Level 1-4) | 5 levels (Negative, Low, Cutoff, Intermediate, High) | | Storage | 2-8°C until expiration date | Same | | Multi-Drug Controls | | | | --- | --- | --- | | Item | Immunalysis Multi-Drug Controls | LZI Multiple Analytes Calibrators and Controls k051088 | | Analytes | Benzoylecgonine, methadone, methamphetamine, morphine, PCP, secobarbital, oxazepam | Benzoylecgonine, d-methamphetamine, methadone, morphine, oxazepam, secobarbital, phencyclidine, propxyphene | | Matrix | Processed, drug-free synthetic urine | Same | | Control Levels | 4 levels (LOW Control 1+2, HIGH Control 1+2) | 2 levels (Control Level 1+2) | | Storage | 2-8°C until expiration date | Same | 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 opiates labeled enzyme glucose-6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of {5} 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 340nm 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 by an in-house technician for 20 days, 2 runs per day in duplicate (N=80) on drug-free negative urine samples spiked with morphine to concentrations of ±0%, ±25%, ±50%, ±75%, and ±100% of each cutoff. The morphine concentrations in spiked samples were confirmed by mass spectrometry. | Qualitative Analysis (for 300ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Negative | | 75 | -75% | 80 | 80 Negative | | 150 | -50% | 80 | 80 Negative | | 225 | -25% | 80 | 80 Negative | | 300 | Cutoff | 80 | 37 Negative/43 Positive | | 375 | +25% | 80 | 80 Positive | | 450 | +50% | 80 | 80 Positive | | 525 | +75% | 80 | 80 Positive | | 600 | +100% | 80 | 80 Positive | | Qualitative Analysis (for 2000ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Negative | | 500 | -75% | 80 | 80 Negative | | 1000 | -50% | 80 | 80 Negative | | 1500 | -25% | 80 | 80 Negative | | 2000 | Cutoff | 80 | 42 Negative/38 Positive | | 2500 | +25% | 80 | 80 Positive | | 3000 | +50% | 80 | 80 Positive | | 3500 | +75% | 80 | 80 Positive | | 4000 | +100% | 80 | 80 Positive | {6} 7 | Semi-Quantitative Analysis (for 300ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Negative | | 75 | -75% | 80 | 80 Negative | | 150 | -50% | 80 | 80 Negative | | 225 | -25% | 80 | 80 Negative | | 300 | Cutoff | 80 | 20 Negative/60 Positive | | 375 | +25% | 80 | 80 Positive | | 450 | +50% | 80 | 80 Positive | | 525 | +75% | 80 | 80 Positive | | 600 | +100% | 80 | 80 Positive | | Semi-Quantitative Analysis (for 2000ng/mL cutoff) | | | | | --- | --- | --- | --- | | Concentration (ng/mL) | % of cutoff | # of determinations | Result | | 0 | -100% | 80 | 80 Negative | | 500 | -75% | 80 | 80 Negative | | 1000 | -50% | 80 | 80 Negative | | 1500 | -25% | 80 | 80 Negative | | 2000 | Cutoff | 80 | 41 Negative/39 Positive | | 2500 | +25% | 80 | 80 Positive | | 3000 | +50% | 80 | 80 Positive | | 3500 | +75% | 80 | 80 Positive | | 4000 | +100% | 80 | 80 Positive | 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 morphine and generating serial dilutions in increments of 10% to achieve concentrations ranging from 100ng/mL to 1100ng/mL for the 300 ng/mL cutoff, and 600 ng/mL to 6600 ng/mL for the 2000 ng/mL cutoff. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below: | Linearity/ Recovery – 300ng/mL | | | | --- | --- | --- | | Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) | | 100 | 91.6 | 91.6 | | 200 | 203.7 | 101.8 | {7} | 300 | 292.8 | 97.6 | | --- | --- | --- | | 400 | 410.1 | 102.5 | | 500 | 488.1 | 97.6 | | 600 | 651.1 | 108.5 | | 700 | 759.4 | 108.5 | | 800 | 840.6 | 105.1 | | 900 | 906.5 | 100.7 | | 1000 | 1024.1 | 102.4 | | 1100 | 1069.9 | 97.3 | | Linearity/ Recovery – 2000ng/mL | | | | --- | --- | --- | | Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) | | 600 | 635.0 | 105.8 | | 1200 | 1295.2 | 107.9 | | 1800 | 1750.9 | 97.3 | | 2000 | 2079.0 | 104.0 | 8 {8} | 2400 | 2231.1 | 93.0 | | --- | --- | --- | | 3000 | 3142.9 | 104.8 | | 3600 | 3852.7 | 107.0 | | 4200 | 4465.4 | 106.3 | | 4800 | 5101.8 | 106.3 | | 5400 | 5789.0 | 107.2 | | 6000 | 5972.3 | 99.5 | | 6600 | 6637.7 | 100.6 | c. Traceability, Stability, Expected values (controls, calibrators, or methods): ## Traceability Calibrators and controls are prepared from a commercially available, certified standard solution. This standard solution is diluted with the negative calibrator matrix to make the calibrator and control materials in the desired concentrations. The concentrations are confirmed by GC/MS or LC/MS-MS. The negative calibrator is a processed, drug-free urine matrix. ## Value Assignment/Expected Values A commercially available standard solution is added to the negative calibrator matrix to make the calibrator and control materials in the desired concentrations. Concentrations are confirmed by GC/MS or LC/MS-MS. If any of the analytes are below the acceptable range, the calibrator or control is adjusted and re-tested. Values are assigned once the GC/MS or LC/MS-MS results are within the acceptable range. The negative calibrator is compared to a reference negative standard to ensure that it is free of analyte. Value is assigned when the test is within the acceptable range. {9} 10 # Stability A closed-vial accelerated stability study and an onboard, open vial stability study were conducted on one lot each of calibrators, and controls. Real-time stability studies are ongoing. All stability protocols were reviewed and found acceptable. These studies support the one year stability claim for closed vials and 28 days stability claim for open vials of calibrators, and controls when stored at 2-8°C. d. Detection limit: Not applicable. e. Analytical specificity: An analytical specificity study to evaluate possible interference from non-structurally and structurally related compounds was performed in the qualitative and semi-quantitative mode for each cutoff concentration. ## Structurally related compounds To evaluate potential cross-reactants for the Immunalysis Opiates Urine Enzyme Immunoassay kit, morphine and other opiates were spiked into drug free urine at concentrations that will yield a result that is equivalent to the 300ng/mL or 2000ng/mL Opiates cutoff. The results were the same for the qualitative and semi-quantitative modes. | Structurally Related Compounds (for 300ng/mL cutoff) | | | | | | --- | --- | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | Result | Morphine Equivalents (ng/mL) | Cross-Reactivity (%) | | 6-Acetylmorphine | 150 | POS | 300 | 200.0 | | Codeine | 200 | POS | 300 | 150.0 | | Dihydrocodeine | 150 | POS | 300 | 200.0 | | Ethylmorphine | 300 | POS | 300 | 100.0 | | Heroin | 300 | POS | 300 | 100.0 | | Hydrocodone | 400 | POS | 300 | 75.0 | | Levorphanol | 8,000 | POS | 300 | 3.8 | | Morphine-3-Glucuronide | 200 | POS | 300 | 150.0 | | Morphine-6-Glucuronide | 100 | POS | 300 | 300.0 | | Hydromorphone | 700 | POS | 300 | 42.9 | | Nalorphine | 2,000 | POS | 300 | 15.0 | | Naloxone | 60,000 | POS | 300 | 0.5 | | Norcodeine | 25,000 | POS | 300 | 1.2 | | Normorphine | 25,000 | POS | 300 | 1.2 | | Oxycodone | 10,000 | POS | 300 | 3.0 | {10} 11 | Oxymorphone | 20,000 | POS | 300 | 1.5 | | --- | --- | --- | --- | --- | | Structurally Related Compounds (for 2000ng/mL cutoff) | | | | | | --- | --- | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | Result | Morphine Equivalents(ng/mL) | Cross-Reactivity (%) | | 6-Acetylmorphine | 2,000 | POS | 2,000 | 100.0 | | Codeine | 2,000 | POS | 2,000 | 100.0 | | Dihydrocodeine | 600 | POS | 2,000 | 333.3 | | Ethylmorphine | 2,000 | POS | 2,000 | 100.0 | | Heroin | 4,000 | POS | 2,000 | 50.0 | | Hydrocodone | 4,000 | POS | 2,000 | 50.0 | | Levorphanol | 100,000 | POS | 2,000 | 2.0 | | Morphine-3-Glucuronide | 2,000 | POS | 2,000 | 100.0 | | Morphine-6-Glucuronide | 600 | POS | 2,000 | 333.3 | | Hydromorphone | 8,000 | POS | 2,000 | 25.0 | | Nalorphine | 28,000 | POS | 2,000 | 7.1 | | Naloxone | 500,000 | POS | 2,000 | 0.4 | | Norcodeine | 300,000 | POS | 2,000 | 0.7 | | Normorphine | 300,000 | POS | 2,000 | 0.7 | | Oxycodone | 100,000 | POS | 2,000 | 2.0 | | Oxymorphone | 200,000 | NEG | 2,000 | 1.0 | ## 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 morphine at $\pm 25\%$ of the 300 cutoff (225 ng/mL and 375ng/mL) and $\pm 25\%$ of the 2000ng/mL cutoff (1500ng/mL and 2500ng/mL). The results were the same for the qualitative and semi-quantitative modes. | Structurally Non-Similar Compounds (for 300ng/mL cutoff) | | | | | --- | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | -25% Cutoff | +25% Cutoff | | | | Result | Result | | 4-Bromo-2,5,Dimethoxy-phenethylamine | 100,000 | Negative | Positive | | Acetaminophen | 500,000 | Negative | Positive | | Acetylsalicylic Acid | 500,000 | Negative | Positive | | Alprazolam | 100,000 | Negative | Positive | | (+) Amphetamine | 500,000 | Negative | Positive | | Amitriptyline | 100,000 | Negative | Positive | | Amobarbital | 100,000 | Negative | Positive | {11} | Benzoylecgonine | 500,000 | Negative | Positive | | --- | --- | --- | --- | | Benzylpiperazine | 100,000 | Negative | Positive | | Bromazepam | 100,000 | Negative | Positive | | Buprenorphine | 100,000 | Negative | Positive | | Buprion | 100,000 | Negative | Positive | | Butabarbital | 100,000 | Negative | Positive | | Caffeine | 500,000 | Negative | Positive | | Carbamazepine | 100,000 | Negative | Positive | | Cocaine | 100,000 | Negative | Positive | | Clomipramine | 100,000 | Negative | Positive | | Clonazepam | 100,000 | Negative | Positive | | Chloropromazine | 100,000 | Negative | Positive | | Cyclobenzaprine | 100,000 | Negative | Positive | | N-Desmethyltapentadol | 100,000 | Negative | Positive | | Desipramine | 100,000 | Negative | Positive | | Dextromethorphan | 100,000 | Negative | Positive | | Diazepam | 100,000 | Negative | Positive | | Diphenhydramine | 500,000 | Negative | Positive | | Doxepin | 100,000 | Negative | Positive | | Ephedrine | 100,000 | Negative | Positive | | EDDP | 100,000 | Negative | Positive | | Ethyl-glucuronide | 100,000 | Negative | Positive | | Fenfluramine | 100,000 | Negative | Positive | | Fluoxetine | 100,000 | Negative | Positive | | Flurazepam | 100,000 | Negative | Positive | | Hexobarbital | 100,000 | Negative | Positive | | Ibuprofen | 100,000 | Negative | Positive | | Imipramine | 100,000 | Negative | Positive | | Ketamine | 100,000 | Negative | Positive | | Lidocaine | 100,000 | Negative | Positive | | LSD | 100,000 | Negative | Positive | | Lorazepam | 100,000 | Negative | Positive | | Maprotiline | 100,000 | Negative | Positive | | MDEA | 100,000 | Negative | Positive | | MDA | 100,000 | Negative | Positive | | MDMA | 100,000 | Negative | Positive | | Meperidine | 50,000 | Negative | Positive | | Methadone | 500,000 | Negative | Positive | | Methaqualone | 100,000 | Negative | Positive | | (+) Methamphetamine | 500,000 | Negative | Positive | | Meprobamate | 100,000 | Negative | Positive | | Naltrexone | 100,000 | Negative | Positive | | Nitrazepam | 100,000 | Negative | Positive | | Norbuprenorphine | 100,000 | Negative | Positive | | Nordiazepam | 100,000 | Negative | Positive | | Nortryptyline | 100,000 | Negative | Positive | 12 {12} | Structurally Non-Similar Compounds (for 2000ng/mL cutoff) | | | | | --- | --- | --- | --- | | Compound | Concentration Tested (ng/mL) | -25% Cutoff | +25% Cutoff | | | | Result | Result | | 4-Bromo-2,5,Dimethoxy-phenethylamine | 100,000 | Negative | Positive | | Acetaminophen | 500,000 | Negative | Positive | | Acetylsalicylic Ac | 500,000 | Negative | Positive | | Alprazolam | 100,000 | Negative | Positive | | (+) Amphetamine | 500,000 | Negative | Positive | | Amitriptyline | 100,000 | Negative | Positive | | Amobarbital | 100,000 | Negative | Positive | | Benzoylecgonine | 500,000 | Negative | Positive | | Benzylpiperazine | 100,000 | Negative | Positive | | Bromazepam | 100,000 | Negative | Positive | | Buprenorphine | 100,000 | Negative | Positive | | Buprion | 100,000 | Negative | Positive | | Butabarbital | 100,000 | Negative | Positive | | Caffeine | 500,000 | Negative | Positive | | Carbamazepine | 100,000 | Negative | Positive | | Cocaine | 100,000 | Negative | Positive | | Clomipramine | 100,000 | Negative | Positive | | Clonazepam | 100,000 | Negative | Positive | {13} | Chloropromazine | 100,000 | Negative | Positive | | --- | --- | --- | --- | | Cyclobenzaprine | 100,000 | Negative | Positive | | N-Desmethyltapentadol | 100,000 | Negative | Positive | | Desipramine | 100,000 | Negative | Positive | | Dextromethorphan | 100,000 | Negative | Positive | | Diazepam | 100,000 | Negative | Positive | | Diphenhydramine | 500,000 | Negative | Positive | | Doxepin | 100,000 | Negative | Positive | | Ephedrine | 100,000 | Negative | Positive | | EDDP | 100,000 | Negative | Positive | | Ethyl-glucuronide | 100,000 | Negative | Positive | | Fenfluramine | 100,000 | Negative | Positive | | Fluoxetine | 100,000 | Negative | Positive | | Flurazepam | 100,000 | Negative | Positive | | Hexobarbital | 100,000 | Negative | Positive | | Ibuprofen | 100,000 | Negative | Positive | | Imipramine | 100,000 | Negative | Positive | | Ketamine | 100,000 | Negative | Positive | | Lidocaine | 100,000 | Negative | Positive | | LSD | 100,000 | Negative | Positive | | Lorazepam | 100,000 | Negative | Positive | | Maprotiline | 100,000 | Negative | Positive | | MDEA | 100,000 | Negative | Positive | | MDA | 100,000 | Negative | Positive | | MDMA | 100,000 | Negative | Positive | | Meperidine | 100,000 | Negative | Positive | | Methadone | 500,000 | Negative | Positive | | Methaqualone | 100,000 | Negative | Positive | | (+) Methamphetamine | 500,000 | Negative | Positive | | Meprobamate | 100,000 | Negative | Positive | | Naltrexone | 100,000 | Negative | Positive | | Nitrazepam | 100,000 | Negative | Positive | | Norbuprenorphine | 100,000 | Negative | Positive | | Nordiazepam | 100,000 | Negative | Positive | | Nortryptyline | 100,000 | Negative | Positive | | Norpropoxyphene | 100,000 | Negative | Positive | | Oxazepam | 100,000 | Negative | Positive | | Pentobarbital | 100,000 | Negative | Positive | | Phenobarbital | 100,000 | Negative | Positive | | Pentazocine | 100,000 | Negative | Positive | | Phencyclidine | 100,000 | Negative | Positive | | Phentermine | 100,000 | Negative | Positive | | Phenylpropanolamine | 500,000 | Negative | Positive | | PMA | 100,000 | Negative | Positive | | (-)Pseudoephedrine | 100,000 | Negative | Positive | | (+)Pseudoephedrine | 100,000 | Negative | Positive | 14 {14} 15 | Phenytoin | 100,000 | Negative | Positive | | --- | --- | --- | --- | | Protryptyline | 100,000 | Negative | Positive | | Ranitidine | 100,000 | Negative | Positive | | Ritalinic Acid | 100,000 | Negative | Positive | | Secobarbital | 100,000 | Negative | Positive | | Sufentanil | 100,000 | Negative | Positive | | Temazepam | 100,000 | Negative | Positive | | 11-nor-9 carboxy THC | 100,000 | Negative | Positive | | Tramadol | 100,000 | Negative | Positive | | Trimipramine | 100,000 | Negative | Positive | | Venlafaxine | 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 morphine at $\pm 25\%$ of the $300\mathrm{ng/mL}$ cutoff (225ng/mL and 375ng/mL) and $2000\mathrm{ng/mL}$ cutoff (1500ng/mL cutoff and 2500ng/mL). The results were the same for the qualitative and semi-quantitative modes. | Endogenous Compounds (for 300ng/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 | | Boric Acid | 1 % w/v | Negative | Negative | | 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 | Negative | | 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 | {15} | Endogenous Compounds (for 2000ng/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 | | **Boric Acid** | **1% w/v** | **Negative** | **Negative** | | 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 | Compounds that showed interference were further evaluated by spiking them into drug free urine containing morphine at $\pm 50\%$ of the cutoff. Riboflavin at $0.0075\mathrm{g / dL}$ caused a false negative response for morphine at $\pm 25\%$ but not at $\pm 50\%$ of the $300\mathrm{ng / mL}$ cutoff. Boric Acid at $1\%$ w/v caused a false negative response for morphine at $\pm 25\%$ and $\pm 50\%$ of the $300\mathrm{ng / mL}$ cutoff, and caused a false negative response for morphine at $\pm 25\%$ but not at $\pm 50\%$ of the $2000\mathrm{ng / mL}$ cutoff. The results were the same for the qualitative and semi-quantitative modes. The following statement is provided in the limitations section of the labeling: "Boric Acid is not recommended as a preservative for urine. Boric Acid and Riboflavin can cause a falsely low test result." ## pH and Specific Gravity For 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 morphine at $\pm 25$ of the $300\mathrm{ng / mL}$ cutoff ($225\mathrm{ng / mL}$ and $375\mathrm{ng / mL}$) and $2000\mathrm{ng / mL}$ cutoff ($1500\mathrm{ng / mL}$ and $2500\mathrm{ng / mL}$). No positive or negative interference was observed at urine pH values ranging from 3.0 to 11.0 for each test mode. For 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 morphine at $\pm 25\%$ of the $300\mathrm{ng / mL}$ cutoff ($225\mathrm{ng / mL}$ and $375\mathrm{ng / mL}$) and $2000\mathrm{ng / mL}$ cutoff ($1500\mathrm{ng / mL}$ and $2500\mathrm{ng / mL}$). No positive or negative interference was observed at urine specific gravity values ranging {16} 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 300 ng/mL and 2000 ng/mL is described in the precision section, M.1.a. above. 2. Comparison studies: a. Method comparison with predicate device: 80 unaltered urine samples from clinical testing laboratories were analyzed by the candidate device in the qualitative and semi-quantitative modes on the Beckman Coulter AU400e clinical chemistry analyzer and the comparative mass spectrometry based quantitative method (LC/MS) for morphine and other opiates. The results from the study are summarized below: | Assay Performance verified by LC/MS (300ng/mL Cutoff - Qualitative) | | | | | | --- | --- | --- | --- | --- | | Candidate Device Results | Total Opiate Concentration | | | | | | < 150ng/mL (<50% cutoff) | 150 ~ 299 ng/mL (-50% to cutoff) | 300 ~ 450 ng/mL (cutoff to +50%) | >450 ng/mL (>50% cutoff) | | Positive | 0 | 1 | 5 | 35 | | Negative | 36 | 3 | 0 | 0 | | Discordant Result Summary (300ng/mL Cutoff – Qualitative) | | | | --- | --- | --- | | Qualitative Results | LC/MS Confirmation | | | Test Device | Qualitative | Total Opiate Concentration (ng/mL) | | Positive | Negative | 200 | % Agreement among positives is 98%. % Agreement among negatives is 100%. | Assay Performance verified by LC/MS (2000ng/mL Cutoff – Qualitative) | | | | | | --- | --- | --- | --- | --- | | Candidate Device Results | Total Opiate Concentration | | | | | | < 1000ng/mL (<50% cutoff) | 1000~1999 ng/mL (-50% to cutoff) | 2000~3000 ng/mL (cutoff to +50%) | >3000 ng/mL (>50% cutoff) | | Positive | 0 | 0 | 5 | 35 | | Negative | 36 | 4 | 0 | 0 | % Agreement among positives is 100%. % Agreement among negatives is 100%. 17 {17} 18 | Assay Performance verified by LC/MS (300ng/mL Cutoff – Semi-quantitative) | | | | | | --- | --- | --- | --- | --- | | Candidate Device Results | Total Opiate Concentration | | | | | | < 150ng/mL (<50% cutoff) | 150 ~ 299 ng/mL (-50% to cutoff) | 300 ~ 450 ng/mL (cutoff to +50%) | > 450 ng/mL (>50% cutoff) | | Positive | 0 | 0 | 5 | 35 | | Negative | 36 | 4 | 0 | 0 | % Agreement among positives is 100%. % Agreement among negatives is 100%. | Assay Performance verified by LC/MS (2000ng/mL Cutoff – Semi-quantitative) | | | | | | --- | --- | --- | --- | --- | | Candidate Device Results | Total Opiate Concentration | | | | | | < 1000ng/mL (<50% cutoff) | 1000~1999 ng/mL (-50% to cutoff) | 2000~3000 ng/mL (cutoff to +50%) | > 3000 ng/mL (>50% cutoff) | | Positive | 0 | 0 | 5 | 35 | | Negative | 36 | 4 | 0 | 0 | % Agreement among positives is 100%. % Agreement among negatives is 100%. b. Matrix comparison: Not applicable. Urine is the only claimed matrix for the candidate device. 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. 4. Clinical cut-off: Not applicable. {18} 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. 19