Chemtrue Drug Screen Cup Tests and Chemtrue Drug Screen Cup Tests with OPI 2000

{0} 1 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k143599 B. Purpose for Submission: New device C. Measurand: Buprenorphine, Amphetamine, Cocaine, Marijuana, Morphine, Opiates, Methamphetamine, Phencyclidine, Benzodiazepines, Barbiturates, Ecstasy, Methadone, Oxycodone and Tricyclic Antidepressants D. Type of Test: Qualitative immunoassay E. Applicant: Chemtron Biotech, Inc. F. Proprietary and Established Names: Chemtrue Drug Screen Cup Tests Chemtrue Drug Screen Cup Tests with OPI 2000 {1} G. Regulatory Information: | | Product Code | Classification | Regulation Section | Panel | | --- | --- | --- | --- | --- | | Buprenorphine | DJG | Class II | 21CFR 862.3650, Opiate Test System | Toxicology (91) | | Amphetamine | DKZ | Class II | 21CFR 862.3100, Amphetamine Test System | Toxicology (91) | | Cocaine | DIO | Class II | 21 CFR 862.3250, Cocaine and metabolites Test System | Toxicology (91) | | Marijuana | LDJ | Class II | 21 CFR 862.3870, Cannabinoids Test System | Toxicology (91) | | Morphine | DNK | Class II | 21 CFR 862.3640, Morphine Test System | Toxicology (91) | | Opiates | DJG | Class II | 21 CFR 862.3650, Opiate Test System | Toxicology (91) | | Methamphetamine | LAF | Class II | 21 CFR 862.3610, Methamphetamine Test System | Toxicology (91) | | Phencyclidine | LCM | Class II | Unclassified, Enzyme immunoassay Phencyclidine | Toxicology (91) | | Benzodiazepines | JXM | Class II | 21 CFR 862.3170, Benzodiazepines Test System | Toxicology (91) | | Barbiturates | DIS | Class II | 21 CFR 862.3150, Barbiturates Test System | Toxicology (91) | | Ecstasy | DJC | Class II | 21 CFR 862.3610, Methamphetamine Test System | Toxicology (91) | | Methadone | DJR | Class II | 21 CFR 862.3620, Methadone Test System | Toxicology (91) | | Oxycodone | DJG | Class II | 21 CFR 862.3650, Opiate Test System | Toxicology (91) | | Tricyclic Antidepressants | LFG | Class II | 21 CFR 862.3910, Tricyclic Antidepressant Drugs Test System | Toxicology (91) | {2} H. Intended Use: 1. Intended use(s): Refer to Indications for Use below 2. Indication(s) for use: Chemtrue Drug Screen Cup Tests The Chemtrue® Drug Screen Cup Tests are rapid lateral flow immunoassays for the qualitative detection of Buprenorphine, Amphetamine, Cocaine, Marijuana, Morphine 300, Methamphetamine, Phencyclidine, Benzodiazepines, Barbiturates, Ecstasy, Methadone, Oxycodone and Tricyclic Antidepressants drugs in human urine. The test cut-off concentrations and the compounds the tests are calibrated to are as follows: | Analyte | Abbreviation | Calibrator | Cutoff Concentration (ng/mL) | | --- | --- | --- | --- | | Buprenorphine | BUP | Buprenorphine | 10 | | Tricyclic Antidepressants | TCA | Nortriptyline | 1000 | | Amphetamine | AMP | d-Amphetamine | 1000 | | Cocaine | COC | Benzoylecgonine | 300 | | Methamphetamine | MAMP | d-Methamphetamine | 1000 | | Morphine | MOR | Morphine | 300 | | Phencyclidine | PCP | Phencyclidine | 25 | | Marijuana | THC | 11-nor-Δ9-THC9 COOH | 50 | | Benzodiazepines | BZO | Oxazepam | 300 | | Barbiturates | BAR | Secobarbital/Pentobarbital | 300 | | Ecstasy | MDMA | d,l-Methylenedioxy methamphetamine | 500 | | Methadone | MTD | Methadone | 300 | | Oxycodone | OXY | Oxycodone | 100 | The Chemtrue® Drug Screen Cup Tests panel can consist of any combination of the above listed drug analytes. The tests are intended for prescription and Over-The-Counter (OTC) use. The tests provide only a preliminary result. A more specific alternative chemical method must be used in order to obtain a confirmed assay result. Gas Chromatography I Mass Spectrometry (GCIMS) or Liquid Chromatography I Mass Spectrometry (LC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drugs of abuse test result, particularly when preliminary positive results are indicated. {3} The tests are not intended to differentiate between drugs of abuse and prescription use of Benzodiazepines, Barbiturates, Buprenorphine, Oxycodone and Tricyclic Antidepressants. There are no uniformly recognized cutoff concentration levels for these drugs in urine. ## Chemtrue Drug Screen Cup Tests with OPI 2000 The Chemtrue Drug Screen Cup Tests with OPI 2000 are rapid lateral flow immunoassays for the qualitative detection of Buprenorphine, Amphetamine, Cocaine, Marijuana, Opiates 2000, Methamphetamine, Phencyclidine, Benzodiazepines, Barbiturates, Ecstasy, Methadone, Oxycodone and Tricyclic Antidepressants drugs in human urine. The test cut-off concentrations and the compounds the tests are calibrated to are as follows: | Analyte | Abbreviation | Calibrator | Cutoff Concentration (ng/mL) | | --- | --- | --- | --- | | Buprenorphine | BUP | Buprenorphine | 10 | | Tricyclic Antidepressants | TCA | Nortriptyline | 1000 | | Amphetamine | AMP | d-Amphetamine | 1000 | | Cocaine | COC | Benzoylecgonine | 300 | | Methamphetamine | MAMP | d-Methamphetamine | 1000 | | Opiates 2000 | OPI | Morphine | 2000 | | Phencyclidine | PCP | Phencyclidine | 25 | | Marijuana | THC | 11-nor-Δ9-THC9 COOH | 50 | | Benzodiazepines | BZO | Oxazepam | 300 | | Barbiturates | BAR | Secobarbital/Pentobarbital | 300 | | Ecstasy | MDMA | d,l-Methylenedioxy methamphetamine | 500 | | Methadone | MTD | Methadone | 300 | | Oxycodone | OXY | Oxycodone | 100 | The Chemtrue Drug Screen Cup Tests with OPI 2000 panel can consist of any combination of the above listed drug analytes. The tests are intended for prescription and Over-The-Counter (OTC) use. The tests provide only a preliminary result. A more specific alternative chemical method must be used in order to obtain a confirmed assay result. Gas Chromatography / Mass Spectrometry (GCIMS) or Liquid Chromatography / Mass Spectrometry (LC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drugs of abuse test result, particularly when preliminary positive results are indicated. {4} The tests are not intended to differentiate between drugs of abuse and prescription use of Benzodiazepines, Barbiturates, Buprenorphine, Oxycodone and Tricyclic Antidepressants. There are no uniformly recognized cutoff concentration levels for these drugs in urine. 3. Special conditions for use statement(s): For in vitro diagnostic use only. 4. Special instrument requirements: Not applicable, as the devices are visually-read single-use devices. I. Device Description: The devices are for use with human urine only. They consist of: - A test cup with 1 to 13 drug test strips - Transport vial, transport bag, and mailing box (for confirmation testing) - Package insert (instructions for use) J. Substantial Equivalence Information: 1. Predicate device name(s): Innovacon Spectrum II Test Card with Integrated Cups OnTrak TesTcup® II Pro 5-AS and OnSite CupKit™ Pro 5-AS 2. Predicate 510(k) number(s): k061718 k060896 3. Comparison with predicate: | Similarities and Differences | | | | --- | --- | --- | | Item | Device | Predicate (k061718 and k060896) | | Intended Use | Same | For the qualitative detection of drugs of abuse in human urine | | Results | Same | Qualitative | | Methodology | Same | Lateral flow, competitive binding immunoassay based on the principle of antigen and antibody immunochemistry. | | Storage | 2 – 30°C until expiration date | k061718: 2 – 30°C until expiration date; k060896: 15 – 30°C until expiration date | {5} | Intended Users | Prescription and over the counter users | Prescription users (k060896); Prescription users, including point-of-care (k061718) | | --- | --- | --- | | Cutoffs (ng/mL) | Buprenorphine – same Barbiturates – same Tricyclic Antidepressants – same Opiates 2000 – same MDMA – same Methadone – same Oxycodone – same Propoxyphene – not included in device Amphetamine – 1000 Benzodiazepines – 300 Cocaine – 300 Methamphetamine – 1000 Phencyclidine – same Marijuana – same Morphine –300 | k061718 Buprenorphine – 10 Barbiturates – 300 Tricyclic Antidepressants – 1000 Opiates 2000 – 2000 MDMA – 500 Methadone – 300 Oxycodone – 100 Propoxyphene – 300 k061718 and k060896 Amphetamine – 1000 / 300 Benzodiazepines – 300 / 200 Cocaine – 300 / 150 Methamphetamine – 1000 /500 / 300 Phencyclidine – 25 Marijuana – 50 k060896 Morphine – 300/2000 | | Format | Cup only | k061718: Cup and Dipcard; k060896: Cup only | ## K. Standard/Guidance Document Referenced (if applicable): Design Considerations for Devices Intended for Home Use - Guidance for Industry and Food and Drug Administration Staff ## L. Test Principle: The Chemtrue® Drug Screen Cup Tests are rapid lateral flow immunoassays in which drug-protein conjugates in the test device compete with drugs or drug metabolites that may be present in urine. On each test strip, a drug-protein conjugate is added to the test band of the membrane – known as the test region (T), and the anti-drug antibody-colloidal gold conjugate pads are placed at the forward end of the membrane. Monoclonal anti-drug antibodies derived from mice are used on the BUP, AMP, COC, MET, MOR, OPI2000, PCP, THC, BAR, MDMA, MTD, and OXY tests. Monoclonal anti-drug antibodies derived from {6} sheep and mice are used on the TCA and BZO tests. If target drugs are present in the urine specimen below its cut-off concentration, the solution of the colored antibody-colloidal gold conjugates moves along with the sample solution by capillary action across the membrane to the immobilized drug-protein conjugate zone on the test band region. The colored antibody-gold conjugates then complexes with the drug-protein conjugates to form visible lines. Therefore, the formation of the visible precipitant in the test band indicates a negative result. If the target drug level exceeds its cut-off concentration, the drug/metabolite antigen competes with drug protein conjugates on the test band region for the limited antibody on the colored drug antibody-colloidal gold conjugate pad. The drug will saturate the limited antibody binding sites and the colored antibody-colloidal gold conjugate cannot bind to the drug-protein conjugate at the test region of the test strip. Therefore, absence of the color band on the test region indicates a preliminary positive result. A band should form in the control region (C) of the devices regardless of the presence of drug in the sample to indicate that the test has been performed properly. ## M. Performance Characteristics (if/when applicable): Performance characteristics for Buprenorphine (BUP) and Tricyclic Antidepressants (TCA) test strips in cup format were established in k142396, unless otherwise noted. The same BUP and TCA test strips from k142396 are used in the candidate devices. ## 1. Analytical performance: ### a. Precision/Reproducibility: The precision performance of the test strips of the devices was evaluated using 3 lots and 3 operators. Drug-free (negative) urine samples were analyzed and also spiked to concentrations of -50% of cutoff, -25% of cutoff, cutoff, cutoff + 25% and cutoff + 50%. Each drug concentration was confirmed by GC/MS. Each lot was evaluated by a different operator and results were collected over ten non-consecutive days. Results are summarized below. | Drug | Concentration Tested | Operator 1/ Lot 1 | Operator 2/ Lot 2 | Operator 3/ Lot 3 | Total of the three operators | | --- | --- | --- | --- | --- | --- | | | | Neg/Pos | Neg/Pos | Neg/Pos | Neg/Pos | | AMP | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 4/6 | 4/6 | 6/4 | 14/16 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | {7} | Drug | Concentration Tested | Operator 1/ Lot 1 | Operator 2/ Lot 2 | Operator 3/ Lot 3 | Total of the three operators | | --- | --- | --- | --- | --- | --- | | | | Neg/Pos | Neg/Pos | Neg/Pos | Neg/Pos | | BAR | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 4/6 | 5/5 | 5/5 | 14/16 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | BZO | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 7/3 | 4/6 | 4/6 | 15/15 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | COC | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 4/6 | 4/6 | 4/6 | 12/18 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | MAMP | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 5/5 | 4/6 | 5/5 | 14/16 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | MOR 300 | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 4/6 | 5/5 | 5/5 | 14/16 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | PCP | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 4/6 | 4/6 | 4/6 | 12/18 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | {8} | Drug | Concentration Tested | Operator 1/ Lot 1 | Operator 2/ Lot 2 | Operator 3/ Lot 3 | Total of the three operators | | --- | --- | --- | --- | --- | --- | | | | Neg/Pos | Neg/Pos | Neg/Pos | Neg/Pos | | MTD | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 6/4 | 6/4 | 5/5 | 17/13 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | OXY | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 5/5 | 3/7 | 5/5 | 13/17 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | OPIATES 2000 | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 5/5 | 5/5 | 2/8 | 12/18 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | THC | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 5/5 | 5/5 | 5/5 | 15/15 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | MDMA | Negative | 70/0 | 70/0 | 70/0 | 210/0 | | | -50% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | -25% of cutoff | 10/0 | 10/0 | 10/0 | 30/0 | | | Cutoff | 4/6 | 5/5 | 4/6 | 13/17 | | | +25% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | | | +50% of cutoff | 0/10 | 0/10 | 0/10 | 0/30 | b. Linearity/assay reportable range: Not applicable. These devices are intended for qualitative use only. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Stability: Device stability has been evaluated through accelerated and real-time studies. The real-time studies are ongoing. Protocols and acceptance criteria were {9} described and found to be acceptable. The manufacturer claims that the devices are stable for two years (24 months) when stored at $2 - 30^{\circ}\mathrm{C}$ . Quality control: Control materials are not supplied with the devices; however the labeling provides information on how to obtain quality control materials. # d. Detection limit: See Precision/Reproducibility section in M.1.a above. # e. Analytical specificity: For each drug, specificity was evaluated by spiking various concentrations of similarly structured drug compounds into drug-free urine. Results are expressed as a minimum concentration of metabolite or compound required to produce a response approximately equivalent to the cutoff concentration of the assay. The percent cross-reactivity of those compounds is listed below with the calibrator analyte(s) in bold: | Target Drug | Compound | Concentration Equivalent to the Cutoff (ng/mL) | Cross-Reactivity (%) | | --- | --- | --- | --- | | AMP | d-Amphetamine | 1000 | 100 | | | Methylenedioxyethylamphetamine (MDEA) | >100,000 | <1 | | | d,l-Methamphetamine | >100,000 | <1 | | | Phenylephrine | >100,000 | <1 | | | d-Methamphetamine | >100,000 | <1 | | | l-Methamphetamine | >100,000 | <1 | | | d,l - Methylenedioxy methamphetamine (MDMA) | >100,000 | <1 | | | l-Amphetamine | >100,000 | <1 | | | Ephedrine | >100,000 | <1 | | | Pseudoephedrine | >100,000 | <1 | | | d/l-Amphetamine | 2500 | 40 | | | d,l-3,4-Methylenedioxyamphetamine (MDA) | 3000 | 33 | | | Phentermine | 5000 | 20 | {10} | BAR | Secobarbital | 300 | 100 | | --- | --- | --- | --- | | Pentobarbital | 300 | 100 | | Alphenal | 500 | 60 | | Amobarbital | 800 | 38 | | Aprobarbital | 500 | 60 | | Barbital | 10,000 | 3 | | Butabarbital | 500 | 60 | | Butalbital | 3000 | 10 | | Cyclopentabarbital | 750 | 40 | | Phenobarbital | 2000 | 15 | | BZO | Oxazepam | 300 | 100 | | Alprazolam | 300 | 100 | | Alpha-Hydroxyalprazolam | 100 | 300 | | Bromazepam | 500 | 60 | | Chlordiazepoxide | 2,500 | 12 | | Clobazam | 200 | 150 | | Clonazepam | 10,000 | 3 | | Clorazepate | 350 | 86 | | Desalkylflurazepam | 65 | 462 | | Diazepam | 200 | 150 | | Estazolam | 500 | 60 | | Flunitrazepam | 375 | 80 | | Flurazepam | 90 | 333 | | Lorazepam | 600 | 50 | | Lormetazepam | 7,500 | 4 | | Midazolam | 900 | 33 | | Nitrazepam | 200 | 150 | | Nordiazepam | 150 | 200 | | Temazepam | 350 | 86 | | Triazolam | 1,000 | 30 | | COC | Benzoylecgonine | 300 | 100 | | Cocaine | 500 | 60 | | Cocaethylene | 20,000 | 1.5 | {11} | MAMP | d-Methamphetamine | 1000 | 100 | | --- | --- | --- | --- | | | 1-Methamphetamine | >100,000 | <1 | | | d,l-Amphetamine | >100,000 | <1 | | | Phentermine | >100,000 | <1 | | | d,l - Methamphetamine | 5000 | 20 | | | d-Amphetamine | 10,000 | 10 | | | l-Amphetamine | >100,000 | <1 | | | Ephedrine | >100,000 | <1 | | | Phenylephrine | 10,000 | 10 | | | Pseudoephedrine | >100,000 | <1 | | | 3,4- Methylenedioxy methamphetamine (MDMA) | 5000 | 20 | | | d,l- Methylenedioxy ethylamphetamine (MDEA) | 100,000 | 1 | | | d,l-3,4- Methylenedioxyamphetamine (MDA) | >100,000 | <1 | | MOR 300 | Morphine | 300 | 100 | | | Codeine | 300 | 100 | | | 6-Acetylmorphine | 500 | 60 | | | Diacetylmorphine (Heroin) | 2,000 | 15 | | | Hydrocodone | 50,000 | <1 | | | Hydromorphone | 5,000 | 6 | | | Oxycodone | 50,000 | 0.6 | | | Oxymorphone | >100,000 | <0.3 | | | Procaine | >100,000 | <0.3 | | PCP | Phencyclidine | 25 | 100 | | | Pheniramine | >100,000 | <1 | | MTD | Methadone | 300 | 100 | | | Doxylamine | 100,000 | 0.3 | | | Pheniramine | >100,000 | <1 | | | 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | >100,000 | <1 | | OXY | Oxycodone | 100 | 100 | | | Codeine | 100,000 | 0.1 | | | Hydrocodone | 100,000 | 0.1 | | | Oxymorphone | 100 | 100 | {12} | OPIATES 2000 | Morphine | 2000 | 100 | | --- | --- | --- | --- | | | Codeine | 2000 | 100 | | | Diacetylmorphine (Heroin) | 2000 | 100 | | | Hydrocodone | 50,000 | 4 | | | Hydromorphone | 50,000 | 4 | | | Oxycodone | 100,000 | 2 | | | 6-Acetylmorphine | 1500 | 133 | | | Oxymorphone | 100,000 | 2 | | | Acetaminophen | 100,000 | 2 | | | Normorphine | 100,000 | 2 | | | Ethylmorphine | 1500 | 133 | | | Norcodeine | 100,000 | 2 | | THC | 11-nor-Δ⁹-THC-9-COOH | 50 | 100 | | | 11-nor-Δ⁸-THC-9-COOH | 30 | 167 | | | Δ⁹-Tetrahydrocannabinol | 12,000 | 0.4 | | | Cannabidiol | >100,000 | <0.05 | | | Cannabinol | >100,000 | <0.05 | | MDMA | d,l - Methylenedioxy methamphetamine (MDMA) | 500 | 100 | | | 1-Methamphetamine | >100,000 | <0.5 | | | Ephedrine | >100,000 | <0.5 | | | Pseudoephedrine | >100,000 | <0.5 | | | d,l- Amphetamine | >100,000 | <0.5 | | | l-Amphetamine | >100,000 | <0.5 | | | Phentermine | >100,000 | <0.5 | | | d,l- Methamphetamine | >100,000 | <0.5 | | | Phenylephrine | >100,000 | <0.5 | | | Methylenedioxy ethylamphetamine (MDEA) | 1000 | 50 | | | d,l-3,4- Methylenedioxyamphetamine (MDA) | 15,000 | 3 | | | d-Methamphetamine | 100,000 | 0.5 | | | d-Amphetamine | 100,000 | 0.5 | The sponsor also evaluated the potential for positive and negative interference from non-structurally related compounds, endogenous compounds, pH, and specific gravity. The structurally unrelated compounds and endogenous substances study was performed by spiking structurally unrelated compounds and endogenous substances at a concentration of $100~\mu \mathrm{g / mL}$ into urine samples containing drug at $\pm 25\%$ of the respective drug cutoff concentrations. The following structurally unrelated substances showed no positive or negative interference in this study: {13} | Acetaminophen | 5, 5-Diphenylhydantoin | Octopamine | | --- | --- | --- | | Acetone | Dopamine | Oxalic Acid | | Acetylsalicylic Acid | Erythromycin | Papaverine | | Amoxicillin | Estradiol | Penicillin-G | | Ampicillin | Estrone | Perphenazine | | R-(-)-Apomorphine | Ethanol | Phenelzine | | L-Ascorbic Acid | Fenofibrate | Phenylethylamine | | Aspirin | Fentanyl | Prednisone | | Aspartame | Fotemustine | Promazine | | Atropine | Furosemide | Promethazine | | Baclofen | Gemfibrozil | d-Propoxyphene | | Benzocaine | Guaiacolglyceryl ether | d,l-Propranolol | | Benzoic Acid | Gentisic acid | Pyridoxine | | Carisoprodol | Hydralazine | Pyrilamine | | Chloramphenicol | Hydrocortisone | Pyrogallol | | Chlordiazepoxide | 3-Hydroxytyramine | Quinidine | | (+)-Chlorpheniramine | (+/-)-Isoproterenol | Quinine | | Chlorpromazine | Ketamine | Quinolinic Acid | | Clofibrate | Meprobamate | Ranitidine | | Clonidine | Methapyrilene | Salicylic Acid | | Cortisone | Methylphenidate | Sulfamethazine | | (-)-Cotinine | Nalidixic Acid | Sulindac | | Creatine Hydrate | Naloxone | Tetracycline | | Cyclobenzaprine | Naltrexone | Tetrahydrozoline | | Cyclodextrin | (+)-Naproxen | Thiamine | | Cyproheptadine | Niacinamide | Thioridazine | | Deoxycorticosterone | Nicotinic Acid | Tramadol | | Dextromethorphan | Nifedipine | Trifluoperazine | | Diclofenac | 19-Norethindrone | Tryptamine | | Diflunisal | Norpropoxyphene | Tyramine | | 4-Dimethyl-aminoantipyrine | Noscapine | Zomepirac sodium salt | | Diphenhydramine | | | The following endogenous substances showed no positive or negative interference in this study: | Albumin | Creatinine | Riboflavin | | --- | --- | --- | | Bilirubin | Glucose | Sodium Chloride | | Cholesterol | Hemoglobin | Uric Acid | Evaluation of Specific Gravity and pH on test results: {14} To evaluate the effect of pH value on the test results, urine controls at $\pm 50\%$ of the cutoff value were used. Each control level was adjusted by either 1N NaOH solution or 1N HCl to pH levels of 2.0, 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0 and 9.0. Each test sample was tested in duplicate. To evaluate the effect of specific gravity, urine controls at $\pm 50\%$ of the cutoff values were spiked with deionized water or sugar to obtain specific gravities of 1.001, 1.010, 1.015, 1.020, 1.025, and 1.030. Each test sample was tested in duplicate. The results demonstrated that pH and specific gravity do not affect the results from the device. # f. Assay cut-off: Characterization of how the device performs analytically around the claimed cutoff concentration appears in the precision section, M.1.a., above. # 2. Comparison studies: The sponsor performed a method comparison study comparing performance of the test strips of the cup devices to the GC/MS reference method. For each drug test, at least 40 unaltered positive clinical samples and 40 unaltered negative clinical samples with known GC/MS values were tested. Results are summarized below: # a. Method comparison with predicate device: Amphetamine | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff -50% | cutoff -50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 16 | 25 | | NEG | 67 | 25 | 1* | 0 | Agreement among positives $= 41 / 42 = 98\%$ Agreement among negatives $= 81 / 81 = 100\%$ *Sample contained amphetamine at 1061 ng/mL Barbiturates | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff -50% | cutoff -50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 12 | 28 | | NEG | 44 | 11 | 0 | 0 | Agreement among positives $= 40 / 40 = 100\%$ Agreement among negatives $= 55 / 55 = 100\%$ {15} Benzodiazepines | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 1* | 15 | 25 | | NEG | 40 | 9 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 49/50 = 98% *Sample contained Oxazepam at 253 ng/mL Cocaine | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 1* | 15 | 25 | | NEG | 40 | 9 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 49/50 = 98% *Sample contained benzoylecgonine at 292 ng/mL Ecstasy | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 1* | 12 | 28 | | NEG | 42 | 14 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 56/57 = 98% *Sample contained MDMA at 498 ng/mL Methamphetamine | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 15 | 25 | | NEG | 40 | 10 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 50/50 = 100% {16} Methadone | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 14 | 26 | | NEG | 40 | 10 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 50/50 = 100% Morphine 300 | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 16 | 74 | | NEG | 40 | 10 | 0 | 0 | Agreement among positives = 90/90 = 100% Agreement among negatives = 50/50 = 100% Oxycodone | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 9 | 31 | | NEG | 40 | 10 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 50/50 = 100% Opiates 2000 | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 1* | 14 | 27 | | NEG | 40 | 9 | 0 | 0 | Agreement among positives = 41/41 = 100% Agreement among negatives = 49/50 = 98% *Sample contained morphine at 1179 ng/mL and codeine at 522 ng/mL Phencyclidine (PCP) | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff –50% | cutoff –50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 1* | 16 | 24 | | NEG | 40 | 10 | 0 | 0 | Agreement among positives = 40/40 = 100% Agreement among negatives = 50/51 = 98% *Sample contained PCP at 24.6 ng/mL {17} THC | Candidate Device Result | Concentration by GC/MS (ng/mL) | | | | | --- | --- | --- | --- | --- | | | ≤ cutoff -50% | cutoff -50% to the cutoff | cutoff to cutoff +50% | ≥ cutoff +50% | | POS | 0 | 0 | 15 | 25 | | NEG | 40 | 11 | 0 | 0 | Agreement among positives $= 40 / 40 = 100\%$ Agreement among negatives $= 51 / 51 = 100\%$ # b. Matrix comparison: Not applicable. This device is for use with urine samples only. # 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): A consumer study was performed for all analytes, including BUP and TCA, to evaluate the ability of untrained users to interpret the devices properly when given only the labeling (package insert) provided with the devices. One hundred (100) intended lay-users participated in this study from three (3) intended user sites with GC/MS confirmed urine samples at the following concentrations: negative, $50\%$ , $75\%$ , $125\%$ and $150\%$ of the cutoff. Samples were created by spiking drugs into drug-free urine pool. Each sample was aliquotted into an individual blind-labeled container. Each lay-user was provided with a package insert in English only and one blind-labeled sample for testing. | Drug (cutoff in ng/mL) | Cutoff | Conc. by GC/MS (ng/mL) | n | Lay Person Results | | %Agreement With GC/MS | | --- | --- | --- | --- | --- | --- | --- | | | | | | Negative | Positive | | | AMP (1000) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 500 | 10 | 10 | 0 | 100 | | | -25% | 750 | 10 | 10 | 0 | 100 | | | +25% | 1250 | 10 | 0 | 10 | 100 | | | +50% | 1500 | 10 | 0 | 10 | 100 | | BAR (300) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 150 | 10 | 10 | 0 | 100 | | | -25% | 225 | 10 | 10 | 0 | 100 | {18} | | +25% | 375 | 10 | 0 | 10 | 100 | | --- | --- | --- | --- | --- | --- | --- | | | +50% | 450 | 10 | 0 | 10 | 100 | | BZO (300) | -100% | 0 | 60 | 60 | 10 | 100 | | --- | --- | --- | --- | --- | --- | --- | | | -50% | 150 | 10 | 10 | 0 | 100 | | | -25% | 225 | 10 | 10 | 0 | 100 | | | +25% | 375 | 10 | 0 | 10 | 100 | | | +50% | 450 | 10 | 0 | 10 | 100 | | BUP (10) | -100% | 0 | 30 | 0 | 30 | 100 | | | -50% | 5 | 30 | 0 | 30 | 100 | | | -25% | 7.5 | 30 | 0 | 30 | 100 | | | +25% | 12.5 | 30 | 30 | 0 | 100 | | | +50% | 15 | 30 | 30 | 0 | 100 | | COC (300) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 150 | 10 | 10 | 0 | 100 | | | -25% | 225 | 10 | 10 | 0 | 100 | | | +25% | 375 | 10 | 0 | 10 | 100 | | | +50% | 450 | 10 | 0 | 10 | 100 | | MDMA (500) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 250 | 10 | 10 | 0 | 100 | | | -25% | 375 | 10 | 10 | 0 | 100 | | | +25% | 625 | 10 | 0 | 10 | 100 | | | +50% | 750 | 10 | 0 | 10 | 100 | | MET (1000) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 500 | 10 | 10 | 0 | 100 | | | -25% | 750 | 10 | 10 | 0 | 100 | | | +25% | 1250 | 10 | 0 | 10 | 100 | | | +50% | 1500 | 10 | 0 | 10 | 100 | | MTD (300) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 150 | 10 | 10 | 0 | 100 | | | -25% | 225 | 10 | 10 | 0 | 100 | | | +25% | 375 | 10 | 0 | 10 | 100 | | | +50% | 450 | 10 | 0 | 10 | 100 | | MOR 300 (300) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 150 | 10 | 10 | 0 | 100 | | | -25% | 225 | 10 | 10 | 0 | 100 | | | +25% | 375 | 10 | 0 | 10 | 100 | | | +50% | 450 | 10 | 0 | 10 | 100 | {19} | OPI 2000 (2000) | -100% | 0 | 60 | 60 | 60 | 10 | | --- | --- | --- | --- | --- | --- | --- | | | -50% | 1000 | 10 | 10 | 10 | 0 | | | -25% | 1500 | 10 | 10 | 10 | 0 | | | +25% | 2500 | 10 | 10 | 0 | 10 | | | +50% | 3000 | 10 | 10 | 0 | 10 | | OXY (100) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 50 | 10 | 10 | 0 | 100 | | | -25% | 75 | 10 | 10 | 0 | 100 | | | +25% | 125 | 10 | 0 | 10 | 100 | | | +50% | 150 | 10 | 0 | 10 | 100 | | PCP (25) | -100% | 0 | 60 | 60 | 10 | 100 | | | -50% | 12.5 | 10 | 10 | 0 | 100 | | | -25% | 18.75 | 10 | 10 | 0 | 100 | | | +25% | 31.25 | 10 | 0 | 10 | 100 | | | +50% | 37.5 | 10 | 0 | 10 | 100 | | TCA (1000) | -100% | 0 | 30 | 0 | 30 | 100 | | | -50% | 500 | 30 | 0 | 30 | 100 | | | -25% | 750 | 30 | 0 | 30 | 100 | | | +25% | 1250 | 30 | 30 | 0 | 100 | | | +50% | 1500 | 30 | 30 | 0 | 100 | | THC (50) | -100% | 0 | 60 | 60 | 0 | 100 | | | -50% | 25 | 10 | 0 | 10 | 100 | | | -25% | 37.5 | 10 | 9 | 1 | 90 | | | +25% | 62.5 | 10 | 10 | 0 | 100 | | | +50% | 75 | 10 | 10 | 0 | 100 | Consumers were also given surveys on the ease of understanding the package insert instructions and $\geq 98\%$ of the lay users indicated that the device instructions can be easily followed. A Flesch-Kincaid reading analysis was performed on the package inserts and the score revealed a reading grade level of less than 7. # 4. Clinical cut-off: Not applicable. # 5. Expected values/Reference range: Not applicable. {20} 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. 21