AMEDICA DRUG SCREEN THC/COC, OP1300, PPX, OXY, BAR/BZO TEST

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY DEVICE ONLY TEMPLATE A. 510(k) Number: K040464 B. Purpose for Submission: New Device C. Analytes: THC (marijuana metabolite), benzoylecgonine, morphine, propoxyphene, oxycodone, secobarbital, and oxazepam D. Type of Test: Qualitative enzyme immunoassay E. Applicant: Amedica Biotech, Inc. F. Proprietary and Established Names: Amedica Drug Screen THC/COC, OPI300, PPX, OXY, BAR/BZO Test G. Regulatory Information: 1. Regulation section: 21 CFR § 862.3870 21 CFR § 862.3250 21 CFR § 862.3650 (opiates) 21 CFR § 862.3700 21 CFR § 862.3650 (oxycodone) 21 CFR § 862.3150 21 CFR § 862.3170 2. Classification: II 3. Product Code: LDJ (Cannabinoid Test System) DIO (Cocaine and Cocaine Metabolite Test System) DJG (Opiate Test System) JXN (Propoxyphene Test System) DJG (Opiate Test System - oxycodone) DIS (Barbiturate Test System) JXM (Benzodiazepine Test System) 4. Panel: {1} Toxicology (91) ## H. Intended Use: 1. Intended use(s): Refer to Indications for use. 2. Indication(s) for use: The Amedica Drug Screen THC/COC, OPI300, PPX, OXY, BAR/BZO Test is an in vitro diagnostic test for the rapid detection of THC, benzoylecgonine, morphine, propoxyphene, oxycodone, secobarbital and oxazepam in human urine at the following cut-off concentration | THC | 11-nor-Δ⁹-THC-9-COOH | 50 ng/ml | | --- | --- | --- | | COC | benzoylecgonine | 300 ng/ml | | OPI | morphine | 300 ng/ml | | PPY | propoxyphene | 300 ng/ml | | OXY | oxycodone | 100 ng/ml | | BAR | secobarbital | 300 ng/ml | | BZO | oxazepam | 300 ng/ml | This test kit is used to obtain a visual, qualitative result and is intended for use in laboratories and workplaces by trained users. It is not intended for over the counter sale. For in vitro diagnostic use Minimum training for operators is defined as those individuals who have received instructions for drugs of abuse testing from a physician or medical review officer. Operators may be lay users with no prior experience in running laboratory tests, but who are expected to perform at least 5 tests per week. Training should cover a variety of topics such as the value of confirmation testing, how to obtain confirmation testing, false positive results, false negative results, and quality control procedures. The sponsor recommends that operators take a written and practical exam before performing any testing and that employers keep documentation of the training. 3. Special condition for use statement(s): The Amedica Drug Screen THC/COC, OPI300, PPX, OXY, BAR/BZO Test provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/Mass spectrometry is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. {2} Page 3 of 27 Tests for barbiturates, benzodiazepines, and opiates cannot distinguish between abused drugs and certain prescribed medications. Certain foods or medications may interfere with tests for opiates and cause false positive results. 4. Special instrument Requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Amedica Drug Screen THC/COC, OPI300, PPX, OXY, BAR/BZO Test uses a nitrocellulose strip in a dip test, cassette (test card) test, and cup test formats. The only difference between the three strips is the length, where the dip test is 84 mm, the cassette test 59 mm, and the cup test 56 mm. In the dipstick format, operators dip the test strip into the urine and the reaction is initiated by movement of the sample through the test strip. In the cassette format, operators add several drops of the sample to the sample well. The test reaction is initiated by movement of the sample through the test strip. In the cup format, test strips are incorporated into the sides of the test cup. Addition of the urine to the test cup brings the test strips in contact with the sample and the sample begins migrating up the test strip. The sponsor recommends a minimum urine volume of 30 mL. J. Substantial Equivalence Information: 1. Predicate device name(s): Amedica Drug Screen THC Test Amedica Drug Screen Cocaine Test Rapid Opiates Test Instant-View Propoxyphene Test Branan Oxycodone Test Amedica Drug Screen MDMA, BAR, BZO, MTD, TCA Test 2. Predicate K number(s): k022955 k022954 k020716 k022915 k030113 k031497 {3} # 3. Comparison with predicate: When compared to the predicates, the candidate device is for the qualitative determination of the same seven analytes in the same matrix, and utilizes the same cutoff concentrations. All of the predicates and the candidate device are visually-read single use devices. The reagent formulations vary between the predicates and the candidate device. | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Type of Test | Single-Use, Qualitative Immunochromatographic Assay | Same | | Cutoffs | THC: 50 ng/mL Cocaine Metab: 300 ng/mL Opiates: 300 ng/mL Propox: 300 ng/mL Oxycod: 100 ng/mL Barb: 300 ng/mL Benz: 300 ng/mL | Same | | Number of Analytes | THC Cocaine Metab Opiates Propox Oxycod | Predicate measures THC Only Predicate measures Cocaine Metab Only Predicate measures Opiates Only Predicate measures Propoxyphene Only Predicate measures Oxycodone Only | | Differences | | | | Item | Device | Predicate | | Number of Analytes | Barbs plus six other analytes Benz plus six other analytes | Predicate measures only Barbs and Benzos Predicate measures only Barbs and Benzos | | Test Formats | Dipstick, Cassette, and Cup | Dipstick and/or Cassette and/or Cup | # K. Standard/Guidance Document Referenced (if applicable): The sponsor referenced the following guidance document(s) in their submission: Premarket Submission and Labeling Recommendations for Drugs of Abuse Screening Tests, published December 2003. The sponsor indicated deviation from this guidance in regards to interference testing. {4} Page 5 of 27 L. Test Principle: The test employs lateral flow immunochromatographic technology. Drug in the sample and drug-labeled conjugate (containing a chromagen) compete for antibody binding sites in the test area of the test strip. Binding of drug in the sample causes the absence of a line at the test area, i.e., a positive result. When drug is not present in the sample, the drug-labeled conjugate binds at the test line, resulting in formation of a line, i.e., a negative result. The absence or presence of the line is determined visually by the operator. The test region of the strips contains protein conjugated to THC, benzoylecgonine, morphine, propoxyphene, oxycodone, barbiturates, and benzodiazepines. The coated pad below the test region contains antibodies to THC, benzoylecgonine, morphine, propoxyphene, oxycodone, barbiturates, and benzodiazepines. The device also has an internal process control which indicates that an adequate volume of sample has been added and that the immunochromatographic strip is intact. Goat anti-rabbit antibodies in the control region combine with a rabbit antibody gold complex to produce a colored product. The user is instructed in the Package Insert that a very faint line in the test region is to be interpreted as a negative result. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Samples used for the precision study consisted of drug free urine spiked with 11-nor-Δ⁹-THC-9-COOH, benzoylecgonine, morphine, propoxyphene, oxycodone, secobarbital, and oxazepam. The sponsor states that the drug concentration was confirmed by GC-MS by the vendor. The testing was done on-site in the sponsor's laboratory. Three operators, who are from the manufacturer's staff, performed the testing over 20 days using three lots of the assay. Two replicates were run per day. {5} Results of the study are presented below: Cannabinoid (THC) Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 25 | 180 | 180/0 | | 37.5 | 180 | 180/0 | | 50 | 180 | 77/103 | | 62.5 | 180 | 39/141 | | 75 | 180 | 0/180 | Cocaine Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 180 | 180/0 | | 225 | 180 | 180/0 | | 300 | 180 | 94/86 | | 375 | 180 | 58/122 | | 450 | 180 | 0/180 | Opiates Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 180 | 180/0 | | 225 | 180 | 180/0 | | 300 | 180 | 94/86 | | 375 | 180 | 53/127 | | 450 | 180 | 0/180 | Propoxyphene Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 180 | 180/0 | | 225 | 180 | 180/0 | | 300 | 180 | 94/86 | | 375 | 180 | 55/125 | | 450 | 180 | 0/180 | {6} Page 7 of 27 ## Oxycodone Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 50 | 180 | 180/0 | | 75 | 180 | 180/0 | | 100 | 180 | 95/85 | | 125 | 180 | 37/143 | | 150 | 180 | 0/180 | ## Barbiturates Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 180 | 180/0 | | 225 | 180 | 180/0 | | 300 | 180 | 101/79 | | 375 | 180 | 57/123 | | 450 | 180 | 0/180 | ## Benzodiazepines Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 180 | 180/0 | | 225 | 180 | 180/0 | | 300 | 180 | 112/68 | | 375 | 180 | 57/123 | | 450 | 180 | 0/180 | The sponsor also provided precision data collected at three workplace sites in order to support a workplace claim. A different operator collected the data at each site and each operator completed the study in one day. Combined results were as follows: ## Cannabinoid (THC) Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 25 | 30 (10 per site) | 28/2 | | 37.5 | 30 (10 per site) | 23/7 | | 50 | 30 (10 per site) | 18/12 | | 62.5 | 30 (10 per site) | 4/26 | | 75 | 30 (10 per site) | 0/30 | {7} Page 8 of 27 ## Cocaine Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 30 (10 per site) | 29/1 | | 225 | 30 (10 per site) | 21/9 | | 300 | 30 (10 per site) | 19/11 | | 375 | 30 (10 per site) | 6/24 | | 450 | 30 (10 per site) | 0/30 | ## Opiates Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 30 (10 per site) | 30/0 | | 225 | 30 (10 per site) | 23/7 | | 300 | 30 (10 per site) | 22/8 | | 375 | 30 (10 per site) | 5/25 | | 450 | 30 (10 per site) | 0/30 | ## Propoxyphene Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 30 (10 per site) | 30/0 | | 225 | 30 (10 per site) | 25/5 | | 300 | 30 (10 per site) | 24/8 | | 375 | 30 (10 per site) | 6/24 | | 450 | 30 (10 per site) | 0/30 | ## Oxycodone Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 50 | 30 (10 per site) | 30/0 | | 75 | 30 (10 per site) | 26/4 | | 100 | 30 (10 per site) | 24/6 | | 125 | 30 (10 per site) | 2/28 | | 150 | 30 (10 per site) | 0/30 | {8} Page 9 of 27 Barbiturates Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 30 (10 per site) | 30/0 | | 225 | 30 (10 per site) | 28/2 | | 300 | 30 (10 per site) | 29/1 | | 375 | 30 (10 per site) | 6/24 | | 450 | 30 (10 per site) | 3/27 | Benzodiazepines Precision Study Results | Concentration of sample, ng/mL | Number of determinations | Results # Neg/ #Pos | | --- | --- | --- | | 150 | 30 (10 per site) | 30/0 | | 225 | 30 (10 per site) | 21/9 | | 300 | 30 (10 per site) | 24/6 | | 375 | 30 (10 per site) | 5/25 | | 450 | 30 (10 per site) | 0/30 | b. Linearity/assay reportable range: Not applicable. The assay is intended for qualitative use. c. Traceability (controls, calibrators, or method): Control materials are required but are not specifically identified in the labeling. The device has an internal process control which indicates that an adequate volume of sample has been added and that the immunochromatographic strip is intact. Users are instructed to follow federal, state, and local guidelines when determining when to run external controls. {9} # d. Detection limit: Sensitivity of this assay is characterized by validating performance around the claimed cutoff concentration of the assay, including a determination of the lowest concentration of drug that is capable of producing a positive result. To determine the analytical sensitivity, 25 replicates were run at drug concentrations from negative to 3X cutoff. NOTE: for the purposes of this experiment, a very faint line in the test region was interpreted as a borderline result near the cutoff. The user is instructed in the Package Insert that a very faint line in the test region is to be interpreted as negative when testing clinical samples. | THC Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 25 | 25 | 25 | 0 | 0 | | 37.5 | 25 | 10 | 15 | 0 | | 50 | 25 | 0 | 13 | 12 | | 62.5 | 25 | 0 | 5 | 20 | | 75 | 25 | 0 | 0 | 25 | | 150 | 25 | 0 | 0 | 25 | {10} | COC Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 150 | 25 | 25 | 0 | 0 | | 225 | 25 | 9 | 16 | 0 | | 300 | 25 | 0 | 14 | 11 | | 375 | 25 | 0 | 8 | 17 | | 450 | 25 | 0 | 0 | 25 | | 900 | 25 | 0 | 0 | 25 | | OPI Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 150 | 25 | 25 | 0 | 0 | | 225 | 25 | 12 | 13 | 0 | | 300 | 25 | 0 | 14 | 11 | | 375 | 25 | 0 | 7 | 18 | | 450 | 25 | 0 | 0 | 25 | | 900 | 25 | 0 | 0 | 25 | | PPY Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 150 | 25 | 25 | 0 | 0 | | 225 | 25 | 11 | 14 | 0 | | 300 | 25 | 0 | 15 | 10 | | 375 | 25 | 0 | 5 | 20 | | 450 | 25 | 0 | 0 | 25 | | 900 | 25 | 0 | 0 | 25 | {11} | BAR Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 50 | 25 | 25 | 0 | 0 | | 75 | 25 | 9 | 16 | 0 | | 100 | 25 | 0 | 10 | 15 | | 125 | 25 | 0 | 8 | 17 | | 150 | 25 | 0 | 0 | 25 | | 300 | 25 | 0 | 0 | 25 | | BZO Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 150 | 25 | 25 | 0 | 0 | | 225 | 25 | 8 | 17 | 0 | | 300 | 25 | 0 | 14 | 11 | | 375 | 25 | 0 | 9 | 16 | | 450 | 25 | 0 | 0 | 25 | | 900 | 25 | 0 | 0 | 25 | | BZO Conc. (ng/ml) | # Tested | # Negative | # Cut-Off (borderline) | # Positive | | --- | --- | --- | --- | --- | | 0 | 25 | 25 | 0 | 0 | | 150 | 25 | 25 | 0 | 0 | | 225 | 25 | 9 | 16 | 0 | | 300 | 25 | 0 | 14 | 11 | | 375 | 25 | 0 | 8 | 17 | | 450 | 25 | 0 | 0 | 25 | {12} Page 13 of 27 | 900 | 25 | 0 | 0 | 25 | | --- | --- | --- | --- | --- | Based on this data, the sensitivity of the assay to the seven analytes is as follows: THC: 50 ng/ml COC: 300 ng/ml OPI: 300 ng/ml PPY: 300 ng/ml OXY: 100 ng/ml BAR: 300 ng/ml BZO: 300 ng/ml {13} Page 14 of 27 e. Analytical specificity: Cross-reactivity was established by spiking various concentrations of similarly structured drug compounds into drug-free urine /a negative control. By analyzing various concentration of each compound the sponsor determined the concentration of the drug that produced a response approximately equivalent to the cutoff concentration of the assay. Results of those studies appear in the table(s) below: Cannabinoids (THC) | Compound | Response equivalent to cutoff in ng/mL | | --- | --- | | 11-Hydroxy-Δ⁹-Tetrahydrocannabinol | 2,500 | | 11-Nor-Δ⁸-Tetrahydrocannabinol carboxylic acid | 50 | | 11-Nor-Δ⁹-Tetrahydrocannabinol carboxylic acid | 50 | | Δ⁸-Tetrahydrocannabinol | 8,000 | | Δ⁹-Tetrahydrocannabinol | 10,000 | | Cannabinol | 10,000 | | Cannabidiol | 100,000 | Cocaine | Compound | Response equivalent to cutoff in ng/mL | | --- | --- | | Benzoylecogonine | 300 | | Cocaine | 50,000 | | Ecgonine | >100,000 | | Ecgonine Methyl Ester | >100,000 | Opiates | Drug compound | Response equivalent to cutoff in ng/mL | | --- | --- | | 6-monoacetylmorphine | 300 | | Codeine | 300 | | Hydrocodone | 3,000 | | Hydromorphone | 3,000 | | Morphine | 300 | | Ethylmorphine | 2,000 | Propoxyphene | Drug compound | Response equivalent to cutoff in ng/mL | | --- | --- | | Propoxyphene | 300 | | Norpropoxyphene | 20,000 | {14} Page 15 of 27 ## Oxycodone | Drug compound | Response equivalent to cutoff in ng/mL | | --- | --- | | Oxycodone | 100 | | Oxymorphone | 80,000 | ## Barbiturates | Compound | Response equivalent to cutoff in ng/mL | | --- | --- | | Secobarbital | 300 | | Phenobarbital | 300 | | Butalbital | 3000 | | Pentobarbital | 400 | | Alphenal | 400 | | Amobarbital | 2000 | | Aprobarbital | 300 | | Barbital | 300 | | Butabarbital | 300 | ## Benzodiazepines | Compound | Response equivalent to cutoff in ng/mL | | --- | --- | | Alprazolam | 200 | | Chlordiazepoxide | 500 | | Diazepam | 300 | | Oxazepam | 300 | | Clonazepam | 50,000 | | Flunitrazepam | 1500 | | Nitrazepam | 20,000 | | Bromazepam | 1500 | | Clobazam | 400 | | Estazolam | 500 | | Flurazepam | 1000 | | Lorazepam | 3000 | | Lometazepam | 10,000 | | Medazepam | 50,000 | | Nordiazepam | 400 | | Prazepam | 5000 | | Temazepam | 3000 | | Triazolam | 50,000 | {15} The following compounds were evaluated for potential positive and/or negative interference with the assay. The compounds were dissolved in $50\%$ cutoff samples to the concentration of $100~\mathrm{ug / ml}$ to evaluate any positive interference effects. An unaltered sample was used as a control. Results are listed below | Compound | THC | COC | OPI | PPX | OXY | BAR | BZO | | --- | --- | --- | --- | --- | --- | --- | --- | | Control | - | - | - | - | - | - | - | | Acetaminophen | - | - | - | - | - | - | - | | Acetone | - | - | - | - | - | - | - | | Albumin | - | - | - | - | - | - | - | | Ampicillin | - | - | - | - | - | - | - | | Amitriptyline | - | - | - | - | - | - | - | | Aspartame | - | - | - | - | - | - | - | | Aspirin | - | - | - | - | - | - | - | | Atropine | - | - | - | - | - | - | - | | Benzocaine | - | - | - | - | - | - | - | | Bilirubin | - | - | - | - | - | - | - | | Caffeine | - | - | - | - | - | - | - | | Chloroquine | - | - | - | - | - | - | - | | Chlorpheniramine | - | - | - | - | - | - | - | | Creatine | - | - | - | - | - | - | - | | Dexbrompheniramine | - | - | - | - | - | - | - | | Dextromethorphan | - | - | - | - | - | - | - | | 4-Dimethylamino antipyrine | - | - | - | - | - | - | - | | Dopamine | - | - | - | - | - | - | - | | (+/-)-Ephedrine | - | - | - | - | - | - | - | | Erythromycin | - | - | - | - | - | - | - | | Ethanol | - | - | - | - | - | - | - | | Furosemide | - | - | - | - | - | - | - | | Guaiacol Glyceryl Ether | - | - | - | - | - | - | - | | Glucose | - | - | - | - | - | - | - | | Hemoglobin | - | - | - | - | - | - | - | | Isoproterenol | - | - | - | - | - | - | - | | Lidocaine | - | - | - | - | - | - | - | | Methylphenidate | - | - | - | - | - | - | - | | N-Methyl-Ephedrine | - | - | - | - | - | - | - | | (+)-Naproxen | - | - | - | - | - | - | - | | Oxalic acid | - | - | - | - | - | - | - | | Penicillin-G | - | - | - | - | - | - | - | | Pheniramine | - | - | - | - | - | - | - | | Phenothiazine | - | - | - | - | - | - | - | | L-Phenylephrine | - | - | - | - | - | - | - | | β-phenylethylamine | - | - | - | - | - | - | - | | Procaine | - | - | - | - | - | - | - | | Quinidine | - | - | - | - | - | - | - | | Ranitidine | - | - | - | - | - | - | - | | Sodium Chloride | - | - | - | - | - | - | - | {16} The compounds were dissolved in $150\%$ cutoff samples to the concentration of $100~\mathrm{ug / ml}$ to evaluate any negative interference effects. An unaltered sample was used as a control. Results are listed below | Compound | THC | COC | OPI | PPX | OXY | BAR | BZO | | --- | --- | --- | --- | --- | --- | --- | --- | | Control | + | + | + | + | + | + | + | | Acetaminophen | + | + | + | + | + | + | + | | Acetone | + | + | + | + | + | + | + | | Albumin | + | + | + | + | + | + | + | | Ampicillin | + | + | + | + | + | + | + | | Amitriptyline | + | + | + | + | + | + | + | | Aspartame | + | + | + | + | + | + | + | | Aspirin | + | + | + | + | + | + | + | | Atropine | + | + | + | + | + | + | + | | Benzocaine | + | + | + | + | + | + | + | | Bilirubin | + | + | + | + | + | + | + | | Caffeine | + | + | + | + | + | + | + | | Chloroquine | + | + | + | + | + | + | + | | Chlorpheniramine | + | + | + | + | + | + | + | | Creatine | + | + | + | + | + | + | + | | Dexbrompheniramine | + | + | + | + | + | + | + | | Dextromethorphan | + | + | + | + | + | + | + | | 4+Dimethylamino antipyrine | + | + | + | + | + | + | + | | Dopamine | + | + | + | + | + | + | + | | (+/+) +Ephedrine | + | + | + | + | + | + | + | | Erythromycin | + | + | + | + | + | + | + | | Ethanol | + | + | + | + | + | + | + | | Furosemide | + | + | + | + | + | + | + | | Guaiacol Glyceryl Ether | + | + | + | + | + | + | + | | Glucose | + | + | + | + | + | + | + | | Hemoglobin | + | + | + | + | + | + | + | | Isoproterenol | + | + | + | + | + | + | + | | Lidocaine | + | + | + | + | + | + | + | | Methylphenidate | + | + | + | + | + | + | + | | N+Methyl+Ephedrine | + | + | + | + | + | + | + | | (+) +Naproxen | + | + | + | + | + | + | + | | Oxalic acid | + | + | + | + | + | + | + | | Penicillin+G | + | + | + | + | + | + | + | | Pheniramine | + | + | + | + | + | + | + | | Phenothiazine | + | + | + | + | + | + | + | | L+Phenylephrine | + | + | + | + | + | + | + | | β+phenylethylamine | + | + | + | + | + | + | + | {17} Page 18 of 27 | Procaine | + | + | + | + | + | + | + | | --- | --- | --- | --- | --- | --- | --- | --- | | Quinidine | + | + | + | + | + | + | + | | Ranitidine | + | + | + | + | + | + | + | | Sodium Chloride | + | + | + | + | + | + | + | | Sulindac | + | + | + | + | + | + | + | | Thioridazine | + | + | + | + | + | + | + | | Trifluoperazine | + | + | + | + | + | + | + | | Tyramine | + | + | + | + | + | + | + | | Vitamin C | + | + | + | + | + | + | + | There is the possibility that other substances and/or factors not listed above may interfere with the test and cause false results, e.g., technical or procedural errors. To test for potential positive/and or negative interference from endogenous conditions the following studies were performed: To evaluate any possible positive interference of pH, acid or base was added to 50% cutoff samples to obtain samples with pH values from 3 to 9. An unaltered sample was used as a control. Results were as follows. | pH | THC | COC | OPI | PPX | OXY | BAR | BZO | | --- | --- | --- | --- | --- | --- | --- | --- | | 7 (Control) | - | - | - | - | - | - | - | | 3 | - | - | - | - | - | - | - | | 4.5 | - | - | - | - | - | - | - | | 5.5 | - | - | - | - | - | - | - | | 8 | - | - | - | - | - | - | - | | 9 | - | - | - | - | - | - | - | To evaluate any possible negative interference of pH, acid or base was added to 150% cutoff samples to obtain samples with pH values from 3 to 9. An unaltered sample was used as a control. Results were as follows. | pH | THC | COC | OPI | PPX | OXY | BAR | BZO | | --- | --- | --- | --- | --- | --- | --- | --- | | 7 (Control) | + | + | + | + | + | + | + | | 3 | - | - | - | - | - | - | - | | 4.5 | + | + | + | + | + | + | + | | 5.5 | + | + | + | + | + | + | + | | 8 | + | + | + | + | + | + | + | | 9 | + | + | + | + | + | + | + | {18} To evaluate any possible positive interference of specific gravity, distilled water or sodium chloride was added to $50\%$ cutoff sample to obtain samples with specific gravity values from 1.002 to 1.03. An unaltered sample was used as a control. Results were as follows. | Specific gravity | THC | COC | OPI | PPX | OXY | BAR | BZO | | --- | --- | --- | --- | --- | --- | --- | --- | | 1.01 (Control) | - | - | - | - | - | - | - | | 1.002 | - | - | - | - | - | - | - | | 1.02 | - | - | - | - | - | - | - | | 1.03 | - | - | - | - | - | - | - | To evaluate any possible negative interference of specific gravity, distilled water or sodium chloride was added to $150\%$ cutoff sample to obtain samples with specific gravity values from 1.002 to 1.03. An unaltered sample was used as a control. Results were as follows. | Specific gravity | THC | COC | OPI | PPX | OXY | BAR | BZO | | --- | --- | --- | --- | --- | --- | --- | --- | | 1.01 (Control) | + | + | + | + | + | + | + | | 1.002 | + | + | + | + | + | + | + | | 1.02 | + | + | + | + | + | + | + | | 1.03 | + | + | + | + | + | + | + | The sponsor did not evaluate the effects of albumin on the assay. # f. Assay cut-off: The identified cutoff concentration of the assays for THC and cocaine metabolite are recommended for use by the Substance Abuse and Mental Health Services Administration (SAMHSA). The cutoff chosen for the opiates assay is different than that recommended by SAMHSA. No recommendations have been made by SAMHSA for propoxyphene, oxycodone, barbiturates, or benzodiazepines. Characterization of how the device performs analytically around the claimed cutoff concentration appears in the precision and sensitivity sections, above. {19} Page 20 of 27 2. Comparison studies: a. Method comparison with predicate device: Forty presumed negative samples were collected from volunteer donors at the sponsor’s facility and tested for all seven analytes by the candidate device and the predicate devices. All forty samples were negative for all analytes using the candidate device and the predicate devices. In a separate study, seven drug groups were evaluated by the candidate device, GC/MS and the predicate devices. The groups consisted of the following: THC group: 95 samples (21 neg, 74 pos) COC group: 86 samples (22 neg, 64 pos) OPIA group: 101 samples (31 neg, 70 pos) PPX group: 115 samples (31 neg, 84 pos) OXY group: 74 samples (21 neg, 53 pos) BAR group: 83 samples (21 neg, 62 pos) BZO group: 79 samples (37 neg, 42 pos) Sample description: Unaltered clinical urine samples were evaluated. An additional 267 diluted samples were also included in the study. The samples were prepared by diluting clinical samples with high drug concentrations with drug-free urine. This was done in order to obtain samples near the cutoff concentration of the assay, because the sponsor was not able to obtain unaltered samples near the cutoff. {20} Page 21 of 27 Samples previously analyzed by GC-MS were selected to be analyzed by the candidate device and the predicate. Results were grouped according to GC-MS concentration. NOTE: the sponsor states that samples were run in duplicate on the candidate device. If there was a discrepancy between the two results the sample was run a third time in order to obtain the final result. The number of times where a third result was required is as follows: THC group: 1/95 samples with GC-MS concentration of 54 ng/mL COC group: 2/86 samples with GC-MS concentrations of 305 and 313 ng/mL OPIA group: none PPX group: 1/115 samples with GC-MS concentration of 284 ng/mL OXY group: none BAR group: none BZO group: none In three of the four cases where a third replicate was run, the final result reported was in agreement with the GC-MS concentration. The study included an adequate number of samples that contained drugs near to the cutoff concentration of the assay. More than 10% of the study samples are evenly distributed between plus and minus 50% of the claimed cutoff concentration for all analytes. The study was performed at the manufacturer's facility by one member of the manufacturer's staff. Candidate Device Results vs. Predicate Device Results - THC | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 71 | 0 | | Negative by Candidate Device | 1 | 63 | % Agreement among positives is 100% % Agreement among negatives is 98% {21} Page 22 of 27 Candidate Device Results vs. stratified GC/MS Values - THC | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 1 | 8 | 63 | | Negative | 12 | 9 | 2 | 0 | GC/MS values used to categorize samples in this table are based on the concentration of THC found in the sample. % Agreement among positives is 97% % Agreement among negatives is 95% NOTE: one sample was run in triplicate to obtain a final result Candidate Device Results vs. Predicate Device Results - COC | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 64 | 1 | | Negative by Candidate Device | 0 | 61 | % Agreement among positives is 98% % Agreement among negatives is 100% {22} Page 23 of 27 # Candidate Device Results vs. stratified GC/MS Values - COC | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 2 | 8 | 54 | | Negative | 11 | 9 | 1 | 0 | GC/MS values used to categorize samples in this table are based on the concentration of BE found in the sample. % Agreement among positives is 98% % Agreement among negatives is 91% NOTE: two samples were run in triplicate to obtain a final result # Candidate Device Results vs. Predicate Device Results - OP | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 69 | 1 | | Negative by Candidate Device | 1 | 70 | % Agreement among positives is 99% % Agreement among negatives is 99% # Candidate Device Results vs. stratified GC/MS Values - OP | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 2 | 9 | 59 | | Negative | 15 | 14 | 2 | 0 | GC/MS values used to categorize samples in this table are determined by adding together codeine and morphine values. % Agreement among positives is 97% % Agreement among negatives is 94% {23} Page 24 of 27 # Candidate Device Results vs. Predicate Device Results - PPX | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 81 | 2 | | Negative by Candidate Device | 4 | 68 | % Agreement among positives is 98% % Agreement among negatives is 94% # Candidate Device Results vs. stratified GC/MS Values - PPX | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 2 | 7 | 74 | | Negative | 20 | 9 | 3 | 0 | GC/MS values used to categorize samples in this table are based on the concentration of propoxyphene found in the sample. % Agreement among positives is 96% % Agreement among negatives is 94% NOTE: one sample was run in triplicate to obtain a final result # Candidate Device Results vs. Predicate Device Results - OXY | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 52 | 1 | | Negative by Candidate Device | 2 | 59 | % Agreement among positives is 98% % Agreement among negatives is 97% {24} Page 25 of 27 # Candidate Device Results vs. stratified GC/MS Values - OXY | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 2 | 8 | 43 | | Negative | 11 | 8 | 2 | 0 | GC/MS values used to categorize samples in this table are based on the concentration of oxycodone found in the sample. % Agreement among positives is 96% % Agreement among negatives is 90% # Candidate Device Results vs. Predicate Device Results - BAR | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 62 | 1 | | Negative by Candidate Device | 1 | 59 | % Agreement among positives is 98% % Agreement among negatives is 98% # Candidate Device Results vs. stratified GC/MS Values - BAR | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 2 | 10 | 51 | | Negative | 10 | 9 | 1 | 0 | GC/MS values used to categorize samples in this table are based on the concentration of butabarbital found in the sample. % Agreement among positives is 98% % Agreement among negatives is 90% {25} Page 26 of 27 # Candidate Device Results vs. Predicate Device Results - BZO | | Positive by Predicate Device | Negative by Predicate Device | | --- | --- | --- | | Positive by Candidate Device | 44 | 0 | | Negative by Candidate Device | 0 | 75 | % Agreement among positives is 100% % Agreement among negatives is 100% # Candidate Device Results vs. stratified GC/MS Values - BZO | Candidate Device Results | Less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) | | --- | --- | --- | --- | --- | | Positive | 0 | 3 | 9 | 32 | | Negative | 25 | 9 | 1 | 0 | GC/MS values used to categorize samples in this table are based on the concentration of oxazepam found in the sample. % Agreement among positives is 98% % Agreement among negatives is 92% b. Matrix comparison: Not applicable. The assay is intended for only one sample matrix. 3. Clinical studies: a. Clinical sensitivity: Not applicable. Clinical studies are not typically submitted for this device type. b. Clinical specificity: Not applicable. Clinical studies are not typically submitted for this device type. c. Other clinical supportive data (when a and b are not applicable): 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. {26} Page 27 of 27 N. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.