RANDOX OPIATES ASSAY

{0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k113747 B. Purpose for Submission: New device C. Measurand: Opiates D. Type of Test: Qualitative and semi-quantitative immunoassay E. Applicant: Randox Laboratories Limited F. Proprietary and Established Names: Randox Opiates Assay Randox Multi Drug Calibrator Set (DOA CAL) Randox Multidrug Control Level 1 (DOA Control 1) Randox Multidrug Control Level 2 (DOA Control 2) G. Regulatory Information: | Product Code | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | DJG | Class II | 21 CFR § 862.3650, Opiates test system | 91-Toxicology | | DLJ | Class II | 21 CFR § 862.3200, Calibrators, Drug specific | 91-Toxicology | | LAS | Class I, reserved | 21 CFR 862.3280 Clinical Toxicology control material | 91-Toxicology | H. Intended Use: 1. Intended use(s): See Indications for use below. {1} 2. Indication(s) for use: Randox Laboratories Ltd. Opiates Assay is an in vitro diagnostic test for the qualitative and semi-quantitative analysis of Opiates in human urine. The cut off for both the qualitative and semi-quantitative application is 2000ng/mL for morphine to which the assay is calibrated. Qualitative and semi-quantitative results can be utilized in the diagnosis and treatment of Opiate use or overdose. The Randox Opiates Assay has been developed for use on the RX series analysers, which includes the RX Daytona and the RX Imola. This in vitro diagnostic device is intended for prescription use only. The semi-quantitative mode is for purposes of (1) Enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS or (2) Permitting laboratories to establish quality control procedures. This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatograph/Mass Spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The Randox Multidrug Calibrator Set is for use on human urine samples. They are liquid calibrators containing Methamphetamine, Secobarbital, Methadone, and Morphine. There are 5 levels of calibrator. They have been developed for use in the calibration of Amphetamine, Barbiturates, Methadone and Opiate assays on the RX series analysers, which includes the RX Daytona and RX Imola. This in vitro diagnostic device is intended for prescription use only. The Randox Multidrug Controls, Level 1 and 2 are for use on human urine samples. They are liquid controls containing Methamphetamine, Secobarbital, Methadone, and Morphine. There are 2 levels of controls. They have been developed for use in the quality control of Amphetamine, Barbiturates, Methadone and Opiate assays on the RX series analysers, which includes the RX Daytona and RX Imola. This in vitro diagnostic device is intended for prescription use only. 3. Special conditions for use statement(s): The assay is for prescription use. 4. Special instrument requirements: Performance studies contained in the 510(k) were carried out on the Rx Daytona and Rx Imola analyzers. {2} 3 I. Device Description: Randox Opiates Assay consists of ready to use reagents. Reagent 1 (R1) contains mouse monoclonal anti-morphine antibodies, glucose-6-phosphate, NAD and sodium azide &lt;0.1 % w/v. Reagent 2 (R2) contains morphine labeled G6PDH, buffer and sodium azide &lt;0.1 % w/v. The calibrators and controls are ready to use human urine-based liquid. Methamphetamine, Secobarbital, and Methadone are previously cleared analytes. J. Substantial Equivalence Information: 1. Predicate device name(s): Microgenics DRI Opiate Assay DRI Multi-Drug Calibrators and Controls 2. Predicate 510(k) number(s): k011150 k983159 3. Comparison with predicate: Assay | Similarities | | | | --- | --- | --- | | Item | New Device Randox Opiates Assay Candidate device (k113747) | Predicate Microgenics DRI Opiates Assay (k011150) | | Intended Use/ Indications for Use | Qualitative and semi-quantitative analysis of Opiates in human urine. | Same | | Cut-off | 2000 ng/mL | 300 ng/mL or 2000 ng/mL | | Sample Type | Human urine | Human urine | | Test Principle | A competitive enzyme immunoassay based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. In the absence of drug in the sample the morphine labeled G6PDH conjugate is bound to antibody and enzyme activity is inhibited. When free drug is present in the | A homogenous enzyme immunoassay based on competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and drug from urine sample for a fixed amount of specific antibody binding sites. Enzyme activity is determined spectrophotometrically at 340nm by measuring its ability to convert NAD to | {3} 4 | Similarities | | | | --- | --- | --- | | Item | New Device Randox Opiates Assay Candidate device (k113747) | Predicate Microgenics DRI Opiates Assay (k011150) | | | sample, antibody binds to the free drug and the unbound morphine labeled G6PDH exhibits its maximum enzyme activity. Active enzyme converts NAD to NADH resulting in an absorbance change measured spectrophotometrically at 340nm. | NADH | | Type of reagent | Liquid ready to use Two reagent assay | Liquid ready to use Two reagent assay | | Methodology | Homogenous enzyme Immunoassay | Homogenous enzyme Immunoassay | | Reagents | R1. Antibody/Substrate Reagent: Mouse monoclonal anti-morphine antibodies, glucose-6-phosphate, NAD and sodium azide <0.1% w/v. R2. Enzyme-Drug Conjugate Reagent: Morphine labeled G6PDH and sodium azide <0.1% w/v | R1. Antibody/Substrate Reagent: Monoclonal anti-morphine antibodies, glucose-6-phosphate, NAD and sodium azide <0.1% w/v. R2. Enzyme Conjugate Reagent: Morphine labeled G6PDH and sodium azide <0.1% w/v | Calibrators and Controls | Similarities | | | | --- | --- | --- | | Item | New Device Randox Opiates Assay Candidate device (k113747) | Predicate DRI Multi-Drug Calibrators and Controls (k983159) | | Intended Use/ Indications for Use | Same | Calibration and quality control of various drug of abuse Assays. | | Analytes | Secobarbital, Methadone, Methamphetamine and Morphine | d-Methamphetamine, Secobarbital, Oxazepam, Benzoylecgonine, Methadone, Methaqualone, Morphine, Phencyclidine and Propoxyphene | {4} 5 | Similarities | | | | --- | --- | --- | | Item | New Device Randox Opiates Assay Candidate device (k113747) | Predicate DRI Multi-Drug Calibrators and Controls (k983159) | | Calibrators | Liquid ready to use (0, 300, 1000, 2000, 4000 ng/mL) | Liquid ready to use (300, 1000, 2000, 4000, 6000 ng/mL) | | Controls | Liquid ready to use 1500, 2500 ng/mL | Liquid ready to use 300, 2000 ng/mL | K. Standard/Guidance Document Referenced (if applicable): EP7-A2 CLSI Interference Testing in Clinical Chemistry EP17-A CLSI Protocols for Determination of Limits of Detection &amp; Limits of Quantitation L. Test Principle: The Randox Laboratory Ltd. Opiates Assay is an immunoassay with ready to use liquid reagent. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. In the absence of drug in the sample, morphine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. When free drug is present in the sample, the antibody will bind to the free drug and the unbound morphine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Precision was determined by spiking Morphine (1 mg/ml solution) into drug free urine at various concentrations (-100%, -75%, -50%, -25%, cut off, +25%, +50%, +75% and +100%). Concentrations were confirmed by GCMS. Intra-assay precision was performed over 20 nonconsecutive days. The between run testing was performed in replicate twice a day for 20 days. The qualitative and semi-quantitative results are presented below: Rx Daytona and Rx Imola: Total Precision for qualitative mode | Sample concentration | No. observation | Rx Daytona | Rx Imola | | --- | --- | --- | --- | | -100% cut off | 80 | 80 negative | 80 negative | | -75% cut off | 80 | 80 negative | 80 negative | | -50% cut off | 80 | 80 negative | 80 negative | {5} 6 | -25% cut off | 80 | 80 negative | 80 negative | | --- | --- | --- | --- | | +25% cut off | 80 | 80 positive | 80 positive | | +50% cut off | 80 | 80 positive | 80 positive | | +75% cut off | 80 | 80 positive | 80 positive | | +100% cut off | 80 | 80 positive | 80 positive | Rx Daytona and Rx Imola: Total Precision for semi-quantitative mode | Sample concentration | No. observations | Rx Daytona | Rx Imola | | --- | --- | --- | --- | | -100% cut off | 80 | 80 negative | 80 negative | | -75% cut off | 80 | 80 negative | 80 negative | | -50% cut off | 80 | 80 negative | 80 negative | | -25% cut off | 80 | 80 negative | 80 negative | | +25% cut off | 80 | 80 positive | 80 positive | | +50% cut off | 80 | 80 positive | 80 positive | | +75% cut off | 80 | 80 positive | 80 positive | | +100% cut off | 80 | 80 positive | 80 positive | b. Linearity/assay reportable range: Recovery across the range was determined by testing a series of samples that were diluted from the high concentration Morphine spiked urine sample. A high urine sample containing around 4000 ng/mL Morphine was serially diluted with analyte-free urine and tested in triplicates in the semi-quantitative mode. The results were averaged and compared to the expected result and the percent recovery was calculated. Results are presented in the tables below. Rx Imola: | Expected Concentration (ng/mL) | Mean Observed Concentration (ng/mL) | Recovery (%) | | --- | --- | --- | | 0 | 0.00 | Not applicable | | 40 | 22.89 | 57.22 | | 80 | 61.05 | 76.31 | | 120 | 80.83 | 67.36 | | 160 | 123.87 | 77.42 | | 200 | 193.14 | 96.57 | | 240 | 242.39 | 101.00 | | 280 | 284.74 | 101.69 | | 320 | 342.59 | 107.06 | | 360 | 358.97 | 99.71 | | 400 | 427.08 | 106.77 | | 800 | 848.26 | 106.03 | | 1200 | 1200.17 | 100.01 | | 1600 | 1554.89 | 97.18 | | 2000 | 1949.07 | 97.45 | {6} 7 | 2400 | 2328.02 | 97.00 | | --- | --- | --- | | 2800 | 2923.36 | 104.41 | | 3200 | 3219.68 | 100.61 | | 3600 | 3543.00 | 98.42 | | 4000 | 4161.60 | 104.04 | Rx Daytona: | Expected Concentration (ng/mL) | Mean Observed Concentration (ng/mL) | Recovery (%) | | --- | --- | --- | | 0 | 0.00 | Not applicable | | 40 | 0.00 | 0.00 | | 80 | 38.00 | 47.50 | | 120 | 131.72 | 109.77 | | 160 | 196.45 | 122.78 | | 200 | 216.18 | 108.09 | | 240 | 260.93 | 108.72 | | 280 | 283.22 | 101.15 | | 320 | 346.30 | 108.22 | | 360 | 371.16 | 103.10 | | 400 | 429.91 | 107.48 | | 800 | 844.61 | 105.58 | | 1200 | 1274.79 | 106.23 | | 1600 | 1663.39 | 103.96 | | 2000 | 1982.23 | 99.11 | | 2400 | 2418.72 | 100.78 | | 2800 | 2902.23 | 103.65 | | 3200 | 3122.82 | 97.59 | | 3600 | 3379.54 | 93.88 | | 4000 | 4388.57 | 109.71 | c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability and value assignment The 5 level multi-drug calibrator (0 ng/mL, 300 ng/mL, 1000 ng/mL, 2000 ng/mL, 4000 ng/mL) and 2 level multi-drug control materials (1500 ng/mL, 2500 ng/mL) are both traceable to master lots that have been GC/MS quantified. The master lots were made by spiking morphine, methadone, methamphetamine and secobarbital at the appropriate levels into a buffered human urine matrix that also contains 0.05% sodium azide. The drugs used to make the calibrators and controls are supplied by Cerilliant Corporation the accuracy of which is ensured by purity determinations (GC/FID, HPLC and NMR) and gravimetric preparation using balances calibrated with NIST traceable weights. Each of the Randox calibrator/control level is value assigned using Rx Daytona and Rx Imola. The {7} target value for each level is the median of the observed values. ## Stability Real time stability testing including shelf-life and on-board stability studies were performed for the assay, controls and calibrators. The acceptance criteria were found to be adequate. The Randox Opiates assay reagents, controls and calibrators are stable for 18 moths when stored unopened at $2 - 8^{\circ}\mathrm{C}$ and 28 days on-board at approximately $10^{\circ}\mathrm{C}$. ## d. Detection limit: Performance at low drug concentrations in the semi-quantitative assay was characterized by determination of recovery (see section b above). ## e. Analytical specificity: The Randox Laboratory Ltd. Opiate Assay was evaluated for interference according to the CLSI Guideline EP7-A2 recommendations. These studies were performed by spiking structurally related and unrelated compounds into drug-free and drug-containing urine samples. Drug-containing urine samples were tested at two different concentrations, $+25\%$ and $-25\%$ of the cut-off concentration of 2000 ng/mL. Drug-free urine samples were used as controls. Percent cross-reactivity was calculated using the cross-reactant concentration that gives a reaction absorbance which matches the reaction absorbance obtained by the cut-off calibrator. The cut-off calibrator concentration divided by the cross-reactant concentration that achieved the matching reactant absorbance $\times 100\%$ gives the percent cross reactivity. These studies were performed on both, the Rx Daytona and Rx Imola analyzers. Similar results were obtained with both analyzers and in both qualitative and semi-quantitative modes. The percent cross-reactivity of the tested compounds are presented below: Structurally related compounds: Rx Daytona Qualitative | Compound | Tested concentration (ng/mL) | Cross-reactivity (%) | | --- | --- | --- | | Morphine | 2000 | 100.00 | | 6 Acetyl-morphine | 2000 | 99.98 | | Ethylmorphine | 1872 | 106.87 | | Codeine | 1785 | 112.03 | | Dihydrocodeine | 4262 | 46.93 | | Morphine-3-β-glucoronide | 83642 | 2.39 | | Hydromorphone | 762735 | 0.26 | | Hydrocodone | 7780 | 25.71 | | Oxycodone | 684002 | 0.29 | | Heroin | 5493 | 36.41 | {8} Rx Imola Qualitative: | Compound | Tested concentration (ng/mL) | Cross-reactivity (%) | | --- | --- | --- | | Morphine | 2000 | 100.00 | | 6 Acetyl-morphine | 1930 | 103.64 | | Ethylmorphine | 2560 | 84.75 | | Codeine | 1882 | 106.26 | | Dihydrocodeine | 5886 | 33.98 | | Morphine-3-β-glucoronide | 87471 | 2.29 | | Hydromorphone | 892374 | 0.22 | | Hydrocodone | 8965 | 22.31 | | Oxycodone | 871511 | 0.23 | | Heroin | 7386 | 27.08 | Rx Daytona Semi-Quantitative | Compound | Tested concentration (ng/mL) | Cross-reactivity (%) | | --- | --- | --- | | Morphine | 2000 | 100.00 | | 6 Acetyl-morphine | 2060 | 97.10 | | Ethylmorphine | 1849 | 108.19 | | Codeine | 1808 | 110.60 | | Dihydrocodeine | 4639 | 43.11 | | Morphine-3-β-glucoronide | 86029 | 2.32 | | Hydromorphone | 803275 | 0.25 | | Hydrocodone | 8471 | 23.61 | | Oxycodone | 712764 | 0.28 | | Heroin | 6035 | 33.14 | Rx Imola Semi-Qualitative: | Compound | Tested concentration (ng/mL) | Cross-reactivity (%) | | --- | --- | --- | | Morphine | 2000 | 100.00 | | 6 Acetyl-morphine | 1801 | 111.07 | | Ethylmorphine | 1827 | 109.48 | | Codeine | 1801 | 111.05 | | Dihydrocodeine | 4637 | 43.13 | | Morphine-3-β-glucoronide | 80900 | 2.47 | | Hydromorphone | 770636 | 0.26 | {9} Structurally unrelated compounds: Rx Daytona: | Compound | Tested Concentration (ng/mL) | -25% of 2000 ng/mL opiate cut-off | | +25% of 2000 ng/mL opiate cut-off | | | --- | --- | --- | --- | --- | --- | | | | Qualitative | Semi-Quantitative | Qualitative | Semi-Quantitative | | 11-hydroxy-delta9-THC | 100,000 | NEG | NEG | POS | POS | | 11-nor9-carboxy-delta9-THC | 100,000 | NEG | NEG | POS | POS | | Amitriptyline | 100,000 | NEG | NEG | POS | POS | | Amobarbital | 100,000 | NEG | NEG | POS | POS | | (+/-) Amphetamine D5 | 100,000 | NEG | NEG | POS | POS | | Ascorbic acid | 100,000 | NEG | NEG | POS | POS | | Aspirin | 100,000 | NEG | NEG | POS | POS | | Benzolyecgonine | 100,000 | NEG | NEG | POS | POS | | B-phenylethylamine | 100,000 | NEG | NEG | POS | POS | | Caffeine | 100,000 | NEG | NEG | POS | POS | | Cannabidiol | 100,000 | NEG | NEG | POS | POS | | Chlorpheniramine | 100,000 | NEG | NEG | POS | POS | | Cocaethylene | 100,000 | NEG | NEG | POS | POS | | Cocaine | 100,000 | NEG | NEG | POS | POS | | Cotinine | 100,000 | NEG | NEG | POS | POS | | Delta9-THC | 100,000 | NEG | NEG | POS | POS | | Diazepam | 100,000 | NEG | NEG | POS | POS | | Ecgonine methyl ester | 100,000 | NEG | NEG | POS | POS | | EDDP | 100,000 | NEG | NEG | POS | POS | | EMDP | 100,000 | NEG | NEG | POS | POS | | d,l-Ephedrine | 100,000 | NEG | NEG | POS | POS | | l-Ephedrine | 100,000 | NEG | NEG | POS | POS | | d-Ephedrine | 100,000 | NEG | NEG | POS | POS | | LAAM | 100,000 | NEG | NEG | POS | POS | | MBDB | 100,000 | NEG | NEG | POS | POS | | MDA | 100,000 | NEG | NEG | POS | POS | | MDEA | 100,000 | NEG | NEG | POS | POS | | MDMA | 100,000 | NEG | NEG | POS | POS | | Methadone | 100,000 | NEG | NEG | POS | POS | | d-Methamphetamine | 100,000 | NEG | NEG | POS | POS | | Paracetamol | 100,000 | NEG | NEG | POS | POS | {10} Rx Imola: | Compound | Tested Concentration (ng/mL) | -25% of 2000 ng/mL opiate cut-off | | +25% of 2000 ng/mL opiate cut-off | | | --- | --- | --- | --- | --- | --- | | | | Qualitative | Semi-Quantitative | Qualitative | Semi-Quantitative | | 11-hydroxy-delta9-THC | 100,000 | NEG | NEG | POS | POS | | 11-nor9-carboxy-delta9-THC | 100,000 | NEG | NEG | POS | POS | | Amitriptyline | 100,000 | NEG | NEG | POS | POS | | Amobarbital | 100,000 | NEG | NEG | POS | POS | | (+/-) Amphetamine D5 | 100,000 | NEG | NEG | POS | POS | | Ascorbic acid | 100,000 | NEG | NEG | POS | POS | | Aspirin | 100,000 | NEG | NEG | POS | POS | | Benzolyecgonine | 100,000 | NEG | NEG | POS | POS | | B-phenylethylamine | 100,000 | NEG | NEG | POS | POS | | Caffeine | 100,000 | NEG | NEG | POS | POS | | Cannabidiol | 100,000 | NEG | NEG | POS | POS | | Chlorpheniramine | 100,000 | NEG | NEG | POS | POS | | Cocaethylene | 100,000 | NEG | NEG | POS | POS | | Cocaine | 100,000 | NEG | NEG | POS | POS | | Cotinine | 100,000 | NEG | NEG | POS | POS | | Delta9-THC | 100,000 | NEG | NEG | POS | POS | | Diazepam | 100,000 | NEG | NEG | POS | POS | | Ecgonine methyl ester | 100,000 | NEG | NEG | POS | POS | | EDDP | 100,000 | NEG | NEG | POS | POS | | EMDP | 100,000 | NEG | NEG | POS | POS | | d,l-Ephedrine | 100,000 | NEG | NEG | POS | POS | | l-Ephedrine | 100,000 | NEG | NEG | POS | POS | | d-Ephedrine | 100,000 | NEG | NEG | POS | POS | | LAAM | 100,000 | NEG | NEG | POS | POS | | MBDB | 100,000 | NEG | NEG | POS | POS | | MDA | 100,000 | NEG | NEG | POS | POS | | MDEA | 100,000 | NEG | NEG | POS | POS | | MDMA | 100,000 | NEG | NEG | POS | POS | {11} 12 | Methadone | 100,000 | NEG | NEG | POS | POS | | --- | --- | --- | --- | --- | --- | | d-Methamphetamine | 100,000 | NEG | NEG | POS | POS | | Paracetamol | 100,000 | NEG | NEG | POS | POS | | S,S (+) Pseudoephedrine | 100,000 | NEG | NEG | POS | POS | | R,R (-) Pseudoephedrine | 100,000 | NEG | NEG | POS | POS | | Temazepam | 100,000 | NEG | NEG | POS | POS | | Ibuprofen | 100,000 | NEG | NEG | POS | POS | | d-amphetamine | 100,000 | NEG | NEG | POS | POS | Endogenous compounds: The following endogenous compounds were added into drug-free urine and urine containing Opiate at the concentrations of $\pm 25\%$ surrounding the assay cut-off. These samples were tested using both, the Rx Daytona and Rx Imola analyzers. The substances listed in the table below were determined not to interfere at the concentration shown: | Compound | Tested Concentration | | --- | --- | | Total bilirubin | 15 mg/dL | | Direct bilirubin | 5 mg/dL | | Hemoglobin | 115 mg/dL | | Creatinine | 30 mg/dL | | Urea | 258 mg/dL | | Glucose | 2000 mg/dL | | HAS | 500 mg/dL | | Ethanol | 1000 mg/dL | | Acetone | 1000 mg/dL | | Gamma globulin | 500 mg/dL | | Oxalic acid | 100 mg/dL | | Riboflavin | 7.5 mg/dL | | Sodium chloride | 6000 mg/dL | | Boric acid | 1000 mg/dL | | Sodium azide | 1000 mg/dL | | Sodium fluoride | 1000 mg/dL | In addition, the performance of the assay was evaluated under varying pH levels of: 3, 5, 7, 9 and 11, which had no effect on results. Further, variations in specific gravity between 1.00 and 1.03 also had no effect on results. These studies were performed at concentrations $\pm 25\%$ of the cut-off. The package insert includes the complete list of all structurally related and unrelated compounds and metabolites tested. {12} f. Assay cut-off: Analytical performance of the device around the claimed cut-off is described in precision section (1 a.) above. 2. Comparison studies: a. Method comparison with predicate device: One hundred twenty eight unaltered clinical urine samples were evaluated by the Randox Opiate assay and compared to a GC/MS. Results from the study are presented below: Rx Daytona – Semi-quantitative | GC/MS for opiates (based on cross reactivity profile) → | Negative | Less than half the Cut-Off | Near Cut-off Negative (concentration between 50% below the cut-off and the cut-off concentration for Opiates) | Near Cut-off Positive (concentration between 50% above the cut-off and the cut-off concentration for Opiates) | High Positive (concentration > 50% above the cut-off concentration for Opiates) | Percent Agreement with GC/MS for Opiates (based on cross reactivity profile) | | --- | --- | --- | --- | --- | --- | --- | | 2000 ng/mL cut-off Opiate Assay ↓ | | | | | | | | Positive | 0 | 0 | 9 | 21 | 41 | 92.5% | | Negative | 43 | 2 | 7 | 5 | 0 | 85.2% | Rx Daytona Qualitative | GC/MS for opiates (based on cross reactivity profile) → | Negative | Less than half the Cut-Off | Near Cut-off Negative (concentration between 50% below the cut-off and the cut-off concentration for Opiates) | Near Cut-off Positive (concentration between 50% above the cut-off and the cut-off concentration for Opiates) | High Positive (concentration > 50% above the cut-off concentration for Opiates) | Percent Agreement with GC/MS for Opiates (based on cross reactivity profile) | | --- | --- | --- | --- | --- | --- | --- | | 2000 ng/mL cut-off Opiate Assay ↓ | | | | | | | | Positive | 0 | 0 | 6 | 19 | 42 | 90.9 | | Negative | 43 | 2 | 10 | 6 | 0 | 90.2 | {13} Rx Imola – Semi-quantitative | GC/MS for opiate (based on cross reactivity profile) → | Negative | Less than half the Cut-Off | Near Cut-off Negative (concentration between 50% below the cut-off and the cut-off concentration for Opiates) | Near Cut-off Positive (concentration between 50% above the cut-off and the cut-off concentration for Opiates) | High Positive (concentration > 50% above the cut-off concentration for Opiates) | Percent Agreement with GC/MS for Opiates (based on cross reactivity profile) | | --- | --- | --- | --- | --- | --- | --- | | 2000 ng/mL cut-off Opiate Assay ↓ | | | | | | | | Positive | 0 | 0 | 9 | 22 | 41 | 94.0 | | Negative | 43 | 2 | 7 | 4 | 0 | 85.2 | Rx Imola – Qualitative | GC/MS for Morphine (based on cross reactivity profile) → | Negative | Less than half the Cut-Off | Near Cut-off Negative (concentration between 50% below the cut-off and the cut-off concentration for Opiates) | Near Cut-off Positive (concentration between 50% above the cut-off and the cut-off concentration for Opiates) | High Positive (concentration > 50% above the cut-off concentration for Opiates) | Percent Agreement with GC/MS for Opiates (based on cross reactivity profile) | | --- | --- | --- | --- | --- | --- | --- | | 2000 ng/mL cut-off Opiate Assay ↓ | | | | | | | | Positive | 0 | 1 | 6 | 22 | 41 | 94.0 | | Negative | 43 | 2 | 9 | 4 | 0 | 88.5 | GC/MS Summary of Discordant Results: Rx Daytona – Semi-quantitative | Cut-off value (ng/mL) for Morphine | Randox Opiates Assay (POS/NEG) | Drug/Metabolite GC/MS value (ng/mL) based on cross reactivity profile | | --- | --- | --- | | 2000 | POS | 1798 (Morphine) | | | POS | 1306 (Morphine) | | | POS | 462 (Morphine) & 629 (Codeine) | | | POS | 588 (Morphine) & 431 (Codeine) | | | POS | 728 (Morphine) & 250 (Codeine) | | | POS | 252 (Morphine) & 784 (Codeine) | | | POS | 1550 (Morphine) | | | POS | 1990 (Morphine) | | | POS | 1550 (Morphine) | | | NEG | 2313 (Morphine) | | | NEG | 1967 (Morphine) & 910 (Hydromorphone) | | | NEG | 2300 (Morphine) | {14} 15 Rx Daytona – Qualitative | Cut-off value (ng/mL) for Morphine | Randox Opiates Assay (POS/NEG) | Drug/Metabolite GC/MS value (ng/mL) based on cross reactivity profile | | --- | --- | --- | | 20008 | POS | 462 (Morphine) & 629 (Codeine) | | | POS | 588 (Morphine) & 431 (Codeine) | | | POS | 728 (Morphine) & 250 (Codeine) | | | POS | 252 (Morphine) & 784 (Codeine) | | | POS | 1990 (Morphine) | | | POS | 1550 (Morphine) | | | NEG | 1967 (Morphine) & 910 (Hydromorphone) | | | NEG | 2313 (Morphine) | | | NEG | 2300 (Morphine) | | | NEG | 2100 (Morphine) | | | NEG | 2500 (Morphine) | | | NEG | 2700 (Morphine) | Rx Imola – Semi-quantitative | Cut-off value (ng/mL) for Morphine | Randox Opiates Assay (POS/NEG) | Drug/Metabolite GC/MS value (ng/mL) based on cross reactivity profile | | --- | --- | --- | | 2000 | POS | 1967 (Morphine) | | | POS | 1306 (Morphine) | | | POS | 462 (Morphine) & 629 (Codeine) | | | POS | 588 (Morphine) & 431 (Codeine) | | | POS | 728 (Morphine) & 250 (Codeine) | | | POS | 252 (Morphine) & 784 (Codeine) | | | POS | 1990 (Morphine) | | | POS | 1550 (Morphine) | | | NEG | 2174 (Morphine) | | | NEG | 2313 (Morphine) | | | NEG | 2300 (Morphine) | | | NEG | 2100 (Morphine) | Rx Imola – Qualitative | Cut-off value (ng/mL) for Morphine | Randox Opiates Assay (POS/NEG) | Drug/Metabolite GC/MS value (ng/mL) based on cross reactivity profile | | --- | --- | --- | | 2000 | POS | 1967 (Morphine) | | | POS | 462 (Morphine) & 629 (Codeine) | | | POS | 588 (Morphine) & 431 (Codeine) | | | POS | 728 (Morphine) & 250 (Codeine) | | | POS | 252 (Morphine) & 784 (Codeine) | | | POS | 1990 (Morphine) | {15} 16 | | POS | 1550 (Morphine) | | --- | --- | --- | | | NEG | 2174 (Morphine) | | | NEG | 2300 (Morphine) | | | NEG | 2100 (Morphine) | | | NEG | 2313 (Morphine) | b. Matrix comparison: Not applicable. The test is only for urine specimens. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. Not reviewed for this device type. b. Clinical specificity: Not applicable. 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. 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.