RANDOX COCAINE METABOLITE

K113751 · Randox Laboratories, Ltd. · DIO · May 8, 2012 · Clinical Toxicology

Device Facts

• Record ID: K113751
• Device Name: RANDOX COCAINE METABOLITE
• Applicant: Randox Laboratories, Ltd.
• Product Code: DIO · Clinical Toxicology
• Decision Date: May 8, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3250
• Device Class: Class 2

Indications for Use

The Randox Laboratories Ltd. Cocaine Metabolite Assay is an in vitro diagnostic test for the qualitative and semi-quantitative detection of Cocaine in human urine. The cut off for both the qualitative and semi-quantitative modes of the assay is 300 ng/ml for benzoylecgonine. Qualitative and semi-quantitative results can be utilized in the diagnosis and treatment of Cocaine use or overdose. The Randox Cocaine Metabolite assay has been developed for use on the RX series analyzers, which includes the RX Daytona and RX imola. This in vitro diagnostic device is intended for prescription use only. The semi-quantitative modes is for purpose 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 result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ 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.

Device Story

Randox Cocaine Metabolite Assay, Multidrug Calibrator Set, and Multidrug Controls are in vitro diagnostic reagents for use on RX series analyzers (RX Daytona, RX Imola). Assay detects Benzoylecgonine in human urine; provides qualitative/semi-quantitative results. Calibrators and controls contain Methamphetamine, Secobarbital, Oxazepam, Benzoylecgonine, and Methadone. Used in clinical laboratory settings by trained personnel. Semi-quantitative mode assists in determining specimen dilution for GC/MS confirmation and establishing quality control. Results are preliminary; clinical judgment required for interpretation. Benefits include rapid screening for Cocaine use/overdose in clinical settings.

Clinical Evidence

No clinical studies performed. Performance established via bench testing and method comparison against GC/MS. Comparison study of 137 urine samples showed high concordance with GC/MS (97.2%–98.6% agreement). Analytical performance included precision, linearity, and cross-reactivity/interference testing.

Technological Characteristics

Liquid-based reagents, calibrators, and controls. Designed for use on RX series automated clinical chemistry analyzers (RX Daytona, RX Imola). Qualitative and semi-quantitative detection via immunoassay principles. Cutoff concentration: 300ng/ml for Benzoylecgonine.

Indications for Use

Indicated for the qualitative and semiquantitative detection of Cocaine (Benzoylecgonine) in human urine at a 300ng/ml cutoff. Intended for use by clinical laboratories to assist in the diagnosis and treatment of Cocaine use or overdose. Requires prescription use. Not for definitive diagnosis; requires confirmation by GC/MS.

Regulatory Classification

Identification

A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.

Special Controls

*Classification.* Class II (special controls). A cocaine and cocaine metabolite test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k113751

B. Purpose for Submission:
New device

C. Measurand:
Cocaine metabolite

D. Type of Test:
Qualitative and semi-quantitative enzyme immunoassay

E. Applicant:
Randox Laboratories Ltd.

F. Proprietary and Established Names:
Randox Cocaine Metabolite Assay
Randox Multidrug Calibrator Set
Randox Multidrug Controls, Level 1&2

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DIO – Cocaine and cocaine metabolite test system | II | 862.3250 | 91-Toxicology |
| DLJ -Clinical toxicology calibrator | II | 862.3200 | 91- Toxicology |
| LAS -Clinical toxicology control material | I, reserved | 862.3280 | 91- Toxicology |

H. Intended Use:
1. Intended use(s):

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See Indications for use below.

## 2. Indication(s) for use:

### Randox Cocaine Metabolite Assay

The Randox Laboratories Ltd. Cocaine Metabolite Assay is an in vitro diagnostic test for the qualitative and semi-quantitative detection of Cocaine in human urine. The cut off for both the qualitative and semi-quantitative modes of the assay is 300 ng/ml for benzoylecgonine. Qualitative and semi-quantitative results can be utilized in the diagnosis and treatment of Cocaine use or overdose. The Randox Cocaine Metabolite assay has been developed for use on the RX series analyzers, which includes the RX Daytona and RX imola.

This in vitro diagnostic device is intended for prescription use only.

The semi-quantitative modes is for purpose 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 result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ 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.

### Randox Multidrug Calibrator Set

The Randox Multidrug Calibrator Set consists of liquid calibrators containing Methamphetamine, Secobarbital, Oxazepam, Benzoylecgonine and Methadone. There are 5 levels of calibrator. They have been developed for use in the calibration of Amphetamine, Barbiturates, Cocaine, and Methadone assays on the RX series analyzers, which includes the RX daytona and RX imola. This in vitro diagnostic device is intended for prescription use only.

### Randox Multidrug Controls, Level 1&2

The Randox Multidrug Controls, Level 1&2 are liquid controls containing Methamphetamine, Secobarbital, Oxazepam, Benzoylecgonine and Methadone. There are 2 levels of controls. They have been developed for use in the quality control of Amphetamine, Barbiturates, Cocaine, and Methadone assays on the RX

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series analyzers, 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):

For prescription use only.

4. Special instrument requirements:

RX series analyzers, which includes the RX daytona and RX imola.

# I. Device Description:

The assay consists of ready-to-use liquid reagents. Reagent 1 contains a mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide $(<0.1\%)$ as a preservative. Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with benzoylecgonine in buffer with sodium azide $(<0.1\%)$ as a preservative.

The calibrators and controls are sold separately. The calibrator has 5 levels and the control has 2 levels. They consist of human urine samples containing benzoylecgonine with sodium azide $(<0.1\%)$ as a preservative.

# J. Substantial Equivalence Information:

1. Predicate device name (s):

Thermo Scientific DRI Cocaine Metabolite Assay

2. Predicate 510(k) number(s):

k960187

3. Comparison with predicate:

| Items | CEDIA Opiate OFT Assay (Candidate Device) | Thermo DRI Cocaine Metabolite Assay (Predicate Device) |
| --- | --- | --- |
| Similarity | | |
| Intended use /Indication for use | Same | Qualitative and semi-quantitative determination of Benzoylecgonine (cocaine metabolite) in human urine. |
| Sample type | Same | Urine |
| Calibrated against | Same | Benzoylecgonine |
| Test Principle | Same | Competitive enzyme immunoassay |
| Cutoff | Same | 300 ng/mL |

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| Reagent | Same | Liquid ready to use, two reagent assay |
| --- | --- | --- |
| Calibrator Levels | Same | 0, 150, 300, 500, 1000 ng/mL |
| Control Levels | Same | 225, 375 ng/mL |

## K. Standard/Guidance Document Referenced (if applicable):

CLSI EP07-A2, Interference Testing in Clinical Chemistry

CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.

## L. Test Principle:

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. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, benzoylecgonine-labelled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound benzoylecgonine-labelled 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:

Benzoylecgonine (BZG) solution (1 mg/ml) was added to a human urine pool to create samples with BZG concentrations ranging from 0 to 611 ng/mL. These samples were tested for precision in qualitative and semi-quantitative modes on RX daytona and RX imola. Each sample was assayed two times per run, 2 runs per day, for 20 days. The results are summarized in the below tables.

RX daytona Semi-Quantitative

| GC/MS Confirmed Conc. (ng/ml) | Conc. relative to cutoff (approximate) | No. of Determinations | Results #Neg/#Pos |
| --- | --- | --- | --- |
| 0 | -100% | 80 | 80 Neg |
| 57 | -75% | 80 | 80 Neg |
| 137 | -50% | 80 | 80 Neg |
| 231 | -25% | 80 | 80 Neg |
| 374 | +25% | 80 | 80 Pos |

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| 398 | +50% | 80 | 80 Pos |
| --- | --- | --- | --- |
| 543 | +75% | 80 | 80 Pos |
| 611 | +100% | 80 | 80 Pos |

## RX daytona Qualitative

| GC/MS Confirmed Conc. (ng/ml) | Conc. relative to cutoff (approximate) | No. of Determinations | Results #Neg/#Pos |
| --- | --- | --- | --- |
| 0 | -100% | 80 | 80 Neg |
| 57 | -75% | 80 | 80 Neg |
| 137 | -50% | 80 | 80 Neg |
| 231 | -25% | 80 | 80 Neg |
| 374 | +25% | 80 | 80 Pos |
| 398 | +50% | 80 | 80 Pos |
| 543 | +75% | 80 | 80 Pos |
| 611 | +100% | 80 | 80 Pos |

## RX imola Semi-Quantitative

| GC/MS Confirmed Conc. (ng/ml) | Conc. relative to cutoff (approximate) | No. of Determinations | Results #Neg/#Pos |
| --- | --- | --- | --- |
| 0 | -100% | 80 | 80 Neg |
| 57 | -75% | 80 | 80 Neg |
| 137 | -50% | 80 | 80 Neg |
| 231 | -25% | 80 | 80 Neg |
| 374 | +25% | 80 | 80 Pos |
| 398 | +50% | 80 | 80 Pos |
| 543 | +75% | 80 | 80 Pos |
| 611 | +100% | 80 | 80 Pos |

## RX imola Qualitative

| GC/MS Confirmed Conc. (ng/ml) | Conc. relative to cutoff (approximate) | No. of Determinations | Results #Neg/#Pos |
| --- | --- | --- | --- |
| 0 | -100% | 80 | 80 Neg |
| 57 | -75% | 80 | 80 Neg |
| 137 | -50% | 80 | 80 Neg |
| 231 | -25% | 80 | 80 Neg |
| 374 | +25% | 80 | 80 Pos |
| 398 | +50% | 80 | 80 Pos |
| 543 | +75% | 80 | 80 Pos |
| 611 | +100% | 80 | 80 Pos |

## Conclusion:

All samples spiked at levels below the cutoff detected as negative and all samples spiked at levels above the cutoff detected as positive.

## b. Linearity/assay reportable range:

Recovery across the range was tested by serially diluting a spiked urine pool containing 1000 ng/mL of benzoylecgonine into concentration levels listed in

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the table below. Each sample was assayed in the semi-quantitative mode. The results were averaged and compared to the expected result and the percent recovery was calculated.

RX imola Semi-Quantitative

| Level (% of 1000 ng/mL) | Expected Conc. (ng/mL) | RX imola Result (ng/mL) | % Recovery |
| --- | --- | --- | --- |
| 0 | 0 | 14.74 | N/A |
| 1 | 10 | 15.88 | 158.77% |
| 2 | 20 | 17.28 | 86.38% |
| 3 | 30 | 19.44 | 64.81% |
| 4 | 40 | 28.35 | 70.88% |
| 5 | 50 | 42.44 | 84.89% |
| 6 | 60 | 44.04 | 73.39% |
| 7 | 70 | 41.21 | 58.88% |
| 8 | 80 | 60.18 | 75.23% |
| 9 | 90 | 72.01 | 80.01% |
| 10 | 100 | 104.89 | 104.89% |
| 20 | 200 | 190.34 | 95.17% |
| 30 | 300 | 299.44 | 99.81% |
| 40 | 400 | 375.34 | 93.83% |
| 50 | 500 | 474.03 | 94.81% |
| 60 | 600 | 576.05 | 96.01% |
| 70 | 700 | 719.66 | 102.81% |
| 80 | 800 | 818.96 | 102.37% |
| 90 | 900 | 901.95 | 100.22% |
| 100 | 1000 | 981.64 | 98.16% |

RX daytona Semi-Quantitative

| Linearity Level (% of 1000 ng/mL) | Expected Conc. (ng/mL) | RX imola Result (ng/mL) | % Recovery |
| --- | --- | --- | --- |
| 0 | 0 | 0.00 | N/A |
| 1 | 10 | 22.11 | 221.13% |
| 2 | 20 | 27.93 | 139.63% |
| 3 | 30 | 41.91 | 139.71% |
| 4 | 40 | 56.36 | 140.90% |
| 5 | 50 | 38.46 | 76.92% |
| 6 | 60 | 66.38 | 110.64% |
| 7 | 70 | 66.94 | 95.62% |
| 8 | 80 | 67.23 | 84.04% |
| 9 | 90 | 68.45 | 76.06% |
| 10 | 100 | 104.05 | 104.05% |
| 20 | 200 | 199.29 | 99.65% |
| 30 | 300 | 308.95 | 102.98% |

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| 40 | 400 | 428.05 | 107.01% |
| --- | --- | --- | --- |
| 50 | 500 | 542.06 | 108.41% |
| 60 | 600 | 621.06 | 103.51% |
| 70 | 700 | 736.18 | 105.17% |
| 80 | 800 | 820.35 | 102.54% |
| 90 | 900 | 885.70 | 98.41% |
| 100 | 1000 | 956.28 | 95.63% |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

## Traceability

The controls and calibrators are prepared using commercially available benzoylecgonine standard the accuracy of which is ensured by purity determinations and gravimetric preparation using balances calibrated with NIST traceable weight. Concentration of drug in the master lots are GC/MS quantified.

## Value assignments

Value assigned to each test lot is the mean of 10 measurements, adjusted by the %CV the master lot (10 measurements) is from its assigned target. The %CV of the master and the test lot measurements should be <5% with the exception of calibrator level 1, where a <10% CV is allowed. The % deviation to the target value should be <5% with the exception of calibrator level 1, where a <10% deviation is allowed.

## Shelf-life stability

Real time and accelerated studies have been conducted. Protocols and acceptance criteria were described and found to be acceptable. The manufacturer's claims and the supporting studies are summarized below:

Calibrators: Real time and accelerated studies support 18 months of shelf life at 2-8°C.

Controls: Accelerated studies support 18 months of shelf life at 2-8°C. Real time testing is on going.

Reagents: Real time studies support 18 months of shelf life at 2-8°C.

## Open-vial stability:

Real time testing supports open-vial stability of 28 days for the Calibrators, Controls and the Reagents.

d. Detection limit:

Not applicable

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e. Analytical specificity:

Cross-reactivity:

The parent drug, metabolites, and drugs commonly found in samples were tested for cross-reactivity with the assay. Test compounds were spiked into GC/MS verified negative urine and each sample was evaluated against the cut-off calibrator (300ng/mL). The percent cross-reactivity of those compounds are presented below:

Structurally Related Compounds RX daytona -Qualitative

| Compound | Tested Conc. (mg/dl) | Response equivalent to 300 ng/ml cut-off | Cross-reactivity % |
| --- | --- | --- | --- |
| Benzoylecgonine | 300 | POS | 100.00% |
| Cocaethylene | 40,298 | POS | 0.74% |
| Cocaine | 24,391 | POS | 1.23% |
| Ecgonine methyl ester | 100,000 | NEG | 0.00% |
| Ecgonine | 68,565 | POS | 0.44% |

Structurally Related Compounds RX imola-Qualitative

| Compound | Conc. Of compound (mg/dl) | Response equivalent to 300 ng/ml cut-off | Cross-reactivity % |
| --- | --- | --- | --- |
| Benzoylecgonine | 300 | POS | 100.00% |
| Cocaethylene | 37,485 | POS | 0.80% |
| Cocaine | 21,753 | POS | 1.38% |
| Ecgonine methyl ester | 100,000 | NEG | 0.00% |
| Ecgonine | 21,753 | POS | 1.38% |

Structurally Related Compounds RX Daytona-Semi Quantitative

| Compound | Tested Conc. (mg/dl) | Response equivalent to 300 ng/ml cut-off | Cross-reactivity % |
| --- | --- | --- | --- |
| Benzoylecgonine | 300 | POS | 100.00% |
| Cocaethylene | 21,423 | POS | 1.40% |
| Cocaine | 17,933 | POS | 1.67% |
| Ecgonine methyl ester | 100,000 | NEG | 0.00% |
| Ecgonine | 59,045 | POS | 0.51% |

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Structurally Related Compounds RX imola-Semi Quantitative

| Compound | Conc. Of compound (mg/dl) | Response equivalent to 300 ng/ml cut-off | Cross-reactivity % |
| --- | --- | --- | --- |
| Benzoylecgonine | 300 | POS | 100.00% |
| Cocaethylene | 44,579 | POS | 0.67% |
| Cocaine | 28,172 | POS | 1.06% |
| Ecgonine methyl ester | 100,000 | NEG | 0.00% |
| Ecgonine | 28,172 | POS | 1.06% |

Structural unrelated

RX daytona (same result were obtained on RX imola)

| Compound | Conc. tested (ng/mL) | -25% of the cutoff | | +25% of the cutoff e | |
| --- | --- | --- | --- | --- | --- |
| | | Qualitative | Semi-quant | Qualitative | Semi-quant |
| 11-hydroxy-delta9-THC | 100,000 | Neg | Neg | Pos | Pos |
| 11-nor9-carboxy-delta9-THC | 100,000 | Neg | Neg | Pos | Pos |
| 6 Acetyl-morphine | 100,000 | Neg | Neg | Pos | Pos |
| Amitriptyline | 100,000 | Neg | Neg | Pos | Pos |
| Amobarbital | 100,000 | Neg | Neg | Pos | Pos |
| (+/-)-amphetamine | 100,000 | Neg | Neg | Pos | Pos |
| Ascorbic acid | 100,000 | Neg | Neg | Pos | Pos |
| Aspirin | 100,000 | Neg | Neg | Pos | Pos |
| β-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 |
| Codeine | 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 |
| Dihydrocodeine | 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 |
| R,R(-) Pseudoephedrine | 100,000 | Neg | Neg | Pos | Pos |
| S,S(+) Pseudoephedrine | 100,000 | Neg | Neg | Pos | Pos |
| Heroin | 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,l-Methamphetamine | 100,000 | Neg | Neg | Pos | Pos |

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| Morphine | 100,000 | Neg | Neg | Pos | Pos |
| --- | --- | --- | --- | --- | --- |
| Oxycodone | 100,000 | Neg | Neg | Pos | Pos |
| Paracetamol | 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 |

## Interference

The potential effect of endogenous compounds and pH on the recovery of BZG using the Randox Cocaine metabolite assay was assessed by spiking known amounts of potentially interfering substances into GC/MS verified negative urine and urine samples with cocaine metabolite concentrations +/- 25% of the assay cut-off. Substances were determined not to interfere with the assay if the recovery of the negative sample was below the assay cut-off and if the +/-25% samples recovered within 10% of a sample containing no interferent.

## Endogenous compounds in negative urine-RX daytona

| Compound | Tested Conc. (mg/dl) | Response to equivalent to 300 ng/ml cutoff | | Cross-reactivity % | |
| --- | --- | --- | --- | --- | --- |
| | | Quali-tative | Semi-quant. | Quali-tative | Semi-quant. |
| Total Bilirubin | 15 | NEG | NEG | 0% | 0% |
| Direct Bilirubin | 5 | NEG | NEG | 0% | 0% |
| Haemoglobin | 115 | NEG | NEG | 0% | 0% |
| Creatinine | 30 | NEG | NEG | 0% | 0% |
| Urea | 258 | NEG | NEG | 0% | 0% |
| Glucose | 2000 | NEG | NEG | 0% | 0% |
| H.S.A. | 500 | NEG | NEG | 0% | 0% |
| Ethanol | 1000 | NEG | NEG | 0% | 0% |
| Acetone | 1000 | NEG | NEG | 0% | 0% |
| Gamma globulin | 500 | NEG | NEG | 0% | 0% |
| Oxalic acid | 100 | NEG | NEG | 0% | 0% |
| Riboflavin | 7.5 | NEG | NEG | 0% | 0% |
| Sodium chloride | 6000 | NEG | NEG | 0% | 0% |
| Boric acid | 1000 | NEG | NEG | 0% | 0% |
| Sodium azide | 1000 | NEG | NEG | 0% | 0% |
| Sodium fluoride | 1000 | NEG | NEG | 0% | 0% |

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Endogenous compounds in +/-25% cutoff urine -RX daytona

| Compound | Tested Conc. (mg/dl) | -25% of 300 ng/ml BZG cutoff | | +25% of 300 ng/ml BZG cutoff | |
| --- | --- | --- | --- | --- | --- |
| | | Quali-tative | Semi-quant. | Quali-tative | Semi-quant. |
| Total Bilirubin | 15 | NEG | NEG | POS | POS |
| Direct Bilirubin | 5 | NEG | NEG | POS | POS |
| Haemoglobin | 115 | NEG | NEG | POS | POS |
| Creatinine | 30 | NEG | NEG | POS | POS |
| Urea | 258 | NEG | NEG | POS | POS |
| Glucose | 2000 | NEG | NEG | POS | POS |
| H.S.A. | 500 | NEG | NEG | POS | POS |
| Ethanol | 1000 | NEG | NEG | POS | POS |
| Acetone | 1000 | NEG | NEG | POS | POS |
| Gamma globulin | 500 | NEG | NEG | POS | POS |
| Oxalic acid | 100 | NEG | NEG | POS | POS |
| Riboflavin | 7.5 | NEG | NEG | POS | POS |
| Sodium chloride | 1500 | NEG | NEG | POS | POS |
| Boric acid | 125 | NEG | NEG | POS | POS |
| Sodium azide | 1000 | NEG | NEG | POS | POS |
| Sodium fluoride | 1000 | NEG | NEG | POS | POS |
| Specific gravity range | 1.00 - 1.03 | NEG | NEG | POS | POS |
| pH range | 3 - 9 | NEG | NEG | POS | POS |

Endogenous compounds in negative urine-RX imola

| Compound | Tested Conc. (mg/dl) | Response to equivalent to 300 ng/ml cutoff | | Cross-reactivity % | |
| --- | --- | --- | --- | --- | --- |
| | | Quali-tative | Semi-quant. | Quali-tative | Semi-quant. |
| Total Bilirubin | 15 | NEG | NEG | 0% | 0% |
| Direct Bilirubin | 5 | NEG | NEG | 0% | 0% |
| Haemoglobin | 115 | NEG | NEG | 0% | 0% |
| Creatinine | 30 | NEG | NEG | 0% | 0% |
| Urea | 258 | NEG | NEG | 0% | 0% |
| Glucose | 2000 | NEG | NEG | 0% | 0% |
| H.S.A. | 500 | NEG | NEG | 0% | 0% |
| Ethanol | 1000 | NEG | NEG | 0% | 0% |
| Acetone | 1000 | NEG | NEG | 0% | 0% |
| Gamma globulin | 500 | NEG | NEG | 0% | 0% |
| Oxalic acid | 100 | NEG | NEG | 0% | 0% |
| Riboflavin | 7.5 | NEG | NEG | 0% | 0% |

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| Sodium chloride | 6000 | NEG | NEG | 0% | 0% |
| --- | --- | --- | --- | --- | --- |
| Boric acid | 1000 | NEG | NEG | 0% | 0% |
| Sodium azide | 1000 | NEG | NEG | 0% | 0% |
| Sodium fluoride | 1000 | NEG | NEG | 0% | 0% |

Endogenous compounds in +/-25% cutoff urine-RX imola

| Compound | Conc. Of compound (mg/dl) | -25% of 300 ng/ml BZG cutoff | | +25% of 300 ng/ml BZG cutoff | |
| --- | --- | --- | --- | --- | --- |
| | | Quali-tative | Semi-quant. | Quali-tative | Semi-quant. |
| Total Bilirubin | 15 | NEG | NEG | POS | POS |
| Direct Bilirubin | 5 | NEG | NEG | POS | POS |
| Haemoglobin | 115 | NEG | NEG | POS | POS |
| Creatinine | 30 | NEG | NEG | POS | POS |
| Urea | 258 | NEG | NEG | POS | POS |
| Glucose | 2000 | NEG | NEG | POS | POS |
| H.S.A. | 500 | NEG | NEG | POS | POS |
| Ethanol | 1000 | NEG | NEG | POS | POS |
| Acetone | 1000 | NEG | NEG | POS | POS |
| Gamma globulin | 500 | NEG | NEG | POS | POS |
| Oxalic acid | 100 | NEG | NEG | POS | POS |
| Riboflavin | 7.5 | NEG | NEG | POS | POS |
| Sodium chloride | 6000 | NEG | NEG | POS | POS |
| Boric acid | 125 | NEG | NEG | POS | POS |
| Sodium azide | 1000 | NEG | NEG | POS | POS |
| Sodium fluoride | 1000 | NEG | NEG | POS | POS |
| Specific gravity range | 1.00 - 1.03 | NEG | NEG | POS | POS |
| pH range | 3 - 9 | NEG | NEG | POS | POS |

f. Assay cut-off:

300 ng/mL

2. Comparison studies:

a. Method comparison with predicate device:

137 urine samples were obtained from a clinical laboratory where they had

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been tested by GC/MS for the presence or absence of Cocaine Metabolites. Among the 137 samples, 70 were positive and 67 were negative for Cocaine Metabolites based on GC/MS test results. These samples were tested with Randox Cocaine Metabolite assay on the Rx Daytona and Rx Imola instruments. Concordance of the results (Randox vs GC/MS) were provided in the below tables.

## RX daytona Semi-Quantitative

| Device Results | Negative by GC/MS | Near Cutoff Negative (between 50% below the cutoff and the cutoff conc.) | Near Cutoff Positive (between the cutoff and 50% above the cutoff conc.) | High Positive (greater than 50% above the cutoff conc.) | % Agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 17 | 53 | 100.0% |
| Neg | 50 | 15 | 1* | 1** | 97.2% |

## RX daytona Qualitative

| Device Results | Negative by GC/MS | Near Cutoff Negative (between 50% below the cutoff and the cutoff conc.) | Near Cutoff Positive (between the cutoff and 50% above the cutoff conc.) | High Positive (greater than 50% above the cutoff conc.) | % Agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 17 | 53 | 100.0% |
| Neg | 50 | 15 | 1* | 1** | 97.2% |

## RX imola Semi-Quantitative

| Device Results | Negative by GC/MS | Near Cutoff Negative (between 50% below the cutoff and the cutoff conc.) | Near Cutoff Positive (between the cutoff and 50% above the cutoff conc.) | High Positive (greater than 50% above the cutoff conc.) | % Agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 18 | 53 | 100.0% |
| Neg | 50 | 15 | 0 | 1** | 98.6% |

## RX imola Qualitative

| Device Results | Negative by GC/MS | Near Cutoff Negative (between 50% below the cutoff and the cutoff conc.) | Near Cutoff Positive (between the cutoff and 50% above the cutoff conc.) | High Positive (greater than 50% above the cutoff conc.) | % Agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 18 | 53 | 100.0% |
| Neg | 50 | 15 | 0 | 1** | 98.6% |

* Discrepant results.
** A root cause analysis has revealed that the labeled GC/MS value on the original sample is incorrect, due to mislabeling of the sample. Repeated

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GC/MS result for the original sample show that the sample is negative for the drug.

## GC/MS SUMMARY OF DISCREPANT RESULT

### RX daytona Semi-Quantitative

| Cut-off Value (ng/mL) | Randox BZG assay (POS/ NEG) | Drug/Metabolite GC/MS value (ng/mL) |
| --- | --- | --- |
| 300 | NEG | 310 (BZG) |

### RX daytona Qualitative

| Cut-off Value (ng/mL) | Randox BZG assay (POS/ NEG) | Drug/Metabolite GC/MS value (ng/mL) |
| --- | --- | --- |
| 300 | NEG | 310 (BZG) |

b. Matrix comparison:

Not applicable. The assay is intended for urine samples only.

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):

Not applicable

4. Clinical cut-off:

Not applicable

5. Expected values/Reference range:

Not applicable

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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.

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