DIMENSION URINE ECSTASY SCREEN FLEX REAGENT CARTRIDGE, MODEL DF 109

K053337 · Dade Behring, Inc. · DKZ · May 19, 2006 · Clinical Toxicology

Device Facts

• Record ID: K053337
• Device Name: DIMENSION URINE ECSTASY SCREEN FLEX REAGENT CARTRIDGE, MODEL DF 109
• Applicant: Dade Behring, Inc.
• Product Code: DKZ · Clinical Toxicology
• Decision Date: May 19, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3100
• Device Class: Class 2

Intended Use

The EXTC Flex® reagent cartridge used on the Dimension® clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semiquantitative determination of methylenedioxymethamphetamine (MDMA) and closely related drugs in human urine using a cutoff of either 300 or 500 ng/mL. Measurements obtained with the EXTC method are used in the diagnosis and treatment of ecstasy use or overdose. The EXTC method provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) 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.

Device Story

The EXTC Flex® reagent cartridge is an in vitro diagnostic device for use on automated clinical chemistry analyzers (e.g., Dimension® RxL, Xpand®). It utilizes a homogeneous enzyme immunoassay based on the competition for antibody binding sites between drug in the urine sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH). The device measures the rate of increasing absorbance at 340 nm as unbound conjugate catalyzes the oxidation of glucose-6-phosphate, reducing NAD+ to NADH. The rate is mathematically related to drug concentration. The device is operated by laboratory professionals in clinical settings. Results are preliminary and require confirmation by a more specific method like GC/MS. The assay aids in the diagnosis and treatment of ecstasy use or overdose and assists in sample dilution preparation for further analysis.

Clinical Evidence

Method comparison studies were conducted comparing the EXTC Flex® reagent cartridge on the Dimension® clinical chemistry system against a GC/MS reference method. At the 300 ng/mL cutoff, the device showed 92% agreement. At the 500 ng/mL cutoff, the device showed 91.2% agreement.

Technological Characteristics

In vitro diagnostic enzyme immunoassay; prepackaged reagents in an eight-well plastic cartridge; designed for use on the Dimension® clinical chemistry system; qualitative and semiquantitative detection of MDMA in urine.

Indications for Use

Indicated for the qualitative and semiquantitative determination of MDMA and related drugs in human urine for the diagnosis and treatment of ecstasy use or overdose. Intended for use with 300 or 500 ng/mL cutoffs. Requires confirmatory testing via GC/MS or other chemical methods.

Regulatory Classification

Identification

An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An amphetamine 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).

Predicate Devices

• Emit® II Plus Ecstasy Assay (k043028)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k053337

B. Purpose for Submission:
New Device

C. Measurand:
Methylenedioxymethamphetamine (MDMA)

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

E. Applicant:
Dade Behring, Inc.

F. Proprietary and Established Names:
Dade Behring Dimension® Urine Ecstasy Screen Flex® reagent cartridge

G. Regulatory Information:
1. Regulation section:
21 CFR 862.3100 (Enzyme Immunoassay, Amphetamine)
2. Classification:
Class II
3. Product Code:
DKZ
4. Panel:
Toxicology (91)

H. Intended Use:
1. Intended use(s):
Refer to Indications for use.
2. Indication(s) for use:
The EXTC Flex® reagent cartridge used on the Dimension® clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of methylenedioxymethamphetamine (MDMA) and closely related drugs in human urine using a cutoff of either 300 or 500 ng/mL. Measurements obtained with the EXTC method are used in the diagnosis and treatment of ecstasy use or overdose.

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The EXTC method provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) 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.

1. Special condition for use statement(s):
Semi-quantitative results may be helpful in estimating the concentrations of drug(s) in samples. This can aid users when they are preparing dilutions of the samples for further analysis.

The assay is not designated for use in point-of-care settings.

Certain foods or medications may interfere with tests for methylenedioxymethamphetamine and cause false positive results.

For professional use only.

2. Special instrument Requirements:
The device is for use on automated clinical chemistry analyzers. Instruments must be capable of maintaining a constant reaction temperature, pipetting samples and reagents, mixing reagents, timing reactions, and measuring enzyme rates precisely.

Performance was demonstrated in this submission on the Dimension® RxL and Xpand® clinical chemistry systems.

F. Device Description:
The Dimension Urine Ecstasy Screen Flex reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight-well cartridge for use on the Dade Behring Dimension clinical chemistry system. Wells 2 and 3 contain enzyme conjugate. Wells 5, 6, and 8 contain antibody substrate. Wells 1 and 7 are empty.

Syva®Emit®II Plus Ecstasy reagents are contained in the EXTC Flex® reagent cartridge. The EXTC cartridge is used on the Dimension® system to provide an automated application of this assay. It is based on the competition of antibody binding sites between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH).

Matched lots of polyclonal antibody reactive to MDMA and MDA-glucose-6-phosphate dehydrogenase conjugate are used in the Syva®Emit®II Plus methodology.

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Formatted: Bullets and Numbering

# G. Substantial Equivalence Information:

1. Predicate device name(s): Emit® II Plus Ecstasy Assay
2. Predicate K number(s): k043028
3. Comparison with predicate: Both devices are for measurement of the same analyte in the same matrix and utilize the same test methodology.

| Item | New Device
EXTC Flex® reagent cartridge | Predicate
Emit® II Plus Ecstasy Assay |
| --- | --- | --- |
| Intended Use | In vitro diagnostic use for the qualitative and semi-quantitative determination of methylenedioxymethamphetamine (MDMA) and closely related drugs in human urine using a cutoff of either 300 or 500 ng/mL. | In vitro diagnostic use for the qualitative and semi-quantitative determination of methylenedioxymethamphetamine (MDMA) and closely related drugs in human urine using a cutoff of either 300 or 500 ng/mL. |
| Principle | Homogeneous enzyme immunoassay | Homogeneous enzyme immunoassay |
| Antibody | Sheep polyclonal antibodies to methylenedioxymethamphetamine (MDMA). | Sheep polyclonal antibodies to methylenedioxymethamphetamine (MDMA). |
| Reagent Composition | **Antibody/Substrate:**
Sheep polyclonal antibodies to methylenedioxymethamphetamine (MDMA), bovine serum albumin, G6P, NAD, preservatives and stabilizers.

**Enzyme Conjugate:**
Methylenedioxyamphetamine (MDA) labeled with bacterial G6PDH, tris buffer, bovine serum albumin, preservatives and stabilizers. | **Antibody/Substrate Reagent A:**
Sheep polyclonal antibodies to methylenedioxymethamphetamine (MDMA), bovine serum albumin, G6P, NAD, preservatives and stabilizers.

**Enzyme Reagent B:**
Methylenedioxyamphetamine (MDA) labeled with bacterial G6PDH, tris buffer, bovine serum albumin, preservatives and stabilizers. |
| Cutoff | 300 ng/mL and 500 ng/mL | 300 ng/mL and 500 ng/mL |
| Semiquantitative Range | 300 ng/mL cutoff: 25 – 450 ng/mL
500 ng/mL cutoff: 75 – 900 ng/mL | 100–1000 ng/mL |

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| Sensitivity | 300 ng/mL cutoff: 25 ng/mL
500 ng/mL cutoff: 75 mg/mL | 75 ng/mL |
| --- | --- | --- |
| Specimen Type | Human urine | Human urine |
| Instrument | Dimension® clinical chemistry system | Chemistry analyzers |

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

Formatted: Bullets and Numbering

Premarket Submission and Labeling Recommendations for Drugs of Abuse Screening Tests - Draft Guidance for Industry and FDA Staff, published December 2003

NCCLS EP5-A: Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline

## I. Test Principle:

The test is an enzyme immunoassay for use on automated clinical chemistry analyzers. Syva® Emit® II Plus Ecstasy reagents are contained in the EXTC Flex® reagent cartridge. The EXTC cartridge is used on the Dimension® system to provide an automated application of this assay. It is based on the competition for antibody binding sites between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH).

The concentration of drug in the sample determines the amount of MDA-glucose-6-phosphate dehydrogenase conjugate that is bound to the antibody. The unbound conjugate catalyzes the oxidation of glucose-6-phosphate with the simultaneous reduction of NAD⁺ to NADH, more rapidly than does the bound conjugate. The rate of increasing absorbance at 340 nm due to the increase in NADH is related to the concentration of drug in the sample by a mathematical function.

## J. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

All performance was established on the Dimension® RxL and Xpand® clinical chemistry systems.

Reproducibility was determined by assaying the cutoff calibrator and ± 25% controls for 20 days, 2 runs per day in duplicate (n = 80). The data were calculated according to the Clinical Laboratory Standard Institute (CLSI) Guideline EP5-A2. Results of the studies are presented below.

Formatted: Bullets and Numbering
Formatted: Bullets and Numbering

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| | Reproducibility at 300 ng/mL cutoffs | | | | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| Calibrator/Control^{d} | | Repeatability | | Within-Lab | |
| | Mean | SD | CV | SD | CV |
| ng/mL | ng/mL | ng/mL | % | ng/mL | % |
| 225 | 244 | 7.2 | 3.0 | 13.1 | 5.4 |
| 300 | 307 | 6.4 | 2.1 | 13.9 | 4.5 |
| 375 | 418 | 12.7 | 3.0 | 17.3 | 4.1 |
| | Reproducibility at 500 ng/mL cutoffs | | | | |
| --- | --- | --- | --- | --- | --- |
| | | | | | |
| Calibrator/Control^{d} | | Repeatability | | Within-Lab | |
| | Mean | SD | CV | SD | CV |
| ng/mL | ng/mL | ng/mL | % | ng/mL | % |
| 375 | 404 | 8.9 | 2.2 | 18.1 | 4.5 |
| 500 | 526 | 13.0 | 2.5 | 26.6 | 5.1 |
| 625 | 661 | 15.1 | 2.3 | 40.4 | 6.1 |

b. Linearity/assay reportable range:
Support for the lower limit of the reportable range is characterized by the sensitivity studies.

Recovery for the EXTC Flex® reagent cartridge was assessed both qualitatively and semi-quantitatively.

Qualitative Recovery
A qualitative recovery study was performed using negative human urine samples spiked with MDMA at the cutoff concentration and at -75%, -50%, -25%, +25%, +50%, +75% and +100% of the cutoff concentration. Samples were assayed in two separate runs, with an n=5 in each run (total of n=10). The mean rate was calculated and compared to the rate of the cutoff calibrator.

The EXTC Flex® reagent cartridge correctly identified each of the mean rates of spiked samples containing less than the cutoff as negative, and each of the mean rates of spiked samples containing greater than the cutoff as positive. Results are shown below.

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| Qualitative Recovery for the 300 ng/mL cutoff | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| MDMA spike concentration | 75 | 150 | 225 | 300 | 375 | 450 | 525* | 600* |
| Mean Rate (maU) | 191.6 | 211.9 | 232.5 | 249.5 | 259.2 | 267.6 | 274.5 | 280.4 |
| Neg/Pos compared to the rate of the c/o calibrator | neg | neg | neg | pos | pos | pos | pos | pos |
| Rate of the cutoff calibrator = 242.0
* outside the assay range | | | | | | | | |
| Qualitative Recovery for the 500 ng/mL cutoff | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| MDMA spike concentration | 125 | 250 | 375 | 500 | 625 | 750 | 875 | 1000* |
| Mean Rate (maU) | 187 | 209 | 228 | 246 | 258 | 267 | 273 | 280 |
| Neg/Pos compared to the rate of the c/o calibrator | neg | neg | neg | pos | pos | pos | pos | pos |
| Rate of the cutoff calibrator = 243.2
* outside the assay range | | | | | | | | |

## Semiquantitative Recovery

A semi-quantitative recovery study was performed using negative human urine samples spiked with MDMA at the cutoff concentration and at -75%, -50%, -25%, +25%, +50%, +75% and +100% of the cutoff concentration. Samples were assayed in two separate runs, with an n=5 in each run (total of n=10). The mean was calculated and compared to the nominal spiked concentration. % recovery was calculated using the following equation.

$$
\% \text{recovery} = \frac{\text{Dim EXTC mean result}}{\sqrt{\text{nominal MDMA spike concentration}}} \times 100
$$

The EXTC Flex® reagent cartridge recovered 80-120% of the nominal spiked concentration for concentrations within the assay range. For the 300 ng/mL cutoff, the

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assay range is 25 – 450 ng/mL. For the 500 ng/mL cutoff, the assay range is 75 – 900 ng/mL. Results are shown below.

| Semi-Quantitative Recovery for the 300 ng/mL cutoff | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| MDMA spike concentration | 75 | 150 | 225 | 300 | 375 | 450 | 525* |
| Mean (ng/mL) | 82 | 178 | 257 | 340 | 409 | 506 | 662 |
| % Recovery | 109.29 | 118.76 | 114.32 | 113.48 | 109.06 | 112.43 | 126.05 |
| * outside the assay range | | | | | | | |
| Semi-Quantitative Recovery for the 500 ng/mL cutoff | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| MDMA Spike Concentration | 125 | 250 | 375 | 500 | 625 | 750 | 875 | 950* | 1000* |
| Mean (ng/mL) | 135 | 278 | 398 | 528 | 647 | 784 | 916 | 1137 | 1273 |
| % Recovery | 107.96 | 111.30 | 106.22 | 105.57 | 103.45 | 104.51 | 104.73 | 119.72 | 127.26 |
| * outside the assay range | | | | | | | | | |

c. Traceability (controls, calibrators, or method):
The Emit II Plus Ecstasy Calibrators/Controls that are referenced in this submission were cleared under 510(k), k043028. Five levels of calibrator/control material, ranging in concentration from 0 to 1000 ng/mL, are specified in the labeling but are supplied separately. Calibrators/controls are drug free urine based materials spiked with known concentrations of MDMA.

Stability studies are summarized for the EXTC Flex® reagent cartridge.

d. Detection limit:
The analytical sensitivity of the EXTC method is 25 ng/mL for the 300 ng/mL cutoff (13 uL sample size) and it represents the lowest concentration of EXTC that can be distinguished from zero. The sensitivity of the EXTC method is 75 ng/mL for the 500 ng/mL cutoff (8 uL sample size). The sponsor defines analytical sensitivity

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as the concentration at two standard deviations above the mean of measurements of the Emit® Calibrator Level 0 Calibrator (n=20) with a confidence of 95%.

e. Analytical specificity:

The tables below list the compounds and the levels at which the compounds have been found to give a response approximately equivalent to that of the selected cutoff (300 or 500 ng/mL methylenedioxymethamphetamine). Each concentration represents the reactivity level for the stated compound when it is added to a negative urine specimen. If a sample contains more than one compound detected by the assay, lower concentrations than those listed below may combine to produce a rate approximately equivalent to or greater than that of the cutoff calibrator.

Concentrations of Ecstasy Related Metabolites that Produce a Positive Result Equivalent to the selected cutoff (300 or 500 ng/mL MDMA)

| Compound | Concentration (ng/mL) at the 300 ng/mL cutoff | Concentration (ng/mL) at the 500 ng/mL cutoff |
| --- | --- | --- |
| MDA
(Methylenedioxyamphetamine) | 350 | 606 |
| MDEA
(Methylenedioxyethylamphetamine) | 243 | 446 |
| MBDB
(N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane) | 219 | 439 |
| BDB
(3,4-(methylenedioxyphenyl)-2-butanamine) | 214 | 575 |
| PMA
(Para-methoxyamphetamine) | 2326 | 39365 |
| PMMA
(Para-methoxymethamphetamine) | 4360 | 5154 |
| HMMA
(4-hydroxy-3-methoxy-methamphetamine) | >40000 | >40000 |

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Concentrations of Structurally Related Compounds that Produce a Positive Result Equivalent to the 300 ng/mL and 500 ng/mL MDMA Cutoffs

| Compound | Concentration (ug/mL) at the 300 ng/mL Cutoff | Concentration (ug/mL) at the 500 ng/mL Cutoff |
| --- | --- | --- |
| D-Amphetamine | >154 | >300 |
| D-Methamphetamine | >62 | >99 |
| D,L-Methamphetamine | >13 | >21 |
| D,L-Amphetamine | >75 | >169 |
| L-Amphetamine | >97 | >246 |
| L-Methamphetamine | >13 | >13 |
| 4-Chloramphetamine | >4 | >10 |
| Benzphetamine | >10 | >10 |
| Buproprion | >500 | >500 |
| Chloroquine | >1000 | >1000 |
| L-Ephedrine | >106 | >234 |
| Fenfluramine | >2 | >4 |
| Mephentermine | >15 | >15 |
| Methoxyphenamine | >1000 | >1000 |
| Nor-pseudoephedrine | >100 | >100 |
| Phenmetrazine | >300 | >300 |
| Phentermine | >150 | >150 |
| Phenylpropanolamine (PPA) | >200 | >200 |
| Propanolol | >15 | >15 |
| Pseudoephedrine | >208 | >359 |
| Quinacrine | >1000 | >1000 |
| Tranylcypromine | >100 | >100 |
| Tyramine | >100 | >100 |

Concentrations of Structurally Unrelated Compounds that Produce a Positive Result Approximately Equivalent to the 300 ng/mL and 500 ng/mL MDMA Cutoff.

| Compound | Concentration (ug/mL) at the 300 ng/mL Cutoff | Concentration (ug/mL) at the 500 ng/mL Cutoff |
| --- | --- | --- |
| Haloperidol | >2 | >7 |
| Isoxsuprine | >8 | >20 |
| Labelatol | >7 | >16 |
| Nylidrin | >7 | >15 |
| Trazodone | >3 | >7 |

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Concentration of Compounds Showing a Negative Response

Each of the following compounds was added to drug free urine and gave negative EXTC results at the concentration listed for either 300 or 500 ng/mL cutoff :

| Compound | Concentration (μg/mL) |
| --- | --- |
| Acetaminophen | 1000 |
| α-Acetyl- N, N-dinormethadol | 25 |
| L-α-Acetylmethadol (LAAM) | 25 |
| N-Acetylprocainamide (NAPA) | 400 |
| Acetylsalicylic Acid | 1000 |
| Albuterol | 1000 |
| p-Aminobenzoic Acid (PABA) | 1000 |
| Amitriptyline | 10 |
| Amoxicillin | 100 |
| Atenolol | 1000 |
| Benzoylecgonine | 1000 |
| Buprenorphine | 100 |
| Caffeine | 1000 |
| Carbamazepine | 250 |
| Carisoprodol | 1000 |
| Chlorpheniramine | 100 |
| Chlorpromazine | 200 |
| Cimetidine | 1000 |
| Clomipramine | 2.5 |
| Clonidine | 1000 |
| Codeine | 500 |
| L-Cotinine | 100 |
| Cyclobenzaprine | 28 |
| Desipramine | 800 |
| Dextromethorphan | 1000 |
| Dextrorphan | 280 |
| Diphenhydramine | 1000 |
| Doxepin | 10 |
| Doxylamine | 500 |
| L-Epinephrine | 1000 |
| 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 1000 |
| Fenoprofen | 1000 |
| Fluoxetine | 500 |
| Furosemide | 1000 |
| Glutethimide | 500 |
| Ibuprofen | 1000 |
| Imipramine | 750 |

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| Compound | Concentration (μg/mL) |
| --- | --- |
| Ketamine | 100 |
| Ketoprofen | 1000 |
| Ketorolac Tromethamine | 350 |
| Lidocaine | 100 |
| LSD | 0.15 |
| Meperidine HCl | 1000 |
| Mescaline | 1500 |
| Metaclopramide | 1000 |
| Methadone | 1000 |
| Methaqualone | 1500 |
| D,L-Methyldopa | 1000 |
| L-Methyldopa | 1000 |
| Monoethylglycinexylidide (MEGX) | 1000 |
| Morphine | 1000 |
| Nalmefene | 20 |
| Naloxone | 500 |
| Naproxen | 1000 |
| Nicotinic Acid | 500 |
| Nitroglycerin | 1000 |
| Noracetylmethadol | 25 |
| 11-nor-Δ9-THC-9-COOH | 100 |
| Nortriptyline | 300 |
| Ofloxacin | 100 |
| Oxazepam | 300 |
| Paroxetine | 5 |
| Phencyclidine | 1000 |
| Phenelzine | 100 |
| L-Phenylcyclohexylamine (PCA) | 50 |
| Phenytoin | 1000 |
| Phthalic Acid | 1000 |
| L-Piperidinocyclohexane Carbonitrile | 50 |
| Procainamide | 1000 |
| Promethazine | 1000 |
| Propoxyphene | 1000 |
| Ranitidine | 900 |
| Sertraline | 10 |
| Scopolamine | 500 |
| Secobarbital | 1000 |
| Thioridazine | 100 |
| Tolmetin Sodium | 2000 |
| Tramadol | 100 |

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| Compound | Concentration (μg/mL) |
| --- | --- |
| Trifluoperazine | 100 |
| Trimethobenzamide | 500 |
| Trimethoprim | 500 |
| Verapamil | 1000 |
| Zidovudine (AZT) | 2000 |
| Zolpidem | 100 |
| **Sympathomimetic Amines** | |
| Diethylpropion | 1000 |
| D,L-Isoproterenol | 1000 |
| Metaproterenol | 10 |
| Methylphenidate (Ritalin®) | 1000 |
| Phendimetrazine | 400 |
| Phenethylamine | 20 |
| Phenylephrine | 20 |
| Propylhexedrine | 125 |
| 3-OH-Tyramine (dopamine) | 300 |

## Interference Testing

Each of the following compounds when added to urine containing methylenedioxymethamphetamine (MDMA) at +/- 25% concentration of the cutoff do not yield a false response relative to the 300 and 500 ng/mL cutoff levels:

| Compound | Concentration |
| --- | --- |
| Acetone | 1.0 g/dL |
| Ascorbic Acid | 1.5 g/dL |
| Bilirubin | 2.0 mg/dL |
| Creatinine | 0.5 g/dL |
| Ethanol | 1.0 g/dL |
| Gamma Globulin | 0.5 g/dL |
| Glucose | 2.0 g/dL |
| Hemoglobin | 115 mg/dL |
| Human Serum Albumin | 0.5 g/dL |
| Oxalic Acid | 0.1 g/dL |
| Riboflavin | 7.5 mg/dL |
| Sodium Chloride | 6.0 g/dL |
| Urea | 6.0 g/dL |

f. Assay cut-off:

Characterization of how the device performs analytically around the claimed cutoff concentrations, 300 or 500 ng/mL, appears in the precision section, above.

2. Comparison studies:

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a. Method comparison with predicate device:

300 ng/mL cutoff

138 urine specimens were tested with the EXTC Flex® cartridge on the Dimension® system (cutoff=300 ng/mL) and compared to results obtained by GC/MS and the 138 urine specimens were tested with the EXTC Flex® cartridge on the Dimension® system (cutoff=300 ng/mL) and compared to results obtained by GC/MS and the Syva® Emit® II Plus Ecstasy Assay (9X029UL) (on the SYVA®-30R Biochemical System - cutoff=300 ng/mL).

| | GC/MS
(cutoff 300 ng/mL MDMA, MDEA or MDA) | |
| --- | --- | --- |
| | + | - |
| EXTC Flex® Reagent | + | 73 |
| Cartridge on Dimension® | - | 0 |
| clinical chemistry system
(cutoff 300 ng/mL) | | 4 |

Discrepants (ng/mL):

| GC/MS MDMA | GC/MS MDA | GC/MS MDEA | Dimension® EXTC |
| --- | --- | --- | --- |
| 310 | 0 | 0 | 60 |
| 350 | 68 | 0 | 132 |
| 349 | 0 | 0 | 245 |
| 313 | 30 | 0 | 278 |
| | SYVA® -30R Biochemical system
(cutoff 300 ng/mL) | |
| --- | --- | --- |
| | + | - |
| EXTC Flex® Reagent | + | 70 |
| Cartridge on Dimension® | - | 3 |
| clinical chemistry system
(cutoff 300 ng/mL) | | 0 |

Discrepants (ng/mL):

| GC/MS MDMA | GC/MS MDA | GC/MS MDEA | Dimension® EXTC | SYVA® 30R |
| --- | --- | --- | --- | --- |
| 529 | 0 | 0 | 381 | 279 |
| 503 | 0 | 0 | 342 | 249 |
| 302 | 0 | 0 | 311 | 221 |

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Contingency table for Dimension® Urine Ecstasy Screen Flex® reagent cartridge 300 ng/mL cutoff

| New Device | Negative by GC/MS or Predicate | Near cutoff Negative (between -50% and cutoff) | Near cutoff Positive (between cutoff and +50%) | GC/MS Positive (greater than +50%) | Percent Agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 6 | 67 | 100% |
| Negative | 51 | 10 | 4 | 0 | 94% |

## 500 ng/mL cutoff

125 urine specimens were tested with the EXTC Flex® cartridge on the Dimension® system (cutoff=500 ng/mL) and compared to results obtained by GC/MS and the Syva® Emit® II Plus Ecstasy Assay (9X029UL) (on the SYVA®-30R Biochemical System - cutoff=500 ng/mL).

### GC/MS (cutoff 500 ng/mL MDMA, MDEA or MDA)

| EXTC Flex® Reagent | + |
| --- | --- |
| Cartridge on Dimension® | - |
| clinical chemistry system (cutoff 500 ng/mL) | - |
| 56 | 2 |
| --- | --- |
| 4 | 63 |

## Discrepants (ng/mL):

| GC/MS MDMA | GC/MS MDA | GC/MS MDEA | Dimension® EXTC |
| --- | --- | --- | --- |
| 503 | 0 | 0 | 316 |
| 503 | 0 | 0 | 365 |
| 529 | 0 | 0 | 369 |
| 545 | 0 | 0 | 407 |
| 451 | 0 | 0 | 532 |
| 464 | 0 | 0 | 600 |

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SYVA®-30R Biochemical system
(cutoff 500 ng/mL)

EXTC Flex® Reagent Cartridge on Dimension® clinical chemistry system (cutoff 500 ng/mL)

| + | - |
| --- | --- |
| 55 | 3 |
| 0 | 67 |

Discrepants (ng/mL):

| GC/MS MDMA | GC/MS MDA | GC/MS MDEA | Dimension® EXTC | SYVA® 30R |
| --- | --- | --- | --- | --- |
| 451 | 0 | 0 | 532 | 464 |
| 813 | 0 | 0 | 502 | 435 |
| 464 | 0 | 0 | 600 | 442 |

Contingency table for Dimension® Urine Ecstasy Screen Flex® reagent cartridge 500 ng/mL cutoff

| New Device | Negative by GC/MS or Predicate | Near cutoff Negative (between -50% and cutoff) | Near cutoff Positive (between cutoff and +50%) | GC/MS Positive (greater than +50%) | Percent Agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 2 | 3 | 53 | 97% |
| Negative | 55 | 8 | 4 | 0 | 94% |

b. Matrix comparison:
Not applicable.

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):

{15}

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4. Clinical cut-off:
Not applicable.

5. Expected values/Reference range:
Not applicable.

**K. Proposed Labeling:**

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10

**L. Conclusion:**

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Formatted: Bullets and Numbering

Formatted: Bullets and Numbering