First Sign Drug of Abuse Dip Card Test (MDMA, EDDP, Nortriptyline), First Sign Drug of Abuse Cup Test (MDMA, EDDP, Nortriptyline)
Device Facts
| Record ID | K160793 |
|---|---|
| Device Name | First Sign Drug of Abuse Dip Card Test (MDMA, EDDP, Nortriptyline), First Sign Drug of Abuse Cup Test (MDMA, EDDP, Nortriptyline) |
| Applicant | W.H.P.M., Inc. |
| Product Code | DJR · Clinical Toxicology |
| Decision Date | Aug 17, 2016 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3620 |
| Device Class | Class 2 |
Indications for Use
First Sign Drug of Abuse MDMA Cup Test First Sign Drug of Abuse MDMA Dip Card Test First Sign Drug of Abuse MDMA Tests are immunoassay tests. The test can detect MDMA in human urine. The cut-off value is 500 ng/mL.. The tests are available in a Cup format and a Dip Card format. The tests provide only preliminary test results. If you want to get a confirmed result, you must use a more specific chemical method. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be used when you get any drug of abuse test result. It should be used particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use. First Sign Drug of Abuse EDDP Cup Test First Sign Drug of Abuse EDDP Dip Card Test First Sign Drug of Abuse EDDP Tests are immunoassay tests. The test can detect EDDP in human urine. The cut-off value is 300 ng/mL. The tests are available in a Cup format and a Dip Card format. The tests provide only preliminary test results. If you want to get a confirmed result, you must use a more specific chemical method. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be used when you get any drug of abuse test result. It should be used particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use. First Sign Drug of Abuse Nortriptyline Cup Test First Sign Drug of Abuse Nortriptyline Dip Card Test First Sign Drug of Abuse Nortriptyline Tests are immunoassay tests. The test can detect Nortriptyline in human urine. The cut-off value is 1,000 ng/mL. The tests are available in a Cup format and a Dip Card format. The tests provide only preliminary test results. If you want to get a confirmed result, you must use a more specific chemical method. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be used when you get any drug of abuse test result. It should be used particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.
Device Story
Lateral flow immunochromatographic assays for qualitative detection of MDMA, EDDP, or Nortriptyline in human urine; available in cup or dip card formats. Principle: competitive binding; target drug in urine competes with drug-conjugate for limited antibody binding sites on particles; absence of test line indicates positive result (drug concentration above cut-off); presence of test line indicates negative result. Control line confirms proper flow. Used in point-of-care or home settings by lay users or clinicians. Provides preliminary results; requires professional clinical judgment and confirmatory testing (GC/MS) for positive results. Benefits include rapid, accessible drug screening.
Clinical Evidence
No clinical trials; performance established via analytical bench testing (precision, specificity, interference, stability) and a lay-user study (n=280 per analyte). Lay-user study confirmed correct results across various concentrations relative to cut-offs. Precision studies performed over 25 days confirmed consistency across lots and formats.
Technological Characteristics
Lateral flow immunochromatographic assay; competitive binding principle; monoclonal mouse antibody; cup or dip card form factor; single-use; qualitative output; visual interpretation. Stable at 4-30°C for 24 months.
Indications for Use
Indicated for qualitative detection of MDMA (500 ng/mL), EDDP (300 ng/mL), or Nortriptyline (1,000 ng/mL) in human urine. Intended for over-the-counter and prescription use as a preliminary screening test. Requires confirmatory testing via GC/MS.
Regulatory Classification
Identification
A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.
Special Controls
*Classification.* Class II (special controls). A methadone 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
- Co-Innovation Rapid Single/Multi Drug Test (K142800)
- Co-Innovation One Step Single/Multi Drug Test (K140748)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k160793
B. Purpose for Submission:
New Device
C. Measurand:
MDMA (Methylenedioxymethaneamphetamine)
EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine)
Nortriptyline
D. Type of Test:
Qualitative Assay
E. Applicant:
W. H. P. M., Inc.
F. Proprietary and Established Names:
First Sign Drug of Abuse MDMA Cup Test
First Sign Drug of Abuse MDMA Dip Card Test
First Sign Drug of Abuse EDDP Cup Test
First Sign Drug of Abuse EDDP Dip Card Test
First Sign Drug of Abuse Nortriptyline Cup Test
First Sign Drug of Abuse Nortriptyline Dip Card Test
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LAF | Class II | 862.3610 | 91-Toxicology |
| DJR | Class II | 862.3620 | 91-Toxicology |
| LFG | Class II | 862.3910 | 91-Toxicology |
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H. Intended Use:
1. Intended use(s):
See indications for Use below.
2. Indication(s) for use:
First Sign Drug of Abuse MDMA Cup Test
First Sign Drug of Abuse MDMA Dip Card Test
First Sign Drug of Abuse MDMA Tests are immunoassay tests. The test can detect MDMA in human urine. The cut-off value is 500 ng/mL. The tests are available in a Cup format and a Dip Card format.
The tests provide only preliminary test results. If you want to get a confirmed result, you must use a more specific chemical method. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be used when you get any drug of abuse test result. It should be used particularly when the preliminary result is positive.
For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.
First Sign Drug of Abuse EDDP Cup Test
First Sign Drug of Abuse EDDP Dip Card Test
First Sign Drug of Abuse EDDP Tests are immunoassay tests. The test can detect EDDP in human urine. The cut-off value is 300 ng/mL. The tests are available in a Cup format and a Dip Card format.
The tests provide only preliminary test results. If you want to get a confirmed result, you must use a more specific chemical method. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be used when you get any drug of abuse test result. It should be used particularly when the preliminary result is positive.
For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.
First Sign Drug of Abuse Nortriptyline Cup Test
First Sign Drug of Abuse Nortriptyline Dip Card Test
First Sign Drug of Abuse Nortriptyline Tests are immunoassay tests. The test can detect Nortriptyline in human urine. The cut-off value is 1,000 ng/mL. The tests are available in a Cup format and a Dip Card format.
The tests provide only preliminary test results. If you want to get a confirmed result, you must use a more specific chemical method. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be used when you get any drug of abuse test result. It should be used particularly
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when the preliminary result is positive.
For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.
3. Special conditions for use statement(s):
For over-the-counter and prescription use
4. Special instrument requirements:
Not applicable. The devices are visually read and single-use.
I. Device Description:
These devices are immunochromatographic assays for MDMA, EDDP and Nortriptyline Urine Tests use a lateral flow, one step system for the qualitative detection of MDMA, EDDP and Nortriptyline in human urine. Each assay uses a monoclonal antibody-dye conjugate against drugs with gold chloride and fixed drug-protein conjugates and antimouse IgG polyclonal antibody in membranes.
The assays in this submission include a dip card and cup formats. Each assay and format is available separately.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Co-Innovation Biotech One Step Single/Multi-Drug Test
2. Predicate 510(k) number(s):
k142800
k140748
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate (k142800) |
| Intended Use | For the qualitative determination of MDMA in human urine. | Rapid Single/Multi-drug test Cup and Rapid Single/Multi-drug test Dipcard are lateral flow chromatographic immunoassays designed to qualitatively detect the presence of drugs and drug metabolites in human urine |
| Calibrator Drug | MDMA | Delta-9-THC-COOH Benzolecgonine |
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| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate (k142800) |
| | | D-Amphetamine
D-Methamphetamine
Morphine
Secobarbital
Oxazepam
3,4-Methylenedioxymethamphetamine
Methadone
Oxycodone
Phencyclidine |
| Methodology | Competitive binding, lateral flow
immunochromatographic assays based
on the principle of antigen
antibody
immunochemistry. | Same |
| Specimen Type | Human Urine | Same |
| Cut-Off Values | 500 ng/mL (MDMA) | Same |
| Intended Populations | For over-the-counter use
and prescription uses | Same |
| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate (k140748) |
| Intended Use | For the qualitative determination of EDDP and Nortriptyline in human urine. | One Step Single/Multi-drug Test Cup and One Step Single/Multi-drug Test Dipcard are lateral flow chromatographic immunoassays designed to qualitatively detect the presence of drugs and drug metabolites in human urine |
| Calibrator Drug | EDDP
Nortriptyline | Buprenorphine
2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine"
Morphine
Propoxyphene
Nortriptyline |
| Methodology | Competitive binding, lateral flow
immunochromatographic assays based
on the principle of antigen
antibody | Same |
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| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate (k140748) |
| | immunochemistry. | |
| **Specimen Type** | Human Urine | Same |
| **Cut-Off Values** | 300 ng/mL (EDDP)
1000 ng/mL
(Nortriptyline) | Same |
| **Intended Populations** | For over-the-counter use
and prescription uses | Same |
K. Standard/Guidance Document Referenced (if applicable):
None were referenced
L. Test Principle:
First Sign Drug of Abuse MDMA Test, First Sign Drug of Abuse EDDP Test and First Sign Drug of Abuse Nortriptyline Test are immunochromatographic assays. Each assay test is a lateral flow system for the qualitative detection of MDMA, or EDDP or Nortriptyline in human urine. During testing, a urine specimen migrates upward by capillary action. If target drugs are present in the urine specimen below its cut-off concentration, it will not saturate the binding sites of its specific antibody (monoclonal mouse antibody) coated on the particles. The antibody-coated particles will then be captured by immobilized drug-conjugate and a visible colored line will show up in the test line region. The colored line will not form in the test line region if the target drug level exceeds its cut-off concentration because it will saturate all the binding sites of the antibody coated on the particles. A band should form in the control region of the devices regardless of the presence of drug or metabolite in the sample.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision studies were carried out for samples with concentrations of -100% cut-off, -75% cut-off, -50% cut-off, -25% cut-off, at the cut-off, +25% cut-off, +50% cut-off, +75% cut-off and +100% cut-off. These samples were prepared by spiking drug in negative urine samples. Each drug concentration was confirmed by GC/MS. All sample aliquots were blinded labeled and randomized. For each concentration, tests were performed two runs per day for 25 days.
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MDMA Dip Card
| MDMA | -100% cut off | -75% cut off | -50% cut off | -25% Cutoff | cut off | +25% cutoff | +50% cutoff | +75% cutoff | +100% cutoff |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
MDMA Cup
| MDMA | -100% cut off | -75% cut off | -50% cut off | -25% Cutoff | cut off | +25% cutoff | +50% cutoff | +75% cutoff | +100% cut off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Lot 4 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 6 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
EDDP Dip Card
| EDDP | -100% cut off | -75% cut off | -50% cut off | -25% Cutoff | cut off | +25% cutoff | +50% cutoff | +75% cutoff | +100% cut off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
EDDP Cup
| EDDP | -100% cut off | -75% cut off | -50% cut off | -25% Cutoff | cut off | +25% cutoff | +50% cutoff | +75% cutoff | +100% cut off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Lot 4 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 6 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
Nortriptyline Dip Card
| Nortriptyline | -100% cut off | -75% cut off | -50% cut off | -25% Cutoff | cut off | +25% cutoff | +50% cutoff | +75% cutoff | +100% cut off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
Nortriptyline Cup
| Nortriptyline | -100% cut off | -75% cut off | -50% cut off | -25% Cutoff | cut off | +25% cutoff | +50% cutoff | +75% cutoff | +100% cut off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Lot 4 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 6 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
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b. Linearity/assay reportable range:
Not applicable, these devices are intended for qualitative use only.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
**Stability**
Real-time and accelerated stability studies were conducted on three lots of each device. The protocols for the stability studies were reviewed and found to be acceptable. The results of these studies indicated that all devices were found to be stable at 4-30°C (39-86°F) for 24 months based on the accelerated stability study at 50°C and a shelf life study at 30°C. Control materials are not provided with the device. The labeling provides information on how to obtain control materials.
**Transportation Study**
A Transportation stability study was conducted on three lots of each device. The protocols for the transportation stability study were reviewed and found to be acceptable. The results of these studies indicated that all devices were found to be stable during transport of the device in temperatures between -20 and 40°C.
d. Detection limit:
Not applicable.
e. Analytical specificity:
Compounds sharing structural or conformational similarity with the analytes were tested for cross-reactivity with the candidate device. The structurally related compounds that exhibited cross-reactivity with the candidate device were titrated to determine the percent cross-reactivity. The concentration (ng/mL) of cross-reactant that gives a response equivalent to the cutoff, and the percent cross-reactivity are presented in the table below.
MDMA Cross Reactivity
| Drugs | Concentration (ng/ml) | Reactivity |
| --- | --- | --- |
| Methylenedioxymethamphetamine (MDMA) | 500 | 100% |
| 3,4-Methylenedioxyamphetamine (MDA) | 8000 | 6.3% |
| 3,4-Methylenedioxyethylamphetamine (MDEA) | 1000 | 50% |
| Ephedrine | 40000 | 1.3% |
| d-methamphetamine | Negative at | Not Detected |
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| Drugs | Concentration (ng/ml) | Reactivity |
| --- | --- | --- |
| | 100000 | |
| d-amphetamine | Negative at 100000 | Not Detected |
| l-amphetamine | Negative at 100000 | Not Detected |
| l-methamphetamine | Negative at 100000 | Not Detected |
## EDDP Cross Reactivity
| Drugs | Concentration (ng/ml) | Reactivity |
| --- | --- | --- |
| EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) | 300 | 100% |
| EMDP (2-Ethyl-5-methyl-3,3-diphenylpyrroline) | Negative at 100000 | Not Detected |
| Disopyramide | Negative at 100000 | Not Detected |
| Methadone | Negative at 100000 | Not Detected |
| LAAM (Levo-alpha-acetylmethadol) | Negative at 100000 | Not Detected |
| Alpha Methadol | Negative at 100000 | Not Detected |
| Doxylamine | Negative at 100000 | Not Detected |
## Nortriptyline Cross Reactivity
| Drugs | Concentration (ng/ml) | Reactivity |
| --- | --- | --- |
| Nortriptyline | 1000 | 100% |
| Amitriptyline | 1500 | 67% |
| Clomipramine | 15000 | 6.7% |
| Desipramine | 1000 | 100% |
| Doxepine | 2000 | 50% |
| Imipramine | 600 | 167% |
| Nordoxepin | 1000 | 100% |
| Promazine | 24000 | 4% |
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# Interference Study
Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drugs. These urine samples were tested using three batches of each device for all formats.
Compounds that showed no interference at a concentration of $100\mu \mathrm{g / mL}$ for different formats (cup, dipcard) are listed below:
MDMA Interference
| 4-Acetamidophenol Acetophenetidin N- Acetylprocainamide Acetylsalicylic acid Aminopyrine Amitryptyline Amobarbital Amoxicillin Ampicillin L-Ascorbic acid Apomorphine Aspartame Atropine Benzilic acid Benzoic acid Benzoylecgonine Bilirubin (±)- Brompheniramine Buspiron Caffeine Cannabidiol Cannabinol Chloralhydrate Chloramphenicol | (L)-Epinephrine Erythromycin β-Estradiol Estrone-3-sulfate Ethyl-p-aminobenzoate Fenoprofen Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone O-Hydroxyhippuric acid 3-Hydroxytyramine Ibuprofen Imipramine Iproniazid (±)-Isoproterenol Isoxsuprine Ketamine Ketoprofen Labetalol Levorphanol Loperamide Maprotiline | Pentobarbital Perphenazine Phencyclidine Phenelzine Phenobarbital Phentermine Trans-2-phenylcyclopropylamine hydrochloride L-Phenylephrine β-Phenylethylamine Phenylpropanolamine Prednisolone Prednisone Procaine Promazine Promethazine DL-Propranolol D-Propoxyphene D-Pseudoephedrine Quinacrine Quinidine Quinine Ranitidine Salicylic acid Secobarbital |
| --- | --- | --- |
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10
| Chlordiazepoxide | Meperidine | Serotonin (5-Hydroxytyramine) |
| --- | --- | --- |
| Chlorothiazide | Meprobamate | Sulfamethazine |
| (±)- | Methadone | Sulindac |
| Chlorpheniramine | Morphine-3-β-Dglucuronide | Sustiva |
| Chlorpromazine | Morphine sulfate | Temazepam |
| Chloroquine | Nalidixic acid | Tetracycline |
| Cholesterol | Naloxone | Tetrahydrocortisone 3-(β-Dglucuronide) |
| Clomipramine | Naltrexone | Tetrahydrozoline |
| Clonidine | Naproxen | Thebaine |
| Cocaethylene | Niacinamide | Theophynine |
| Cocaine | Nifedipine | Thiamine |
| hydrochloride | Nimesulidate | Thioridazine |
| Codeine | Norcodein | Tolbutamide |
| Cortisone | Norethindrone | Trazodone |
| (-) Cotinine | D-Norpropoxyphene | Triamterene |
| Creatinine | Noscapine | DL-Tyrosine |
| Deoxycorticosterone | D,L-Octopamine | Trifluoperazine |
| Dextromethorphan | Oxalic acid | Trimethoprim |
| Diclofenac | Oxazepam | Trimipramine |
| Diazepam | Oxolinic acid | Tryptamine |
| Diflunisal | Oxycodone | D L-Tryptophan |
| Digoxin | Oxymetazoline | Tyramine |
| Dicylamine | Papaverine | Uric acid |
| Diphenylhydantoin | Penicillin-G | Verapamil |
| Doxylamine | Pentazocinehydrochloride | Zomepirac |
| Ecgonine | | |
| hydrochloride | | |
| Ecgonine | | |
| methylester | | |
| 1R,2S Ephedrine | | |
## EDDP Interference
| Acetaminophen | Ecgonine hydrochloride | O-Hydroxyhippuric acid |
| --- | --- | --- |
| Acetophenetidin | Ecgonine methylester | Oxalic acid |
| Acetylsalicylic acid | (IR,2S)(-)Ephedrine | Oxazepam |
| Amobarbital | Erythromycin | Oxolinic acid |
| Aminopyrine | β-Estradiol | Oxycodone |
| Amitryptyline | Estrone-3-sulfate | Oxymetazoline |
| Amoxicillin | Ethyl-p-aminobenzoate | Papaverine |
| DL-Amphetamine | Fenoprofen | Penicillin-G |
| sulfate | Furosemide | Pentazocine |
| Ampicillin | Gentisic acid | Pentobarbital |
| Apomorphine | Hemoglobin | Perphenazine |
| Ascorbic acid | Hydralazine | Phencyclidine |
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| Aspartame
Atropine
Benzilic acid
Benzoic acid
Benzoylecgonine
Bilirubin
Brompheniramine
Caffeine
Cannabidiol
Cannabinol
Chloralhydrate
Chloramphenicol
Chlorothiazide
(±) -
Chlorpheniramine
Chlorpromazine
Chloroquine
Cholesterol
Clomipramine
Clonidine
Cocaine
hydrochloride
Codeine
(-) Cotinine
Cortisone
Creatinine
Deoxycorticosterone
Dextromethorphan
Diazepam
Diclofenac
Diflunisal
Digoxin
Diphenhydramine
D-Norpropoxyphene
D-Propoxyphene
D,L-Tyrosine
DL-Octopamine
DL-Propranolol | Hydrochlorothiazide
Hydrocodone
Hydrocortisone
p-Hydroxyamphetamine
p-Hydroxymethamphetamine
3-Hydroxytyramine
Ibuprofen
Imipramine
(-) Isoproterenol
Isoxsuprine
Ketamine
Ketoprofen
Labetalol
Levorphanol
Loperamide
L-Phenylephrine
Maprotiline
Meperidine
Meprobamate
Methamphetamine
Methoxyphenamine
(±) - 3,4-Methylenedioxy-amphetamine
hydrochloride
(±)-3,4-Methylenedioxy-methamphetamine
hydrochloride
Morphine Sulfate
Morphine-3-β-D
glucuronide
N-Acetylprocainamide
Nalidixic acid
Naloxone
Naltrexone
Naproxen
Niacinamide
Nifedipine
Norcodein
Norethindrone
Noscapine | Phenelzine
Phenobarbital
Phentermine
β-Phenylethylamine
Phenylpropanolamine
Prednisolone
Prednisone
Procaine
Promazine
Promethazine
Quinidine
Quinine
Ranitidine
Salicylic acid
Secobarbital
Serotonin
Sulfamethazine
Sulindac
Temazepam
Tetracycline
Tetrahydrocortisone 3- (β-D-glucuronide)
Tetrahydrozoline
Thebaine
Thiamine
Thioridazine
Triamterene
Trifluoperazine
Trimethoprim
Trimipramine
Tryptamine
DL-Tryptophan
Tyramine
Uric acid
Verapamil
Zomepirac |
| --- | --- | --- |
## Nortriptyline Interference
| 4-Acetamidophenol
Acetophenetidin
N- | Erythromycin
β-Estradiol
Estrone-3-sulfate | Oxycodone
Oxymetazoline
Papaverine |
| --- | --- | --- |
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| Acetylprocainamide | Ethyl-p-aminobenzoate | Penicillin-G |
| --- | --- | --- |
| Acetylsalicylic acid | | Pentazocine hydrochloride |
| Aminopyrine | Fenoprofen | Pentobarbital |
| Amobarbital | Furosemide | Perphenazine |
| Amoxicillin | Gentisic acid | Phencyclidine |
| Ampicillin | Hemoglobin | Phenelzine |
| L-ascorbic acid | Hydralazine | Phenobarbital |
| DL-Amphetamine | Hydrochlorothiazide | Phentermine |
| Hydrochlorothiazide | Hydrocodone | β-Phenylethylamine |
| Phenobarbital | Hydrocortisone | Trans-2- |
| sulfate | O-Hydroxyhippuric acid | phenylcyclopropylamine |
| Apomorphine | p-Hydroxyamphetamine | hydrochloride |
| Aspartame | | L-Phenylephrine |
| Atropine | p-Hydroxy- | Phenylpropanolamine |
| Benzilic acid | methamphetamine | Prednisolone |
| Benzoic acid | 3-Hydroxytyramine | Prednisone |
| Benzoylecgonine | Ibuprofen | Procaine |
| Benzphetamine | Iproniazid | DL-Propranolol |
| Bilirubin | (±) - Isoproterenol | D-Propoxyphene |
| (±) - | Isoxsuprine | D-Pseudoephedrine |
| Brompheniramine | Ketamine | Quinacrine |
| Caffeine | Ketoprofen | Quinidine |
| Cannabidiol | Labetalol | Quinine |
| Cannabinol | Loperamide | Ranitidine |
| Chloralhydrate | MDE | Salicylic acid |
| Chloramphenicol | Meperidine | Secobarbital |
| Chlorothiazide | Meprobamate | Serotonin |
| (±) | Methadone | Sulfamethazine |
| Chlorpheniramine | (L)Methamphetamine | Sulindac |
| Chlorpromazine | Methoxyphenamine | Tetracycline |
| Chloroquine | (±)-3,4- | Tetrahydrocortisone 3-(β-D- |
| Cholesterol | Methylenedioxyamphetamine | glucuronide) |
| Clonidine | | Tetrahydrozoline |
| Cocaethylene | hydrochloride | Thiamine |
| Cocaine | Morphine-3-β- | Thioridazine |
| hydrochloride | Dglucuronide Morphine | DL-Tyrosine |
| Codeine | sulfate | Tolbutamide |
| Cortisone | Nalidixic acid | Triamterene |
| (-) Cotinine | Naloxone | Trifluoperazine |
| Creatinine | Naltrexone | Trimethoprim |
| Deoxycorticosterone | Naproxen | Tryptamine |
| Dextromethorphan | Niacinamide | DL-Tryptophan |
| Diclofenac | Nifedipine | Tyramine |
| Diflunisal | Norcodeine | Verapamil |
| Digoxin | Norethindrone | Zomepirac |
| Diphenhydramine | D-Norpropoxyphene | |
12
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| Doxylamine
Ecgonine
hydrochloride
Ecgonine
methylester
Ephedrine
(L) - Epinephrine | Noscapine
Oxalic acid
Oxazepam
Oxolinic acid | |
| --- | --- | --- |
## Effect of Urine Specific Gravity and Urine pH
To investigate the effect of urine specific gravity and urine pH, urine samples with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with target drugs at 25% below and 25% above cut-off levels. These samples were tested using three batches of each device for all formats. Results were all positive for samples at and above +25% cut-off and all negative for samples at and below -25% Cut-Off. There were no differences observed for different formats.
f. Assay cut-off:
Characterization of how the device performs analytically around the claimed cutoff concentration is described in the precision section, M.1.a. above.
2. Comparison studies:
a. Method comparison with predicate device:
The method comparison studies for the First Sign Drug of Abuse tests (MDMA, EDDP and Nortriptyline) were performed in-house with three different laboratory assistants for each format of the device. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples for each drug. The samples were blind labeled and compared to GC/MS results.
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MDMA Dip Card
| Test | | Drug-free | Low Negative (<50% the cutoff conc) | Near Cutoff Negative (Between <50% below up to the cutoff conc) | Near Cutoff Positive (Between the cutoff and 50% above cutoff conc) | High Positive (>50% above the cutoff conc) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator A | Positive | 0 | 0 | 0 | 13 | 26 |
| | Negative | 10 | 10 | 20 | 1† | 0 |
| Operator B | Positive | 0 | 0 | 1* | 14 | 26 |
| | Negative | 10 | 10 | 19 | 0 | 0 |
| Operator C | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
% agreement among positives is 98.3%
% agreement among negatives is 98.3%
* Samples contained MDMA at 474 and 468 ng/mL
† Samples contained MDMA at 544 and 561 ng/mL
MDMA Cup
| Test | | Drug-free | Low Negative (<50% the cutoff conc) | Near Cutoff Negative (Between <50% below up to the cutoff conc) | Near Cutoff Positive (Between the cutoff and 50% above cutoff conc) | High Positive (>50% above the cutoff conc) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator A | Positive | 0 | 0 | 1* | 14 | 26 |
| | Negative | 10 | 10 | 10 | 0 | 0 |
| Operator B | Positive | 0 | 0 | 0 | 13 | 26 |
| | Negative | 10 | 10 | 20 | 1† | 0 |
| Operator C | Positive | 0 | 0 | 1* | 14 | 26 |
| | Negative | 10 | 10 | 19 | 0 | 0 |
{14}
% agreement among positives is $99.2\%$
% agreement among negatives is $98.3\%$
* Samples contained MDMA at 470 and ${477}\mathrm{\;{ng}}/\mathrm{{mL}}$
† Samples contained MDMA at 517 ng/mL
EDDP Dip Card
| Test | | Drug-free | Low Negative (<50% the cutoff conc) | Near Cutoff Negative (Between <50% below up to the cutoff conc) | Near Cutoff Positive (Between the cutoff and 50% above cutoff conc) | High Positive (>50% above the cutoff conc) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator A | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
| Operator B | Positive | 0 | 0 | 1* | 14 | 26 |
| | Negative | 10 | 10 | 19 | 0 | 0 |
| Operator C | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
% agreement among positives is $98.3\%$
% agreement among negatives is $97.5\%$
* Samples contained EDDP at 260, 269, and ${276}\mathrm{\;{ng}}/\mathrm{{mL}}$
† Samples contained EDDP at 340 and ${344}\mathrm{\;{ng}}/\mathrm{{mL}}$
EDDP Cup
| Test | | Drug-free | Low Negative (<50% the cutoff conc) | Near Cutoff Negative (Between <50% below up to the cutoff conc) | Near Cutoff Positive (Between the cutoff and 50% above cutoff conc) | High Positive (>50% above the cutoff conc) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator A | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
| Operator B | Positive | 0 | 0 | 0 | 13 | 26 |
| | Negative | 10 | 10 | 20 | 1† | 0 |
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16
| Operator C | Positive | 0 | 0 | 1* | 13 | 26 |
| --- | --- | --- | --- | --- | --- | --- |
| | Negative | 10 | 10 | 19 | 1† | 0 |
% agreement among positives is 97.5%
% agreement among negatives is 98.3%
* Samples contained EDDP at 266 and 269 ng/mL
† Samples contained EDDP at 340, 342, and 344 ng/mL
## Nortriptyline Dip Card
| Test | | Drug-free | Low Negative (<50% the cutoff conc) | Near Cutoff Negative (Between <50% below up to the cutoff conc) | Near Cutoff Positive (Between the cutoff and 50% above cutoff conc) | High Positive (>50% above the cutoff conc) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator A | Positive | 0 | 0 | 1* | 14 | 26 |
| | Negative | 10 | 10 | 19 | 0 | 0 |
| Operator B | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
| Operator C | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
% agreement among positives is 98.3%
% agreement among negatives is 97.5%
* Samples contained Nortriptyline at 851, 863, and 879 ng/mL
† Samples contained Nortriptyline at 1069 and 1125 ng/mL
## Nortriptyline Cup
| Test | | Drug-free | Low Negative (<50% the cutoff conc) | Near Cutoff Negative (Between <50% below up to the cutoff conc) | Near Cutoff Positive (Between the cutoff and 50% above cutoff conc) | High Positive (>50% above the cutoff conc) |
| --- | --- | --- | --- | --- | --- | --- |
| Operator A | Positive | 0 | 0 | 1* | 13 | 26 |
| | Negative | 10 | 10 | 19 | 1† | 0 |
| Operator B | Positive | 0 | 0 | 1* | 14 | 26 |
| | Negative | 10 | 10 | 19 | 0 | 0 |
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17
| Operator C | Positive | 0 | 0 | 0 | 13 | 26 |
| --- | --- | --- | --- | --- | --- | --- |
| | Negative | 10 | 10 | 20 | 1† | 0 |
% agreement among positives is 98.3%
% agreement among negatives is 98.3%
* Samples contained Nortriptyline at 851 and 870 ng/mL
† Samples contained Nortriptyline at 1084 and 1135 ng/mL
b. Matrix comparison:
N/A
3. Clinical studies:
a. Clinical Sensitivity:
N/A
b. Clinical specificity:
N/A
c. Other clinical supportive data (when a. and b. are not applicable):
## Lay User Study
A lay user study was performed at three intended user sites with 280 lay persons testing the MDMA devices, 280 lay persons testing the EDDP devices and 280 lay persons testing the Nortriptyline devices. A total of 140 females and 140 males tested the MDMA samples, 141 females and 139 males tested EDDP samples, and 141 females and 139 males tested the Nortriptyline samples. They had diverse educational and professional backgrounds and ranged in age from 21 to >50 years. Urine samples were prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers and blind-labeled. Each participant was provided with the package insert, 1 blind labeled sample and a device.
Lay-users were also given surveys on the ease of understanding the package insert instructions. All lay users indicated that the device instructions can be easily followed. A Flesch-Kincaid reading analysis was performed on each package insert and the scores revealed a reading Grade Level of 7.
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18
MDMA Dip Card
| % of Cutoff | Number of samples | MDMA Concentration by GC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100%Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75%Cutoff | 20 | 115 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 237 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 358 | 0 | 20 | 100 |
| +25% Cutoff | 20 | 598 | 19 | 1 | 95 |
| +50% Cutoff | 20 | 755 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 912 | 20 | 0 | 100 |
MDMA Cup
| % of Cutoff | Number of samples | MDMA Concentration by GC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100%Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75%Cutoff | 20 | 115 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 237 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 358 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 598 | 20 | 0 | 100 |
| +50% Cutoff | 20 | 755 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 912 | 20 | 0 | 100 |
{18}
EDDP Dip Card
| % of Cutoff | Number of samples | EDDP Concentration by GC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100%Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75%Cutoff | 20 | 81 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 157 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 235 | 2 | 18 | 90 |
| +25% Cutoff | 20 | 410 | 20 | 0 | 100 |
| +50% Cutoff | 20 | 485 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 566 | 20 | 0 | 100 |
EDDP Cup
| % of Cutoff | Number of samples | EDDP Concentration by GC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100%Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75%Cutoff | 20 | 81 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 157 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 235 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 410 | 20 | 0 | 100 |
| +50% Cutoff | 20 | 485 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 566 | 20 | 0 | 100 |
{19}
20
# Nortriptyline Dip Card
| % of Cutoff | Number of samples | Nortriptyline Concentration by GC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100%Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75%Cutoff | 20 | 261 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 495 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 720 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 1180 | 20 | 0 | 100 |
| +50% Cutoff | 20 | 1485 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 1687 | 20 | 0 | 100 |
# Nortriptyline Cup
| % of Cutoff | Number of samples | Nortriptyline Concentration by GC/MS (ng/mL) | Lay person results | | The percentage of correct results (%) |
| --- | --- | --- | --- | --- | --- |
| | | | No. of Positive | No. of Negative | |
| -100%Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75%Cutoff | 20 | 261 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 495 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 720 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 1180 | 19 | 1 | 95 |
| +50% Cutoff | 20 | 1485 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 1687 | 20 | 0 | 100 |
4. Clinical cut-off:
N/A
5. Expected values/Reference range:
N/A
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
{20}
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
21
