CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine
Device Facts
| Record ID | K142609 |
|---|---|
| Device Name | CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine |
| Applicant | Guangzhou Wondfo Biotech Co., Ltd. |
| Product Code | LFG · Clinical Toxicology |
| Decision Date | Dec 18, 2014 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3910 |
| Device Class | Class 2 |
Indications for Use
CR3 Keyless Split Sample Cup Nortriptyline–Buprenorphine is a rapid test for the qualitative detection of Nortriptyline (a major metabolite of Tricyclic Antidepressants) and Buprenorphine in human urine at a cutoff concentration of 1000ng/mL and 10ng/mL, respectively. The test is the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained. The test is intended for over-the-counter and for prescription use. The test may yield preliminary positive results even when prescription drugs including Tricyclic Antidepressants and Buprenorphine are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Nortriptyline and Buprenorphine in urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. 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. For in vitro diagnostic use only.
Device Story
Rapid, single-use, visually read lateral flow immunoassay cup; detects Nortriptyline (1000ng/mL cutoff) and Buprenorphine (10ng/mL cutoff) in human urine. Principle: competitive binding; urine sample migrates via capillary action across membrane pre-coated with drug-protein conjugates and anti-drug antibody-dye conjugates. Negative result: colored line in Test Region (T) (analyte below cutoff). Positive result: no line in Test Region (analyte above cutoff). Control line (C) confirms proper flow. Includes integrated temperature strip (32-38°C) to verify sample validity. Used by lay users (OTC) or clinicians (prescription) to screen for drug presence; preliminary results require laboratory confirmation via GC/MS. Benefits: provides immediate, point-of-care screening for drug presence.
Clinical Evidence
Bench testing only. Precision/reproducibility studies performed over 25 days. Analytical specificity evaluated against numerous compounds; no interference observed. Method comparison against GC/MS using 80 clinical samples showed high agreement. Lay-user study (n=260) confirmed ability of non-professionals to perform test and interpret results; Flesch-Kincaid grade level <7. Temperature strip accuracy validated against thermometer and user study (n=100).
Technological Characteristics
Lateral flow immunochromatographic assay; mouse monoclonal anti-drug antibody-dye conjugates; fixed drug-protein conjugates; anti-mouse IgG polyclonal antibodies. Single-use cup form factor. Visual readout. Integrated temperature strip (32-38°C). No energy source required. Stable at 4-30°C for 18 months.
Indications for Use
Indicated for qualitative detection of Nortriptyline and Buprenorphine in human urine for OTC and prescription use. Not intended to distinguish between prescription use and abuse. Requires confirmatory testing via GC/MS for positive results.
Regulatory Classification
Identification
A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in serum. The tricyclic antidepressant drugs include imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, and doxepin. Measurements obtained by this device are used in the diagnosis and treatment of chronic depression to ensure appropriate therapy.
Special Controls
*Classification.* Class II (special controls). A tricyclic antidepressant drugs 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
- UCP Multi-Drug Test Key Cups (k132812)
Related Devices
- K151348 — Healgen Propoxyphene Test (Strip, Cassette, Cup, Dip Card), Healgen Nortriptyline Test (Strip, Cassette, Cup, Dip Card), Healgen EDDP (Methadone Metabolite) Test (Strip, Cassette, Cup, Dip Card) · Healgen Scientific,, LLC · Aug 18, 2015
Submission Summary (Full Text)
{0}
1
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
K142609
B. Purpose for Submission:
New Device
C. Measurand:
Nortriptyline and Buprenorphine
D. Type of Test:
Qualitative chromatographic immunoassay
E. Applicant:
Guangzhou Wondfo Biotech Co., Ltd.
F. Proprietary and Established Names:
CR3 Keyless Split Sample Cup Nortriptyline–Buprenorphine
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | Class II | 21 CFR part 862.3650
Opiate test system | Toxicology (91) |
| LFG | Class II | 21 CFR part 862.3910
Tricyclic antidepressant drugs
test system | Toxicology (91) |
{1}
H. Intended Use:
1. Intended use(s):
Please see Indications for Use below.
2. Indication(s) for use:
CR3 Keyless Split Sample Cup Nortriptyline–Buprenorphine is a rapid test for the qualitative detection of Nortriptyline (a major metabolite of Tricyclic Antidepressants) and Buprenorphine in human urine at a cutoff concentration of 1000ng/mL and 10ng/mL, respectively. The test is the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained. The test is intended for over-the-counter and for prescription use.
The test may yield preliminary positive results even when prescription drugs including Tricyclic Antidepressants and Buprenorphine are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Nortriptyline and Buprenorphine in urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. 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.
For in vitro diagnostic use only.
3. Special conditions for use statement(s):
For Prescription and Over-the-counter Use
4. Special instrument requirements:
Not applicable; this is a visually read single use device.
I. Device Description:
The CR3 Keyless Split Sample Cup Nortriptyline–Buprenorphine test uses immunochromatographic assays for nortriptyline and buprenorphine. The test is a lateral flow system for the qualitative detection of nortriptyline and buprenorphine in human urine.
J. Substantial Equivalence Information:
1. Predicate device name(s):
UCP Multi-Drug Test Key Cups
{2}
2. Predicate 510(k) number(s):
k132812
3. Comparison with predicate:
| Item | Device | Predicate |
| --- | --- | --- |
| Indication(s) for use | For the qualitative determination of drugs of abuse in human urine | Same |
| Methodology | Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry. | Same |
| Results | Qualitative | Same |
| Specimen Type | Human urine | Same |
| Cut Off Values | Nortriptyline: 1000ng/ml Buprenorphine: 10ng/ml | Same for Tricyclic Antidepressant (Nortriptyline) and Buprenorphine |
| Configurations | Cup | Same |
| Conditions for Use | Over-the-Counter & Prescription Use | Over-the-counter |
# K. Standard/Guidance Document Referenced (if applicable):
None were referenced.
# L. Test Principle:
The CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine test is a rapid flow chromatographic immunoassay for the qualitative detection of Nortriptyline and Buprenorphine in urine samples. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre-coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the
{3}
Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the Test Region, indicating a potentially positive result. A band should form in the Control Region (C) of the device 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. For each concentration, tests were performed two runs per day for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:
#### For Nortriptyline testing
| Lot | -100% cut-off | -75% cut-off | -50% cut-off | -25% cut-off | cut-off | +25% cut-off | +50% cut-off | +75% cut-off | +100% cut-off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 44+/6- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
#### For Buprenorphine testing
| Lot | -100% cut-off | -75% cut-off | 50% cut-off | -25% cut-off | cut-off | +25% cut-off | +50% cut-off | +75% cut-off | +100% cut-off |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
{4}
b. Linearity/assay reportable range:
Not applicable.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Shelf stability for the CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine was performed using accelerated and real-time stability testing. Protocols and acceptance criteria were reviewed and found to be acceptable. The sponsor claims that the device is stable at 4-30°C for 18 months.
Control materials are not provided with the device. The labeling provides information on how to obtain control materials.
d. Detection limit:
Not applicable.
e. Analytical specificity:
Potential interfering substances found in human urine of physiological or pathological conditions were added at a concentration of 100μg/mL to drug-free urine and to urine containing target drugs (nortriptyline or buprenorphine) at 25% below and 25% above the cut-off. The samples were tested using three lots of the CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine by three different operators. The compounds below showed no interference:
**Nortriptyline**
| 4-Acetamidophenol | Erythromycin | Oxycodone |
| --- | --- | --- |
| Acetophenetidin | β-Estradiol | Oxymetazoline |
| N-Acetylprocainamide | Estrone-3-sulfate | Papaverine |
| Acetylsalicylic acid | Ethyl-p-aminobenzoate | Penicillin-G |
| Aminopyrine | Fenoprofen | Pentazocine hydrochloride |
| Amobarbital | Furosemide | Pentobarbital |
| Amoxicillin | Gentisic acid | Perphenazine |
| Ampicillin | Hemoglobin | Phencyclidine |
| L-ascorbic acid | Hydralazine | Phenelzine |
| DL-Amphetamine sulfate | Hydrochlorothiazide | Phenobarbital |
| Apomorphine | Hydrocodone | Phentermine |
| Aspartame | Hydrocortisone | β-Phenylethylamine |
| Atropine | O-Hydroxyhippuric acid | Trans-2-phenylcyclopropylamine hydrochloride |
| Benzilic acid | p-Hydroxyamphetamine | L-Phenylephrine |
| Benzoic acid | p-Hydroxy-methamphetamine | Phenylpropanolamine |
{5}
6
| Benzoylecgonine | 3-Hydroxytyramine | Prednisolone |
| --- | --- | --- |
| Benzphetamine | Ibuprofen | Prednisone |
| Bilirubin | Iproniazid | Procaine |
| (±) - Brompheniramine | (±) – Isoproterenol | DL-Propanolol |
| Caffeine | Isoxuprine | D-Propoxyphene |
| Cannabidiol | Ketamine | D-Pseudoephedrine |
| Cannabinol | Ketoprofen | Quinacrine |
| Chloralhydrate | Labetalol | Quinidine |
| Chloramphenicol | Loperamide | Quinine |
| Chlorothiazide | MDE | Ranitidine |
| (±) Chlorpheniramine | Meperidine | Salicylic acid |
| Chlorpromazine | Meprobamate | Secobarbital |
| Chlorquine | Methadone | Serotonin |
| Cholesterol | (L)Methamphetamine | Sulfamethazine |
| Clonidine | Methoxyphenamine | Sulindac |
| Cocaethylene | (±)-3,4-Methylenedioxyamphetamine hydrochloride | Tetracycline |
| Cocaine hydrochloride | (+)3,4-Methylenedioxymethamphetamine hydrochloride | Tetrahydrocortisone, 3-acetate |
| Codeine | Morphine-3-β-D-glucuronide | Tetrahydrocortisone 3-(β-D-glucuronide) |
| Cortisone | Morphine sulfate | Tetrahydrozoline |
| (-) Cotinine | Nalidixic acid | Thiamine |
| Creatinine | Naloxone | Thioridazine |
| Deoxycorticosterone | Naltrexone | DL-Tyrosine |
| Dextromethorphan | Naproxen | Tolbutamide |
| Diclofenac | Niacinamide | Triamterene |
| Diflunisal | Nifedipine | Trifluoperazine |
| Digoxin | Norcodeine | Trimethoprim |
| Diphenhydramine | Norethindrone | Tryptamine |
| Doxylamine | D-Norpropoxyphene | DL-Tryptophan |
| hetamine hydrochloride | 3-acetate | |
| Codeine | Morphine-3-β-D-glucuronide | Tetrahydrocortisone 3-(β-D-glucuronide) |
| Cortisone | Morphine sulfate | Tetrahydrozoline |
| (-) Cotinine | Nalidixic acid | Thiamine |
| Creatinine | Naloxone | Thioridazine |
| Deoxycorticosterone | Naltrexone | DL-Tyrosine |
| Dextromethorphan | Naproxen | Tolbutamide |
| Diclofenac | Niacinamide | Triamterene |
| Diflunisal | Nifedipine | Trifluoperazine |
| Digoxin | Norcodeine | Trimethoprim |
| Diphenhydramine | Norethindrone | Tryptamine |
| Doxylamine | D-Norpropoxyphene | DL-Tryptophan |
{6}
7
Ecgonine hydrochloride
Ecgonine methylester
Ephedrine
(L)-Epinephrine
Noscapine
Oxalic acid
Oxazepam
Oxolinic acid
Tyramine
Uric acid
Verapamil
Zomepirac
# Buprenorphine
4-Acetamidophenol
Acetophenetidin
N-Acetylprocainamide
Acetylsalicylic acid
Aminopyrine
Amobarbital
Amoxicillin
Ampicillin
L-ascorbic acid
DL-Amphetamine sulfate
Apomorphine
Aspartame
Atropine
Benzilic acid
Benzoic acid
Benzoylecgonine
Benzphetamine
Bilirubin
(±)-Brompheniramine
Caffeine
Cannabidiol
Cannabinol
Chloralhydrate
Chloramphenicol
Chlorothiazide
(±) Chlorpheniramine
Chlorpromazine
Chlorquine
Cholesterol
Clonidine
Cocaethylene
Cocaine hydrochloride
Erythromycin
β-Estradiol
Estrone-3-sulfate
Ethyl-p-aminobenzoate
Fenoprofen
Furosemide
Gentisic acid
Hemoglobin
Hydralazine
Hydrochlorothiazide
Hydrocodone
Hydrocortisone
O-Hydroxyhippuric acid
p-Hydroxyamphetamine
p-Hydroxymethamphetamine
3-Hydroxytyramine
Ibuprofen
Iproniazid
(±)-Isoproterenol
Isoxsuprine
Ketamine
Ketoprofen
Labetalol
Loperamide
MDE
Meperidine
Meprobamate
Methadone
(L)Methamphetamine
Methoxyphenamine
(±)-3,4-Methylenedioxyamphetamine hydrochloride
(+)-3,4-Methylenedioxymethamp
Oxycodone
Oxymetazoline
Papaverine
Penicillin-G
Pentazocine hydrochloride
Pentobarbital
Perphenazine
Phencyclidine
Phenelzine
Phenobarbital
Phentermine
β-Phenylethylamine
Trans-2-phenylcyclopropylamine hydrochloride
L-Phenylephrine
Phenylpropanolamine
Prednisolone
Prednisone
Procaine
DL-Propanolol
D-Propoxyphene
D-Pseudoephedrine
Quinacrine
Quinidine
Quinine
Ranitidine
Salicylic acid
Secobarbital
Serotonin
Sulfamethazine
Sulindac
Tetracycline
Tetrahydrocortisone,
{7}
8
hetamine hydrochloride 3-acetate
Codeine
Morphine-3-β-D-glucuronide Tetrahydrocortisone 3-(β-D-glucuronide)
Cortisone
Morphine sulfate Tetrahydrozoline
(-) Cotinine
Nalidixic acid Thiamine
Creatinine
Naloxone Thioridazine
Deoxycorticosterone
Naltrexone DL-Tyrosine
Dextromethorphan
Naproxen Tolbutamide
Diclofenac
Niacinamide Triamterene
Diflunisal
Nifedipine Trifluoperazine
Digoxin
Norcodeine Trimethoprim
Diphenhydramine
Norethindrone Tryptamine
Doxylamine
D-Norpropoxyphene DL-Tryptophan
Ecgonine hydrochloride
Noscapine Tyramine
Ecgonine methylester
Oxalic acid Uric acid
Ephedrine
Oxazepam Verapamil
(L) - Epinephrine
Oxolinic acid Zomepirac
Cross-reactivity was tested by adding various drug metabolites and other components that are likely to be present in negative urine samples. The drug metabolites and other components were tested at different concentrations. These samples were tested using three lots of the CR3 Keyless Split Sample Cup Nortriptyline–Buprenorphine by three different operators. The obtained lowest detectable concentration was used to calculate the cross-reactivity. Results are shown below:
# Nortriptyline
| Compound | Result | % Cross-Reactivity |
| --- | --- | --- |
| Nortriptyline | Positive at 1000 ng/mL | 100% |
| Nordoxepine | Positive at 1,000 ng/mL | 100% |
| Trimipramine | Positive at 3,000 ng/mL | 33% |
| Amitriptyline | Positive at 1,500 ng/mL | 67% |
| Promazine | Positive at 1,500 ng/mL | 67% |
| Desipramine | Positive at 200 ng/mL | 500% |
| Imipramine | Positive at 400 ng/mL | 250% |
| Clomipramine | Positive at 12,500 ng/mL | 8% |
| Doxepine | Positive at 2,000 ng/mL | 50% |
| Maprotiline | Positive at 2,000 ng/mL | 50% |
| Promethazine | Positive at 25,000 ng/mL | 4% |
{8}
9
# Buprenorphine
| BUP
(Buprenorphine, Cut-off=10 ng/mL) | Result | % Cross-Reactivity |
| --- | --- | --- |
| Buprenorphine | Positive at 10 ng/mL | 100% |
| Buprenorphine -3-D-Glucuronide | Positive at 15 ng/mL | 67% |
| Norbuprenorphine | Positive at 20 ng/mL | 50% |
| Norbuprenorphine -3-D-Glucuronide | Positive at 200 ng/mL | 5% |
| Morphine | >100,000 | <0.1% |
| Oxymorphone | >100,000 | <0.1% |
| Hydromorphone | >100,000 | <0.1% |
# Effect of Specific Gravity and pH
Twelve urine samples of normal, high, and low specific gravity ranges (1.000 to 1.035) were collected and spiked with either Nortriptyline or Buprenorphine at 25% below and 25% above the corresponding cut-off levels. The samples were tested using three lots of the CR3Keyless Split Sample Cup Nortriptyline–Buprenorphine by three different operators.
The pH of an aliquot negative urine pool was adjusted to pH ranges of 4.00 to 9.00 in 1 pH unit increments and spiked with Nortriptyline or Buprenorphine at 25% below and 25% above the corresponding cut-off levels. The samples were tested using three lots of the CR3Keyless Split Sample Cup Nortriptyline–Buprenorphine by three different operators.
The device performance was found to not be affected by varying urine specific gravity and pH.
f. Assay cut-off:
Analytical performance of the device around the claimed cutoff is described in precision section (M.1.a.) above.
{9}
10
2. Comparison studies:
a. Method comparison with predicate device:
The method comparison for the CR3 Keyless Split Sample Cup Nortriptyline–Buprenorphine was performed by three operators. Eighty (40 negative and 40 positive) unaltered clinical samples were masked, randomized and tested. The obtained test results were compared to GC/MS results. The results are presented in the table below:
Nortriptyline
| Operators | Results | Negative | Low Negative by GC/MS (less than -50%) | Near Cutoff Negative by GC/MS (Between -50% and cutoff) | Near Cutoff Positive by GC/MS (Between the cutoff and +50%) | High Positive by GC/MS (greater than +50%) |
| --- | --- | --- | --- | --- | --- | --- |
| Viewer A | Positive | 0 | 0 | 3 | 9 | 28 |
| | Negative | 10 | 19 | 8 | 3 | 0 |
| Viewer B | Positive | 0 | 0 | 4 | 9 | 28 |
| | Negative | 10 | 19 | 7 | 3 | 0 |
| Viewer C | Positive | 0 | 0 | 3 | 8 | 28 |
| | Negative | 10 | 19 | 8 | 4 | 0 |
Discordant table:
| Viewer | Sample number | GC/MS result | Viewer result |
| --- | --- | --- | --- |
| Viewer A | TCAC1061 | 919 | positive |
| Viewer A | TCAC1062 | 964 | positive |
| Viewer A | TCAC1063 | 944 | positive |
| Viewer A | TCAC1064 | 1082 | negative |
| Viewer A | TCAC1065 | 1012 | negative |
| Viewer A | TCA 1218 | 1245 | negative |
| Viewer B | TCAC1034 | 754 | positive |
| Viewer B | TCAC1061 | 919 | positive |
| Viewer B | TCAC1062 | 964 | positive |
| Viewer B | TCAC1063 | 944 | positive |
| Viewer B | TCAC1064 | 1082 | negative |
| Viewer B | TCAC1065 | 1012 | negative |
| Viewer B | TCAC1093 | 1237 | negative |
{10}
Buprenorphine:
| Group Operators | Results | Negative | Low Negative by GC/MS (less than -50%) | Near Cutoff Negative by GC/MS (Between -50% and cutoff) | Near Cutoff Positive by GC/MS (Between the cutoff and +50%) | High Positive by GC/MS (greater than +50%) |
| --- | --- | --- | --- | --- | --- | --- |
| Viewer A | Positive | 0 | 0 | 3 | 13 | 23 |
| | Negative | 10 | 11 | 16 | 4 | 0 |
| Viewer B | Positive | 0 | 0 | 4 | 13 | 23 |
| | Negative | 10 | 11 | 15 | 4 | 0 |
| Viewer C | Positive | 0 | 0 | 5 | 14 | 23 |
| | Negative | 10 | 11 | 14 | 3 | 0 |
Discordant table:
| Viewer | Sample number | GC/MS result | viewer results |
| --- | --- | --- | --- |
| Viewer A | BUPC1063 | 9 | positive |
| Viewer A | BUPC1064 | 9 | positive |
| Viewer A | BUP1217 | 9 | positive |
| Viewer A | BUPC1061 | 11 | negative |
| Viewer A | BUPC1062 | 10 | negative |
| Viewer A | BUPC1093 | 12 | negative |
| Viewer A | BUP1224 | 11 | negative |
| Viewer B | BUPC1063 | 9 | positive |
| Viewer B | BUPC1064 | 9 | positive |
| Viewer B | BUP1216 | 8 | positive |
| Viewer B | BUP1217 | 9 | positive |
| Viewer B | BUPC1061 | 11 | negative |
| Viewer B | BUPC1062 | 10 | negative |
{11}
| Viewer B | BUPC1091 | 12 | negative |
| --- | --- | --- | --- |
| Viewer B | BUP1224 | 11 | negative |
| Viewer C | BUPC1033 | 8 | positive |
| Viewer C | BUPC1065 | 9 | positive |
| Viewer C | BUP1213 | 9 | positive |
| Viewer C | BUP1216 | 8 | positive |
| Viewer C | BUP1217 | 9 | positive |
| Viewer C | BUPC1061 | 11 | negative |
| Viewer C | BUPC1091 | 12 | negative |
| Viewer C | BUP1224 | 11 | negative |
b. Matrix comparison:
Not applicable.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Lay-user study
A lay user study was performed at three sites with 260 participants (20 tested drug-free samples, 120 tested nortriptyline samples, and 120 tested buprenorphine 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; -100%, +/-75%, +/-50%, +/-25% of the cut-off by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:
{12}
| Drug | Concentration | # of Samples | Negative | Positive | % Agreement With GC/MS |
| --- | --- | --- | --- | --- | --- |
| Drug -free | -100% | 20 | 20 | 0 | 100% |
| Nortriptyline | -75% | 20 | 20 | 0 | 100% |
| | -50% | 20 | 20 | 0 | 100% |
| | -25% | 20 | 17 | 3 | 85% |
| | +25% | 20 | 3 | 17 | 85% |
| | +50% | 20 | 0 | 20 | 100% |
| | +75% | 20 | 0 | 20 | 100% |
| Buprenorphine | -75% | 20 | 20 | 0 | 100% |
| | -50% | 20 | 20 | 0 | 100% |
| | -25% | 20 | 18 | 2 | 90% |
| | +25% | 20 | 3 | 17 | 85% |
| | +50% | 20 | 0 | 20 | 100% |
| | +75% | 20 | 0 | 20 | 100% |
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 the package insert and the score revealed a reading grade level of less than 7.
## Temperature Strip
The temperature test strip that is a part of the test cup was evaluated for accuracy. The temperature test strip provides a reading in the temperature range of 32 to 38°C. To test for accuracy, water samples were adjusted to different temperatures (32, 33, 34, 36, 37 and 38 °C) and added to device test cups. Technicians read the temperature on the strip on the cup and recorded the results. The temperature of the water samples were also measured with a separate thermometer. Results obtained from the temperature strip were consistent with the thermometer readings.
To validate the performance of the temperature test strip in the hands of the intended user, a user study was conducted. In this user study, 100 lay users filled the device test cups with urine according to the device labeling and used the temperature test strip to record the temperature of their samples. Results were compared to readings of the same samples by professionals. The study demonstrated that the lay users could accurately read the test strip. Urine samples in the study were within the temperature range of the test strip.
## 4. Clinical cut-off:
Not applicable.
{13}
5. Expected values/Reference range:
Not applicable.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
14
