CR3 Keyless Split Sample Cup Oxycodone - Cannabinoids

K150179 · Guangzhou Wondfo Biotech Co., Ltd. · DJG · Feb 25, 2015 · Clinical Toxicology

Device Facts

• Record ID: K150179
• Device Name: CR3 Keyless Split Sample Cup Oxycodone - Cannabinoids
• Applicant: Guangzhou Wondfo Biotech Co., Ltd.
• Product Code: DJG · Clinical Toxicology
• Decision Date: Feb 25, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Intended Use

CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids is a rapid test for the qualitative detection of Oxycodone and Cannabinoids in human urine at a cutoff concentration of 100 ng/mL and 50 ng/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 the prescription drug Oxycodone is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Oxycodone in urine. The CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids 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

Lateral flow immunochromatographic assay for qualitative detection of Oxycodone and Cannabinoids in human urine; cup-based format. Principle: competitive binding; mouse monoclonal anti-drug antibody-dye conjugate binds to immobilized drug-protein conjugate on membrane. 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. Used in clinical or home settings; operated by lay users or clinicians. Provides preliminary screening; positive results require laboratory confirmation via GC/MS. Assists in identifying potential drug presence to guide clinical decision-making or further diagnostic testing.

Clinical Evidence

No clinical studies performed. Evidence consists of bench testing: precision studies (3 operators, 25 days), analytical cut-off verification, interference testing (100+ compounds), specificity/cross-reactivity, and method comparison against GC/MS (80 clinical samples). Lay-user study (n=260) demonstrated 85-100% agreement with GC/MS across various concentrations and confirmed readability of instructions (Flesch-Kincaid grade <7).

Technological Characteristics

Lateral flow immunochromatographic assay. Components: mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, anti-mouse IgG polyclonal antibodies on membrane. Form factor: cup. No energy source required. Stability: 18 months at 4-30°C.

Indications for Use

Indicated for qualitative detection of Oxycodone (100 ng/mL) and Cannabinoids (50 ng/mL) in human urine. Intended for OTC and prescription use as a preliminary screening tool. Not intended to distinguish between prescription use and abuse. Requires confirmatory testing (GC/MS) for positive results.

Regulatory Classification

Identification

An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.

Special Controls

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

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of a caduceus, a symbol often associated with healthcare, featuring a staff with a serpent entwined around it.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 26, 2015

GUANGZHOU WONDFO BIOTECH CO., LTD. C/O JOE SHIA BUSINESS DIRECTOR 504 EAST DIAMOND AVE. SUITE F GAITHERSBURG MD 20878

Re: K150179

Trade/Device Name: CR3 Keyless Split Sample Cup Oxycodone - Cannabinoids Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG, LDJ Dated: January 23, 2015 Received: January 27, 2015

Dear Mr. Joe Shia:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

# Stayce Beck -S

For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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#### Indications for Use

510(k) Number (if known) k150179

Device Name

CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids

#### Indications for Use (Describe)

CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids is a rapid test for the qualitative detection of Oxycodone and Cannabinoids in human urine at a cutoff concentration of 100 ng/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 the prescription drug Oxycodone is ingescribed doses, it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Oxycodone in urine. The CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids test provides only preliminary test results. A more specific alternative chemical 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.

Type of Use (Select one or both, as applicable)

> Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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### 510(k) SUMMARY

| 1. Date: | February 18, 2015 |
|--------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 2. Submitter: | Guangzhou Wondfo Biotech Co., Ltd.<br>No.8 Lizhishan Road, Science City, Luogang District, Guangzhou, P.R.<br>China 510663 |
| 3. Contact person: | Joe Shia<br>LSI International Inc.<br>504 East Diamond Ave., Suite F<br>Gaithersburg, MD 20878<br>Telephone: [phone]<br>Fax: [phone]<br>Email:[e-mail] |

- CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids 4. Device Name:

| Classification: | Class II | |
|-----------------|------------------------------------------|------------|
| Product Code | CFR # | Panel |
| DJG | 21 CFR, 862.3650 Opiate Test System | Toxicology |
| LDJ | 21 CFR, 862.3870 Cannabinoid Test System | Toxicology |

- 5. Predicate Devices: K122904 Wondfo Multi-Drug Urine Test Cup
- 6. Intended Use:

CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids is a rapid test for the qualitative detection of Oxycodone and Cannabinoids in human urine at a cutoff concentration of 100 ng/mL and 50 ng/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 the prescription drug Oxycodone is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Oxycodone in urine. The CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids 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.

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For in vitro diagnostic use only.

- 7. Device Description:
The CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids test uses immunochromatographic assays for Oxycodone and Cannabinoids. The test is a lateral flow system for the qualitative detection of oxycodone and cannabinoids in human urine. 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.

| Item | Device | Predicate - K122904 |
|-----------------------|----------------------------------------------------------------------------------------------------------------------------|-------------------------------------|
| 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 | Oxycodone: 100ng/ml<br>Cannabinoids: 50ng/ml | Same for Oxycodone and Cannabinoids |
| Configurations | Cup | Cup, Dipcard |
| Conditions for Use | Over-the-Counter & Prescription Use | Same |

- 8. Substantial Equivalence Information
- 9. Test Principle
The CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids test is a rapid test for the qualitative detection of Oxycodone and Cannabinoids in urine samples and contains lateral flow chromatographic immunoassays for oxycodone and cannabinoids. 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 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 conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in

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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.

- 10. Performance Characteristics
- 1. Analytical Performance
- a. Precision

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 and +100% cut-off. For each concentration, tests were performed two runs per day by three operators for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:

| Result<br>OXY | -100%<br>cut-off | -75%<br>cut-off | -50%<br>cut-off | -25%<br>cut-off | cut-off | +25%<br>cut-off | +50%<br>cut-off | +75%<br>cut-off | +100%<br>cut-off |
|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| W12410301CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W12410302CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W12410303CU5 | 50-/0+ | 50-/0+ | 50-10+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

A. For Oxycodone (OXY) testing

B. For Cannabinoids (THC) testing

| Result<br>THC | -100%<br>cut-off | -75%<br>cut-off | -50%<br>cut- off | -25%<br>cut-off | cut-off | +25%<br>cut-off | +50%<br>cut-off | +75%<br>cut-off | +100%<br>cut-off |
|---------------|------------------|-----------------|------------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| W12410301CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| w12410302CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| w12410303CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

- b. Linearity
Not applicable.

- c. Stability
The CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids is stable at 4-30°C for 18 months as determined by conducting accelerated and real-time stability testing.

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Control materials are not provided with the device. The labeling provides information on how to obtain control materials.

- d. Cut-off
Cut-off studies were conducted using a total of 125 oxycodone samples and 125 cannabinoids samples equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs. These samples were tested using three different lots by three different operators. Results were all positive at +25% and +50% cut-off and all negative at -25% and -50% cut-off for both oxycodone and cannabinoids. The following cut-off values for the test devices have been verified.

| Test | Calibrator | Cut-off<br>(ng/ml) |
|--------------------|----------------------|--------------------|
| Oxycodone (OXY) | Oxycodone | 100 |
| Cannabinoids (THC) | 11-nor-Δ9-THC-9-COOH | 50 |

#### e. Interference

Potential interfering substances found in human urine of physiological conditions were added to urine containing target drugs (oxycodone or cannabinoids) at 25% below and 25% above the cut-off. These urine samples were tested using three batches of the CR3Keyless Split Sample Cup Oxycodone - Cannabinoids by three different operators. Compounds that showed no interference at a concentration of 100µg/mL are summarized below:

#### Oxycodone

| 4-Acetamidophenol | Ecgonine methylester | Papaverine |
|----------------------|------------------------|---------------------|
| Acetophenetidin | L-Ephedrine | Penicillin-G |
| N-Acetylprocainamide | Erythromycin | Pentobarbital |
| Acetylsalicylic acid | ß-Estradiol | Perphenazine |
| Aminopyrine | Estrone-3-sulfate | Phenelzine |
| Amitryptyline | Ethyl-p-aminobenzoate | Phenobarbital |
| Amoxicillin | Fenoprofen | L-Phenylephrine |
| Ampicillin | Furosemide | β-Phenyllethylamine |
| Ascorbic acid | Gentisic acid | Phenylpropanolamine |
| D,L-Amphetamine | Hemoglobin | Prednisolone |
| L-Amphetamine | Hydralazine | Prednisone |
| Apomorphine | Hydrochlorothiazide | Procaine |
| Aspartame | Hydrocortisone | D,L-Propanolol |
| Atropine | O-Hydroxyhippuric acid | D-Propoxyphene |
| Benzilic acid | 3-Hydroxytyramine | D-Pseudoephedrine |
| Benzoic acid | Ibuprofen | Quinidine |

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Benzoylecgonine Benzphetamine Bilirubin Caffeine Chloralhydrate Chloramphenicol Chlorothiazide D,L-Chlolrpheniramine Chlorpromazine Chlorquine Cholesterol Clomipramine Clonidine Cocaine hydrochloride Cortisone L-Cotinine Creatinine Deoxycorticosterone Dextromethorphan Diazepam Diclofenac Diflunisal Digoxin Diphenhydramine Doxylamine Ecgonine hydrochloride

#### Cannabinoids

- 4-Acetamidophenol Acetophenetidin N-Acetylprocainamide Acetylsalicylic acid Aminopyrine Amitryptyline Amoxicillin Ampicillin Ascorbic acid D,L-Amphetamine L-Amphetamine Apomorphine
D, L-Isoproterenol Isoxsuprine Ketamine Ketoprofen Labetalol Loperamide Maprotiline Meprobamate Methadone Methoxyphenamine (+) 3,4-Methylenedioxyamphetamine (+)3,4-Methylenedioxymethamphetamine Morphine-3-β-Dglucuronide Naloxone Nalidixic acid Naltrexone Naproxen Niacinamide Nifedipine Norethindrone D-Norpropoxyphene Noscapine Oxalic acid Oxolinic acid Oxymetazoline p-Hydroxymethamphetamine

- L-Ephedrine Erythromycin ß-Estradiol Estrone-3-sulfate Ethyl-p-aminobenzoate Fenoprofen Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone
Quinine Ranitidine Salicylic acid Secobarbital Serotonin (5-Hydroxytyramine) Sulfamethazine Sulindac Tetracycline Tetrahydrocortisone, 3 Acetate Tetrahydrocortisone3 (ß-Dglucuronide) Tetrahydrozoline Thebaine Thiamine Thioridazine D, L-Thyroxine Tolbutamine Triamterene Trifluoperazine Trimethoprim D, L-Tryptophan Tyramine D, L-Tyrosine Uric acid Verapamil Zomepirac

p-Hydroxymethamphetamine Papaverine Penicillin-G Pentobarbital Perphenazine Phencyclidin Phenelzine Phenobarbital L-Phenylephrine β-Phenyllethylamine Phenylpropanolamine Prednisolone

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Aspartame Hydrocortisone Prednisone Atropine O-Hydroxyhippuric acid Procaine Benzilic acid 3-Hydroxytyramine D,L-Propanolol Ibuprofen Benzoic acid D-Propoxyphene Benzoylecgonine D, L-Isoproterenol D-Pseudoephedrine Benzphetamine Isoxsuprine Quinidine Bilirubin Ketamine Quinine Caffeine Ketoprofen Ranitidine Chloralhydrate Labetalol Salicylic acid Chloramphenicol Loperamide Secobarbital Serotonin (5-Hydroxytyramine) Chlorothiazide Maprotiline D,L-Chlolrpheniramine Meprobamate Sulfamethazine Chlorpromazine Methadone Sulindac Chlorquine Methoxyphenamine Tetracycline (+) 3,4-Methylenedioxyamphetamine Cholesterol Tetrahydrocortisone, 3 Acetate Tetrahydrocortisone3 Clomipramine (+)3,4-Methylenedioxymethamphetamine (ß-Dglucuronide) Clonidine Morphine-3-β-Dglucuronide Tetrahydrozoline Cocaine hydrochloride Naloxone Thebaine Codeine Nalidixic acid Thiamine Cortisone Thioridazine Naltrexone L-Cotinine Naproxen D, L-Thyroxine Creatinine Niacinamide Tolbutamine Deoxycorticosterone Nifedipine Triamterene Dextromethorphan Norcodeine Trifluoperazine Diazepam Norethindrone Trimethoprim Diclofenac D-Norpropoxyphene D, L-Tryptophan Diflunisal Noscapine Tyramine Digoxin Oxalic acid D, L-Tyrosine Diphenhydramine Oxazepam Uric acid Doxylamine Oxolinic acid Verapamil Ecgonine hydrochloride Oxycodone Zomepirac Ecgonine methylester Oxymetazoline

- f. Specificity
To test the specificity, drug metabolites and other components that are likely to be present in urine samples were tested. The target drug (Oxycodone or Cannabinoids), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Keyless Split Sample Cup Oxycodone-Cannabinoids by three different operators. The drug metabolites and other components were tested at different concentrations. The obtained lowest detectable concentration was used to calculate the cross-reactivity. Results are shown in the following tables.

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| OXY<br>(Oxycodone,<br>Cut-off=100 ng/mL) | Result | %<br>Cross-Reactivity |
|------------------------------------------|--------------------------|-----------------------|
| Oxycodone | Positive at 100 ng/mL | 100% |
| Dihydrocodeine | Positive at 20000 ng/mL | 0.5% |
| Hydrocodone | Positive at 10000 ng/mL | 1% |
| Oxymorphone | Positive at 1000 ng/mL | 10% |
| Codeine | Positive at 100000 ng/mL | 0.1% |
| Hydromorphone | Positive at 100000 ng/mL | 0.1% |
| Morphine | Negative at 100000 ng/mL | Not detected |
| Acetylmorphine | Negative at 100000 ng/mL | Not detected |
| Buprenorphine | Negative at 100000 ng/mL | Not detected |
| Ethylmorphine | Negative at 100000 ng/mL | Not detected |
| Thebaine | Negative at 100000 ng/mL | Not detected |

| THC<br>(11-nor-Δ9-THC-9-COOH,<br>Cut-off=50 ng/mL) | Result | %<br>Cross-Reactivity |
|----------------------------------------------------|--------------------------|-----------------------|
| 11-nor-Δ9-THC-9-COOH | Positive at 50 ng/mL | 100% |
| 11-nor-Δ8-THC-9-COOH | Positive at 30 ng/mL | 167% |
| 11-hydroxy-Δ9-Tetra<br>hydrocannabinol | Positive at 2500 ng/mL | 2% |
| (-)-11-nor-9-carboxy-Δ<br>9-THC | Positive at 50 ng/mL | 100% |
| 11-nor-Δ9-THC-carboxy<br>glucuronide | Positive at 100 ng/mL | 50% |
| Δ8- Tetrahydrocannabinol | Positive at 7500 ng/mL | 0.6% |
| Δ9- Tetrahydrocannabinol | Positive at 10000 ng/mL | 0.5% |
| Cannabinol | Positive at 100000 ng/mL | 0.05% |
| Cannabidiol | Positive at 100000 ng/mL | 0.05% |

# g. Effect of Specific Gravity and Urine pH

Twelve urine samples of normal, high, and low specific gravity ranges (1.000 to 1.035) were collected and spiked with either Oxycodone or Cannabinoids at 25% below and 25% above the corresponding cut-off level. These samples were tested using three batches of the CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids 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 Oxycodone or Cannabinoids at 25% below and 25% above the

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corresponding cut-off levels. These samples were tested using three batches of the CR3 Keyless Split Sample Cup Oxycodone -Cannabinoids by three different operators.

The device performance was found not affected by varying specific gravity and pH.

- 2. Comparison Studies
The method comparison for the CR3 Keyless Split Sample Cup Oxycodone - Cannabinoids was performed in-house with three laboratory assistants. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were masked and randomized. The obtained test results were compared to GC/MS results. The results are presented in the table below:

| Oxycodone | | | | | | |
|--------------------|----------|----------|----------------------------------------------------|------------------------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------|
| Group<br>Operators | | Negative | Low<br>Negative by<br>GC/MS<br>(less than<br>-50%) | Near Cutoff<br>Negative by<br>GC/MS<br>(Between<br>-50% and<br>cutoff) | Near Cutoff<br>Positive by<br>GC/MS<br>(Between<br>the cutoff<br>and +50%) | High<br>Positive by<br>GC/MS<br>(greater<br>than +50%) |
| Viewer A | Positive | 0 | 0 | 4 | 18 | 19 |
| | Negative | 10 | 17 | 9 | 3 | 0 |
| Viewer B | Positive | 0 | 0 | 3 | 18 | 19 |
| | Negative | 10 | 17 | 10 | 3 | 0 |
| Viewer C | Positive | 0 | 0 | 3 | 18 | 19 |
| | Negative | 10 | 17 | 10 | 3 | 0 |

Discordant table:

| Viewer | Sample number | GC/MS result | Viewer result |
|----------|---------------|--------------|---------------|
| Viewer A | OXYC1063 | 95 | positive |
| Viewer A | OXYC1064 | 98 | positive |
| Viewer A | OXY1218 | 89 | positive |
| Viewer A | OXY1224 | 94 | positive |
| Viewer A | OXYC1062 | 100 | negative |
| Viewer A | OXY1215 | 102 | negative |
| Viewer A | OXY1221 | 101 | negative |
| Viewer B | OXYC1063 | 95 | positive |
| Viewer B | OXYC1064 | 98 | positive |
| Viewer B | OXY1224 | 94 | positive |
| Viewer B | OXYC1062 | 100 | negative |
| Viewer B | OXY1215 | 102 | negative |
| Viewer B | OXY1221 | 101 | negative |

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| Viewer C | OXYC1063 | 95 | positive |
|----------|----------|-----|----------|
| Viewer C | OXYC1064 | 98 | positive |
| Viewer C | OXY1224 | 94 | positive |
| Viewer C | OXYC1062 | 100 | negative |
| Viewer C | OXY1215 | 102 | negative |
| Viewer C | OXY1221 | 101 | negative |

# Cannabinoids

| Group<br>Operators | | Negative | Low<br>Negative by<br>GC/MS<br>(less than<br>-50%) | Near Cutoff<br>Negative by<br>GC/MS<br>(Between<br>-50% and<br>cutoff) | Near Cutoff<br>Positive by<br>GC/MS<br>(Between<br>the cutoff<br>and +50%) | High<br>Positive by<br>GC/MS<br>(greater<br>than +50%) |
|--------------------|----------|----------|----------------------------------------------------|------------------------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------|
| Viewer A | Positive | 0 | 0 | 3 | 17 | 20 |
| | Negative | 10 | 10 | 17 | 3 | 0 |
| Viewer B | Positive | 0 | 0 | 3 | 16 | 20 |
| | Negative | 10 | 10 | 17 | 4 | 0 |
| Viewer C | Positive | 0 | 0 | 4 | 16 | 20 |
| | Negative | 10 | 10 | 16 | 4 | 0 |

Discordant table:

| Viewer | Sample number | GC/MS result | Viewer result |
|----------|---------------|--------------|---------------|
| Viewer A | THC1206 | 48 | positive |
| Viewer A | THC1214 | 49 | positive |
| Viewer A | THC1223 | 48 | positive |
| Viewer A | THC1220 | 52 | negative |
| Viewer A | THC1229 | 51 | negative |
| Viewer A | THC1231 | 50 | negative |
| Viewer B | THC1206 | 48 | positive |
| Viewer B | THC1214 | 49 | positive |
| Viewer B | THC1223 | 48 | positive |
| Viewer B | THC1219 | 53 | negative |
| Viewer B | THC1220 | 52 | negative |
| Viewer B | THC1229 | 51 | negative |
| Viewer B | THC1231 | 50 | negative |
| Viewer C | THCC1065 | 49 | positive |
| Viewer C | THC1206 | 48 | positive |
| Viewer C | THC1214 | 49 | positive |
| Viewer C | THC1223 | 48 | positive |
| Viewer C | THC1219 | 53 | negative |

{12}------------------------------------------------

| Viewer C | THC1220 | 52 | negative |
|----------|---------|----|----------|
| Viewer C | THC1229 | 51 | negative |
| Viewer C | THC1231 | 50 | negative |

Lay-user study

A lay user study was performed at three intended user sites with 260 lay persons, of which, 20 tested for drug-free samples, 120 for oxycodone samples, 120 for cannabinoids 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%, +/-25% of the cut-off 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, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:

| Cup format | | | OTC user | | % Agreement |
|--------------|---------------|-------------------|----------|----------|-------------|
| Drug | Concentration | Number of samples | Negative | Positive | With GC/MS |
| Drug -free | -100% | 20 | 20 | 0 | 100% |
| Oxycodone | -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% |
| Cannabinoids | -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% |

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.

- 3. Clinical Studies
Not applicable.

## 11. Conclusion

{13}------------------------------------------------

Based on the test principle and performance characteristics of the device, it's concluded that CR3 Keyless Split Sample Cup Oxycodone –Cannabinoids is substantially equivalent to the predicate.