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 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.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the CR3 Keyless Split Sample Cup Oxycodone-Cannabinoids device:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for overall device performance in a pass/fail manner. Instead, it presents various performance characteristics intended to demonstrate substantial equivalence to a predicate device. I will infer performance goals from the reported data.

Performance Characteristic	Acceptance Criteria (Inferred from data/standards)	Reported Device Performance (Oxycodone)	Reported Device Performance (Cannabinoids)
Precision	Consistent results across concentrations and operators	At cut-off: 42-43 positives/7-8 negatives (out of 50 total detections per lot)	At cut-off: 42-43 positives/7-8 negatives (out of 50 total detections per lot)
	100% agreement for concentrations +/-100% of cut-off outside the gray zone	100% agreement (50-/0+ for -100% to -25% cut-off; 50+/0- for +25% to +100% cut-off)	100% agreement (50-/0+ for -100% to -25% cut-off; 50+/0- for +25% to +100% cut-off)
Cut-off Verification	All samples at +25% and +50% cut-off are positive. All samples at -25% and -50% cut-off are negative.	All positive at +25% and +50% cut-off. All negative at -25% and -50% cut-off.	All positive at +25% and +50% cut-off. All negative at -25% and -50% cut-off.
Interference	No interference from common physiological substances.	No interference reported for a list of 60+ substances at 100µg/mL.	No interference reported for a list of 60+ substances at 100µg/mL.
Specificity	Demonstrate cross-reactivity for related compounds, if any.	Oxycodone: 100%, Dihydrocodeine: 0.5%, Hydrocodone: 1%, Oxymorphone: 10%, Codeine: 0.1%, Hydromorphone: 0.1%. No detection for Morphine, Acetylmorphine, Buprenorphine, Ethylmorphine, Thebaine.	11-nor-Δ9-THC-9-COOH: 100%, 11-nor-Δ8-THC-9-COOH: 167%, 11-hydroxy-Δ9-Tetrahydrocannabinol: 2%, (-)-11-nor-9-carboxy-Δ9-THC: 100%, 11-nor-Δ9-THC-carboxyglucuronide: 50%, Δ8- Tetrahydrocannabinol: 0.6%, Δ9- Tetrahydrocannabinol: 0.5%, Cannabinol: 0.05%, Cannabidiol: 0.05%.
Effects of Specific Gravity & pH	Device performance not affected by varying specific gravity (1.000-1.035) and pH (4.00-9.00).	Performance found not affected.	Performance found not affected.
Method Comparison (Professional User)	High agreement with GC/MS, especially outside the "near cutoff" range. Acceptable discordance near cut-off.	For Oxycodone (cutoff 100 ng/mL): Good agreement (many 0 negatives for positive, many 0 positives for negative). Discordant samples typically within +/-5% of cutoff.	For Cannabinoids (cutoff 50 ng/mL): Good agreement (many 0 negatives for positive, many 0 positives for negative). Discordant samples typically within +/-5% of cutoff.
Lay-User Study Agreement with GC/MS	High agreement rate, particularly for drug-free and concentrations significantly above/below cut-off.	Oxycodone: 100% for drug-free, -75%, -50%, +50%, +75%. 85% for -25% and +25%.	Cannabinoids: 100% for -75%, -50%, +50%, +75%. 85% for -25% and +25%.
Lay-User Study Ease of Use	Instructions can be easily followed. Flesch-Kincaid reading grade level < 7.	All lay users indicated instructions were easy to follow. Reading grade level < 7.	All lay users indicated instructions were easy to follow. Reading grade level < 7.

2. Sample Sizes and Data Provenance

Precision Study Test Set: For each concentration of Oxycodone and Cannabinoids (-100%, -75%, -50%, -25%, cut-off, +25%, +50%, +75%, +100% cut-off), tests were performed for 25 days, with 2 runs per day, by 3 operators. This means for each concentration level, there were 25 days * 2 runs/day * 1 detection/run = 50 detections per lot. With 3 lots tested, the total number of detections at each concentration level could be inferred as 50 * 3 = 150. The data provenance is not explicitly stated beyond "performed in-house".
Cut-off Study Test Set: 125 Oxycodone samples and 125 Cannabinoids samples. The samples were distributed equally at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs. The data provenance is not explicitly stated beyond "conducted".
Interference Study Test Set: Not explicitly stated as a number of samples, but samples were prepared with target drugs at 25% below and 25% above the cut-off (for both drug types) and tested with three batches by three operators. For the list of non-interfering substances, the concentration was 100µg/mL.
Specificity Study Test Set: Samples prepared with target drugs, drug metabolites, and related compounds at various concentrations. Tested using three batches by three operators.
Specific Gravity and pH Study Test Set: 12 urine samples covering normal, high, and low specific gravity ranges (1.000 to 1.035). Aliquots of negative urine were adjusted to pH ranges of 4.00 to 9.00. These were spiked with drugs at 25% below and 25% above the cut-off. Samples were tested using three batches by three operators.
Method Comparison Test Set (Professional User): 80 unaltered clinical samples (40 negative and 40 positive) for each drug (Oxycodone and Cannabinoids), totaling 160 samples. The data provenance is "clinical samples" and "performed in-house". This implies they were real-world urine samples.
Lay-User Study Test Set: 260 lay persons tested samples.
- 20 drug-free samples
- 120 oxycodone samples (20 samples for each concentration: -75%, -50%, -25%, +25%, +50%, +75% of cut-off)
- 120 cannabinoids samples (20 samples for each concentration: -75%, -50%, -25%, +25%, +50%, +75% of cut-off)
  The samples were "blind-labeled and randomized." The data provenance involved "three intended user sites".

3. Number of Experts and Qualifications for Ground Truth for Test Set

Method Comparison Study: The ground truth for the 80 clinical samples was established by GC/MS (Gas Chromatography/Mass Spectrometry), which is considered the "preferred confirmatory method" and a gold standard for drug quantification in urine. No human experts were used to establish the ground truth for this test set as it was an objective analytical method.
Lay-User Study: The ground truth for the lay-user study samples was established by GC/MS as well, which confirmed the concentrations of the prepared urine samples.

4. Adjudication Method for the Test Set

Method Comparison Study: No adjudication method is described for the "Viewer" results (which appear to be the device results interpreted by the laboratory assistants). The individual results of Viewer A, B, and C are presented. The comparison is made against the GC/MS ground truth.
Lay-User Study: Similarly, no adjudication method is described. Each participant (lay user) provided their own result, which was then compared to the GC/MS-confirmed concentration of the sample they received.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done to assess how human readers improve with AI vs. without AI assistance.
The device is an in vitro diagnostic (IVD) device, specifically a rapid test cup for qualitative detection of drugs in urine. It does not involve AI assistance for human readers/interpretation. The "Viewers" in the method comparison study were likely laboratory assistants reading the visual result of the test strip, not clinical "readers" of complex images or data that AI might typically assist.

6. Standalone Performance Study (Algorithm Only)

Yes, a standalone performance study was done in the sense that the device itself (the test cup) provides a qualitative result based on immunochromatographic assays, independent of human interpretation for its operational mechanism. The "Performance Characteristics" section (Precision, Cut-off, Interference, Specificity, Effect of Specific Gravity and pH) describes the analytical performance of the device itself.
The "Method Comparison" and "Lay-user study" then evaluate how well the device's output (the visual line) correlates with the GC/MS ground truth, showing the device's standalone accuracy when read by both professional and lay users.

7. Type of Ground Truth Used

GC/MS (Gas Chromatography/Mass Spectrometry) was used as the ground truth for determining drug concentrations for the method comparison study and the lay-user study. This is an objective, analytical gold standard method.
For the precision, cut-off, interference, and specificity studies, the ground truth was established by known spiked concentrations of the analytes (Oxycodone, Cannabinoids) or interfering substances.

8. Sample Size for the Training Set

The document implies that prior predicate devices (K122904) might have contributed to the knowledge base, but it does not describe a specific "training set" in the context of an algorithm or AI model development. This is a traditional IVD immunoassay device, which does not typically undergo a "training" phase like machine learning models. Its performance is inherent to its biochemical design.

9. How the Ground Truth for the Training Set Was Established

Since there's no traditional "training set" for an algorithm, this question is not directly applicable. The performance characteristics are based on laboratory experiments using samples with known, spiked concentrations of analytes.

Summary

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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 (800) 638 2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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.No.8 Lizhishan Road, Science City, Luogang District, Guangzhou, P.R.China 510663
3. Contact person:	Joe ShiaLSI International Inc.504 East Diamond Ave., Suite FGaithersburg, MD 20878Telephone: 240-505-7880Fax: 301-916-6213Email:shiajl@yahoo.com

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

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

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For in vitro diagnostic use only.

1. 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/mlCannabinoids: 50ng/ml	Same for Oxycodone and Cannabinoids
Configurations	Cup	Cup, Dipcard
Conditions for Use	Over-the-Counter & Prescription Use	Same

1. Substantial Equivalence Information
1. 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.

1. 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:

ResultOXY	-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
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

ResultTHC	-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
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(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(Oxycodone,Cut-off=100 ng/mL)	Result	%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(11-nor-Δ9-THC-9-COOH,Cut-off=50 ng/mL)	Result	%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-Tetrahydrocannabinol	Positive at 2500 ng/mL	2%
(-)-11-nor-9-carboxy-Δ9-THC	Positive at 50 ng/mL	100%
11-nor-Δ9-THC-carboxyglucuronide	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.

1. 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
GroupOperators		Negative	LowNegative byGC/MS(less than-50%)	Near CutoffNegative byGC/MS(Between-50% andcutoff)	Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%)	HighPositive byGC/MS(greaterthan +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

GroupOperators		Negative	LowNegative byGC/MS(less than-50%)	Near CutoffNegative byGC/MS(Between-50% andcutoff)	Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%)	HighPositive byGC/MS(greaterthan +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

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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.

1. Clinical Studies
  Not applicable.

11. Conclusion

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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.

Regulation Number and Section

§ 862.3650 Opiate test system.

(a)
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.(b)
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).