Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on immunochromatographic assays and lateral flow systems, which are traditional chemical/biological testing methods. There is no mention of AI, ML, image processing, or any computational analysis of data that would suggest the use of these technologies.

Therapeutic

No
The device is an in vitro diagnostic (IVD) test used for qualitative detection of substances in urine, which provides preliminary results for diagnostic purposes rather than directly treating or preventing disease.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states "For in vitro diagnostic use only."

SaMD (Software as a Medical Device)

No

The device description clearly indicates it is a physical test kit (immunochromatographic assay, lateral flow system) for detecting substances in urine, not a software application.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For in vitro diagnostic use only."
Nature of the Test: The device is designed to test human urine samples in vitro (outside of the body) to detect the presence of specific substances (Morphine and Methamphetamine). This is a core characteristic of IVD devices.
Purpose: The test is used to provide preliminary diagnostic information about the presence of drugs of abuse in a sample. While it requires confirmation, its initial purpose is diagnostic.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

CR3 Keyless Split Sample Cup Morphine-Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL, respectively. The test is the first step in a two-step process. The 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 CR3 Keyless Split Sample Cup Morphine-Methamphetamine 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.

Product codes

DNK, LAF

Device Description

The CR3 Keyless Split Sample Cup Morphine-Methamphetamine test uses immunochromatographic assays for Morphine and Methamphetamine. The test is a lateral flow system for the qualitative detection of Morphine and Methamphetamine 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

"The test is intended for The test is intended for over-the-counter and for prescription use." and "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 morphine samples, 120 for methamphetamine samples."

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

"The method comparison for the CR3 Keyless Split Sample Cup Morphine - Methamphetamine 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." "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 morphine samples, 120 for methamphetamine 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 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."

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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.
- Morphine (MOP) testing:
  - At -100%, -75%, -50%, -25% cut-off: All 50 tests per lot showed negative results.
  - At cut-off: Lot 1 and Lot 3 showed 42+/8- results, Lot 2 showed 43+/7-.
  - At +25%, +50%, +75%, +100% cut-off: All 50 tests per lot showed positive results.
- Methamphetamine (MET) testing:
  - At -100%, -75%, -50%, -25% cut-off: All 50 tests per lot showed negative results.
  - At cut-off: Lot 1 showed 43+/7-, Lot 2 and Lot 3 showed 42+/8-.
  - At +25%, +50%, +75%, +100% cut-off: All 50 tests per lot showed positive results.
b. Linearity: Not applicable.
c. Stability: The CR3 Keyless Split Sample Cup Morphine-Methamphetamine is stable at 4-30℃ for 18 months as determined by conducting accelerated and real-time stability testing.
d. Cut-off: Cut-off studies were conducted using a total of 125 morphine samples and 125 methamphetamine 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 morphine and methamphetamine.
- Morphine (MOP) Cut-off: 300 ng/mL
- Methamphetamine (MET) Cut-off: 1000 ng/mL
e. Interference: Potential interfering substances found in human urine of physiological conditions were added to urine containing target drugs (morphine or methamphetamine) at 25% below and 25% above the cut-off. These urine samples were tested using three batches of the CR3 Keyless Split Sample Cup Morphine-Methamphetamine by three different operators. Numerous compounds showed no interference at a concentration of 100ug/mL.
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 (Morphine or Methamphetamine), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Keyless Split Sample Cup Morphine-Methamphetamine by three different operators.
- MOP (Morphine, Cut-off=300 ng/mL): Morphine, Normorphine, 6-Monoacetylmorphine, Codeine, Ethyl Morphine, Heroine showed 100% cross-reactivity. Hydrocodone and Hydromorphone showed 6% cross-reactivity. Morphinie-3-β-d-glucuronide showed 30% cross-reactivity. Thebaine showed 1% cross-reactivity. Oxycodone and Oxymorphone were not detected.
- MET (D-Methamphetamine, Cut-off=1000 ng/mL): D-Methamphetamine, (+/-)3,4-Methylenedioxy-n-ethylamphetamine (MDEA), D/L-Methamphetamine, p-Hydroxymethamphetamine, (+/-)3,4-Methylenedioxyamphetamine (MDA) showed 100% cross-reactivity. (+/-)3,4-methylenedioxymethamphetamine (MDMA) showed 50% cross-reactivity. D-Amphetamine, Chloroquine, (+/-)-Ephedrine, β-Phenylethylamine showed 2% cross-reactivity. L-Amphetamine showed 1.3% cross-reactivity. L-Methamphetamine showed 4% cross-reactivity. Trimethobenzamide showed 10% cross-reactivity.
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 Morphine or Methamphetamine at 25% below and 25% above the corresponding cut-off level. 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 Morphine or Methamphetamine at 25% below and 25% above the corresponding cut-off levels. These samples were tested using three batches of the CR3 Keyless Split Sample Cup Morphine - Methamphetamine by three different operators. The device performance was found to not be affected by varying specific gravity and pH.

2. Comparison Studies

Method Comparison: Performed in-house with three laboratory assistants. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. Samples were masked and randomized. Results were compared to GC/MS results.
- Morphine: For Viewer A, B, and C, all 10 Negative (GC/MS: +50%), all 20 samples were correctly identified as positive by all viewers. Discordant results near cutoff were provided.
- Methamphetamine: For Viewer A, B, and C, all 10 Negative (GC/MS: +50%), Viewer A had 17 positives and 0 negatives, Viewer B and C had 19 positives and 0 negatives. Discordant results near cutoff were provided.
Lay-user study: Performed at three intended user sites with 260 lay persons. 20 tested for drug-free, 120 for morphine, 120 for methamphetamine. Samples were prepared at various concentrations (-100%, +/-75%, +/-50%, +/-25% of the cut-off) and confirmed by GC/MS. Each participant received a package insert, a blind-labeled sample, and a device.
- Drug-free: 100% agreement (20/20 negative).
- Morphine:
  - -75%, -50%: 100% agreement (20/20 negative).
  - -25%: 85% agreement (17 negative, 3 positive).
  - +25%: 85% agreement (3 negative, 17 positive).
  - +50%, +75%: 100% agreement (20/20 positive).
- Methamphetamine:
  - -75%, -50%: 100% agreement (20/20 negative).
  - -25%: 85% agreement (17 negative, 3 positive).
  - +25%: 85% agreement (3 negative, 17 positive).
  - +50%, +75%: 100% agreement (20/20 positive).
- Lay-users indicated instructions were easy to follow (Flesch-Kincaid reading grade level of

Regulation Number and Section

§ 862.3640 Morphine test system.

(a)
Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of morphine use or overdose and in monitoring levels of morphine and its analogs to ensure appropriate therapy.(b)
Classification. Class II (special controls). A morphine 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).

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other to create a unified shape.

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

September 18, 2015

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

Re: K150602

Trade/Device Name: CR3 Keyless Split Sample Cup Morphine - Methamphetamine Regulation Number: 21 CFR 862.3640 Regulation Name: Morphine test system Regulatory Class: II Product Code: DNK, LAF Dated: March 3, 2015 Received: March 10, 2015

Dear Mr. Joe Shia:

This letter corrects our substantially equivalent letter of April 7, 2015.

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

1

Page 2 - Mr. Joe Shia

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 of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 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/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 vours.

Courtney H. Lias -S

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

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name

CR3 Keyless Split Sample Cup Morphine - Methamphetamine

Indications for Use (Describe)

CR3 Keyless Split Sample Cup Morphine-Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL, respectively. The test is the first step in a two-step process. The 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 CR3 Keyless Split Sample Cup Morphine-Methamphetamine 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.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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510(k) SUMMARY

1. Date:	March 31, 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 Shia
LSI International Inc.
504 East Diamond Ave., Suite F
Gaithersburg, MD 20878
Telephone: 240-505-7880
Fax: 301-916-6213
Email:shiajl@yahoo.com

CR3 Keyless Split Sample Cup Morphine Methamphetamine 4. Device Name:

Classification:	Class II
Product Code	CFR #	Panel
DNK	21 CFR, 862.3640 Morphine Test System	Toxicology
LAF	21 CFR, 862.3610 Methamphetamine Test System	Toxicology

1. Predicate Devices: K142580
  Chemtrue Multi-Panel DOA DipCard Tests
1. Intended Use:
  CR3 Keyless Split Sample Cup Morphine-Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 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 CR3 Keyless Split Sample Cup Morphine-Methamphetamine 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.

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7. Device Description:

The CR3 Keyless Split Sample Cup Morphine-Methamphetamine test uses immunochromatographic assays for Morphine and Methamphetamine. The test is a lateral flow system for the qualitative detection of Morphine and Methamphetamine 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 - K142580
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	Morphine: 300ng/ml
Methamphetamine: 1000ng/ml	Same for Morphine and
Methamphetamine
Configurations	Cup	Dipcard
Conditions for
Use	Over-the-Counter & Prescription
Use	Same

1. Substantial Equivalence Information

9. Test Principle

The CR3 Keyless Split Sample Cup Morphine-Methamphetamine test is a rapid test for the qualitative detection of Morphine and Methamphetamine in urine samples and contains lateral flow chromatographic immunoassays for Morphine and Methamphetamine. 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 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.

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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
MOP | -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 |
|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

A. For Morphine (MOP) testing

B. For Methamphetamine (MET) testing

| Result
MET | -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 |
|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

b. Linearity
Not applicable.
c. Stability
The CR3 Keyless Split Sample Cup Morphine-Methamphetamine is stable at 4-30℃ for 18 months as determined by conducting accelerated and real-time stability testing.

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

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d. Cut-off

Cut-off studies were conducted using a total of 125 morphine samples and 125 methamphetamine 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 morphine and methamphetamine. The following cut-off values for the test devices have been verified.

| Test | Calibrator | Cut-off
(ng/ml) |
|-----------------------|-------------------|--------------------|
| Morphine (MOP) | Morphine | 300 |
| Methamphetamine (MET) | D-Methamphetamine | 1000 |

e. Interference

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

Morphine

4-Acetamidophenol	Ecgonine methylester	Oxolinic acid
Acetaminophen	(-)-Y-Ephedrine	Oxycodone
Acetophenetidin	Erythromycin	Oxymetazoline
N-Acetylprocainamide	Fenoprofen	Penicillin-G
Acetylsalicylate	Furosemide	Pentobarbital
Aminopyrine	Gentisic acid	Perphenazine
Amityptyline	Hemoglobin	Phencyclidine
Amorbarbital	Hydralazine	Phenelzine
Amoxicillin	Hydrochlorothiazide	Phenobarbital
Ampicillin	Hydrocortisone	L-Phenylephrine
1-Ascorbic Acid	O-Hydroxyhippuric acid	b-Phenylethylamine
Apormorphine	p-Hydroxy-methamphetamine	Phenylpropanotamine
Aspartame	3-Hydroxytyramine	Prednisone
Atropine	Ibuprofen	Prednisolone
Benzilic acid	Imipramine	Procaine
Benzoic acid	(±)Isoproterenol	D.L-Propanolol
Benzoylecgonine	Isoxsuprine	D-Propoxyphene
Bilirubin	Ketamine	D-Pseudoephedrine
Caffeine	Ketoprofen	Quinine

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Cannabidiol Chloralhvdrate Chloramphenicol Chlordiazepoxide Chlorothiazide Chlorpromazine Chlorquine Cholesterol Clomipramine Clonidine

Cocaine hydrochloride (-)cotinine Creatinine Dextromethlorphan Deoxycorticosterone Diazepam DicloIrfenac Diflunisal Diaoxin Diphenhydramine Doxylamine Ecgonine hydrochloride ß-Estradiol Estrone-3-sulfate

Methamphetamine

4-Acetamidophenol Acetaminophen Acetophenetidin N-Acetvprocainamide Acetylsalicylate Aminopyrine Amityptyline Amorbarbital Amoxicillin Ampicillin l-Ascorbic Acid Apormorphine Aspartame

Labetalol Loperamide Loxapine succinate Maprotiline Meperidine Meprobamate Methadone Methoxyphenamine (+)3,4-Methylenedioxy-amphetamine (+)3,4-Methylenedioxy-methamphetamine

Nalidixic acid Nalorphine Naloxone Naltrexone Naproxen Niacinamide Nifedipine Norethindrone D-Norpropoxyphene Noscapine D.L-Octopamine Oxalic acid

Oxazepam Papaverine

Estrone-3-sulfate Erythromycin Fenoprofen Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone O-Hydroxyhippuric acid 3-Hydroxytyramine Ibuprofen

Ranitidine Salicylic acid Secobarbital Serotonin (5-Hydroxytyramine) Sulfamethazine Sulindac Temazepam Tetracycline Tetrahydrocortisone,3 Acetate Tetrahydrocortisone 3 (ß-D glucuronide) Tetrahydrozoline Thiamine Thioridazine D.L-Tyrosine Tolbutamide Triamterene Trifluoperazine Trimethoprim Triyptamine D.L-Tryptophan Tyramine Uric acid

Verapamil Zomepirac

Oxycodone Papaverine Penicillin-G Pentobarbital Perphenazine Phencyclidine Phenelzine Phenobarbital L-Phenylephrine Phenylpropanotamine Prednisone Prednisolone Procaine

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Atropine Imipramine D.L-Propanolol Benzilic acid (±)Isoproterenol Benzoic acid Isoxsuprine Benzoylecgonine Quinine Ketamine Bilirubin Ketoprofen Caffeine Labetalol Cannabidiol Loperamide Chloralhvdrate Loxapine succinate Chloramphenicol Maprotiline Chlordiazepoxide Meperidine Chlorothiazide Meprobamate Chlorpromazine Methadone Cholesterol Methoxyphenamine Clomipramine Morphine-3-B-Dglucuronide Clonidine Nalidixic acid Cocaine hydrochloride Nalorphine Codeine Naloxone (-)cotinine Naltrexone Creatinine Naproxen Niacinamide Dextromethlorphan Deoxycorticosterone Nifedipine Diazepam Norethindrone DicloIrfenac D-Norpropoxyphene Diflunisal Noscapine Diaoxin D.L-Octopamine Diphenhydramine Oxalic acid Doxylamine Oxazepam Ecgonine Verapamil Oxolinic acid hydrochloride ß-Estradiol Oxymetazoline Ecgonine methylester

D-Propoxyphene D-Pseudoephedrine Ranitidine Salicylic acid Secobarbital Serotonin (5-Hydroxytyramine) Sulfamethazine Sulindac Temazepam Tetracycline Tetrahydrocortisone,3 Acetate Tetrahydrocortisone 3 (ß-D glucuronide) Tetrahydrozoline Thebaine Thiamine Thioridazine D.L-Tyrosine Tolbutamide Triamterene Trifluoperazine Trimethoprim Triyptamine D.L-Tryptophan Tyramine Uric acid
Zomepirac
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 (Morphine or Methamphetamine), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Keyless Split Sample Cup Morphine-Methamphetamine 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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| MOP
(Morphine,
Cut-off=300 ng/mL) | Result | %
Cross-Reactivity |
|-----------------------------------------|---------------------------|-----------------------|
| Morphine | Positive at 300 ng/mL | 100% |
| Normorphine | Positive at 300 ng/mL | 100% |
| 6-Monoacetylmorphine | Positive at 300 ng/mL | 100% |
| Codeine | Positive at 300 ng/mL | 100% |
| Ethyl Morphine | Positive at 300 ng/mL | 100% |
| Heroine | Positive at 300 ng/mL | 100% |
| Hydrocodone | Positive at 5,000 ng/mL | 6% |
| Hydromorphone | Positive at 5,000 ng/mL | 6% |
| Morphinie-3-β-d-glucuronide | Positive at 1,000 ng/mL | 30% |
| Thebaine | Positive at 30,000 ng/mL | 1% |
| Oxycodone | Negative at 100,000 ng/mL | Not detected |
| Oxymorphone | Negative at 100,000 ng/mL | Not detected |

| MET
(D-Methamphetamine,
Cut-off=1000 ng/mL) | Result | %
Cross-Reactivity |
|------------------------------------------------------|--------------------------|-----------------------|
| D-Methamphetamine | Positive at 1,000 ng/mL | 100% |
| (+/-)3,4-Methylenedioxy-n-et
hylamphetamine(MDEA) | Positive at 1,000 ng/mL | 100% |
| D/L-Methamphetamine | Positive at 1,000 ng/mL | 100% |
| p-Hydroxymethamphetamine | Positive at 1,000 ng/mL | 100% |
| D-Amphetamine | Positive at 50,000 ng/mL | 2% |
| L-Amphetamine | Positive at 75,000 ng/mL | 1.3% |
| Chloroquine | Positive at 50,000 ng/mL | 2% |
| (+/-)-Ephedrine | Positive at 50,000 ng/mL | 2% |
| L-Methamphetamine | Positive at 25,000 ng/mL | 4% |
| (+/-)3,4-Methylenedioxyamph
etamine (MDA) | Positive at 1,000 ng/mL | 100% |
| (+/-)3,4-methylenedioxymeth
amphetamine(MDMA) | Positive at 2,000 ng/mL | 50% |
| β-Phenylethylamine | Positive at 50,000 ng/mL | 2% |
| Trimethobenzamide | Positive at 10,000 ng/mL | 10% |

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 Morphine or Methamphetamine at 25% below and 25% above

10

the corresponding cut-off level. These samples were tested using three batches of the CR3 Keyless Split Sample Cup Morphine-Methamphetamine 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 Morphine or Methamphetamine at 25% below and 25% above the corresponding cut-off levels. These samples were tested using three batches of the CR3 Keyless Split Sample Cup Morphine - Methamphetamine by three different operators.

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

1. Comparison Studies
  The method comparison for the CR3 Keyless Split Sample Cup Morphine - Methamphetamine 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:

| Group
Operators | | 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 | 17 | 20 |
| | Negative | 10 | 18 | 9 | 3 | 0 |
| Viewer B | Positive | 0 | 0 | 4 | 16 | 20 |
| | Negative | 10 | 18 | 8 | 4 | 0 |
| Viewer C | Positive | 0 | 0 | 3 | 16 | 20 |
| | Negative | 10 | 18 | 9 | 4 | 0 |

Morphine

Discordant table:

Viewer	Sample number	GC/MS result	Viewer result
Viewer A	MOPC3061	291	positive
Viewer A	MOP3211	289	positive
Viewer A	MOP3224	294	positive
Viewer A	MOP3216	304	negative
Viewer A	MOP3221	311	negative
Viewer A	MOP3228	301	negative
Viewer B	MOPC3061	291	positive
Viewer B	MOP3211	289	positive

11

Viewer B	MOP3214	267	positive
Viewer B	MOP3224	294	positive
Viewer B	MOP3216	304	negative
Viewer B	MOP3221	311	negative
Viewer B	MOP3223	319	negative
Viewer B	MOP3228	301	negative
Viewer C	MOPC3061	291	positive
Viewer C	MOP3211	289	positive
Viewer C	MOP3224	294	positive
Viewer C	MOP3216	304	negative
Viewer C	MOP3221	311	negative
Viewer C	MOP3223	319	negative
Viewer C	MOP3228	301	negative

Methamphetamine

| Group
Operators | | 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%) |
|--------------------|----------|----------|----------------------------------------------------|------------------------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------|
| | | Positive | 0 | 0 | 3 | 17 |
| Viewer A | Negative | 10 | 10 | 17 | 4 | 0 |
| | Positive | 0 | 0 | 3 | 18 | 19 |
| Viewer B | Negative | 10 | 10 | 17 | 3 | 0 |
| | Positive | 0 | 0 | 3 | 18 | 19 |
| Viewer C | Negative | 10 | 10 | 17 | 3 | 0 |

Discordant table:

Viewer	Sample number	GC/MS result	viewer results
Viewer A	METC1062	962	positive
Viewer A	MET1208	તે જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધ	positive
Viewer A	MET1217	978	positive
Viewer A	MET1219	1009	negative
Viewer A	MET1224	1024	negative
Viewer A	MET1226	1012	negative
Viewer A	METC1124	1003	negative
Viewer B	METC1062	962	positive
Viewer B	MET1208	તે જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે ખેત-ઉપયોગ વસવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છ	positive
Viewer B	MET1217	978	positive
Viewer B	MET1219	1009	negative

12

Viewer B	MET1226	1024	negative
Viewer B	METC1124	1003	negative
Viewer C	METC1062	962	positive
Viewer C	MET1208	985	positive
Viewer C	MET1217	978	positive
Viewer C	MET1219	1009	negative
Viewer C	MET1226	1024	negative
Viewer C	METC1124	1003	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 morphine samples, 120 for methamphetamine 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 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%
Morphine	-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%
Methamphetamine	-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

13

Not applicable.

11. Conclusion

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