CR3 KEYLESS SPLIT SAMPLE CUP PHENCYCLIDIEN - METHYLENEDIOXYMETHAMPHETAMINE

• K Number: K142044
• Device Name: CR3 KEYLESS SPLIT SAMPLE CUP PHENCYCLIDIEN - METHYLENEDIOXYMETHAMPHETAMINE
• Manufacturer: Guangzhou Wondfo Biotech Co., Ltd.
• Date Cleared: 2014-08-25 ( 28 days)
• Product Code: LCM LAF
• Regulation Number: N/A

Intended Use

CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine is a rapid test for the qualitative detection of Phencyclidine and Methylenedioxymethamphetamine in human urine at a cutoff concentration of 25ng/mL and 500ng/mL. respectively. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.

Device Description

The CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine test uses immunochromatographic assays for phencyclidine and methylenedioxymethamphetamine. The test is a lateral flow, one step system for the qualitative detection of phencyclidine and methylenedioxymethamphetamine in human urine.

Predicate Devices

K130665

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on immunochromatographic assays and comparison to GC/MS, with no mention of AI or ML algorithms for interpretation or analysis.

Therapeutic

No
The device is an in vitro diagnostic (IVD) test for detecting specific substances in urine, providing only preliminary test results. It does not treat or alleviate a disease or condition.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states "For in vitro diagnostic use only." This indicates that the device is used for diagnostic purposes.

SaMD (Software as a Medical Device)

No

The device description clearly states it is a "lateral flow, one step system" and an "immunochromatographic assay," which are hardware-based in vitro diagnostic tests. The summary describes performance studies involving physical urine samples and comparisons to GC/MS, a laboratory instrument. There is no mention of software as the primary or sole component of the device.

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 performs a test on a biological sample (human urine) to detect the presence of specific substances (Phencyclidine and Methylenedioxymethamphetamine) for diagnostic purposes (identifying potential drug use). This aligns with the definition of an in vitro diagnostic device.
• Intended Use: The intended use is for qualitative detection of drugs in human urine, which is a common application for IVD devices.
• Regulatory Context: The mention of "over-the-counter and for prescription use" and the inclusion of performance studies (comparison to GC/MS, lay-user study, analytical performance) are typical characteristics of devices undergoing regulatory review as IVDs.
• Predicate Devices: The listing of predicate devices with K numbers (K130665) further indicates that this device is being compared to other legally marketed IVD devices.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine is a rapid test for the qualitative detection of Phencyclidine and Methylenedioxymethamphetamine in human urine at a cutoff concentration of 25ng/mL and 500ng/mL, respectively.

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.

Product codes (comma separated list FDA assigned to the subject device)

LAF, LCM

Device Description

The CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine test uses immunochromatographic assays for phencyclidine and methylenedioxymethamphetamine. The test is a lateral flow, one step system for the qualitative detection of phencyclidine and methylenedioxymethamphetamine in human urine.

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

It is intended for over-the-counter and for prescription use.

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

Comparison Studies Test Set:

• Sample Size: 80 unaltered clinical samples (40 negative and 40 positive) for Phencyclidine and Methylenedioxymethamphetamine each.
• Data Source: In-house clinical samples.
• Annotation Protocol: Samples were masked and randomized. Results were compared to GC/MS results.

Lay-user study Test Set:

• Sample Size: 260 lay persons, of which 20 tested for drug-free samples, 120 for phencyclidine samples, 120 for methylenedioxymethamphetamine samples.
• Data Source: Drug-free pooled urine specimens spiked with drug(s) at various concentrations (-100%, +/-75%, +/-25% of the cut-off). Concentrations confirmed by GC/MS.
• Annotation Protocol: 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)

Analytical Performance - Precision Study:

• Study type: Precision study
• Sample size: For each concentration level (-100% cut-off, -75% cut-off, -50% cut-off, -25% cut-off, at the cut-off, +25% cut-off, +50% cut-off , +75% cut-off and +100% cut-off), tests were performed two runs per day for 25 days. Total of 50 tests per concentration level per lot.
• Key Results:
  • Phencyclidine (PCP) and Methylenedioxymethamphetamine (MDMA) results varied around the cut-off, showing a mix of positive and negative results, but were consistently negative significantly below cut-off and consistently positive significantly above cut-off. For example, at cut-off, Phencyclidine showed 42+/8- for the first lot, and MDMA showed 42+/8- for the first lot.

Analytical Performance - Cut-off Study:

• Study type: Cut-off verification
• Sample size: 125 phencyclidine samples and 125 methylenedioxymethamphetamine samples, equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs.
• Key Results: Results were all positive at +25% and +50% cut-off and all negative at -25% and -50% cut-off for both phencyclidine and methylenedioxymethamphetamine.

Analytical Performance - Interference Study:

• Study type: Interference study
• Sample size: Not explicitly stated, but involved testing various potential interfering substances in drug-free urine and urine containing target drugs.
• Key Results: A list of compounds that showed no interference at a concentration of 100µg/mL was provided for both Phencyclidine and Methylenedioxymethamphetamine.

Analytical Performance - Specificity Study:

• Study type: Specificity study (Cross-reactivity)
• Sample size: Not explicitly stated.
• Key Results:
  • Phencyclidine: 4-Hydroxyphencyclidine showed 0.2% cross-reactivity at 12,500 ng/mL.
  • Methylenedioxymethamphetamine: 3,4-Methylenedioxyamphetamine HCl (MDA) showed 16.7% cross-reactivity at 3000 ng/mL. 3,4-Methylenedioxyethylamphetamine (MDEA) showed 167% cross-reactivity at 300 ng/mL. d-methamphetamine and d-amphetamine were not detected at >100,000.

Analytical Performance - Effect of Urinary Density and pH Study:

• Study type: Evaluation of external factors
• Sample size: Twelve urine samples of normal, high, and low specific density ranges (1.000 to 1.035). Urine pool adjusted to pH ranges of 4.00 to 9.00 in 1 pH unit increments.
• Key Results: The device performance was found not affected by varying urine density and pH.

Comparison Studies:

• Study type: Method comparison
• Sample size: 80 unaltered clinical samples (40 negative and 40 positive) for Phencyclidine; 80 unaltered clinical samples (40 negative and 40 positive) for Methylenedioxymethamphetamine.
• Key Results: Comparison tables show concordance and discordance between the device results and GC/MS results across different concentration ranges. For Phencyclidine, Viewer A had 3 positive results for samples in the "Near Cutoff Negative" range and 3 negative results for samples in the "Near Cutoff Positive" range, and other viewers showed similar patterns. For Methylenedioxymethamphetamine, Viewer A had 4 positive results for samples in the "Near Cutoff Negative" range and 4 negative results for samples in the "Near Cutoff Positive" range, and other viewers showed similar patterns. Discordant tables provide specific sample numbers, GC/MS results, and viewer results for discrepancies.

Lay-user study:

• Study type: Lay user performance
• Sample size: 260 lay persons (20 for drug-free, 120 for phencyclidine, 120 for methylenedioxymethamphetamine).
• Key Results:
  • Drug-free samples: 100% agreement with GC/MS (20 negative).
  • Phencyclidine:
    • -75%: 100% agreement (20 negative).
    • -50%: 100% agreement (20 negative).
    • -25%: 85% agreement (17 negative, 3 positive).
    • +25%: 85% agreement (3 negative, 17 positive).
    • +50%: 100% agreement (20 positive).
    • +75%: 100% agreement (20 positive).
  • Methylenedioxymethamphetamine:
    • -75%: 100% agreement (20 negative).
    • -50%: 100% agreement (20 negative).
    • -25%: 90% agreement (18 negative, 2 positive).
    • +25%: 85% agreement (3 negative, 17 positive).
    • +50%: 100% agreement (20 positive).
    • +75%: 100% agreement (20 positive).
  • All lay users indicated that the device instructions can be easily followed. Flesch-Kincaid reading analysis showed a reading grade level of less than 7 for the package insert.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not explicitly stated as separated metrics. Performance is presented in tables showing positive/negative counts versus GC/MS results, and percentage agreement based on GC/MS.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K130665

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

N/A

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 is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of a stylized eagle with three human profiles incorporated into its design.

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

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

August 25, 2014

Re: K142044

Trade/Device Name: CR3 Keyless Split Sample Cup Phencyclidine-Methylenedioxymethamphetamine Regulation Number: 21 CFR 862.3610 Regulation Name: Methamphetamine test system Regulatory Class: II Product Code: LAF, LCM Dated: July 24, 2014 Received: July 28, 2014

Dear 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/ResourcesforYou/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,

Katherine Serrano -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

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known)

Device Name

CR3 Kevless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine

Indications for Use (Describe)

CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamine is a rapid test for the qualitative detection of Phencyclidine and Methylenedioxymethamphetamine in human urine at a cutoff concentration of 25ng/mL and 500ng/mL. respectively.

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.

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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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FORM FDA 3881 (1/14)

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510(k) SUMMARY

1. Date:	August 21, 2014
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: [phone]
Fax: [phone]
Email: [e-mail]
4. Device Name:	CR3 Keyless Split Sample Cup Phencyclidine –
Methylenedioxymethamphetamine
Classification:	Product Code CFR #
LCM Unclassified
LAF 21CFR 862.3610
5. Predicate Devices:	K130665
Wondfo Multi-Drug Urine Test Cup
Wondfo Multi-Drug Urine Test Panel

• 6. Intended Use
     CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine is a rapid test for the qualitative detection of Phencyclidine and Methylenediox ymethamphetamine in human urine at a cutoff concentration of 25ng/mL and 500ng/mL, respectively.

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

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For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.

• 7. Device Description
     The CR3 Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine test uses immunochromatographic assays for phencyclidine and methylenedioxymethamphetamine. The test is a lateral flow, one step system for the qualitative detection of phencyclidine and methylenedioxymethamphetamine in human urine.

Item	Device	Predicate
Indication(s) for use	For the qualitative determination of Phencyclidine and
Methylenedioxymethamphetamine in human urine	Same, but also detects other drugs in human urine
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	Phencyclidine: 25ng/ml
Methylenedioxymethamphetamine: 500ng/ml	Same for Phencyclidine and
Methylenedioxymethamphetamine
Configurations	Cup	Cup, Panel
Conditions for Use	Over-the-Counter & Prescription Use	Same

• 8. Substantial Equivalence Information

9. Test Principle

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

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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.

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 , +75% cut-off and +100% cut-off. For each concentration, tests were performed two runs per day for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:

| Result
PCP | -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 |
|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| W11810501CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11810502CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11810503CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

A. For Phencyclidine (PCP) testing

B. For Methylenedioxymethamphetamine (MDMA) testing

| Result
MDMA | -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 |
|----------------|------------------|---------------------|--------------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| W11810501CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11810502CU5 | 50-/0+ | 50-10+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11810503CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

• b. Linearity

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Not applicable.

• c. Stability
  The CR3 Keyless Split Sample Cup Phencyclidine -Methylenedioxymethamphetamine is stable at 4-30°C 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.

• d. Cut-off
  A total of 125 phencyclidine samples and 125 methylenedioxymethamphetamine samples equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs were labeled by a person who prepared them and would not participate in the sample testing. 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 phencyclidine and methylenedioxymethamphetamine. The following cut-off values for the test devices have been verified.

| Test | Calibrator | Cut-off
(ng/ml) |
|--------------------------------------|-------------------------------|--------------------|
| Phencyclidine (PCP) | phencyclidine | 25 |
| Methylenedioxymethamphetamine (MDMA) | methylenedioxymethamphetamine | 500 |

e. Interference

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

Phencyclidine

Acetaminophen	(-) Y Ephedrine	Oxycodone
Acetophenetidin	Erythromycin	Oxymetazoline
N-Acetylprocainamide	β-Estradiol	Papaverine
Acetylsalicylic acid	Estrone-3-sulfate	Penicillin-G

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Aminopyrine Amitryptyline Amobarbital Amoxicillin Ampicillin Ascorbic acid D.L-Amphetamine Apomorphine acid Aspartame Atropine Benzilic acid Benzoic acid Benzoylecgonine Benzphetamine Bilirubin Brompheniramine Caffeine Cannabidiol Cannabinol Chloralhydrate Chloramphenicol Chlordiazepoxide Chlorothiazide (±) Chlorpheniramine Chlorpromazine Chlorquine Cholesterol Clomipramine Clonidine Cocaine hydrochloride Codeine Cortisone (-) Cotinine Creatinine Deoxycorticosterone Dextromethorphan Diazepam Diclofenac Diflunisal Digoxin

Ethyl-p-aminobenzoate Fenoprofen Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone O-Hydroxyhippuric p-Hydroxymethamphetamine 3-Hydroxytyramine Ibuprofen Imipramine Iproniazid (±) - Isoproterenol Isoxsuprine Ketamine Ketoprofen Labetalol Loperamide Maprotiline Meperidine Meprobamate Methadone Methoxyphenamine (+) 3,4-Methylenedioxyamphetamine (+)3,4-Methylenedioxymethamphetamine Morphine-3-B-D glucuronide Morphine Sulfate Nalidixic acid Naloxone Naltrexone Naproxen Niacinamide Nifedipine Norcodein Norethindrone D-Norpropox yphene Noscapine

Pentazocine hydrochloride Pentobarbital Perphenazine Phenelzine Phenobarbital Phentermine L-Phenylephrine ß-Phenylethylamine Phenylpropanolamine Prednisolone Prednisone Procaine Promazine Promethazine D.L-Propanolol D-Propoxyphene D-Pseudoephedrine Ouinidine Ouinine Ranitidine Salicylic acid Secobarbital Serotonin (5-Hydroxytyramine) Sulfamethazine Sulindac Temazepam Tetracycline Tetrahydrocortisone, 3acetate Tetrahydrocortisone3 (ß-D glucuronide) Tetrahydrozoline Thiamine Thioridazine D, L-Tyrosine Tolbutamide Triamterene Trifluoperazine Trimethoprim Trimipramine Tryptamine D, L-Tryptophan

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Diphenhydramine Doxylamine Ecgonine hydrochloride Ecgonine methylester

D.L-Octopamine Oxalic acid Oxazepam Oxolinic acid

Methylenedioxymethamphetamine

• 4-Acetamidophenol Acetophenetidin N-Acetylprocainamide Acetylsalicylic acid Aminopyrine Amitryptyline
  Amobarbital Amoxicillin Ampicillin L-Ascorbic acid Apomorphine Aspartame Atropine Benzilic acid Benzoic acid Benzoylecgonine Bilirubin (±) - Brompheniramine Buspiron Caffeine Cannabidiol Cannabinol Chloralhydrate Chloramphenicol

Chlordiazepoxide Chlorothiazide (±) - Chlorpheniramine Chlorpromazine Chlorquine Methylphenidate Cholesterol

Clomipramine

(L) – Epinephrine Erythromycin ß-Estradiol Estrone-3-sulfate Ethyl-p-aminobenzoate Fenoprofen

Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone O-Hydroxyhippuric acid 3-Hydroxytyramine Ibuprofen Imipramine Iproniazid (±) — Isoproterenol Isoxsuprine Ketamine Ketoprofen Labetalol Levorphanol

Loperamide Maprotiline Meperidine Meprobamate Methadone

Morphine-3-β-Dglucuronide

Morphine sulfate

Tyramine Uric acid Verapamil Zomepirac

Perphenazine Phencyclidine Phenelzine Phenobarbital Phentermine Trans-2-phenylcyclopropyl amine hydrochloride L-Phenylephrine ß-Phenylethylamine Phenylpropanolamine Prednisolone Prednisone Procaine Promazine Promethazine DL-Propranolol D-Propox vphene D-Pseudoephedrine Ouinacrine Quinidine Quinine Ranitidine Salicylic acid Secobarbital Serotonin (5-Hydroxytyramine) Sulfamethazine Sulindac Sustiva Temazepam Tetracycline Tetrahydrocortisone, 3-acetate Tetrahydrocortisone 3-(ß-Dglucuronide)

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Clonidine	Nalidixic acid	Tetrahydrozoline
Cocaethylene	Naloxone	Thebaine
Cocaine hydrochloride	Naltrexone	Theophylline
Codeine	Naproxen	Thiamine
Cortisone	Niacinamide	Thioridazine
(-) Cotinine	Nifedipine	Tolbutamide
Creatinine	Nimesulidate	Trans-2-
phenylcyclopropylamine
Deoxycorticosterone	Norcodein	Trazodone
Dextromethorphan	Norethindrone	Triamterene
Diclofenac	D-Norpropoxyphene	DL-Tyrosine
Diazepam	Noscapine	Trifluoperazine
Diflunisal	D,L-Octopamine	Trimethoprim
Digoxin	Oxalic acid	Trimipramine
Dicylomine	Oxazepam	Tryptamine
Diphenhydramine	Oxolinic acid	D L-Tryptophan
5,5 - Diphenylhydantoin	Oxycodone	Tyramine
Doxylamine	Oxymetazoline	Uric acid
Ecgonine hydrochloride	Papaverine	Verapamil
Ecgonine methylester	Penicillin-G	Zomepirac
(-) – Ψ-Ephedrine	Pentazocinehydrochloride
1R,2S Ephedrine	Pentobarbital

• 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 (Phencyclidine or Methylenedioxymethamphetamine), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine 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.

| PCP
(Phencyclidine,
Cut-off=25 ng/mL) | Result | %
Cross-Reactivity |
|---------------------------------------------|--------------------------|-----------------------|
| Phencyclidine | Positive at 25 ng/mL | 100% |
| 4-Hydroxyphencyclidine | Positive at 12,500 ng/mL | 0.2% |

10

| MDMA
(Methylenedioxymethamphetamine,

Cut-off=500 ng/mL)	Result	% Cross-Reactivity
Methylenedioxymethamphetamine	Positive at 500 ng/mL	100%
3,4-Methylenedioxyamphetamine HCl
(MDA)	Positive at 3000 ng/mL	16.7%
3,4-Methylenedioxyethylamphetamine
(MDEA)	Positive at 300 ng/mL	167%
d-methamphetamine	>100,000	Not detected
d-amphetamine	>100,000	Not detected

g. Effect of Urinary Density and pH

Twelve urine samples of normal, high, and low specific density ranges (1.000 to 1.035) were collected and spiked with either phencyclidine or methylenedioxymethamphetamine at 25% below and 25% above the corresponding cut-off level. These samples were tested using three batches of the CR3Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine 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 phencyclidine or methylenedioxymethamphetamine at 25% below and 25% above the corresponding cut-off levels. These samples were tested using three batches of the CR3Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine by three different operators.

The device performance was found not affected by varying urine density and pH.

• 2. Comparison Studies
     The method comparison for the CR3 Keyless Split Sample Cup Phencyclidine -Methylenedioxymethamphetamine 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 are compared to GC/MS results. The results are presented in the table below:

Phencyclidine

11

| 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 | 3 | 16 | 20 |
| | Negative | 10 | 18 | 9 | 4 | 0 |
| Viewer C | Positive | 0 | 0 | 3 | 17 | 20 |
| | Negative | 10 | 18 | 9 | 3 | 0 |

Discordant table:

Viewer	Sample number	GC/MS result	Viewer result
Viewer A	PCPC1061	24	positive
Viewer A	PCPC1062	24	positive
Viewer A	PCPC1064	23	positive
Viewer A	PCPC1063	26	negative
Viewer A	PCPC1065	25	negative
Viewer A	PCP1214	25	negative
Viewer B	PCPC1061	24	positive
Viewer B	PCPC1062	24	positive
Viewer B	PCPC1064	23	positive
Viewer B	PCPC1063	26	negative
Viewer B	PCPC1065	25	negative
Viewer B	PCP1213	27	negative
Viewer B	PCP1214	25	negative
Viewer C	PCPC1034	21	positive
Viewer C	PCPC1062	24	positive
Viewer C	PCPC1064	23	positive
Viewer C	PCPC1065	25	negative
Viewer C	PCP1213	27	negative
Viewer C	PCP1214	25	negative

Methylenedioxymethamphetamine

12

| 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 | 4 | 16 | 20 |
| | Negative | 10 | 10 | 16 | 4 | 0 |
| Viewer B | Positive | 0 | 0 | 3 | 17 | 20 |
| | Negative | 10 | 10 | 17 | 3 | 0 |
| Viewer C | Positive | 0 | 0 | 4 | 17 | 20 |
| | Negative | 10 | 10 | 16 | 3 | 0 |

Discordant table:

Viewer	Sample number	GC/MS result	viewer results
Viewer A	MDMA5213	498	positive
Viewer A	MDMA5216	482	positive
Viewer A	MDMA5223	494	positive
Viewer A	MDMA5224	478	positive
Viewer A	MDMAC5061	532	negative
Viewer A	MDMAC5062	544	negative
Viewer A	MDMAC5063	509	negative
Viewer A	MDMAC5064	521	negative
Viewer B	MDMA5216	482	positive
Viewer B	MDMA5223	494	positive
Viewer B	MDMA5224	478	positive
Viewer B	MDMAC5061	532	negative
Viewer B	MDMAC5063	509	negative
Viewer B	MDMAC5064	521	negative
Viewer C	MDMA5213	498	positive
Viewer C	MDMA5213	498	positive
Viewer C	MDMA5223	494	positive
Viewer C	MDMA5216	482	positive
Viewer C	MDMAC5061	532	negative
Viewer C	MDMAC5063	509	negative
Viewer C	MDMAC5064	521	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 phencyclidine samples, 120 for methylenedioxymethamphetamine samples. They had diverse educational and professional backgrounds and ranged in age from 21 to

13

50 years. Urine samples were prepared at the following concentrations; -100%, +/-75%, +/-25% of the cut-off by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:

| Cup format | | Number
of
samples | OTC user | | % Agreement
With
GC/MS |
|---------------|------------------------------------|-------------------------|----------|----------|------------------------------|
| Drug | Concentration | | Negative | Positive | |
| Drug -free | -100% | 20 | 20 | 0 | 100% |
| Phencyclidine | -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% |
| | Methylenedioxy-
methamphetamine | -75% | 20 | 20 | 0 |
| -50% | | 20 | 20 | 0 | 100% |
| -25% | | 20 | 18 | 2 | 90% |
| +25% | | 20 | 3 | 17 | 85% |
| +50% | | 20 | 0 | 20 | 100% |
| +75% | | 20 | 0 | 20 | 100% |

Lay-users were also given surveys on the ease of understanding the package insert instructions. All lay users indicated that the device instructions can be easily followed A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7.

• 3. Clinical Studies
     Not applicable
• 11. Conclusion
      Based on the test principle and performance characteristics of the device, it's concluded that CR Keyless Split Sample Cup Phencyclidine - Methylenedioxymethamphetamine is substantially equivalent to the predicate.