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.

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.

AI/ML Overview

The acceptance criteria and the study proving the device meets these criteria are detailed in the provided document.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for the overall device performance in a consolidated table. However, implied acceptance criteria can be derived from the precision and lay-user study results, particularly around the cutoff concentrations. For the purpose of this response, I will synthesize the observed performance from the precision and lay-user studies as the "reported device performance" against common expectations for such devices.

Implied Acceptance Criteria and Reported Device Performance for Morphine (MOP) and Methamphetamine (MET) Detection:

Criteria Category	Specific Criterion (Implied)	Reported Device Performance (Morphine)	Reported Device Performance (Methamphetamine)
Precision (Analytical)	Accurate detection near cut-off (300 ng/mL for MOP, 1000 ng/mL for MET) across multiple lots and operators.	- At Cut-off: 84-86% positive (42-43+/8-7-) out of 50 tests per lot. - +25% to +100% Cut-off: 100% positive (50+/0-) per lot. - -100% to -25% Cut-off: 100% negative (50-/0+) per lot.	- At Cut-off: 84-86% positive (42-43+/8-7-) out of 50 tests per lot. - +25% to +100% Cut-off: 100% positive (50+/0-) per lot. - -100% to -25% Cut-off: 100% negative (50-/0+) per lot.
Cut-off Verification	All samples -25% and -50% of cut-off should be negative; all samples +25% and +50% of cut-off should be positive.	All samples at -25% and -50% cut-off were negative. All samples at +25% and +50% cut-off were positive.	All samples at -25% and -50% cut-off were negative. All samples at +25% and +50% cut-off were positive.
Lay-User Accuracy	High agreement with GC/MS, especially at and away from cut-off.	- -100% to -50% Cut-off: 100% agreement. - -25% Cut-off: 85% agreement (17 negative, 3 positive). - +25% Cut-off: 85% agreement (3 negative, 17 positive). - +50% to +75% Cut-off: 100% agreement.	- -100% to -50% Cut-off: 100% agreement. - -25% Cut-off: 85% agreement (17 negative, 3 positive). - +25% Cut-off: 85% agreement (3 negative, 17 positive). - +50% to +75% Cut-off: 100% agreement.
Lay-User Usability	Clear instructions, easy to follow.	All lay users indicated instructions were easy to follow. Flesch-Kincaid grade level < 7.	All lay users indicated instructions were easy to follow. Flesch-Kincaid grade level < 7.

2. Sample Size Used for the Test Set and Data Provenance

Precision Study:
- For each concentration level (-100% to +100% of cut-off), 50 tests were performed per lot. With 9 concentration levels and 3 lots, this implies a total of 450 tests per drug (Morphine and Methamphetamine).
- Data Provenance: Not explicitly stated, but the study was "carried out" by the manufacturer. It is implied to be a prospective analytical study using spiked samples designed to test device precision. The samples were "masked and randomized."
Cut-off Study:
- A total of 125 morphine samples and 125 methamphetamine samples were used. These were distributed at -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs.
- Data Provenance: Not explicitly stated, but "samples were tested using three different lots by three different operators." This is an analytical study.
Interference Study:
- Not specified, but likely in-house analytical testing using spiked urine samples.
Specificity Study:
- Not specified, but likely in-house analytical testing using spiked urine samples.
Effect of Specific Gravity and Urine pH Study:
- 12 urine samples (normal, high, low specific gravity) were spiked for each drug.
- pH study: Aliquots of negative urine pool adjusted to pH 4.00-9.00 (6 increments) were spiked for each drug.
- Data Provenance: In-house analytical testing.
Comparison Studies (Algorithm Only / Standalone Study Implicit):
- 80 unaltered clinical samples (40 negative and 40 positive) were used for each drug (Morphine and Methamphetamine).
- Data Provenance: "In-house with three laboratory assistants." The samples were "unaltered clinical samples," suggesting real human urine samples, and were "masked and randomized." The country of origin is not specified but implicitly where the manufacturing facility is located (Guangzhou, P.R. China) or where the testing was conducted. This study appears to be a standalone performance evaluation against a gold standard method.
Lay-User Study:
- 260 lay persons participated.
- Sample distribution: 20 drug-free samples, 120 morphine samples, and 120 methamphetamine samples.
- Sample concentrations: -100%, +/-75%, +/-50%, +/-25% of the cut-off.
- Data Provenance: Clinical study performed "at three intended user sites" using spiked drug-free pooled urine specimens. The samples were "blind-labeled and randomized."

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

Precision, Cut-off, Interference, Specificity, Specific Gravity/pH Studies: "Three operators" conducted these tests, but their qualifications are not specified beyond being "operators." The ground truth for these analytical studies was based on the precisely known concentrations of spiked drug analytes.
Comparison Studies (Clinical Samples):
- Ground truth was established by GC/MS (Gas Chromatography/Mass Spectrometry), which is the preferred confirmatory method for drug testing and considered a gold standard. No human experts are explicitly mentioned for establishing ground truth from GC/MS, as it is an objective analytical method.
- Three "laboratory assistants" were the "operators" who read the device results. Their qualifications are not specified.
Lay-User Study:
- The ground truth for the spiked concentrations was "confirmed by GC/MS." No human experts are explicitly mentioned for establishing ground truth from GC/MS.

4. Adjudication Method for the Test Set

The document does not describe a formal "adjudication method" involving multiple readers for reconciling discrepancies in the test results.

Precision, Cut-off, Interference, Specificity, Specific Gravity/pH Studies: The results are presented as counts (e.g., 50-/0+), implying individual test outcomes were recorded, not adjudicated.
Comparison Studies: Three "Viewers" (A, B, C) individually read the results of the 80 clinical samples for each drug. Their individual results are reported, including discordant cases, but there's no mention of a consensus or adjudication process among them. Each viewer's performance is listed separately.
Lay-User Study: Each participant (lay person) received one device and one blind-labeled sample. Their individual interpretation was recorded and compared to the GC/MS confirmed concentration. No adjudication among lay users is mentioned.

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

No, a formal MRMC comparative effectiveness study, comparing human readers with and without AI assistance, was not explicitly performed or reported.

The "Comparison Studies" involved three "laboratory assistants" (referred to as Viewers A, B, C) interpreting device results. This is a multi-reader study, and the cases were clinical samples. However, there's no "AI assistance" component mentioned to evaluate an improvement effect size over unassisted human reading. The device itself is an immunochromatographic rapid test, not an AI-powered diagnostic.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was implicitly done.

The "Comparison Studies" section evaluates the performance of the CR3 Keyless Split Sample Cup Morphine - Methamphetamine device alone against GC/MS results for "unaltered clinical samples." The device itself is the "algorithm only" in this context, as it is a rapid diagnostic test providing a qualitative result (positive/negative line on the strip). The three laboratory assistants are merely "reading" the output of the device. The data provided in the tables for "Viewer A, B, C" in the Comparison Studies section actually reflect the performance of the device as interpreted by different individuals.

7. Type of Ground Truth Used

For all analytical studies (Precision, Cut-off, Interference, Specificity, Specific Gravity/pH): The ground truth was based on known spiked concentrations of the target analytes in urine.
For Comparison Studies (Clinical Samples) and Lay-User Study: The ground truth was established using GC/MS (Gas Chromatography/Mass Spectrometry), which is considered a definitive analytical method for confirming drug presence and concentration.

8. Sample Size for the Training Set

The document describes premarket performance characteristics and refers to a "device" that is an immunochromatographic assay. This type of device does not typically involve a "training set" in the context of machine learning or AI models. Its performance is based on the chemical and biological properties of its reagents and manufacturing process, which are developed and validated through iterative R&D. Therefore, a specific "training set" as understood in AI/ML is not applicable to this device.

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

As noted above, a "training set" in the AI/ML sense is not applicable to this device. The development and optimization of such a rapid test involve extensive in-house analytical testing using known concentrations of analytes and interferents, which serve to refine the device design and manufacturing.

Summary

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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

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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.

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)

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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 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 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.

For in vitro diagnostic use only.

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7. Device Description:

Item	Device	Predicate - K142580
Indication(s)for use	For the qualitative determination ofdrugs of abuse in human urine	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assaysbased on the principle of antigenantibody immunochemistry.	Same
Results	Qualitative	Same
SpecimenType	Human urine	Same
Cut Off Values	Morphine: 300ng/mlMethamphetamine: 1000ng/ml	Same for Morphine andMethamphetamine
Configurations	Cup	Dipcard
Conditions forUse	Over-the-Counter & PrescriptionUse	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:

ResultMOP	-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

ResultMET	-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-ethylamphetamine(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-Methylenedioxyamphetamine (MDA)	Positive at 1,000 ng/mL	100%
(+/-)3,4-methylenedioxymethamphetamine(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

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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:

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	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

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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

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%)
		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

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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

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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.

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).