CR3 Keyless Split Sample Cup Secobarbital-Methadone is a rapid test for the qualitative detection of Secobarbital and Methadone in human urine at a cutoff concentration of 300ng/mL for each of the drugs.

The test may yield preliminary positive results when prescription drugs Secobarbital and Methadone are ingested, even at or above therapeutic doses. There are no uniformly recognized drug levels for Secobarbital and Methadone in urine. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry 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 Secobarbital - Methadone test uses immunochromatographic assays for secobarbital and methadone. The test is a lateral flow system for the qualitative detection of secobarbital and methadone in human urine. The test is the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CR3 Keyless Split Sample Cup Secobarbital-Methadone device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a separate section with specific numerical targets. Instead, it describes performance characteristics that would be used to demonstrate substantial equivalence to a predicate device. For the purpose of this response, I've interpreted the demonstrated performance in the "Performance Characteristics" section as meeting assumed acceptance criteria for effective drug detection. The key performance indicators addressed are precision, cut-off values, interference, specificity, and comparison to GC/MS.

Since this is a qualitative test, metrics like sensitivity, specificity, and accuracy are inferred from the comparison study and precision data, rather than being explicitly stated as separate acceptance criteria with target percentages for positive/negative agreement.

Feature	Acceptance Criteria (Implied)	Reported Device Performance (Summary)
Qualitative Detection	Must accurately detect Secobarbital and Methadone qualitatively in urine.	The device provides preliminary positive or negative results. Confirmed by GC/MS.
Cut-off Concentration	300 ng/mL for Secobarbital and Methadone.	Verified at 300 ng/mL for both Secobarbital and Methadone.
Precision	Consistent and reliable results across operators and runs for concentrations around the cut-off.	For concentrations below 25% of cut-off, 100% negative results. For concentrations above 25% of cut-off, 100% positive results. At the cut-off, good agreement (e.g., Secobarbital: 41-43 positive out of 50 tests).
Linearity	Not applicable for a qualitative test.	Not applicable.
Stability	Stable for a reasonable shelf life.	Stable at 4-30°C for 18 months.
Interference	Minimal interference from common substances and physiological conditions.	No interference from a long list of compounds at 100ug/mL. Performance not affected by varying specific gravity and pH.
Specificity	Differentiate between target drugs and structurally similar compounds.	Detailed cross-reactivity data provided for Secobarbital and Methadone, showing varying degrees of cross-reactivity with related substances at different concentrations.
Comparison to GC/MS (Analytical Accuracy)	High concordance with GC/MS for both negative and positive samples.	Secobarbital:Viewer A: 0 false negatives high/low positive, 4 false positives near cutoff negativeViewer B: 0 false negatives high/low positive, 3 false positives near cutoff negativeViewer C: 0 false negatives high/low positive, 3 false positives near cutoff negativeMethadone:Viewer A: 0 false negatives high/low positive, 3 false positives near cutoff negativeViewer B: 0 false negatives high/low positive, 5 false positives near cutoff negativeViewer C: 0 false negatives high/low positive, 4 false positives near cutoff negative(Results are grouped and not shown as overall percentage agreement.)
Lay-User Interpretability	The device should be easily used and interpreted by lay users.	100% agreement for drug-free, -75%, -50% cut-off samples. 80-85% agreement for -25% and +25% cut-off samples. 100% agreement for +50% and +75% cut-off samples. Instructions easily followed, reading grade level below 7.

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

Precision Study:
- For each concentration level (-100% cut-off, -75%, -50%, -25%, at cut-off, +25%, +50%, +75%, +100% cut-off): 50 tests (performed 2 runs/day by 3 operators for 25 days, which means 25 days * 2 runs/day * 1 test/run = 50 tests per operator for each concentration level. However, the tables show combined results for W12010501CU5, W12010502CU5, W12010503CU5, suggesting these are the operators, each performing 50 tests for each concentration).
Cut-off Verification:
- 125 Secobarbital samples and 125 Methadone samples.
Interference Study:
- Not specified as a number of samples, but target drugs were spiked into urine with potential interferents at 25% below and 25% above the cut-off.
Specificity Study:
- Not specified as a number of samples, but drug metabolites and related compounds were tested at different concentrations.
Comparison Studies (Lab-based):
- 80 unaltered clinical samples (40 negative and 40 positive) for Secobarbital.
- 80 unaltered clinical samples (40 negative and 40 positive) for Methadone.
Lay-User Study:
- 260 lay persons.
- 20 drug-free samples.
- 120 Secobarbital samples (across different concentrations).
- 120 Methadone samples (across different concentrations).
Data Provenance: The document does not explicitly state the country of origin for the clinical samples. The precision and analytical studies appear to be "in-house" (performed by the manufacturer). The comparison study used "unaltered clinical samples." The lay-user study was performed "at three intended user sites." The data appears to be retrospective as samples were collected and then tested.

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

Ground Truth Establishment for Comparison Studies (Lab-based):
- Method: Gas Chromatography/Mass Spectrometry (GC/MS).
- Experts: The specific number and qualifications of experts performing the GC/MS analysis are not mentioned. GC/MS is an objective analytical method, so "experts" in the sense of clinical decision-makers might not be directly applicable for establishing the ground truth concentrations. However, skilled laboratory personnel are required to operate and interpret GC/MS results.
Ground Truth Establishment for Lay-User Study:
- Method: GC/MS was used to confirm the concentrations of the spiked urine samples.
- Experts: Not explicitly stated, as above.

4. Adjudication Method for the Test Set

Precision Study: "All sample aliquots were masked and randomized." Results were presented by operator but no explicit adjudication method (e.g., 2+1) is mentioned for discrepancies.
Comparison Studies (Lab-based): "The samples were masked and randomized." The results of the device were compared to GC/MS. No explicit adjudication method is mentioned. The comparison study involved three "Viewer" operators (Viewer A, B, C) who manually read the device results. Their individual discordant results with GC/MS are listed, but there's no mention of a consensus or adjudication process among these viewers.
Lay-User Study: Samples were "blind-labeled and randomized." There is no mention of an adjudication method for participant readings. The agreement is reported as a percentage with GC/MS.

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

No MRMC comparative effectiveness study was explicitly done to assess how much human readers improve with AI vs. without AI assistance.
The study involved multiple readers (three lab assistants in the comparison study, and 260 lay users in the lay-user study) and multiple cases. However, it was a standalone device performance study comparing the device output (read by humans) to a reference standard (GC/MS), not a comparative effectiveness study of human performance with vs. without AI. The device itself is a simple, qualitative rapid test, not an AI-assisted diagnostic tool.

6. Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, in essence, the fundamental performance of the device itself (the "algorithm" in a chemical sense) was evaluated standalone. The precision, cut-off, interference, and specificity sections describe the inherent analytical performance of the test strips. The "viewers" in the comparison study are interpreting the visual lines on the device, rather than interacting with an algorithm that provides output. The device itself is a standalone qualitative test.

7. Type of Ground Truth Used

Analytical Chemical Method (GC/MS): For both the internal performance characterization (precision, cut-off verification, interference, specificity) and the comparison studies, Gas Chromatography/Mass Spectrometry (GC/MS) was used as the reference standard to establish the ground truth concentrations of Secobarbital and Methadone.

8. Sample Size for the Training Set

Not Applicable / Not Mentioned. This is a chemical assay (immunochromatographic), not a machine learning or AI-based device that typically requires a "training set." The development of such assays involves chemical optimization and validation, rather than a separate training phase with a distinct dataset.

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

Not Applicable / Not Mentioned. As noted above, there isn't a "training set" in the context of this device type. The ground truth for analytical validation (e.g., precision, specificity, calibration) would be established by preparing samples with known concentrations using high-purity standards and analytical techniques like GC/MS.

Summary

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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 REGULATORY CONSULTANT 504 EAST DIAMOND AVE. SUITE F GAITHERSBURG MD 20878

January 13, 2015

Re: K143535

Trade/Device Name: CR3 Keyless Split Sample Cup Secobarbital-Methadone Regulation Number: 21 CFR 862.3150 Regulation Name: Barbiturate test system Regulatory Class: II Product Code: DIS. DJR Dated: December 9, 2014 Received: December 15, 2014

Dear Mr. Joe Shia:

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

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

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

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

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

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

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely yours,

Stayce Beck -S

For :

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

Enclosure

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Indications for Use

510(k) Number (if known) K143535

Device Name

CR3 Keyless Split Sample Cup Secobarbital-Methadone

Indications for Use (Describe)

For in vitro diagnostic use only

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

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:	January 8, 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 Secobarbital-Methadone 4. Device Name:

Classification:	Class II
Product Code	CFR #	Panel
DIS	21 CFR, 862.3150 Barbiturate Test System	Toxicology
DJR	21 CFR, 862.3620 Methadone Test System	Toxicology

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

6. Intended Use:

The test may yield preliminary positive results when prescription drugs Secobarbital and Methadone are ingested, even at or above therapeutic doses. There are no uniformly recognized drug levels for Secobarbital and Methadone in urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry 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:

Item	Device	Predicate - K122904
Indication(s) for use	For the qualitative determination of drugs of abuse in human urine	Same
Methodology	Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry.	Same
Results	Qualitative	Same
Specimen Type	Human urine	Same
Cut Off Values	Secobarbital: 300ng/mlMethadone: 300ng/ml	Same for Secobarbital and Methadone
Configurations	Cup	Cup, Dipcard
Conditions for Use	Over-the-Counter & Prescription Use	Same

1. Substantial Equivalence Information

9. Test Principle

The CR3 Keyless Split Sample Cup Secobarbital – Methadone test is a rapid test for the qualitative detection of Secobarbital and Methadone in urine samples and contains lateral flow chromatographic immunoassays for secobarbital and methadone. 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:

ResultBAR	-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
W12010501CU5	50-/0+	50-/0+	50-/0+	50-/0+	43+/7-	50+/0-	50+/0-	50+/0-	50+/0-
W12010502CU5	50-/0+	50-/0+	50-/0+	50-/0+	42+/8-	50+/0-	50+/0-	50+/0-	50+/0-
W12010503CU5	50-/0+	50-/0+	50-/0+	50-/0+	42+/8-	50+/0-	50+/0-	50+/0-	50+/0-

A. For Secobarbital (BAR) testing

ResultMTD	-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
W12010501CU5	50-/0+	50-/0+	50-/0+	50-/0+	43+/7-	50+/0-	50+/0-	50+/0-	50+/0-
W12010502CU5	50-/0+	50-/0+	50-/0+	50-/0+	41+/9-	50+/0-	50+/0-	50+/0-	50+/0-
W12010503CU5	50-/0+	50-/0+	50-/0+	50-/0+	42+/8-	50+/0-	50+/0-	50+/0-	50+/0-

B. For Methadone (MTD) testing

b. Linearity
Not applicable.
c. Stability
The CR3 Keyless Split Sample Cup Secobarbital – Methadone 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.

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d. Cut-off

A total of 125 secobarbital samples and 125 methadone 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 secobarbital and methadone. The following cut-off values for the test devices have been verified.

Test	Calibrator	Cut-off(ng/ml)
Secobarbital (BAR )	Secobarbital	300
Methadone (MTD)	Methadone	300

e. Interference

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

Secobarbital

Acetaminophen	Erythromycin	O-Hydroxyhippuric acid
Acetophenetidin	ß-Estradiol	D,L-Octopamine
Acetylsalicylic acid	Estrone-3-sulfate	Oxalic acid
Aminopyrine	Ethyl-p-aminobenzoate	Oxazepam
Amitryptyline	Fenoprofen	Oxolinic acid
Amoxicillin	Furosemide	Oxycodone
DL-Amphetamine sulfate	Gentisic acid	Oxymetazoline
Ampicillin	Hemoglobin	Papaverine
Apomorphine	Hydralazine	Penicillin-G
Ascorbic acid	Hydrochlorothiazide	Pentazocaine
Aspartame	Hydrocodone	Perphenazine
Atropine	Hydrocortisone	Phencyclidine
Benzilic acid	p-Hydroxyamphetamine	Phenelzine
Benzoic acid	p-Hydroxymethamphetamine	ß-Phenylethlamine
Benzoylecgonine	3-Hydroxytyramine	Phenylpropanolamine
Bilirubin	Ibuprofen	Prednisolone
Brompheniramine	Imipramine	Prednisone
Caffeine	(-) Isoproterenol	Procaine

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Cannabidiol Cannabinol Chloralhydrate Chloramphenicol Chlorothiazide (±) Chlorpheniramine Chlorpromazine Chlorquine Cholesterol Clomipramine Clonidine Cocaine hydrochloride Codeine Cortisone

(-) Cotinine

Creatinine Deoxycorticosterone Dextromethorphan Diazepam Diclofenac Diflunisal Digoxin Diphenhydramine Doxylamine Ecgonine hydrochloride Ecgonine methylester (IR,2S)(-)Ephedrine

Methadone

Acetaminophen Acetophenetidin Acetylsalicylic acid Amobarbital Aminopyrine Amitryptyline Amoxicillin DL-Amphetamine sulfate Ampicillin Apomorphine
Isoxsuprine Ketamine Ketoprofen Labetalol Levorphanol Loperamide L-Phenylephrine Maprotiline Meperidine Meprobamate Morphine-3-B-D glucuronide Methadone Methamphetamine ±) - 3,4-Methylenedioxy- amphetamine hydrochloride (±)-3,4-Methylenedioxymethamphetamine hydrochloride Morphine Sulfate N-Acetylprocainamide Nalidixic acid Naloxone Naltrexone Naproxen Niacinamide Nifedipine Norcodein Norethindrone D-Norpropox yphene Noscapine

Ecgonine methylester (IR,2S)(-)Ephedrine Erythromycin ß-Estradiol Estrone-3-sulfate Ethyl-p-aminobenzoate Fenoprofen Furosemide Gentisic acid Hemoglobin

Promazine Promethazine D,L-Propanolol D-Propoxyphene Quinidine Quinine Ranitidine Salicylic acid Serotonin Sulfamethazine Sulindac Temazepam Tetracycline Tetrahydrozoline

Thebaine

Thiamine Thioridazine Triamterene Trifluoperazine Trimethoprim Trimipramine Tryptamine D, L-Tyrosine Uric acid Verapamil Zomepirac

Oxazepam Oxolinic acid Oxycodone Oxymetazoline Papaverine Penicillin-G Pentazocine Pentobarbital Perphenazine Phencyclidine

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Ascorbic acid Aspartame Atropine Benzilic acid Benzoic acid Benzoylecgonine Bilirubin Brompheniramine Caffeine Cannabidiol Cannabinol Chloralhydrate Chloramphenicol Chlorothiazide (±) - Chlorpheniramine Chlorpromazine Chlorquine Cholesterol Clomipramine Clonidine Cocaine hydrochloride Codeine (-) Cotinine Cortisone Creatinine Deoxycorticosterone Dextromethorphan Diazepam Diclofenac Diflunisal Digoxin Diphenhydramine D-Norpropox yphene D-Propoxyphene D,L-Tyrosine

DL-Octopamine

Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone p-Hydroxyamphetamine p-Hydroxymethamphetamine 3-Hydroxytyramine Ibuprofen Imipramine (-) Isoproterenol Isoxsuprine Ketamine Ketoprofen Labetalol Levorphanol Loperamide L-Phenylephrine Maprotiline Meperidine Meprobamate

Methamphetamine

Methoxyphenamine

(±) - 3,4-Methylenedioxyamphetamine hydrochloride (±)-3,4-Methylenedioxymethamphetamine hydrochloride Morphine Sulfate Morphine-3-B-D glucuronide N-Acetylprocainamide Nalidixic acid Naloxone Naltrexone Naproxen Niacinamide Nifedipine Norcodein Norethindrone Noscapine

Phenelzine Phenobarbital Phentermine β-Phenylethylamine Phenylpropanolamine Prednisolone Prednisone Procaine Promazine Promethazine Quinidine Quinine Ranitidine Salicylic acid Secobarbital Serotonin Sulfamethazine Sulindac Temazepam Tetracycline

Tetrahydrocortisone, 3-acetate

Tetrahydrocortisone 3-(ß-D-glucuronide) Tetrahydrozoline

Thebaine

Thiamine Thioridazine Triamterene Trifluoperazine Trimethoprim Trimipramine Tryptamine DL-Tryptophan Tyramine Uric acid Verapamil Zomepirac

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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 (Secobarbital or Methadone), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Keyless Split Sample Cup Secobarbital –Methadone 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.

BAR(Secobarbital,Cut-off=300 ng/mL)	Result	%Cross-Reactivity
Secobarbital	Positive at 300 ng/mL	100%
Amobarbital	Positive at 300 ng/mL	100%
Alphenol	Positive at 150 ng/mL	200%
Aprobarbital	Positive at 200 ng/mL	150%
Butabarbital	Positive at 75 ng/mL	400%
Butathal	Positive at 100 ng/mL	300%
Butalbital	Positive at 2,500 ng/mL	12%
Cyclopentobarbital	Positive at 600 ng/mL	50%
Pentobarbital	Positive at 300 ng/mL	100%
Phenobarbital	Positive at 100 ng/mL	300%

MTD(Methadone,Cut-off=300 ng/mL)	Result	%Cross-Reactivity
Methadone	Positive at 300 ng/mL	100%
Doxylamine	Positive at 50,000 ng/mL	0.6%

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 Secobarbital or Methadone at 25% below and 25% above the corresponding cut-off level. These samples were tested using three batches of the CR3 Keyless Split Sample Cup Secobarbital-Methadone 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 Secobarbital or Methadone at 25% below and 25% above the

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

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

1. Comparison Studies
  The method comparison for the CR3 Keyless Split Sample Cup Secobarbital-Methadone 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%)
	Positive	0	0	4	15	20
Viewer A	Negative	10	13	13	5	0
	Positive	0	0	3	17	20
Viewer B	Negative	10	13	14	3	0
Viewer C	Positive	0	0	3	17	20
	Negative	10	13	14	3	0

Secobarbital

Discordant table:

Viewer	Sample number	GC/MS result	Viewer result
Viewer A	BARC3061	281	positive
Viewer A	BARC3062	275	positive
Viewer A	BARC3063	302	negative
Viewer A	BARC3065	314	negative
Viewer A	BAR 3212	278	positive
Viewer A	BAR 3214	293	positive
Viewer A	BAR 3218	305	negative
Viewer A	BAR 3223	317	negative
Viewer A	BAR 3229	309	negative
Viewer B	BARC3061	281	positive
Viewer B	BARC3063	302	negative
Viewer B	BARC3064	297	positive
Viewer B	BARC3065	314	negative

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Viewer B	BAR 3214	293	positive
Viewer B	BAR 3227	314	negative
Viewer C	BARC3062	275	positive
Viewer C	BARC3063	302	negative
Viewer C	BARC3064	297	positive
Viewer C	BAR 3214	293	positive
Viewer C	BAR 3218	305	negative
Viewer C	BAR 3227	314	negative

Methadone

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	12	15	3	0
Viewer B	Positive	0	0	5	16	20
	Negative	10	12	13	4	0
Viewer C	Positive	0	0	4	17	20
	Negative	10	12	14	3	0

Discordant table:

Viewer	Sample number	GC/MS result	viewer results
Viewer A	MTDC3063	304	negative
Viewer A	MTDC3065	291	positive
Viewer A	MTD 3211	284	positive
Viewer A	MTD 3214	299	positive
Viewer A	MTD 3220	306	negative
Viewer A	MTD 3226	301	negative
Viewer B	MTDC3061	297	positive
Viewer B	MTDC3062	313	negative
Viewer B	MTDC3063	304	negative
Viewer B	MTDC3064	286	positive
Viewer B	MTDC3065	291	positive
Viewer B	MTD 3211	284	positive
Viewer B	MTD 3214	299	positive
Viewer B	MTD 3224	311	negative
Viewer B	MTD 3226	301	negative
Viewer C	MTDC3061	297	positive

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Viewer C	MTDC3062	313	negative
Viewer C	MTDC3065	291	positive
Viewer C	MTD 3214	299	positive
Viewer C	MTD 3216	278	positive
Viewer C	MTD 3220	306	negative
Viewer C	MTD 3224	311	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 secobarbital samples, 120 for methadone 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		Numberofsamples	OTC user		% AgreementWithGC/MS
Drug	Concentration		Negative	Positive
Drug -free	-100%	20	20	0	100%
Secobarbital	-75%	20	20	0	100%
	-50%	20	20	0	100%
	-25%	20	17	3	85%
	+25%	20	4	16	80%
	+50%	20	0	20	100%
	+75%	20	0	20	100%
Methadone	-75%	20	20	0	100%
	-50%	20	20	0	100%
	-25%	20	16	4	80%
	+25%	20	4	16	80%
	+50%	20	0	20	100%
	+75%	20	0	20	100%

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

1. Clinical Studies
  Not applicable.

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11. Conclusion

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

Regulation Number and Section

§ 862.3150 Barbiturate test system.

(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate 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).