(29 days)
Not Found
No
The device description and performance studies focus on immunochromatographic assays and lateral flow technology, which are traditional diagnostic methods. There is no mention of AI, ML, or any computational analysis of the results. The "Not Found" entries for AI/ML mentions and training/test set descriptions further support this conclusion.
No.
This device is an in vitro diagnostic (IVD) test for the qualitative detection of specific drugs in urine and is intended for preliminary screening, not for therapeutic purposes.
Yes
The device is described as an "in vitro diagnostic use only" test for the qualitative detection of Secobarbital and Methadone in human urine and provides "preliminary positive results," which are then subject to confirmatory testing. These characteristics are consistent with a diagnostic device.
No
The device is a lateral flow immunochromatographic assay, which is a physical test strip/cup that detects substances in urine. It is a hardware-based in vitro diagnostic device, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For in vitro diagnostic use only."
- Nature of the Test: The device is designed to test human urine in vitro (outside the body) to detect the presence of specific substances (Secobarbital and Methadone). This is the fundamental definition of an in vitro diagnostic test.
- Device Description: The description details an "immunochromatographic assay" and a "lateral flow system for the qualitative detection... in human urine," which are common characteristics of IVD devices.
- Performance Studies: The document describes various performance studies (Analytical Performance, Comparison Studies, Lay-user study) that are typical for evaluating the performance of an IVD device.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K122904) indicates that this device is being compared to a previously cleared IVD device, a standard process for regulatory submission of IVDs.
All these factors strongly indicate that the CR3 Keyless Split Sample Cup Secobarbital-Methadone is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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
Product codes (comma separated list FDA assigned to the subject device)
DIS, DJR
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Human urine
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Over-the-Counter & 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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
-
Analytical Performance:
- 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.
- 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.
- 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.
- 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.
- 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. 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 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.
-
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.
-
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. 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.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Lay-user study (Agreement with GC/MS):
- Drug-free (-100%): 100%
- Secobarbital:
- -75%: 100%
- -50%: 100%
- -25%: 85%
- +25%: 80%
- +50%: 100%
- +75%: 100%
- Methadone:
- -75%: 100%
- -50%: 100%
- -25%: 80%
- +25%: 80%
- +50%: 100%
- +75%: 100%
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.
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
§ 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).
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of a caduceus, which is a symbol often associated with healthcare and medicine.
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.
1
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
2
Indications for Use
510(k) Number (if known) K143535
Device Name
CR3 Keyless Split Sample Cup Secobarbital-Methadone
Indications for Use (Describe)
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
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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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
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See PRA Statement below.
3
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 Shia |
| LSI International Inc. | |
| 504 East Diamond Ave., Suite F | |
| Gaithersburg, MD 20878 | |
| Telephone: 240-505-7880 | |
| Fax: 301-916-6213 | |
| Email:shiajl@yahoo.com |
- CR3 Keyless Split Sample Cup 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 |
-
- Predicate Devices: K122904 Wondfo Multi-Drug Urine Test Cup
6. Intended Use:
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 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.
4
7. 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.
| 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/ml | |
| Methadone: 300ng/ml | Same for Secobarbital and Methadone | |
| Configurations | Cup | Cup, Dipcard |
| Conditions for Use | Over-the-Counter & Prescription Use | Same |
-
- 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.
5
10. Performance Characteristics
-
- Analytical Performance
- a. Precision
Precision studies were carried out for samples with concentrations of -100% cut-off, -75% cut-off, -50% cut-off, -25% cut-off, at the cut-off, +25% cut-off, +50% cut-off and +100% cut-off. For each concentration, tests were performed two runs per day by three operators for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:
| Result
BAR | -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
| Result
MTD | -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.
6
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 |
7
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
8
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
9
- 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
10
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.
-
- 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:
- Comparison Studies
| Group
Operators | | Negative | Low
Negative by
GC/MS
(less than
-50%) | Near Cutoff
Negative by
GC/MS
(Between
-50% and
cutoff) | Near Cutoff
Positive by
GC/MS
(Between
the cutoff
and +50%) | High
Positive by
GC/MS
(greater
than +50%) |
|--------------------|----------|----------|----------------------------------------------------|------------------------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------|
| | Positive | 0 | 0 | 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 |
11
| 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
| 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 | 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 |
12
| 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 | | Number
of
samples | OTC user | | % Agreement
With
GC/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.
-
- Clinical Studies
Not applicable.
- Clinical Studies
13
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.