(93 days)
Not Found
No
The device description and performance studies focus on immunochromatographic assays and lateral flow technology, with no mention of AI or ML. The analysis of results is based on visual interpretation of the test lines, not algorithmic processing.
No
This device is for in vitro diagnostic use, specifically for qualitative detection of substances in urine, not for treating any condition.
Yes
Explanation: The Intended Use section explicitly states, "For in vitro diagnostic use only." It is designed for the qualitative detection of specific substances in human urine, which is a diagnostic purpose.
No
The device is a physical test cup for detecting substances in urine, not a software application.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For in vitro diagnostic use only."
- Nature of the Test: The device performs a rapid test for the qualitative detection of substances (Nortriptyline and Buprenorphine) in a human biological sample (urine). This is a hallmark of in vitro diagnostics, which are tests performed on samples taken from the human body.
- Purpose: The test is intended to provide information about the presence of specific drugs in a person's system, which is used for diagnostic purposes (even if preliminary).
The other information provided, such as the device description, performance studies, and comparison to a predicate device, further supports its classification as an IVD.
N/A
Intended Use / Indications for Use
CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine is a rapid test for the qualitative detection of Nortriptyline (a major metabolite of Tricyclic Antidepressants) and Buprenorphine in human urine at a cutoff concentration of 1000ng/mL and 10ng/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 test may yield preliminary positive results even when prescription drugs including Tricyclic Antidepressants and Buprenorphine are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Nortriptyline 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. GC/MS is the preferred confirmatory method. Clinical consideration and professional iudgment 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)
LFG, DJG
Device Description
The CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine test uses immunochromatographic assays for nortriptyline and buprenorphine. The test is a lateral flow, one step system for the qualitative detection of nortriptyline and buprenorphine in human urine.
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 and for prescription use.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Precision Study:
- Description: Precision studies were carried out for samples with concentrations of -100% cut-off, -75% cut-off, -50% cut-off, -25% cut-off, at the cut-off, +25% cut-off, +50% cut-off , +75% cut-off and +100% cut-off. For each concentration, tests were performed two runs per day for 25 days.
- Sample Size: 50 tests per concentration (2 runs/day * 25 days).
- Data Source: Samples with known concentrations relative to the cut-off.
- Annotation Protocol: All sample aliquots were masked and randomized.
Cut-off Verification:
- Description: 125 nortriptyline samples and 125 buprenorphine samples equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs were tested.
- Sample Size: 250 total samples (125 for nortriptyline, 125 for buprenorphine).
- Data Source: Samples with known concentrations labeled by a person who prepared them but would not participate in testing.
- Annotation Protocol: Samples were tested using three different lots by three different operators.
Interference Study:
- Description: Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and to urine containing target drugs (nortriptyline or buprenorphine) at 25% below and 25% above the cut-off.
- Sample Size: Not explicitly stated, but implied multiple samples for each substance at two concentrations.
- Data Source: Urine samples spiked with interfering substances and/or target drugs.
- Annotation Protocol: Tested using three batches of the subject device by three different operators.
Specificity Study:
- Description: Drug metabolites and other components that are likely to be present in urine samples were tested. The target drug (Nortriptyline or Buprenorphine), its drug metabolites and the related compounds were studied at different concentrations.
- Sample Size: Not explicitly stated, but multiple samples for each compound at various concentrations are implied.
- Data Source: Urine samples spiked with drug metabolites and related compounds.
- Annotation Protocol: Tested using three batches of the subject device by three different operators.
Effect of Specific Gravity and pH Study:
- Description: Twelve urine samples of normal, high, and low specific gravity ranges (1.000 to 1.035) were collected and spiked with either Nortriptyline or Buprenorphine 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 Nortriptyline or Buprenorphine at 25% below and 25% above the corresponding cut-off levels.
- Sample Size: 12 urine samples for specific gravity study, number of samples for pH study not explicitly stated but implied.
- Data Source: Urine samples with varying specific gravity and pH, spiked with drugs.
- Annotation Protocol: Tested using three batches of the subject device by three different operators.
Comparison Studies (Performance against GC/MS):
- Description: The method comparison for the CR2 Keyless Split Sample Cup Nortriptyline-Buprenorphine was performed in-house with three laboratory assistants. Operators ran unaltered clinical samples compared to GC/MS results.
- Sample Size: 80 (40 negative and 40 positive) unaltered clinical samples.
- Data Source: Unaltered clinical samples.
- Annotation Protocol: Samples were masked and randomized. Results were compared to GC/MS.
Lay-user study:
- Description: A lay user study was performed at three intended user sites focusing on the ease of understanding package insert instructions. Urine samples were prepared at various concentrations.
- Sample Size: 260 lay persons, of which, 20 tested for drug-free samples, 120 for nortriptyline samples, 120 for buprenorphine samples.
- Data Source: Urine samples prepared by spiking drug(s) into drug free-pooled urine specimens, with concentrations confirmed by GC/MS.
- Annotation Protocol: Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
1. Analytical Performance
- Precision:
- Study Type: Precision study.
- Sample Size: For each concentration level (-100%, -75%, -50%, -25%, at the cut-off, +25%, +50%, +75%, +100% cut-off), tests were performed two runs per day for 25 days, implying 50 tests per concentration.
- Key Results:
- Nortriptyline (TCA) testing:
- At -100%, -75%, -50%, -25% cut-off: 50 negative / 0 positive for all three unspecified "W" samples.
- At cut-off: "W11910601CU5" 44 positive / 6 negative; "W11910602CU5" 43 positive / 7 negative; "W11910603CU5" 43 positive / 7 negative.
- At +25%, +50%, +75%, +100% cut-off: 50 positive / 0 negative for all three unspecified "W" samples.
- Buprenorphine (BUP) testing:
- At -100%, -75%, -50%, -25% cut-off: 50 negative / 0 positive for all three unspecified "W" samples.
- At cut-off: "W11910601CU5" 42 positive / 8 negative; "W11910602CU5" 43 positive / 7 negative; "W11910603CU5" 43 positive / 7 negative.
- At +25%, +50%, +75%, +100% cut-off: 50 positive / 0 negative for all three unspecified "W" samples.
- Nortriptyline (TCA) testing:
- Linearity: Not applicable.
- Stability:
- Study Type: Accelerated and real-time stability testing.
- Key Results: The device is stable at 4-30°C for 18 months.
- Cut-off:
- Study Type: Cut-off verification.
- Sample Size: 125 nortriptyline samples and 125 buprenorphine samples.
- Key Results: All samples were positive at +25% and +50% cut-off and all negative at -25% and -50% cut-off for both nortriptyline and buprenorphine.
- Nortriptyline (TCA) Cut-off: 1000 ng/mL
- Buprenorphine (BUP) Cut-off: 10 ng/mL
- Interference:
- Study Type: Interference study with common substances.
- Key Results: Numerous compounds, including 4-Acetamidophenol, Aspirin, Caffeine, Ibuprofen, Morphine sulfate, etc., showed no interference at a concentration of 100µg/mL for both Nortriptyline and Buprenorphine tests.
- Specificity (Cross-reactivity):
- Study Type: Specificity testing with drug metabolites and related compounds.
- Key Results:
- Nortriptyline (TCA) (Cut-off=1000 ng/mL):
- Nortriptyline: 100% cross-reactivity at 1000 ng/mL.
- Nordoxepine: 100% cross-reactivity at 1,000 ng/mL.
- Trimipramiine: 33% cross-reactivity at 3,000 ng/mL.
- Amitriptyline: 67% cross-reactivity at 1,500 ng/mL.
- Desipramine: 500% cross-reactivity at 200 ng/mL.
- Imipramine: 250% cross-reactivity at 400 ng/mL.
- Clomipramine: 8% cross-reactivity at 12,500 ng/mL.
- Buprenorphine (BUP) (Cut-off=10 ng/mL):
- Buprenorphine: 100% cross-reactivity at 10 ng/mL.
- Buprenorphine -3-D-Glucuronide: 67% cross-reactivity at 15 ng/mL.
- Norbuprenorphine: 50% cross-reactivity at 20 ng/mL.
- Norbuprenorphine -3-D-Glucuronide: 5% cross-reactivity at 200 ng/mL.
- Morphine, Oxymorphone, Hydromorphone: 100,000 ng/mL.
- Nortriptyline (TCA) (Cut-off=1000 ng/mL):
- Effect of Specific Gravity and pH:
- Study Type: Evaluation of device performance under varying specific gravity and pH conditions.
- Key Results: The device performance was found not affected by varying specific gravity and pH.
2. Comparison Studies
- Comparison to GC/MS (Laboratory Assistants):
- Study Type: Method comparison study with laboratory assistants using 80 clinical samples.
- Sample Size: 80 (40 negative and 40 positive) unaltered clinical samples.
- Key Results (Nortriptyline): Data presented in tables showing agreement and discordant results compared to GC/MS. For "Viewer A", "Viewer B", and "Viewer C" (representing laboratory assistants), the number of positive and negative results across different GC/MS concentration ranges (Negative, Low Negative, Near Cutoff Negative, Near Cutoff Positive, High Positive) are provided. Discordant samples with GC/MS results and viewer results are listed.
- Key Results (Buprenorphine): Similar data presentation as above for Nortriptyline, showing agreement and discordant results compared to GC/MS for "Viewer A", "Viewer B", and "Viewer C".
- Lay-user study:
- Study Type: Lay-user study evaluating ease of use and agreement with GC/MS results.
- Sample Size: 260 lay persons (20 for drug-free, 120 for nortriptyline, 120 for buprenorphine samples).
- Key Results:
- Overall Agreement with GC/MS (Nortriptyline):
- Drug-free (-100%, -75%, -50% concentrations): 100% Agreement.
- -25% concentration: 85% Agreement (17 negative, 3 positive out of 20).
- +25% concentration: 85% Agreement (3 negative, 17 positive out of 20).
- +50%, +75% concentrations: 100% Agreement.
- Overall Agreement with GC/MS (Buprenorphine):
- -75%, -50% concentrations: 100% Agreement.
- -25% concentration: 90% Agreement (18 negative, 2 positive out of 20).
- +25% concentration: 85% Agreement (3 negative, 17 positive out of 20).
- +50%, +75% concentrations: 100% Agreement.
- Usability: All lay users indicated that the device instructions can be easily followed. The package insert had a Flesch-Kincaid reading grade level of less than 7.
- Overall Agreement with GC/MS (Nortriptyline):
3. Clinical Studies
- Study Type: Not applicable.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Key metrics for precision tests (count of positive/negative results at various concentrations relative to cutoff) and specific gravity/pH tests (not affected). Cross-reactivity in percentage for various similar analytes. Agreement percentages for the lay-user study for various concentrations (-100% to +75% of cut-off) relative to GC/MS results.
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
§ 862.3910 Tricyclic antidepressant drugs test system.
(a)
Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in serum. The tricyclic antidepressant drugs include imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, and doxepin. Measurements obtained by this device are used in the diagnosis and treatment of chronic depression to ensure appropriate therapy.(b)
Classification. Class II (special controls). A tricyclic antidepressant drugs 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).
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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an emblem featuring a stylized depiction of three human profiles facing to the right, with flowing lines suggesting movement or connection.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 18, 2014
GUANGZHOU WONDFO BIOTECH CO., LTD. C/O JOE SHIA LSI INTERNATIONAL INC. 504 EAST DIAMOND AVE. SUITE F GAITHERSBURG MD 20878
Re: K142609
Trade/Device Name: CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine Regulation Number: 21 CFR 862.3910 Regulation Name: Tricyclic antidepressant drugs test system Regulatory Class: II Product Code: LFG. DJG Dated: October 13, 2014 Received: October 16, 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,
Katherine Serrano -S
For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.
510(k) Number (if known) K142609
Device Name
CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine
Indications for Use (Describe)
CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine is a rapid test for the qualitative detection of Nortriptyline (a major metabolite of Tricyclic Antidepressants) and Buprenorphine in human urine at a cutoff concentration of 1000ng/mL and 10ng/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 test may yield preliminary positive results even when prescription drugs including Tricyclic Antidepressants and Buprenorphine are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Nortriptyline 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. GC/MS is the preferred confirmatory method. Clinical consideration and professional iudgment 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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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510(k) SUMMARY
| 1. Date: | December 10, 2014 | ||
|---|---|---|---|
| 2. | Submitter: | Guangzhou Wondfo Biotech Co., Ltd. | |
| No.8 Lizhishan Road, Science City, Luogang District, | |||
| Guangzhou, P.R. China 510663 | |||
| 3. Contact person: | Joe Shia | ||
| Fax: 301-916-6213 | LSI International Inc. | ||
| 504 East Diamond Ave., Suite F | |||
| Gaithersburg, MD 20878 | |||
| Telephone: 240-505-7880 | |||
| Email:shiajl(@yahoo.com | |||
| 4. | Device Name: | CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine | |
| Classification: | Class II | ||
| Product | |||
| Code | |||
| LFG | |||
| DIG | CFR # | ||
| 21CFR 862.3910 | |||
| 21CFR 862.3650 | |||
| 5. Predicate Devices: | K132812 | UCP Multi-Drug Test Key Cups |
-
- Intended Use
CR3 Keyless Split Sample Cup Nortriptyline-Buprenorphine is a rapid test for the qualitative detection of Nortriptyline (a major metabolite of Tricyclic Antidepressants) and Buprenorphine in human urine at a cutoff concentration of 1000ng/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.
- Intended Use
The test may yield preliminary positive results even when prescription drugs including Tricyclic Antidepressants and Buprenorphine are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Nortriptyline and Buprenorphine in urine. The test provides only preliminary test results. A more specific alternative chemical
4
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 Nortriptyline-Buprenorphine test uses immunochromatographic assays for nortriptyline and buprenorphine. The test is a lateral flow, one step system for the qualitative detection of nortriptyline and buprenorphine in human urine.
- Device Description
| Item | Device | Predicate |
|---|---|---|
| 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 | Nortriptyline: 1000ng/ml | |
| Buprenorphine: 10ng/ml | Same for | |
| Nortriptyline and | ||
| Buprenorphine | ||
| Configurations | Cup | Cup |
| Conditions for | ||
| Use | Over-the-Counter & Prescription | |
| Use | Same |
-
- Substantial Equivalence Information
9. Test Principle
The CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine test is a rapid test for the qualitative detection of Nortriptyline and Buprenorphine in urine samples and contains lateral flow chromatographic immunoassays for nortriptyline and buprenorphine. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the
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device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre-coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample.
-
- 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 , +75% cut-off and +100% cut-off. For each concentration, tests were performed two runs per day for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:
| Result
TCA | -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 |
|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| W11910601CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 44+/6- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11910602CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11910603CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
A. For Nortriptyline (TCA) testing
B. For Buprenorphine (BUP) testing
| Result
BUP | -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 |
|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| W11910601CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11910602CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11910603CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
- b. Linearity
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Not applicable.
- c. Stability
The CR3 Keyless Split Sample Cup Nortriptyline - Buprenorphine is stable at 4-30°C for 18 months as determined by conducting accelerated and real-time stability testing.
Control materials are not provided with the device. The labeling provides information on how to obtain control materials.
- d. Cut-off
A total of 125 nortriptyline samples and 125 buprenorphine samples equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs were labeled by a person who prepared them and would not participate in the sample testing. These samples were tested using three different lots by three different operators. Results were all positive at +25% and +50% cut-off and all negative at -25% and -50% cut-off for both nortriptyline and buprenorphine. The following cut-off values for the test devices have been verified.
| Test | Calibrator | Cut-off
(ng/ml) |
|---------------------|---------------|--------------------|
| Nortriptyline (TCA) | nortriptyline | 1000 |
| Buprenorphine (BUP) | buprenorphine | 10 |
- e. Interference
Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and to urine containing target drugs (nortriptyline or buprenorphine) at 25% below and 25% above the cut-off. These urine samples were tested using three batches of the CR3Keyless Split Sample Cup Nortriptyline - Buprenorphine by three different operators. Compounds that showed no interference at a concentration of 100µg/mL are summarized below:
Nortriptyline
| 4-Acetamidophenol | Erythromycin | Oxycodone |
|---|---|---|
| Acetophenetidin | β-Estradiol | Oxymetazoline |
| N-Acetylprocainamide | Estrone-3-sulfate | Papaverine |
| Acetylsalicylic acid | Ethyl-p-aminobenzoate | Penicillin-G |
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| Aminopyrine | Fenoprofen | Pentazocine hydrochloride |
|---|---|---|
| Amobarbital | Furosemide | Pentobarbital |
| Amoxicillin | Gentisic acid | Perphenazine |
| Ampicillin | Hemoglobin | Phencyclidine |
| L-ascorbic acid | Hydralazine | Phenelzine |
| DL-Amphetamine sulfate | Hydrochlorothiazide | Phenobarbital |
| Apomorphine | Hydrocodone | Phentermine |
| Aspartame | Hydrocortisone | β-Phenylethylamine |
| Atropine | O-Hydroxyhippuric acid | Trans-2-phenylcyclopropyl |
| amine hydrochloride | ||
| Benzilic acid | p-Hydroxyamphetamine | L-Phenylephrine |
| Benzoic acid | p-Hydroxy- methamphetamine | Phenylpropanolamine |
| Benzoylecgonine | 3-Hydroxytyramine | Prednisolone |
| Benzphetamine | Ibuprofen | Prednisone |
| Bilirubin | Iproniazid | Procaine |
| (±) - Brompheniramine | (±) - Isoproterenol | DL-Propanolol |
| Caffeine | Isoxsuprine | D-Propoxyphene |
| Cannabidiol | Ketamine | D-Pseudoephedrine |
| Cannabinol | Ketoprofen | Quinacrine |
| Chloralhydrate | Labetalol | Quinidine |
| Chloramphenicol | Loperamide | Quinine |
| Chlorothiazide | MDE | Ranitidine |
| (±) Chlorpheniramine | Meperidine | Salicylic acid |
| Chlorpromazine | Meprobamate | Secobarbital |
| Chlorquine | Methadone | Serotonin |
| Cholesterol | (L)Methamphetamine | Sulfamethazine |
| Clonidine | Methoxyphenamine | Sulindac |
| Cocaethylene | (±)-3,4-Methylenedioxyamphetamine hydrochloride | Tetracycline |
| Cocaine hydrochloride | (+)3,4-Methylenedioxymethamphetamine hydrochloride | Tetrahydrocortisone, |
| 3-acetate | ||
| Codeine | Morphine-3-β-D-Glucuronide | Tetrahydrocortisone, |
| 3-(β-D-glucuronide) | ||
| Cortisone | Morphine sulfate | Tetrahydrozoline |
| (-) Cotinine | Nalidixic acid | Thiamine |
| Creatinine | Naloxone | Thioridazine |
| Deoxycorticosterone | Naltrexone | DL-Tyrosine |
| Dextromethorphan | Naproxen | Tolbutamide |
| Diclofenac | Niacinamide | Triamterene |
| Diflunisal | Nifedipine | Trifluoperazine |
| Digoxin | Norcodeine | Trimethoprim |
8
| Diphenhydramine |
|---|
| Doxylamine |
| Ecgonine hydrochloride |
| Ecgonine methylester |
| Ephedrine |
| (L) - Epinephrine |
Buprenorphine
4-Acetamidophenol Acetophenetidin N-Acetylprocainamide Acetylsalicylic acid Aminopyrine Amobarbital Amoxicillin Ampicillin L-ascorbic acid DL-Amphetamine sulfate Apomorphine Aspartame Atropine Benzilic acid Benzoic acid Benzoylecgonine Benzphetamine Bilirubin (±) - Brompheniramine Caffeine Cannabidiol Cannabinol Chloralhydrate Chloramphenicol Chlorothiazide (±) Chlorpheniramine Chlorpromazine Chlorquine Cholesterol
Clonidine
Norethindrone D-Norpropoxyphene Noscapine Oxalic acid Oxazepam Oxolinic acid
Erythromycin ß-Estradiol Estrone-3-sulfate Ethyl-p-aminobenzoate Fenoprofen Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone O-Hydroxyhippuric acid p-Hydroxyamphetamine p-Hydroxy- methamphetamine 3-Hydroxytyramine Ibuprofen Iproniazid (±) - Isoproterenol Isoxsuprine Ketamine Ketoprofen Labetalol Loperamide MDE Meperidine Meprobamate Methadone (L)Methamphetamine Methoxyphenamine
Tryptamine DL-Tryptophan Tyramine Uric acid Verapamil Zomepirac
Oxycodone Oxymetazoline Papaverine Penicillin-G Pentazocine hydrochloride Pentobarbital Perphenazine Phencyclidine Phenelzine Phenobarbital Phentermine β-Phenylethylamine Trans-2-phenylcyclopropyl amine hydrochloride L-Phenylephrine Phenylpropanolamine Prednisolone Prednisone Procaine DL-Propanolol D-Propoxyphene D-Pseudoephedrine Quinacrine Quinidine Quinine Ranitidine Salicylic acid Secobarbital Serotonin Sulfamethazine Sulindac
9
| Cocaethylene | (±)-3,4-Methylenedioxyamphetamine hydrochloride | Tetracycline |
|---|---|---|
| Cocaine hydrochloride | (+)3,4-Methylenedioxymethamphetamine hydrochloride | Tetrahydrocortisone, |
| 3-acetate | ||
| Codeine | Morphine-3-β-Dglucuronide | Tetrahydrocortisone |
| 3-(β-D-glucuronide) | ||
| Cortisone | Morphine sulfate | Tetrahydrozoline |
| (-) Cotinine | Nalidixic acid | Thiamine |
| Creatinine | Naloxone | Thioridazine |
| Deoxycorticosterone | Naltrexone | DL-Tyrosine |
| Dextromethorphan | Naproxen | Tolbutamide |
| Diclofenac | Niacinamide | Triamterene |
| Diflunisal | Nifedipine | Trifluoperazine |
| Digoxin | Norcodeine | Trimethoprim |
| Diphenhydramine | Norethindrone | Tryptamine |
| Doxylamine | D-Norpropoxyphene | DL-Tryptophan |
| Ecgonine hydrochloride | Noscapine | Tyramine |
| Ecgonine methylester | Oxalic acid | Uric acid |
| Ephedrine | Oxazepam | Verapamil |
| (L) - Epinephrine | Oxolinic acid | Zomepirac |
- ﻧﮯ Specificity
To test the specificity, drug metabolites and other components that are likely to be present in urine samples were tested. The target drug (Nortriptyline or Buprenorphine), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Keyless Split Sample Cup Nortriptyline-Buprenorphine 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.
| TCA
(Nortriptyline,
Cut-off=1000 ng/mL) | Result | %
Cross-Reactivity |
|-----------------------------------------------|--------------------------|-----------------------|
| Nortriptyline | Positive at 1000 ng/mL | 100% |
| Nordoxepine | Positive at 1,000 ng/mL | 100% |
| Trimipramiine | Positive at 3,000 ng/mL | 33% |
| Amitriptyline | Positive at 1,500 ng/mL | 67% |
| Promazine | Positive at 1,500 ng/mL | 67% |
| Desipramine | Positive at 200 ng/mL | 500% |
| Imipramine | Positive at 400 ng/mL | 250% |
| Clomipramine | Positive at 12,500 ng/mL | 8% |
10
| Doxepine | Positive at 2,000 ng/mL | 50% |
|---|---|---|
| Maprotiline | Positive at 2,000 ng/mL | 50% |
| Promethazine | Positive at 25,000 ng/mL | 4% |
| BUP
(Buprenorphine,
Cut-off=10 ng/mL) | Result | %
Cross-Reactivity |
|---------------------------------------------|-----------------------|-----------------------|
| Buprenorphine | Positive at 10 ng/mL | 100% |
| Buprenorphine -3-D-Glucuronide | Positive at 15 ng/mL | 67% |
| Norbuprenorphine | Positive at 20 ng/mL | 50% |
| Norbuprenorphine -3-D-Glucuronide | Positive at 200 ng/mL | 5% |
| Morphine | >100,000 | 100,000 | 100,000 | 50 years. Urine samples were prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cut-off by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:
| Cup format | | Number
of
samples | OTC user | | %Agreement
With
GC/MS |
|---------------|---------------|-------------------------|----------|----------|-----------------------------|
| Drug | Concentration | | Negative | Positive | |
| Drug -free | -100% | 20 | 20 | 0 | 100% |
| | -75% | 20 | 20 | 0 | 100% |
| Nortriptyline | -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% |
| Buprenorphine | -75% | 20 | 20 | 0 | 100% |
| | -50% | 20 | 20 | 0 | 100% |
| | -25% | 20 | 18 | 2 | 90% |
| | +25% | 20 | 3 | 17 | 85% |
| | +50% | 20 | 0 | 20 | 100% |
| | +75% | 20 | 0 | 20 | 100% |
Lay-users were also given surveys on the ease of understanding the package insert instructions. All lay users indicated that the device instructions can be easily followed A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7.
-
- Clinical Studies
Not applicable
- Clinical Studies
11. Conclusion
Based on the test principle and performance characteristics of the device, it's concluded that CR Keyless Split Sample Cup Nortriptyline -Buprenorphine is substantially equivalent to the predicate.