(411 days)
Not Found
No
The device description and performance studies describe a lateral flow immunoassay, which is a chemical and biological test method, not a software-based technology like AI/ML. There is no mention of AI, ML, or any computational analysis of the results.
No
The device is described as a rapid lateral flow immunoassay for the detection of various substances in oral fluid, providing preliminary diagnostic information, not a therapy or treatment.
Yes
The device qualitatively detects the presence of specific substances (drugs) in human oral fluid, which is a form of diagnostic testing to identify the presence of these compounds in the body.
No
The device description explicitly states that the device consists of a "cube device, an oral fluid collection swab and a package insert," indicating physical hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states the detection of specific substances (drugs) in human oral fluid. This is a biological sample taken from the body.
- Device Description: The device is described as an "immunochromatographic assay that uses a lateral flow system for the qualitative detection" of these substances in human oral fluid. This describes a test performed in vitro (outside the body) on a biological sample.
- Anatomical Site: The sample is "Oral fluid," which is a biological specimen.
- Performance Studies: The performance studies involve testing the device with biological samples (oral fluid) and comparing the results to other analytical methods (LC/MS).
- Predicate Device: The predicate device listed (K171403; OralTox™ Oral Fluid Drug Test) is also an IVD for drug testing in oral fluid.
All these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in the examination of specimens derived from the human body to provide information for diagnostic, monitoring, or compatibility purposes. In this case, the information is the presence or absence of specific drugs in oral fluid.
N/A
Intended Use / Indications for Use
The LYHER® Oral fluid Multi-Drug Test Kit (Cube) is a rapid lateral flow immunoassay for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and Delta-9-Tetrahydrocanabinol in human oral fluid. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:
| Test | Calibrator | Cut-off (ng/mL) |
|---|---|---|
| Opiates(OPI) | Morphine | 40 |
| Cocaine (COC) | Benzoylecgonine | 20 |
| Amphetamine (AMP) | d-Amphetamine | 50 |
| Marijuana (THC) | Delta-9-Tetrahydrocannabinol | 40 |
| Methamphetamine (MET) | d-Methamphetamine | 50 |
| Phencyclidine (PCP) | Phencyclidine | 10 |
The single or multi-test panels can consist of the above insted analytes in anycombination, up to a maximum of 6 analytes. The tests provide only a preliminary result. A more specific alternate chemical must be used in order to obtain a confirmed analytical test result. Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.
Product codes (comma separated list FDA assigned to the subject device)
DJC, DIO, DJG, DKZ, LCM, LDJ
Device Description
The LYHER® Oral fluid Multi-Drug Test Kit (Cube) is an immunochromatographic assay that uses a lateral flow system for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and Delta-9-Tetrahydrocannabinol in human oral fluid. The LYHER® Oral fluid Multi-Drug Test Kit (Cube) device consists of a cube device, an oral fluid collection swab and a package insert.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
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)
Performance Characteristics:
-
Analytical Performance
- Precision-Reproducibility-Cut-Off: Samples with concentrations of -100%, -75%, -50%, -25%, cut off, +25%, +50%, +75%, and +100% cut off were prepared by spiking drug in negative oral fluid samples, confirmed by LC/MS. Tests were performed two runs per day for 30 days per device lot in a randomized order by 3 operators.
- Stability: Device stable at 2-30 degrees C for 24 months based on real-time study.
- Interference: Potential interfering substances (various compounds, food items, hemoglobin, cigarette smoking) were added to drug-free oral fluid and target drugs oral fluid at concentrations 50% below and 50% above cut-off levels. Tested using three batches of the device. None showed interference at specified concentrations.
- Specificity: Drug metabolites and other components were tested using three batches of the device to determine cross-reactivity.
- Effect of Oral fluid pH: Oral fluid samples with pH 3 to 9 spiked with target drugs at 50% below and 50% above cut-off levels were tested using three lots of the device. Results were all positive for samples at and above +50% cut-off and all negative for samples at and below -50% cut-off.
- Drug Recovery Study: Negative oral fluid samples spiked to -50% and +50% of cut-off. Samples transferred to devices and stored at room temperature, -20 degrees C and 40 degrees C. Over 90% recoveries observed for all drugs. Oral fluid samples can be stored in the device at -20 degrees C for at least 3 months and shipped overnight for LC/MS confirmation.
-
Comparison Studies:
- Method comparison studies for the LYHER Oral fluid Multi-Drug Test Kit (Cube) were performed at three testing sites with three operators at each site. Operators tested the samples using the candidate device and the results were compared to LC/MS results.
- Sample size for each drug (D-Amphetamine, Cocaine, d-Methamphetamine, Morphine, Phencyclidine, Delta-9-Tetrahydrocannabinol) including all operators and sites: 360 negative oral fluid samples, 93/69/63/57/51/93 samples for +50% cut off. For positive results, 0 samples for negative oral fluid and +50% cut off, 183/186/189/180/192/195 samples tested positive.
-
Clinical Studies: Not Applicable.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found (results provided in raw counts of positive/negative calls relative to cut-off levels, not aggregated metrics)
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
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 18, 2025
Hangzhou Laihe Biotech Co., Ltd. % Ethan Liu RA Specialist Shanghai Thinkwell Consulting Co., Ltd. Xinling Rd., 211/6F Shanghai. 201100 China
Re: K240287
Trade/Device Name: LYHER® Oral fluid Multi-Drug Test Kit (Cube) Regulation Number: 21 CFR 862.3610 Regulation Name: Methamphetamine Test System Regulatory Class: Class II Product Code: DJC, DIO, DJG, DKZ, LCM, LDJ Dated: January 24, 2025 Received: February 6, 2025
Dear Ethan Liu:
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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.
1
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportinemdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory
2
assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-torres -S
Marianela Perez-Torres, Ph.D. Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
Indications for Use
510(k) Number (if known) K240287
Device Name
LYHER® Oral fluid Multi-Drug Test Kit (Cube)
Indications for Use (Describe)
The LYHER® Oral fluid Multi-Drug Test Kit (Cube) is a rapid lateral flow immunoassay for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and Delta-9-Tetrahydrocanabinol in human oral fluid. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:
| Test | Calibrator | Cut-off (ng/mL) |
|---|---|---|
| Opiates(OPI) | Morphine | 40 |
| Cocaine (COC) | Benzoylecgonine | 20 |
| Amphetamine (AMP) | d-Amphetamine | 50 |
| Marijuana (THC) | Delta-9-Tetrahydrocannabinol | 40 |
| Methamphetamine (MET) | d-Methamphetamine | 50 |
| Phencyclidine (PCP) | Phencyclidine | 10 |
The single or multi-test panels can consist of the above insted analytes in anycombination, up to a maximum of 6 analytes. The tests provide only a preliminary result. A more specific alternate chemical must be used in order to obtain a confirmed analytical test result. Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.
| Type of Use (Select one or both, as applicable) | ||||
|---|---|---|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | ||||
| 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."
4
510(k) Summary K240287
This summary of 510(k) safety and effectiveness information is being submitted in accordance with requirements of 21 CFR Part 807.92.
1. Submitter
| Submitted by: | Hangzhou Laihe Biotech Co., Ltd. |
|---|---|
| Address: Room 401-406, F1-3, Building 1, No.425 | |
| Miaohouwang Road, Xixing Street, Binjiang | |
| District, Hangzhou, 310051 Zhejiang P.R. China | |
| Tel.: +86 571 8765 3090 | |
| Fax: +86 571 8665 8000 | |
| www.lyher.com | |
| Contact Person: | Ethan Liu |
| Shanghai Thinkwell Consulting Co., Ltd | |
| Address:Xinling Rd., 211/6F Shanghai, 201100,P.R. | |
| China | |
| Phone:0086-15216699240 | |
| Email:xtdeepwater@126.com | |
| Date Prepared: | March 6, 2025 |
2. Device
LYHER® Oral fluid Multi-Drug Test Kit (Cube)
Classification:
| Product Code | CFR # | Panel |
|---|---|---|
| DJC | 862.3610/Methamphetamine | |
| test system. | Toxicology | |
| DIO | 862.3250/Cocaine system. | Toxicology |
| DJG | 862.3650/Opiate test system. | Toxicology |
| DKZ | 862.3100/Amphetamine Test | |
| System | Toxicology | |
| LCM | Unclassified | Toxicology |
| LDJ | 862.3870/Cannabinoid test | |
| system. | Toxicology |
3. Predicate Device:
OralTox™ Oral Fluid Drug Test, K171403
5
4. Device Description
The LYHER® Oral fluid Multi-Drug Test Kit (Cube) is an immunochromatographic assay that uses a lateral flow system for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and Delta-9-Tetrahydrocannabinol in human oral fluid. The LYHER® Oral fluid Multi-Drug Test Kit (Cube) device consists of a cube device, an oral fluid collection swab and a package insert.
5. Intended Use / Indications for Use:
The LYHER® Oral fluid Multi-Drug Test Kit (Cube) is a rapid lateral flow immunoassay for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and Delta-9-Tetrahydrocannabinol in human oral fluid. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:
| Test | Calibrator | Cut-off (ng/mL) |
|---|---|---|
| Opiates(OPI) | Morphine | 40 |
| Cocaine (COC) | Benzoylecgonine | 20 |
| Amphetamine (AMP) | d-Amphetamine | 50 |
| Marijuana (THC) | Delta-9- | |
| Tetrahydrocannabinol | 40 | |
| Methamphetamine (MET) | d-Methamphetamine | 50 |
| Phencyclidine (PCP) | Phencyclidine | 10 |
The single or multi-test panels can consist of the above listed analytes in any combination, up to a maximum of 6 analytes.
The tests provide only a preliminary result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical test result. Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography/Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.
6. Substantial Equivalence
A summary comparison of features of the LYHER® Oral fluid Multi-Drug Test Kit (Cube) and the predicate devices is provided in following tables.
6
| Item | Proposed Device | Predicate
Device-K171403 | | | | | | | | | | | | | | |
|-----------------------|----------------------------------------------------------------------------------------------------------------------|-----------------------------|--|--|--|--|--|--|--|--|--|--|--|--|--|------|
| Similarities | | | | | | | | | | | | | | | | |
| Indication(s) for Use | For the qualitative determination of drugs of abuse in human oral fluid. | Same | | | | | | | | | | | | | | |
| Methodology | Competitive binding, Lateral flow immunochromatographic assay based on principle of antigen antibody immunochemistry | Same | | | | | | | | | | | | | | |
| Type of Test | Qualitative | Same | | | | | | | | | | | | | | |
| Specimen Type | Human oral fluid | Same | | | | | | | | | | | | | | |
| Cut-off Values | Test Cut-off (ng/mL) OPI 40 COC 20 AMP 50 THC 40 MET 50 PCP 10 | | | | | | | | | | | | | | | Same |
| Intended Use | For prescription use. | Same | | | | | | | | | | | | | | |
| Differences | | | | | | | | | | | | | | | | |
| Configurations | Cube | Cups | | | | | | | | | | | | | | |
7. Test Principle
Each device employs lateral flow immunochromatographic technology and is based on the principle of competitive binding. Drugs, if present in concentrations below the cutoff level, will not saturate the binding sites of the antibody coated particles on the drug specific test strips. The goat-anti-rabbit IgG antibody-coated particles will then be captured by immobilized drug-specific conjugate. If the level of drug in the oral fluid specimen is below the cutoff concentration, the T line appears as a visible burgundy line. If the level of drug in the oral fluid specimen is above the cutoff, no T line develops. The control line (C line) serves as an internal quality control. The control line should always appear as a burgundy-colored band regardless of the presence of the drug, if enough sample volume has been added to the test and if the sample has correctly migrated up the test strip.
Testing is based on the principle of a competitive immunochemical reaction between a chemically labeled drug (drug-protein conjugate) and the drug or drug metabolites which may be present in the oral fluid sample competing for the limited antibody binding sites.
8. Performance Characteristics
8.1 Analytical Performance
- a. Precision-Reproducibility-Cut-Off
7
Precision-Reproducibility-Cut-Off studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cut off, +25% cut off, +50% cut off , +75% cut off and +100% cut off. These samples were prepared by spiking drug in negative oral fluid samples. Each drug concentration was confirmed by LC/MS. All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing. For each concentration, tests were performed two runs per day for 30 days per device lot in a randomized order. The data is summarized below.
| Operator 1 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| -100% | ||||||||||
| cut off | -75% | |||||||||
| cut off | -50% | |||||||||
| cut off | -25% | |||||||||
| cut off | Cut off | +25% | ||||||||
| cut off | +50% | |||||||||
| Cut | ||||||||||
| off | +75% | |||||||||
| cut off | +100% | |||||||||
| cut off | ||||||||||
| Lot | ||||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 47+/13- | ર્ડન/2- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 47+/13- | ર્સન/ર- | 60+/0- | 60+/0- | 60+/0- | |
| Operator 2 | ||||||||||
| Lot | ||||||||||
| Drug | -100% | |||||||||
| cut off | -75% | |||||||||
| cut off | -50% | |||||||||
| cut off | -25% | |||||||||
| cut off | Cut off | +25% | ||||||||
| cut off | +50% | |||||||||
| Cut | ||||||||||
| off | +75% | |||||||||
| cut off | +100% | |||||||||
| cut off | ||||||||||
| Lot | ||||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 47+/13- | ર્સન/ર- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 47+/13- | ર્રન/ર- | 60+/0- | 60+/0- | 60+/0- | |
| Operator 3 | ||||||||||
| Lot | ||||||||||
| Drug | -100% | |||||||||
| cut off | -75% | |||||||||
| cut off | -50% | |||||||||
| cut off | -25% | |||||||||
| cut off | Cut off | +25% | ||||||||
| cut off | +50% | |||||||||
| Cut | ||||||||||
| off | +75% | |||||||||
| cut off | +100% | |||||||||
| cut off | ||||||||||
| Lot | ||||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 47+/13- | 56+/4- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | ૨+/૨૨- | 47+/13- | 56+/4- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- |
Amphetamine
8
| Cocaine |
|---|
| Operator 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut | |||||||||
| off | -50% | ||||||||
| cut | |||||||||
| off | -25% | ||||||||
| cut | |||||||||
| off | Cut off | +25% | |||||||
| cut | |||||||||
| off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut | |||||||||
| off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Operator 2 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut | |||||||||
| off | -50% | ||||||||
| cut | |||||||||
| off | -25% | ||||||||
| cut | |||||||||
| off | Cut off | +25% | |||||||
| cut | |||||||||
| off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut | |||||||||
| off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Operator 3 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut | |||||||||
| off | -50% | ||||||||
| cut | |||||||||
| off | -25% | ||||||||
| cut | |||||||||
| off | Cut off | +25% | |||||||
| cut | |||||||||
| off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut | |||||||||
| off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
9
| Methamphetamine | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Operator 1 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 47+/13- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- |
| Operator 2 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 47+/13- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Operator 3 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot 1 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 47+/13- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
Methamphetamine
10
| Morphine | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Operator 1 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Operator 2 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Operator 3 | |||||||||
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
Morphine
11
| Operator 1 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Lot | ||||||||||
| Drug | -100% | |||||||||
| cut off | -75% | |||||||||
| cut off | -50% | |||||||||
| cut off | -25% | |||||||||
| cut off | Cut off | +25% | ||||||||
| cut off | +50% | |||||||||
| Cut | ||||||||||
| off | +75% | |||||||||
| cut off | +100% | |||||||||
| cut off | ||||||||||
| Lot | ||||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- | |
| Operator 2 | ||||||||||
| Lot | ||||||||||
| Drug | -100% | |||||||||
| cut off | -75% | |||||||||
| cut off | -50% | |||||||||
| cut off | -25% | |||||||||
| cut off | Cut off | +25% | ||||||||
| cut off | +50% | |||||||||
| Cut | ||||||||||
| off | +75% | |||||||||
| cut off | +100% | |||||||||
| cut off | ||||||||||
| Lot | ||||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Operator 3 | ||||||||||
| Lot | ||||||||||
| Drug | -100% | |||||||||
| cut off | -75% | |||||||||
| cut off | -50% | |||||||||
| cut off | -25% | |||||||||
| cut off | Cut off | +25% | ||||||||
| cut off | +50% | |||||||||
| Cut | ||||||||||
| off | +75% | |||||||||
| cut off | +100% | |||||||||
| cut off | ||||||||||
| Lot | ||||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot | ||||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
Phencyclidine
12
| Operator 1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Lot | |||||||||
| Drug | -100% | ||||||||
| cut off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Operator 2 | |||||||||
| Lot | |||||||||
| Drug | 100% | ||||||||
| cut | |||||||||
| off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 5+/55- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Operator 3 | |||||||||
| Lot | |||||||||
| Drug | 100% | ||||||||
| cut | |||||||||
| off | -75% | ||||||||
| cut off | -50% | ||||||||
| cut off | -25% | ||||||||
| cut off | Cut off | +25% | |||||||
| cut off | +50% | ||||||||
| Cut | |||||||||
| off | +75% | ||||||||
| cut off | +100% | ||||||||
| cut off | |||||||||
| Lot | |||||||||
| 1 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 2 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot | |||||||||
| 3 | 0+/60- | 0+/60- | 0+/60- | 6+/54- | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
Marijuana (THC)
The following cut-off values for the candidate devices have been verified.
| Calibrator | Cut-off (ng/mL) |
|---|---|
| d-Amphetamine | 50 |
| Benzoylecgonine | 20 |
| d-Methamphetamine | 50 |
| Morphine | 40 |
| Phencyclidine | 10 |
| Delta-9-Tetrahydrocannabinol | 40 |
13
b. Linearity Not applicable.
c. Stability
Device stability has been evaluated through accelerated and real-time studies. The devices are stable at 2-30°C for 24 months based on the real time stability study at room temperature.
d. Interference
Potential interfering substances were added to drug-free oral fluid and target drugs oral fluid with concentrations at 50% below and 50% above cut-off levels. These oral fluid samples were tested using three batches of the device. Compounds that showed no interference for all the six drugs at a concentration of 10 µg/mL are summarized in the following table.
| Acetaminophen | Dextromethorphan | Naltrexone |
|---|---|---|
| Acetylcodeine | Digoxin | Naproxen |
| Allobarbital | Dihydrocodeine | Nicotinamide |
| Alprazolam | diltiazem HCl | Nicotine |
| Amobarbital | Diphenhydramine | |
| HCl | Noscapine | |
| Apomorphine | DL-Propranolol | Omeprazole |
| Atenolol | Doxylamine | Papaverine |
| Atropine | Ecgonine methylester | Pentazocine |
| Baclofen | Estradiol | Phentermine |
| Benzocaine | Estrone | Phenylpropanolamine |
| Butabarbital | Fluconazole | Phenytoin |
| Caffeine | Furosemide | Pioglitazone HCl |
| Cannabidiol | Hexobarbital | Prednisolone |
| Carbamazepine | Hydrochlorothiazide | Prednisone |
| Chlordiazepoxide | Ibuprofen | Procainamide HCl |
| Chlorpromazine | Imipramine | Procaine HC1 |
| Cimetidine | Lamotrigine | Promethazine |
| Citalopram HBr | Levetiracetam | Quinine HCl |
| Clobazam | Lidocaine | R,R(-)- |
| Pseudoephedrine | ||
| Clomipramine | Lormetazepam | Salicylic Acid |
| Clonazepam | L-Thyroxine | Sertraline HCl |
| Clonidine | Metformin HCl | Simvastin |
| Clopidogrel bisulfate | Methylphenidate HCl | Theophylline |
| Cortisol | Metoprolol | Thiamine |
| Cotinine | Metronidazole | Topiramate |
| d,l-Salbutamol | Montelukast sodium | |
| salt | Valproic Acid | |
| Deoxycorticosterone | Naloxone | Verapamil |
| Zonisamide |
14
Food items such as methanol cough drops, cough syrup, cola, mouthwash, coffee, tea, milk, sugar, chewing gum, alcohol, baking soda, salt, cranberry juice, orange juice, food coloring (red, blue, green), toothpaste, tomatoes and MSG were added in either drug-free oral fluid or oral fluid containing the target drug with concentrations of 50% below and 50% above cutoff levels to a concentration of 5%. None of the substances showed interference. Hemoglobin showed no interference at 100 ug/mL. Cigarette smoking showed no interference.
e. Specificity
To test specificity, drug metabolites and other components that are likely to interfere in oral fluid samples were tested using three batches of the device. The following are summaries.
| Amphetamine (AMP)
(Cut-off=50 ng/mL) | Result Positive at
(ng/mL) | % Cross
Reactivity |
|------------------------------------------|-------------------------------|-----------------------|
| D-Amphetamine | 50 | 100.00% |
| L-Amphetamine | 4000 | 1.25% |
| D,L-Amphetamine | 125 | 40.00% |
| Methoxyamphetamine | 500 | 10% |
| Methylenedioxyamphetamine(MDA) | 150 | 33% |
| Benzodioxolylbutanamine (BDB) | 10000 | 0.5% |
| 3-Hydroxy Tyramine | 5000 | 1% |
| d,l-p-Chloramphetamine | 500 | 10% |
| Phenethylamine | 4000 | 1.25% |
| Hydroxyamphetamine | 800 | +50%
cut off |
|---------------------------------------|----------------|------------------------|------------------|-------------------------|-----------------------------|------------------|
| Total (all
operators
and sites) | Negative | 360 | 93 | 74 | 9 | 0 |
| | Positive | 0 | 0 | 1 | 180 | 183 |
Cocaine
| Operator | Test
result | Negative
oral fluid | +50%
cut off |
|---------------------------------------|----------------|------------------------|------------------|-------------------------|-----------------------------|------------------|
| Total (all
operators
and sites) | Negative | 360 | 69 | 83 | 8 | 0 |
| Total (all
operators
and sites) | Positive | 0 | 0 | 4 | 172 | 186 |
d-Methamphetamine
| Operator | Test
result | Negative
oral fluid | +50%
cut off |
|---------------------------------------|----------------|------------------------|------------------|-------------------------|-----------------------------|------------------|
| Total (all
operators
and sites) | Negative | 360 | 63 | 70 | 7 | 0 |
| Total (all
operators
and sites) | Positive | 0 | 0 | 2 | 164 | 189 |
Morphine
| Operator | Test
result | Negative
oral fluid | +50%
cut off |
|---------------------------------------|----------------|------------------------|------------------|-------------------------|----------------------------|------------------|
| Total (all
operators
and sites) | Negative | 360 | 57 | 84 | 6 | 0 |
| Total (all
operators
and sites) | Positive | 0 | 0 | 3 | 183 | 180 |
Phencyclidine
| Operator | Test
result | Negative
oral fluid | +50%
cut off |
|---------------------------------------|----------------|------------------------|------------------|-------------------------|-----------------------------|------------------|
| Total (all
operators
and sites) | Negative | 360 | 51 | 109 | 13 | 0 |
| Total (all
operators
and sites) | Positive | 0 | 0 | 5 | 170 | 192 |
19
| Operator | Test
result | Negative
oral fluid | +50%
cut off |
|------------------------------------|----------------|------------------------|------------------|-------------------------|-----------------------------|------------------|
| Total (all operators
and sites) | Negative | 360 | 93 | 96 | 8 | 0 |
| Total (all operators
and sites) | Positive | 0 | 0 | 3 | 172 | 195 |
Delta-9-Tetrahydrocannabinol
8.3 Clinical Studies Not Applicable.
9. Conclusion
Based on the test principle and acceptable performance characteristics including precision, interference, specificity, and method comparison studies of the devices, it's concluded that the LYHER Oral fluid Multi-Drug Test Kit(Cube) is substantially equivalent to the predicate.