(40 days)
Not Found
No
The device description and performance studies describe a standard lateral flow immunoassay, which does not inherently involve AI or ML. There are no mentions of AI, ML, or image processing in the provided text.
No
This device is for the qualitative detection of fentanyl in urine, serving as a diagnostic tool, not for treatment.
Yes
This device is a diagnostic device as it performs qualitative detection of fentanyl and its major metabolite in human urine, providing a preliminary test result for the presence of these substances.
No
The device description explicitly states it consists of a "Test Panel" and a "package insert," and that the Test Panel is sealed in an "aluminum pouch." This indicates a physical, hardware-based test kit, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states the device is for the "qualitative detection of fentanyl, the major metabolite of fentaryl in human urine". This is a diagnostic purpose, specifically identifying the presence of a substance in a biological sample.
- Sample Type: The device analyzes "human urine", which is a biological specimen.
- Method: It uses an "immunochromatographic assay", which is a common method for in vitro diagnostic tests.
- Device Description: The description confirms it's an "immunoassay intended for the qualitative detection of fentanyl and norfentany] in human urine".
- Performance Studies: The document describes performance studies using "clinical samples" and comparing results to a reference method (LC/MS), which are typical for evaluating the performance of an IVD.
- Lay User Study: The inclusion of a lay user study for the "Home Use" version further indicates its intended use as a diagnostic device that can be used by individuals.
All these factors align with the definition of an In Vitro Diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnostic purposes.
N/A
Intended Use / Indications for Use
Hightop® Home Use Fentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:
| Analyte | Cut-off Level |
|---|---|
| Fentanyl (FYL) | 1ng/mL |
| Norfentanyl (NFYL) | 5ng/mL |
The test is available in a single test of FYL or a Double panel of FYL and NFYL. It is intended for OTC use. The test provides only a preliminary test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
Hightop® Fentanyl/Norfentany] Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:
| Analyte | Calibrator | Cut-off level |
|---|---|---|
| Fentanyl (FYL) | Fentanyl | 1ng/mL |
| Norfentanyl (NFYL) | Norfentanyl | 5ng/mL |
The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL. The test panel provides only a preliminary test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
The test panel is not intended to distinguish between prescription use or abuse of fentanyl. Clinical consideration and professional judgment should be applied to the test result, particularly in evaluating a preliminary positive result.
Product codes (comma separated list FDA assigned to the subject device)
NGL
Device Description
The Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel and Hightop® Fentanyl Norfentanyl Urine Rapid Test Panel are immunoassays intended for the qualitative detection of fentanyl and norfentanyl in human urine. Each Hightop® fentanyl urine test device consists of a Test Panel and a package insert. Each Test Panel is sealed with sachets of desiccant in an aluminum pouch.
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
For OTC 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: 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 for each target drug (fentanyl or norfentanyl) were prepared by spiking into negative urine samples. Each concentration was confirmed by LC/MS. All sample aliquots were blindly labeled. For each concentration, six tests per day were performed for 10 days per device lot in a randomized order. Total tests per concentration per lot: 60.
Interference Study: Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drug fentanyl urine with concentrations at 50% below and 50% above Cut-Off levels. These urine samples were tested using three batches of each device.
Specificity Study: Drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of device.
Effect of Urine Specific Gravity and Urine pH Study: Urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with targets fentanyl and norfentanyl at 50% below and 50% above Cut-Off levels. These samples were tested using three lots of device.
Comparison Studies: Method comparison studies were performed by three different operators. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were blind labeled and compared to LC/MS results.
Lay-user study: A lay user study was performed at three testing sites using three different lots (1 lot per test site) with 140 lay persons. Urine samples were prepared at the following concentrations: -100%, +/-75%, +/-50%, +/-25% of the cut-offs by spiking drug(s) into drug-free-pooled urine specimens. The concentrations of the samples were confirmed by LC/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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance - Precision:
- Fentanyl (Cut-off 1ng/mL):
- For -100%, -75%, -50%, -25% cut-off levels, 179/180 or 180/180 samples were correctly identified as negative across 3 lots.
- For cut-off level, 116/180 samples were positive, 64/180 were negative.
- For +25%, +50%, +75%, +100% cut-off levels, 180/180 samples were correctly identified as positive across 3 lots.
- Norfentanyl (Cut-off 5ng/mL):
- For -100%, -75%, -50% cut-off levels, 180/180 samples were correctly identified as negative across 3 lots.
- For -25% cut-off level (3.75 ng/mL), 175/180 samples were negative, 5/180 were positive.
- For cut-off level (5 ng/mL), 100/180 samples were positive, 80/180 were negative.
- For +25%, +50%, +75%, +100% cut-off levels, 180/180 samples were correctly identified as positive across 3 lots.
Analytical Performance - Stability: The devices are stable at 36-86F for 24 months based on the accelerate stability study.
Analytical Performance - Interference: No interference was observed for a large list of compounds tested at 100 µg/mL or specified concentrations when tested with drug-free urine and fentanyl urine at 50% below and 50% above cut-off levels.
Analytical Performance - Specificity (Cross-Reactivity):
- Fentanyl (Cutoff=1ng/mL): Fentanyl showed 100% cross-reactivity at 1 ng/mL. Other fentanyl analogs showed varying degrees of cross-reactivity (e.g., Acetyl fentanyl 20% at 5 ng/mL, Butyryl fentanyl 10% at 10 ng/mL, Carfentanil 10% at 10 ng/mL, Furanyl Fentanyl 5% at 20 ng/mL). Norfentanyl showed 100000 ng/mL.
- Norfentanyl (Cutoff=5ng/mL): Norfentanyl showed 100% cross-reactivity at 5 ng/mL. Fentanyl showed 55.6% cross-reactivity at 9 ng/mL. Other compounds showed varying degrees of cross-reactivity.
- The following opioids were tested at 100 ug/mL and showed no cross-reactivity: 6-Acetyl morphine, Amphetamine, Buprenorphine, Buprenorphineglucuronide, Codeine, Dextromethorphan, Dihydrocodeine, EDDP, EMDP, Fluoxetine, Heroin, Hydrocodone, Hydromorphone, Ketamine, Levorphanol, Meperidine, Methadone, Morphine, Morphine-3-glucuronide, Naloxone, Naltrexone, Norbuprenorphine, Norcodeine, Norketamine, Normeperidine, Normorphine, Noroxycodone, Oxycodone, Oxymorphone, Pentazocine (Talwin), Pipamperone, Tapentadol, Thioridazine, Tilidine, Tramadol, Tramadol-O-Desmethyl, Tramadol-N-Desmethyl, Tramadol-N-Desmethyl.
Analytical Performance - Effect of Urine Specific Gravity and Urine pH: Results were all positive for samples at and above +50% Cut-Offs and all negative for samples at and below -50% Cut-Offs for urine samples with 1.000 to 1.035 specific gravity or pH 4 to 9.
Comparison Studies (with LC/MS):
- Fentanyl:
- Total 240 samples per operator (40 negative, 40 positive).
- Operator 1: Identified 19 samples LC/MS 0.7880 and 0.7912 as Positive (false positive at Near Cutoff Negative). Identified 1 sample LC/MS 1.0078 as Negative (false negative at Near Cutoff Positive).
- Operator 2: Identified 19 samples LC/MS 0.7912 and 0.7874 as Positive (false positive at Near Cutoff Negative). Identified 1 sample LC/MS 1.0282 as Negative (false negative at Near Cutoff Positive).
- Operator 3: Identified 19 samples LC/MS 0.7880 as Positive (false positive at Near Cutoff Negative). Identified 1 sample LC/MS 1.0811 as Negative (false negative at Near Cutoff Positive).
- Norfentanyl:
- Total 240 samples per operator (40 negative, 40 positive).
- Operator 1: Identified 1 sample LC/MS 4.6743 as Positive (false positive at Near Cutoff Negative). Identified 1 sample LC/MS 5.1608 as Negative (false negative at Near Cutoff Positive).
- Operator 2: Identified 2 samples LC/MS 4.6743, 4.1946 as Positive (false positive at Near Cutoff Negative). Identified 2 samples LC/MS 5.1303, 5.0744 as Negative (false negative at Near Cutoff Positive).
- Operator 3: Identified 1 sample LC/MS 4.1946 as Positive (false positive at Near Cutoff Negative). Identified 1 sample LC/MS 5.0744 as Negative (false negative at Near Cutoff Positive).
Lay-user study (Home Use): Sample size 140 lay persons.
- Fentanyl:
- 100% correct results for -100%, -75%, -50%, -25% Cutoff (all negative).
- 100% correct results for +25%, +50%, +75% Cutoff (all positive).
- Norfentanyl:
- 100% correct results for -100%, -75%, -50% Cutoff (all negative).
- 95.0% correct results for -25% Cutoff (1 false positive out of 20 samples).
- 100% correct results for +25%, +50%, +75% Cutoff (all positive).
- All lay users indicated that the device instructions can be easily followed. Flesch-Kincaid reading analysis of the package insert revealed a reading grade level of less than 7.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not directly provided as Sensitivity, Specificity, PPV, NPV values in a summarized table, but can be inferred from the performance study tables.
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.
AllTest Fentanyl Urine Test Cassette (K233417)
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
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: on the left, there is the Department of Health & Human Services logo, which features an abstract caduceus symbol. To the right of this is the FDA logo, which includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
Oingdao HIGHTOP Biotech Co., Ltd. % Jenny Xia Director LSI International Inc 504E Diamond Ave., Suite H Gaithersburg, Maryland 20877
Re: K241969
Trade/Device Name: Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel: Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Code: NGL Dated: July 3, 2024 Received: July 5, 2024
Dear Jenny Xia:
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.
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).
1
Your device is also subject to, among other requirements, the Quality System (QS) 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 (QS) 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.
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-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-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-regulatoryassistance/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,
Joseph A. Digitally signed by Kotarek -S Date: 2024.08.14
Joseph Kotarek, Ph.D. Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K241969
Device Name
Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel
Indications for Use (Describe)
Hightop® Home Use Fentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl, the major metabolite of fentaryl in human urine at the cut-off concentrations listed below:
| Analyte | Cut-off Level |
|---|---|
| Fentanyl (FYL) | 1ng/mL |
| Norfentanyl (NFYL) | 5ng/mL |
The test is available in a single test of FYL or a Double panel of FYL and NFYL. It is intended for OTC use. The test provides only a preliminary test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
Hightop® Fentanyl/Norfentany] Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:
| Analyte | Calibrator | Cut-off level |
|---|---|---|
| Fentanyl (FYL) | Fentanyl | 1ng/mL |
| Norfentanyl (NFYL) | Norfentanyl | 5ng/mL |
The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL. The test panel provides only a preliminary test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
The test panel is not intended to distinguish between prescription use or abuse of fentanyl. Clinical consideration and professional judgment should be applied to the test result, particularly in evaluating a preliminary positive result.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
3
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4
510(k) SUMMARY K241969
| 1. Date: | July 3, 2024 |
|---|---|
| 2. Submitter: | Qingdao HIGHTOP Biotech Co., Ltd. |
| No.369 Hedong Road, Qingdao, Shandong 266112 | |
| China | |
| 3. Contact person: | Jenny Xia |
| LSI International Inc. | |
| 504E Diamond Ave., Suite H | |
| Gaithersburg, MD 20877 | |
| Telephone: 240-505-7880 | |
| Email: jxia@lsi-consulting.org | |
| 4. Device Names: | Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel |
| Classification: | Class 2 | ||
|---|---|---|---|
| Product Code | Classification | Regulation Section | Panel |
| NGL | II | 21 CFR § 862.3650 | |
| Opiate Test System | Toxicology (91) |
Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel
-
- Predicate Devices:
AllTest Fentanyl Urine Test Cassette (K233417)
- Predicate Devices:
-
- Indications for Use
Hightop® Home Use Fentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl and norfentany], the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:
- Indications for Use
| Analyte | Cut-off Level |
|---|---|
| Fentanyl (FYL) | 1ng/mL |
| Norfentanyl (NFYL) | 5ng/mL |
The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL. It is intended for OTC use.
The test provides only a preliminary test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl and norfentanyl, the major metabolite of fentanyl in human urine at the cut-off concentrations listed below:
| Analyte | Calibrator | cut-off level |
|---|---|---|
| Fentanyl (FYL) | Fentanyl | 1ng/mL |
| Norfentanyl (NFYL) | Norfentanyl | 5ng/mL |
The test is available in a single test of FYL or NFYL or a Double panel of FYL and NFYL.
5
The test panel provides only a preliminary test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
The test panel is not intended to distinguish between prescription use or abuse of fentanyl. Clinical consideration and professional judgment should be applied to the test result, particularly in evaluating a preliminary positive result.
-
- Device Description
The Hightop® Home Use Fentanyl/Norfentanyl Urine Rapid Test Panel and Hightop® Fentanyl Norfentanyl Urine Rapid Test Panel are immunoassays intended for the qualitative detection of fentanyl and norfentany] in human urine. Each Hightop® fentanyl urine test device consists of a Test Panel and a package insert. Each Test Panel is sealed with sachets of desiccant in an aluminum pouch.
- Device Description
-
- Substantial Equivalence Information
A summary comparison of features of the Hightop® Fentanyl Test and the predicate devices is provided in following table.
- Substantial Equivalence Information
| Item | Device | Predicate – K233417 |
|---|---|---|
| Indication(s) | ||
| for Use | For the qualitative determination of | |
| fentanyl in human urine. | Same | |
| Calibrator and Cut-Off | ||
| Values | Fentanyl (FTY) | |
| 1 ng/ml | ||
| Norfentanyl (NFTY) | ||
| 5 ng/ml | Fentanyl (FTY) | |
| 1 ng/ml | ||
| Methodology | Competitive binding, lateral flow | |
| immunochromatographic assays based | ||
| on the principle of antigen antibody | ||
| immunochemistry. | Same | |
| Type of Test | Qualitative | Same |
| Specimen Type | Human Urine | Same |
| Intended Use | For OTC use | Same |
| Configurations | Panel | Cassette |
| Storage | 2-30°C | 4-30°C |
Table 1: Features Comparison of Hightop® Fentanyl Urine Test and the Predicate Device
9. Test Principle
The Hightop® Home Use Fentanyl Urine Rapid Test Panel and Hightop® Fentanyl/Norfentanyl Urine Rapid Test Panel are immunoassays based on the principle of competitive binding.
During testing, a urine specimen migrates upward by capillary action. Each target drug, if present in the urine specimen below its cutoff, will not saturate the binding sites of antibodycoated particles in the test device. The antibody-coated particles will then be captured by immobilized drug conjugate and a visible colored line will show up in the test line region. The
6
colored line will not form in the test line region if the drug level exceeds the cutoff because it will saturate all the binding sites of anti-drug antibodies.
To serve as a procedural control, a colored line will always appear at the control line region indicating that proper volume of specimen has been added and membrane wicking has occurred.
10. Performance Characteristics
-
- Analytical Performance
- Precision a.
Precision 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 for each target drug. These samples were prepared by spiking fentanyl or norfentanyl in negative urine samples. Each fentanyl or norfentanyl 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 six tests per day for 10 days per device lot in a randomized order.
Fentanyl
| Lot
Number | -100%
cut off | -75%
cut off | -50%
cut off | -25%
cutoff | cut off | +25%
cut off | +50%
cut off | +75%
cut off | +100%
cut off |
|---------------|------------------|-----------------|-----------------|----------------|---------|-----------------|-----------------|-----------------|------------------|
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 40+/20- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 38+/22- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 38+/22- | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
Norfentanyl
| Lot
Number | -100%
cut off | -75%
cut off | -50%
cut off | -25%
cutoff | +25%
cut off | +50%
cut off | +75%
cut off | +100%
cut off |
|---------------|------------------|-----------------|-----------------|----------------|-----------------|-----------------|-----------------|------------------|
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 58-/2+ | 35+/25- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 58-/2+ | 32+/28- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 33+/27- | 60+/0- | 60+/0- | 60+/0- |
Stability C.
The devices are stable at 36-86F for 24 months based on the accelerate stability study.
d. Interference
Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drug fentanyl urine with concentrations at 50% below and 50% above Cut-Off levels. These urine samples were tested using three batches of each device. Compounds that showed no interference at a concentration of 100µg/mL or specified concentrations are summarized in the following tables.
| Acetaminophen | Ecgonine methyl
ester | Oxolinic acid |
|-----------------------------------|---------------------------|---------------------------------------|
| Acetone (1000 mg/dL) | Ephedrine | Oxymetazoline |
| Acetophenetidin | Erythromycin | Papaverine |
| Acetylsalicylic acid | Estradiol | Penicillin G |
| Albumin (100 mg/dL) | Estrone | Perphenazine |
| Albuterol | Ethanol (1%) | Phencyclidine |
| 7-Aminonitrazepam | Fenfluramine | Phenelzine |
| Amitriptyline | Fenofibrate | Phenobarbital |
| Amlodipine besylate | Fenoprofen | Phentermine |
| Amobarbital | Fluphenazine | Phenylethylamine |
| Amoxicillin | Fotemustine | Prednisone |
| Ampicillin | Furosemide | Promazine |
| Apomorphine | Galactose | Promethazine |
| Ascorbic acid | γ-Globulin (500 mg/dL) | Propoxyphene |
| Aspartame | Gemfibrozil | Propranolol |
| Aspirin | Gentisic acid | Pseudoephedrine |
| Atropine | Glucose (3000 mg/dL) | Pyridoxine |
| Baclofen | Guaiacolglyceryl
ether | Pyrilamine |
| Benzilic acid | Hemoglobin | Pyrogallol |
| Benzocaine | Hexobarbital | Quinidine |
| Benzoic acid | Hydralazine | Quinine |
| Benzoylecgonine | Hydrochlorothiazide | Quinolinic Acid |
| Benzylpiperiazine | Hydrocortisone | Ranitidine |
| Bilirubin | Hydroxybutyric
Acid | Riboflavin |
| Boric Acid (1%) | Ibuprofen | Salicylic acid |
| Bromo-2,5,Dimethoxyphenethylamine | Imipramine | Secobarbital |
| Bupropion | Isoproterenol | Serotonin |
| Caffeine | Isoxsuprine (10 μg/mL) | Sodium Azide |
| Carbamazepine | Ketoprofen | Sulfamethazine |
| Carisoprodol | Labetalol | Sulindac |
| Cetirizine | Lamotrigine | Tetracycline |
| Chloral hydrate | Lidocaine | Tetrahydrocortisone3-(β-Dglucuronide) |
| Chloramphenicol | Lisinopril | Tetrahydrocortisone 3-acetate |
| Chlordiazepoxide | Loperamide | Tetrahydrozoline |
| Chlorothiazide | Loratidine | Thiamine |
| Chlorpheniramine | Maprotiline | Triamterene |
| Chlorpromazine | Meperidine | Trifluoperazine |
| Cholesterol | Meprobamate | Trifluoromethylphenyl-piperazine |
| Clofibrate | Methapyrilene | Trimethoprim |
| Clomipramine | Methaqualone | Tryptamine |
| Clonidine | Methoxyphenamine | Tyramine |
| Cortisone | Methylphenidate | Urea (2000 mg/dL) |
| Cotinine | Metoprolol | Uric acid |
| Creatine Hydrate | Metronidazole | Valproic acid (250 μg/mL) |
| Creatinine | N-Acetylprocainamide | Venlafaxine |
| Cyclobenzaprine | N-desmethyl
Tapentadol | Verapamil |
| γ-Cyclodextrin | Nacl (4000 mg/dL) | Zolpidem |
| Cyproheptadine | Nalidixic acid | Zomepirac |
| Demoxepam | Naproxen | 7-Aminoflunitrazepam |
| Deoxycorticosterone | Niacinamide | Metformin |
| Desipramine | Nicotine | Norpseudoephedrine |
| Diclofenac | Nicotinic Acid | Oxazepam Glucuronide |
| Diflunisal | Nifedipine | Lorazepam Glucuronide |
| Digoxin | Norethindrone | LSD |
| Dimethyl-aminoantipyrine | Norpropoxyphene | THC |
| Diphenhydramine | Nortriptyline | L-thyroxine |
| Diphenylhydantoin | Noscapine | Dextromethorphan |
| DL-Tryptophan | O-Hydroxyhippuric
acid | Ketamine |
| DL-Tyrosine | Octopamine | Thioridazine |
| Dopamine (Hydroxytyramine) | Oxalic acid
(100mg/dL) | |
| Doxepin | Oxazepam | |
7
8
e. Specificity
To test specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of device. The lowest concentration that caused a positive result for each compound are listed below in ng/mL. If no cross reactivity was observed then the highest concentration tested is listed.
| Fentanyl (Cutoff=1ng/mL) | Minimum
concentration
required to obtain a
positive result | % Cross-
Reactivity |
|------------------------------------|---------------------------------------------------------------------|------------------------|
| Fentanyl | 1 | 100 |
| Norfentanyl | >100000 | 100000 | 100000 | 20000 | 20000 | 100000 | 20000 | 20000 | 20000 | 100000 | 20000 | 100000 | 20000 | 20000 | 50 years. Urine samples were prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cut-offs by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/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:
| % of Cutoff | Number
of
samples | Fentanyl Concentration
by LC/MS
(ng/mL) | Lay person results | | The
percentage of
correct results
(%) |
|--------------|-------------------------|-----------------------------------------------|--------------------|--------------------|------------------------------------------------|
| | | | No. of
Positive | No. of
Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100.0% |
| -75% Cutoff | 20 | 0.24 | 0 | 20 | 100.0% |
| -50% Cutoff | 20 | 0.47 | 0 | 20 | 100.0% |
| -25% Cutoff | 20 | 0.72 | 0 | 20 | 100.0% |
| +25% Cutoff | 20 | 1.21 | 20 | 0 | 100.0% |
| +50% Cutoff | 20 | 1.50 | 20 | 0 | 100.0% |
| +75% Cutoff | 20 | 1.81 | 20 | 0 | 100.0% |
12
| % of Cutoff | Number of samples | Norfentanyl Concentration by LC/MS (ng/mL) | Lay person results | The percentage of correct results (%) | |
|---|---|---|---|---|---|
| No. of Positive | No. of Negative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100.0% |
| -75% Cutoff | 20 | 1.33 | 0 | 20 | 100.0% |
| -50% Cutoff | 20 | 2.63 | 0 | 20 | 100.0% |
| -25% Cutoff | 20 | 4.06 | 1 | 19 | 95.0% |
| +25% Cutoff | 20 | 6.03 | 20 | 0 | 100.0% |
| +50% Cutoff | 20 | 7.29 | 20 | 0 | 100.0% |
| +75% Cutoff | 20 | 9.08 | 20 | 0 | 100.0% |
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.
11. Conclusion
Based on the test principle and acceptable performance characteristics including precision, cut-off, interference, specificity, method comparison and Lay-user studies of the devices, it's concluded a substantial equivalence decision.