(150 days)
Not Found
No
The description details a standard fluorescence immunoassay and a reader that scans the test strip and displays results. There is no mention of AI, ML, or any complex algorithms beyond basic signal processing for fluorescence detection and comparison to a cutoff. The performance studies are standard analytical and comparison studies, not indicative of AI/ML training or validation.
No.
The device is an in vitro diagnostic (IVD) test kit used to detect fentanyl in urine, which provides preliminary diagnostic results rather than directly treating a medical condition.
Yes
The "Intended Use / Indications for Use" section explicitly states, "It is for in vitro diagnostic use only." and "BioSieve™ ToxiSmart FIA Reader is a portable fluorescence instrument for in vitro diagnostic use only."
No
The device description clearly outlines a physical instrument (BioSieve™ ToxiSmart FIA Reader) that performs the fluorescence immunoassay and scans the test strip. This involves hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "It is for in vitro diagnostic use only." and "BioSieve™ ToxiSmart FIA Reader is a portable fluorescence instrument for in vitro diagnostic use only."
- Intended Use: The device is intended for the qualitative determination of fentanyl in human urine, which is a biological specimen. This is a classic application of in vitro diagnostics.
- Methodology: The device uses a fluorescence immunoassay (FIA) to analyze the sample outside of the body.
- Care Setting: It is intended for use in a laboratory or point-of-care setting, which are typical environments for IVD testing.
- Regulatory Context: The submission includes performance studies comparing the device to a confirmatory method (LC/MS-MS) and references predicate devices with K numbers, indicating it is undergoing regulatory review as an IVD.
N/A
Intended Use / Indications for Use
BioSieve™ Fentanyl FIA Test Kit is a fluorescence immunoassay (FIA) for the qualitative determination of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use with BioSieve™ ToxiSmart FIA Reader.
It is for in vitro diagnostic use only. It is intended for prescription use.
The tests provide only preliminary results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS-MS) is the preferred confirmatory method.
Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.
BioSieve™ ToxiSmart FIA Reader is a portable fluorescence instrument for in vitro diagnostic use only. The Reader is designed to perform in vitro diagnostic tests on urine specimens. This Reader can be used in a laboratory or in a point-of-care setting.
Product codes (comma separated list FDA assigned to the subject device)
DJG, KHO
Device Description
This test uses a lateral flow design with location-dependent lines and zones. BioSieve™ ToxiSmart FIA Reader scans the test strip and displays results. The sample is added to the sample well of the test card, and the sample is drawn by capillary action into and through the fluorescent labeled pad, through the nitrocellulose strip and into the adsorption pad. Within the fluorescent labeled pad, the specimen comes into contact with antibodies conjugated with fluorescent microspheres. During this interaction, if the amount of fentanyl antigen in the sample is greater than or equal to the cutoff value, the antigen in the sample and the fluorescence-labeled antibody bind to the FTY antigenantibody complex when the sample passes through a pad of fluorescence-microbead-labeled antibody conjugate. As the sample flows and reaches the FTY antigen coated by the T-line of nitrocellulose membrane, the FTY antigen coated by the T-line antigen in the sample competitively bind the FTY antibody labeled with fluorescence, then the T-line captures fluorescence signal is weaker than the cutoff fluorescence signal. When the samples do not contain fentanyl antigen or levels below the cutoff value, as the sample flow, fluorescent microsphere labeled antibody to nitrocellulose membrane T line captures fluorescent signal is stronger than the cutoff fluorescence signal. Whether or not FTY antigen was present in the sample, the rabbit IgG fluorescent microsphere conjugate not bound to the test line continued to flow with the rest of the sample and soon encountered a control line composed of goatanti-rabbit IgG. The position of C-line will accumulate fluorescence signal. The C-line control area was scanned to confirm that adequate sample flow had occurred. High resolution, narrow band SMD LED was used as light source in the Immunofluorescence Analyzer. The central wavelength of the excitation spectrum is 365nm. The central response wavelength is 610nm.
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
It is intended for prescription use.
This Reader can be used in a laboratory or in a point-of-care setting.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance (Precision):
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 were tested. Each fentanyl concentration was confirmed by LC/MS-MS. For each concentration, tests were performed six runs per day for 10 days per device lot in a randomized order. Each device was read on one BioSieve™ ToxiSmart FIA Reader.
Key results:
Lot 1:
-100% cut off: 60-/0+
-75% cut off: 60-/0+
-50% cut off: 60-/0+
-25% cutoff: 58-/2+
cut off: 28-/32+
+25% cut off: 60+/0-
+50% cut off: 60+/0-
+75% cut off: 60+/0-
+100% cut off: 60+/0-
Lot 2:
-100% cut off: 60-/0+
-75% cut off: 60-/0+
-50% cut off: 60-/0+
-25% cutoff: 60-/0+
cut off: 28-/32+
+25% cut off: 60+/0-
+50% cut off: 60+/0-
+75% cut off: 60+/0-
+100% cut off: 60+/0-
Lot 3:
-100% cut off: 60-/0+
-75% cut off: 60-/0+
-50% cut off: 60-/0+
-25% cutoff: 59-/1+
cut off: 29-/31+
+25% cut off: 60+/0-
+50% cut off: 60+/0-
+75% cut off: 60+/0-
+100% cut off: 60+/0-
Stability Study:
The devices are stable at 2-30°C for 24 months based on the accelerated stability study at 45°C.
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. Compounds that showed no interference at a concentration of 100µg/mL or specified concentrations were summarized (list of compounds provided in the extract).
Specificity Study:
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 and their cross-reactivity were listed (table provided in the extract).
Other Metabolites and opioids compounds were tested at a concentration of 100 µg/mL. Negative results were obtained for all these compounds, indicating no cross-reactivity.
Effect of Urine Specific Gravity and Urine pH:
Urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with target fentanyl at 50% below and 50% above Cut-Off levels. Tested by three different operators per lot of device, with a total of three lots. Results were all positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off.
Comparison Studies:
Method comparison studies were performed at three different testing sites. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were blind labeled and compared to LC-MS/MS results.
Sample Size: 80 unaltered clinical samples (40 negative, 40 positive).
Key Results: Tables of results for Site 1, Site 2, and Site 3, showing the number of positive and negative results across different concentration ranges compared to LC-MS/MS. Discordant results were also listed with their LC-MS/MS result and BioSieve result.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not explicitly stated as Sensitivity, Specificity, PPV, NPV directly, but data for discordance and precision is provided in the Performance Studies section.
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.
Superbio Fentanyl Urine Detection Kit, K220046; Superbio Immunofluorescence Analyzer EASY-11, K220046
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).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services seal on the left and the FDA acronym along with the full name of the agency on the right. The FDA acronym is in a blue square, followed by the words "U.S. Food & Drug Administration" in blue.
VivaChek Biotech (Hangzhou) Co., Ltd % Joe Shia Director LSI International Inc 504 E Diamond Ave., Suite H Gaithersburg, Maryland 20877
Re: K240124
Trade/Device Name: BioSieve™ Fentanyl FIA Test Kit; BioSieve™ ToxiSmart FIA Reader Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Code: DJG, KHO Dated: May 10, 2024 Received: May 10, 2024
Dear 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 (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 Joseph A. Kotarek -S
Date: 2024.06.14
14:08:09 -04'00'
Joseph Kotarek 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
2
Indications for Use
510(k) Number (if known) K240124
Device Name BioSieve™ Fentanyl FIA Test Kit BioSieve™ ToxiSmart FIA Reader
Indications for Use (Describe)
BioSieve™ Fentanyl FIA Test Kit is a fluorescence immunoassay (FIA) for the qualitative determination of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use with BioSieve™ ToxiSmart FIA Reader.
It is for in vitro diagnostic use only. It is intended for prescription use.
The tests provide only preliminary results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS-MS) is the preferred confirmatory method.
Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.
BioSieve™ ToxiSmart FIA Reader is a portable fluorescence instrument for in vitro diagnostic use only. The Reader is designed to perform in vitro diagnostic tests on urine specimens. This Reader can be used in a laboratory or in a point-ofcare setting.
| 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) | Prescription Use (Part 21 CFR 801 Subpart D) | Prescription Use (Part 21 CFR 801 Subpart D) | Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) | Over-The-Counter Use (21 CFR 801 Subpart C) | Over-The-Counter Use (21 CFR 801 Subpart C) | ||
| Prescription Use (Part 21 CFR 801 Subpart D) | Prescription Use (Part 21 CFR 801 Subpart D) | Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) | Over-The-Counter Use (21 CFR 801 Subpart C) | Over-The-Counter Use (21 CFR 801 Subpart C) | |||
| Prescription Use (Part 21 CFR 801 Subpart D) | Prescription Use (Part 21 CFR 801 Subpart D) | |||||||
| Prescription Use (Part 21 CFR 801 Subpart D) | ||||||||
| Over-The-Counter Use (21 CFR 801 Subpart C) | Over-The-Counter Use (21 CFR 801 Subpart C) | |||||||
| 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."
3
510(k) SUMMAR Y
K240124
| 1. Date: | June 12, 2024 |
|---|---|
| 2. Submitter: | VivaChek Biotech (Hangzhou) Co., Ltd. |
| Level 2, Block 2, 146 East Chaofeng | |
| Rd. Yuhang Economy Development | |
| Zone Hangzhou 311100 Zhejiang | |
| P.R. China | |
| 3. Contact person: | Joe Shia |
| LSI International Inc. | |
| 504E Diamond Ave., Suite I | |
| Gaithersburg, MD 20877 | |
| Telephone: 240-505-7880 | |
| Email: shiajl@yahoo.com | |
| 4. Device Names: | BioSieve™ Fentanyl FIA Test Kit |
| Classification: Class 2 | |||
|---|---|---|---|
| Product Code | Classification | Regulation Section | Panel |
| DJG | II | 21 CFR § 862.3650 | |
| Opiate Test System | Toxicology (91) | ||
| KHO | I | 21 CFR § 862.2560 | |
| Fluorometer for clinical use | Clinical Chemistry |
BioSieve™ ToxiSmart FIA Reader
5. Predicate Devices:
Superbio Fentanyl Urine Detection Kit, K220046; Superbio Immunofluorescence Analyzer EASY-11, K220046
-
- Indications for Use
BioSieve™ Fentanyl FIA Test Kit is a fluorescence immunoassay (FIA) for the qualitative determination of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use with BioSieve™ ToxiSmart FIA Reader.
- Indications for Use
It is for in vitro diagnostic use only. It is intended for prescription use.
The tests provide only preliminary results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS-MS) is the preferred confirmatory method.
Clinical consideration and professional judgment should be exercised with any drug test result. particularly when the preliminary test result is positive.
BioSieve™ ToxiSmart FIA Reader is a portable fluorescence instrument for in vitro diagnostic use only. The Reader is designed to perform in vitro diagnostic tests on urine specimens. This Reader can be used in a laboratory or in a point-of-care setting.
-
- Device Description
This test uses a lateral flow design with location-dependent lines and zones. BioSieve™ ToxiSmart FIA Reader scans the test strip and displays results. The sample is added to the sample well of the
- Device Description
4
test card, and the sample is drawn by capillary action into and through the fluorescent labeled pad, through the nitrocellulose strip and into the adsorption pad. Within the fluorescent labeled pad, the specimen comes into contact with antibodies conjugated with fluorescent microspheres. During this interaction, if the amount of fentanyl antigen in the sample is greater than or equal to the cutoff value, the antigen in the sample and the fluorescence-labeled antibody bind to the FTY antigenantibody complex when the sample passes through a pad of fluorescence-microbead-labeled antibody conjugate. As the sample flows and reaches the FTY antigen coated by the T-line of nitrocellulose membrane, the FTY antigen coated by the T-line antigen in the sample competitively bind the FTY antibody labeled with fluorescence, then the T-line captures fluorescence signal is weaker than the cutoff fluorescence signal. When the samples do not contain fentanyl antigen or levels below the cutoff value, as the sample flow, fluorescent microsphere labeled antibody to nitrocellulose membrane T line captures fluorescent signal is stronger than the cutoff fluorescence signal. Whether or not FTY antigen was present in the sample, the rabbit IgG fluorescent microsphere conjugate not bound to the test line continued to flow with the rest of the sample and soon encountered a control line composed of goatanti-rabbit IgG. The position of C-line will accumulate fluorescence signal. The C-line control area was scanned to confirm that adequate sample flow had occurred. High resolution, narrow band SMD LED was used as light source in the Immunofluorescence Analyzer. The central wavelength of the excitation spectrum is 365nm. The central response wavelength is 610nm.
-
- Substantial Equivalence Information
A summary comparison of features of the BioSieve™ Fentanyl FIA Test Kit and the predicate devices is provided in following table.
- Substantial Equivalence Information
| Item | Device | Predicate - K220046 |
|---|---|---|
| Indication(s) | ||
| for Use | For the qualitative determination of | |
| fentanyl in human urine. | Same | |
| Calibrator and Cut-Off | ||
| Values | Fentanyl (FTY) | |
| 1 ng/ml | Same | |
| 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 prescription use | Same |
| Configurations | Test Card (chip on the back) | Test Card (no back chip) |
| Platform Required | Immunofluorescence Analyzer | Same |
| Storage | 2-30°C | 4-30°C |
| Item | Device | Predicate - K220046 |
| Intended Use/ Indication for | ||
| Use | Immunofluorescence analyzer | |
| designed to perform in vitro | ||
| diagnostic tests on clinical | ||
| specimens including drug urine | Same | |
| Principles of Assay | ||
| Operation | Competitive immunofluorescence | |
| immunoassay | Same | |
| Calibration Check | A Quality control test device is supplied | |
| with the Reader and used for check the | ||
| Reader optics and calculation systems. | A Quality control card is | |
| supplied with Easy-11 and | ||
| used for check Easy-11 optics | ||
| and calculation. systems. | ||
| Development Modes | Two basic assay development modes: | |
| • Standard test: In standard test, the user | ||
| insert the Reader immediately after | ||
| adding the sample, and the Reader will | ||
| display the test result when the | ||
| countdown is finished | ||
| • Quick test: In the quick test, the user | ||
| need insert the Reader after the reaction | ||
| time is completed, and the Reader will | ||
| display the test result in a few seconds. | Two basic assay development | |
| modes: | ||
| • Standard test: In standard test, | ||
| the user immediately inserts | ||
| Test Cassette into Easy-11 and | ||
| click "start test". Easy-11 | ||
| automatically counts the time. | ||
| • Quick test: Manually timing, | ||
| then insert the test card into | ||
| Easy-11, and click "Start Test". | ||
| The instrument will read the | ||
| results. | ||
| User interface | 1.54 inch LCD Screen display | 8 inch Color LCD touchscreen |
| display | ||
| Barcode scanner (sample) | Not equipped with a barcode scanner | Same |
| Assay/instrument | ||
| interface | Drawer | Same |
| Light Source | LED Light | Same |
| Power Supply | Powered by a 3.7V lithium-ion battery | |
| Two charging methods: | ||
| 1.Type C & USB 2 in 1 cable (computer | ||
| charging) | ||
| 2.Type C & USB 2 in 1 cable with the AC | ||
| adapter (wall charging) | ||
| Input: 100-240V~, 50/60Hz, 0.2A Max; | ||
| Output: 5.0V=, 1.0A | AC100-240V | |
| Dimensions | 12.45 cm x 7.25 cm x 4 cm | 28 cm x 28 cm x 16 cm |
Table 1: Features Comparison of BioSieve™ Fentanyl FIA Test Kit and the Predicate Devices
Table 2: Instrument Similarities and Differences
5
6
9. Test Principle
BioSieve™ Fentanyl FIA Test Kit uses the principle of competitive and fluorescence immunochromatography assay. The nitrocellulose membrane test area (T) of the test strip is correspondingly coated with fentanyl-bovine serum albumin conjugate, and the quality control area (C) is coated with goat anti-rabbit lgG polyclonal antibody. Both Fentanyl monoclonal antibody and rabbit lgG polyclonal antibody labeled with fluorescent microspheres are embedded on the conjugate pad. The labeled antibody will flow forward with the sample, when the urine sample is applied to the sample well of the test device. When the concentration of fentanyl in the sample is higher than or equal to the cut-off of the product, it will compete with the corresponding conjugate coated on the test area (T) to bind to the fluorescently labeled monoclonal antibody, the fluorescence signal rendering of the test line is inhibited and the result is positive; while when the sample does not contain fentanyl or its concentration is lower than the cut-off of the product, the corresponding conjugate on the test line reacts with sufficient fluorescently-labeled monoclonal antibodies, the test line will have fluorescence signal and the result is negative. The quality control area (C) will develop fluorescence signal, which is the criteria for judging whether the test process is normal or not. Signal intensity of fluorescence is detected by BioSieve™ ToxiSmart FIA Reader.
10. Performance Characteristics
-
- Analytical Performance
- a. Precision
Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cut off, +25% cut off, +50% cut off, +75% cut off and +100% cut off. These samples were prepared by spiking fentanyl in negative samples. Each fentanyl concentration was confirmed by LC/MS-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 runs per day for 10 days per device lot in a randomized order. Each device was read on one BioSieve™ ToxiSmart FIA Reader. The results obtained are summarized in the following tables.
| 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+ | 58-/2+ | 28-/32+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 28-/32+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 59-/1+ | 29-/31+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
c. Stability
The devices are stable at 2-30°C for 24 months based on the accelerated stability study at 45°C. The real time stability study is ongoing.
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
7
concentration of 100µg/mL or specified concentrations are summarized in the following tables.
| Acetaminophen | Doxepin (50 µg/mL) | Nortriptyline (25 µg/mL) |
|---|---|---|
| Acetone (1000 mg/dL) | Ecgonine methyl ester | Noscapine |
| Acetophenetidin | Ephedrine | O-Hydroxyhippuric acid |
| Acetylsalicylic acid | Erythromycin | Octopamine |
| Albumin (100 mg/dL) | Ethanol (1%) | Oxalic acid (100 mg/dL) |
| Albuterol | Fenoprofen | Oxazepam |
| Aminopyrine | Fluphenazine | Oxolinic acid |
| Amitriptyline (35 µg/mL) | Furosemide | Oxymetazoline |
| Amobarbital | Galactose (10 mg/dL) | Papaverine |
| Amoxicillin | Gamma Globulin (500 mg/dL) | Penicillin G |
| Ampicillin | Gentisic acid | Perphenazine |
| Apomorphine | Glucose (3000 mg/dL) | Phencyclidine |
| Ascorbic acid | Hemoglobin | Phenelzine |
| Aspartame | Hydralazine | Phenobarbital |
| Atropine | Hydrochlorothiazide | Prednisone |
| Benzilic acid | Hydrocortisone | Propoxyphene (50 µg/mL) |
| Benzoic acid | Hydroxytyramine | Propranolol |
| Benzoylecgonine | Ibuprofen | Pseudoephedrine |
| Bilirubin | Imipramine (30 µg/mL) | Quinine |
| Boric Acid (1%) | Isoproterenol | Ranitidine |
| Bupropion (50 µg/mL) | Isoxsuprine | Riboflavin (7.5 mg/dL) |
| Caffeine | Ketamine | Salicylic acid |
| Carbamazepine | Ketoprofen | Secobarbital |
| Chloral hydrate | Labetalol | Serotonin (5-Hydroxytyramine) |
| Chloramphenicol | Lidocaine (50 µg/mL) | Sulfamethazine |
| Chlorothiazide | Loperamide | Sulindac |
| Chlorpromazine | Maprotiline (50 µg/mL) | Tetrahydrocortisone 3-(β-Dglucuronide) |
| Cholesterol | Meperidine | Tetrahydrocortisone 3-acetate |
| Clomipramine (50 µg/mL) | Meprobamate | Tetrahydrozoline |
| Clonidine | Methapyrilene (10 µg/mL) | Thiamine |
| Cortisone | Methaqualone (50 µg/mL) | Thioridazine |
| Cotinine | Methoxyphenamine | Triamterene |
| Creatinine | Metronidazole (300 µg/mL) | Trifluoperazine |
| Cyclobenzaprine (10 µg/mL) | N-Acetylprocainamide | Trimethoprim |
| Deoxycorticosterone | NaCl (4000 mg/dL) | Tyramine |
| Desipramine (50 µg/mL) | Nalidixic acid | Urea (2000 mg/dL) |
| Dextromethorphan | Naloxone | Uric acid |
| Diclofenac | Naltrexone | Valproic acid (250 µg/mL) |
| Diflunisal | Naproxen | Venlafaxine |
| Digoxin | Niacinamide | Verapamil |
| Diphenhydramine | Nicotine (10 µg/mL) | Zomepirac |
| DL-Tryptophan | Nifedipine | β-Estradiol |
| DL-Tyrosine | Norethindrone |
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.
| Drug | Concentration
(ng/mL) | % Cross-
Reactivity |
|-----------------|--------------------------|------------------------|
| Acetyl fentanyl | 1.2 | 83.33 |
| Acrylfentanyl | 1.2 | 83.33 |
8
| Drug | Concentration
(ng/mL) | % Cross-
Reactivity |
|-----------------------------------|--------------------------|------------------------|
| ω-1-Hydroxyfentanyl | 20000 | 0.01 |
| Isobutyryl fentanyl | 1.5 | 66.67 |
| Ocfentanil | 1.5 | 66.67 |
| Butyryl fentanyl | 1.6 | 62.50 |
| Furanyl fentanyl | 1.75 | 57.14 |
| Valeryl fentanyl | 2.5 | 40.00 |
| (±) β-
hydroxythiofentanyl | 2.8 | 35.71 |
| 4-Fluoro-
isobutyrylfentanyl | 3 | 33.33 |
| Para-fluorobutyryl
fentanyl | 3 | 33.33 |
| Para-fluoro fentanyl | 3 | 33.33 |
| (±)-3-cis-methyl
fentanyl | 5 | 20.00 |
| Carfentanil | 500 | 0.20 |
| Sufentanil | 625 | 0.16 |
| Alfentanil | 100000 | 0.00 |
| Despropionyl fentanyl
(4-ANPP) | 50000 | 0.00 |
The following other Metabolites and opioids compounds were tested at a concentration of 100 µg/mL. Negative results were obtained for all these compounds. There is no cross-reactivity for these compounds using the BioSieve™ Fentanyl FIA Test Kit.
| Remifentanil | Norfentanyl | Acetyl norfentanyl |
|---|---|---|
| Norcarfentanil | 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 | Risperidone |
| Tapentadol | Thioridazine | Tilidine |
| Tramadol | Tramadol-O- Desmethyl | Tramadol-N- |
| Desmethyl |
9
-
f. Effect of Urine Specific Gravity and Urine pH
To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with target fentanyl at 50% below and 50% above Cut-Off levels. by three different operators per lot of device, with a total of three lots. Results were all positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off. -
- Comparison Studies
Method comparison studies for the BioSieve™ Fentanyl FIA Test Kit. were performed at three different testing sites. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were blind labeled and compared to LC-MS/MS results. The results are presented in the tables below.
- Comparison Studies
| | | Negative | Low
Negative by
LC-MS/MS
(less than
-50%) | Near Cutoff
Negative by
LC-MS/MS
(Between
-50% and
cutoff) | Near Cutoff
Positive by
LC-MS/MS
(Between the
cutoff and
+50%) | High Positive
by LC-
MS/MS
(greater than
+50%) |
|-----------|----------|----------|-------------------------------------------------------|---------------------------------------------------------------------------|-------------------------------------------------------------------------------|------------------------------------------------------------|
| Site
1 | Positive | 0 | 0 | 4 | 19 | 20 |
| | Negative | 10 | 18 | 8 | 1 | 0 |
| Site
2 | Positive | 0 | 0 | 3 | 18 | 20 |
| | Negative | 10 | 18 | 9 | 2 | 0 |
| Site
3 | Positive | 0 | 0 | 2 | 19 | 20 |
| | Negative | 10 | 18 | 10 | 1 | 0 |
| Discordant Results | |
|---|---|
| Operator | Sample Number | LC-MS/MS
Result | BioSieve
Results |
|----------|---------------|--------------------|---------------------|
| Site 1 | VCFC021 | 0.849 | Positive |
| Site 1 | VCFC075 | 0.875 | Positive |
| Site 1 | VCFC059 | 0.985 | Positive |
| Site 1 | VCFC048 | 0.946 | Positive |
| Site 1 | VCFC057 | 1.063 | Negative |
| Site 2 | VCFC030 | 0.892 | Positive |
| Site 2 | VCFC010 | 0.934 | Positive |
| Site 2 | VCFC059 | 0.985 | Positive |
| Site 2 | VCFC057 | 1.063 | Negative |
| Site 2 | VCFC036 | 1.104 | Negative |
| Site 3 | VCFC010 | 0.934 | Positive |
| Site 3 | VCFC048 | 0.946 | Positive |
| Site 3 | VCFC070 | 1.129 | Negative |
-
- Clinical Studies
10
Not applicable.
11. Conclusion
Based on the test principle and acceptable performance characteristics including precision, cut-off, interference, specificity, and method comparison studies of the devices, it's concluded a substantial equivalence decision.