BioSieve™ Fentanyl FIA Test Kit; BioSieve™ ToxiSmart FIA Reader

K240124 · Vivachek Biotech (Hangzhou) Co., Ltd. · DJG · Jun 14, 2024 · Clinical Toxicology

Device Facts

• Record ID: K240124
• Device Name: BioSieve™ Fentanyl FIA Test Kit; BioSieve™ ToxiSmart FIA Reader
• Applicant: Vivachek Biotech (Hangzhou) Co., Ltd.
• Product Code: DJG · Clinical Toxicology
• Decision Date: Jun 14, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

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.

Device Story

Device consists of BioSieve™ Fentanyl FIA Test Kit (lateral flow cassette) and BioSieve™ ToxiSmart FIA Reader. Input: human urine sample applied to test cassette. Principle: competitive fluorescence immunochromatography; fentanyl in sample competes with fentanyl-BSA conjugate on membrane for fluorescently-labeled monoclonal antibodies. Reader measures fluorescence signal at test and control lines. Output: qualitative positive/negative result displayed on reader screen. Used in labs or point-of-care settings by healthcare professionals. Provides preliminary results requiring confirmation by GC/MS or LC/MS-MS. Clinical decision-making relies on professional judgment; positive results indicate potential fentanyl presence. Benefits include rapid, portable screening for fentanyl exposure.

Clinical Evidence

Bench testing only. Precision studies evaluated performance across 9 concentrations (-100% to +100% cutoff) over 10 days. Method comparison study at three sites using 80 clinical samples compared results against LC-MS/MS. Interference and specificity studies confirmed no cross-reactivity with common metabolites or opioids at 100 µg/mL. No clinical studies were performed.

Technological Characteristics

Lateral flow immunochromatographic assay; competitive binding principle. Materials: nitrocellulose membrane, fentanyl-BSA conjugate, goat anti-rabbit IgG. Reader: portable fluorescence instrument, 365nm LED excitation, 610nm response wavelength. Power: 3.7V lithium-ion battery, Type-C/USB charging. Dimensions: 12.45 cm x 7.25 cm x 4 cm. Connectivity: standalone. Software: embedded firmware for signal processing and result calculation.

Indications for Use

Indicated for the qualitative detection of fentanyl in human urine at a 1.0 ng/mL cutoff. Intended for prescription use in laboratory or point-of-care settings to provide preliminary results requiring confirmation by GC/MS or LC/MS-MS.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• Superbio Fentanyl Urine Detection Kit, Superbio Immunofluorescence Analyzer EASY-11 (K220046)

Submission Summary (Full Text)

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FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number

K240124

B Applicant

VivaChek Biotech (Hangzhou) Co., Ltd

C Proprietary and Established Names

BioSieve™ Fentanyl FIA Test Kit; BioSieve™ ToxiSmart FIA Reader

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | Class II | 21 CFR 862.3650 - Opiate Test System | TX - Clinical Toxicology |
| KHO | Class I | 21 CFR 862.2560 - Fluorometer for clinical use | CH - Clinical Chemistry |

## II Submission/Device Overview:

A Purpose for Submission:

New device

B Measurand:

Fentanyl

C Type of Test:

Qualitative, fluorescence immunoassay (FIA)

## III Intended Use/Indications for Use:

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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A Intended Use(s):

See Indications for Use below.

B Indication(s) 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 method 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.

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

Strips are not for visual read.

D Special Instrument Requirements:

BioSieve™ ToxiSmart FIA Reader

IV Device/System Characteristics:

A Device Description:

The assay consists of a test strip enclosed in a plastic cassette, a dropper, the BioSieve ToxiSmart FIA Reader, and associated labeling. External quality control materials are recommended but not included.

B Principle of Operation:

The BioSieve™ Fentanyl FIA Test Kit uses the principle of competitive and fluorescence immunochromatography. The nitrocellulose membrane test area (T) of the test strip is coated

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with fentanyl-bovine serum albumin conjugate, and the quality control area (C) is coated with goat anti-rabbit IgG polyclonal antibody. Both Fentanyl monoclonal antibody and rabbit IgG 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. Thus, fluorescence signal rendering of the test line is inhibited and the result is positive. If 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. Thus, the test line will develop a fluorescence signal and the result is negative. The quality control area (C) will also develop a fluorescence signal, indicating that the testing has been performed correctly.

## C Instrument Description Information:

1. Instrument Name:
BioSieve ToxiSmart FIA Reader

2. Specimen Identification:
Sample identification numbers must be entered manually by the user.

3. Specimen Sampling and Handling:
Specimen collection, preparation, and handling conditions are described in the package insert of the assay.

4. Calibration:
The analyzer is factory calibrated and does not need to be recalibrated by the operator.

5. Quality Control:
Quality control materials are recommended but not provided.

6. Operation Instruction:
BioSieve ToxiSmart FIA Reader provides two test modes: Standard and Quick.

Before the start of each mode, the reagent ID chip is inserted and the operator selects the sample type and test item. The test card is then removed from the protective pouch and placed on a horizontal flat surface.

- Under the standard test mode, the sample is dropped into a sample well using the provided dropper. The test card with the sample is then placed into the instrument and the operator starts the test by pressing the "Start test" button on the instrument which

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automatically starts a timer. At the end of the incubation period, the instrument will record the test results and the result will be available for reading and printing to the operator.

- Under the quick test mode, the sample is dropped into a sample well using the provided dropper. The test card with the sample is kept on a flat surface outside of the instrument and manually incubated using a timer. At the end of the incubation period, the test card with the patient sample is inserted into the instrument and the operator starts the test by pressing the "Start test" button on the instrument. The instrument will record the test results and the result will be available for reading and printing to the operator.

V Substantial Equivalence Information:

A Predicate Device Name(s):

Superbio Fentanyl Urine Detection Kit, Superbio Immunofluorescence Analyzer EASY-11

B Predicate 510(k) Number(s):

K220046

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K240124 | K220046 |
| --- | --- | --- |
| Device Trade Name | BioSieve™ Fentanyl FIA Test Kit, BioSieve™ ToxiSmart FIA Reader | Superbio Fentanyl Urine Detection Kit, Superbio Immunofluorescence Analyzer EASY-11 |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For the qualitative determination of fentanyl in human urine | Same |
| Calibrator and Cut-Off Values | 1 mg/mL | Same |
| Methodology | Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry | Same |
| Specimen Type | Urine | Same |
| Analyzer | Immunofluorescence Analyzer | Same |

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| General Device Characteristic Differences | | |
| --- | --- | --- |
| Power Supply | 3.7V lithium-ion battery | Mains (AC) powered |
| User interface | 1.54 inch LCD display | 8 inch color LCD touchscreen display |
| Dimensions | 4.90 inches (12.45 cm) x 2.85 inches (7.25 cm) x 1.57 inches (4 cm) | 11.0 in (28 cm) x 11.0 in (28 cm) x 6.3 in (16 cm) |

VI Standards/Guidance Documents Referenced:

None referenced.

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

Precision studies were carried out for samples with concentrations of -100% cutoff, -75% cutoff, -50% cutoff, -25% cutoff, cutoff, +25% cutoff, +50% cutoff, +75% cutoff and +100% cutoff for fentanyl cut off concentration of 1 ng/mL. Samples with concentration of -100% cutoff were drug-free urines samples. Other samples were prepared by spiking target drug fentanyl in drug-free urine samples. Each drug concentration was confirmed by LC-MS/MS. All sample aliquots were blindly labeled by the person who prepared the samples but didn't take part in the sample testing. A sequential randomization algorithm was applied to assign the prepared samples to an arbitrary number.

The precision data was collected using three lots of reagent, three analyzers, and three sites, with one replicate per run per lot, with two runs per day collected over 10 days.

Each study site has at least one test operator to perform the test. There are six tests per day per concentration at each site (2 runs per day × 3 lots × 9 concentrations) for a total 54 tests per day per site. Results are summarized in the table below:

| Lot Number | -100%cut off | -75% cut off | -50% cut off | -25% cut off | cut off |
| --- | --- | --- | --- | --- | --- |
| Lot 1 | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 58 (-) / 2(+) | 28 (-) / 32 (+) |
| Lot 2 | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 28 (-) /32 (+) |
| Lot 3 | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 59 (-) / 1 (+) | 29 (-) / 31 (+) |
| Lot Number | +25% cut off | +50% cut off | +75% cut off | +100% cut off | |
| Lot 1 | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | |
| Lot 2 | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | |
| Lot 3 | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | 60 (-) / 0 (+) | |

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2. **Linearity:**
Not applicable, this device is intended for qualitative use only

3. **Analytical Specificity/Interference:**

**Specificity Using Drug Free Samples:**
The sponsor performed a specificity study to demonstrate negative results on drug-free samples using the BioSieve™ Fentanyl FIA Test Kit. In the study, 30 drug-free urine samples were collected. The concentration of these samples were tested and confirmed by LC-MS. The test was performed using three (3) analyzers, three (3) lots and three (3) operators. All tested samples had the expected negative result.

**Cross Reactivity:**
The sponsor performed a study to verify potential cross-reactants using the target drug, drug metabolites and other related compounds.

Target drugs, drug metabolites and other components that are likely to interfere in urine samples were added to drug-free urine at different concentrations of compounds and tested using three (3) different instruments, three (3) different lots, and three (3) operators. The lowest concentration that caused a positive result for each compound are listed below.

Percent cross reactivity of a compound is calculated by dividing the cutoff concentration by the minimum concentration required to obtain a positive result and then multiplying by 100%. The results are listed in the table below:

| Fentanyl (Cutoff = 1 ng/mL) | Minimum Concentration Required to Obtain a Positive Result (ng/mL) | % Cross-Reactivity |
| --- | --- | --- |
| Acetyl fentanyl | 1.2 | 83.33 |
| Acrylfentanyl | 1.2 | 83.33 |
| ω-1-Hydroxyfentanyl | 20000 | 0.005 |
| 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-fluoro-fentanyl | 3 | 33.33 |
| Para-fluoro butyryl | 3 | 33.33 |
| (±)-3-cis-methyl fentanyl | 5 | 20.00 |

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| Fentanyl (Cutoff = 1 ng/mL) | Minimum Concentration Required to Obtain a Positive Result (ng/mL) | % Cross-Reactivity |
| --- | --- | --- |
| Carfentanil | 500 | 0.20 |
| Sufentanil | 625 | 0.16 |
| Alfentanil | 100000 | 0.001 |
| Despropionyl fentanyl (4-ANPP) | 50000 | 0.002 |
| Remifentanil | >100000 | Not detected |
| Norfentanyl | >100000 | Not detected |
| Acetyl norfentanyl | >100000 | Not detected |
| Norcarfentanil | >100000 | Not detected |

The following opioid compounds were tested and produced a negative result at a concentration of 100 µg/ml:

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, Trazodone

Interference:

1. Interference Study on the Effect of Specific Gravity and pH:

To investigate the effect of urine specific gravity and urine pH, urine samples with specific gravity of 1.000 to 1.035 and urine samples with a pH of 4 to 9, in 1 pH unit increments, were spiked with target fentanyl at 50% below and 50% above cutoff levels. These samples were tested using three (3) lots of device, three (3) instruments and three (3) different operators. Results were all positive for samples at +50% cutoff and all negative for samples at and below -50% cutoff. The results demonstrate that varying ranges of specific gravity and pH do not interfere with the BioSieve™ Fentanyl Test Kit (FIA).

2. Interfering Substances

Potential interfering substances found in human urine of physiological or pathological conditions were added at a concentration of 100 µg/mL or as specified in the table below.

The potential interferents were added to drug-free urine spiked with fentanyl to concentrations at 50% below and 50% above cutoff levels. These urine samples were

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tested using three (3) lots of the device and three (3) instruments by three (3) operators. The following compounds all produced the expected negative or positive result with the BioSieve™ Fentanyl Test Kit (FIA):

| 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-D-glucuronide) |
| 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 |

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| 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 | |

4. Assay Reportable Range:

Not applicable, this device is intended for qualitative use only.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

The assay is traceable to a commercial standard from Cerilliant Corp.

6. Detection Limit:

Not applicable

7. Assay Cut-Off:

Analytical performance of the device around the claimed cutoff is described in the precision section VII.A1. above.

8. Accuracy (Instrument):

See accuracy study in Section VII.B.1.

9. Carry-Over:

To assess the possibility of carryover, the sponsor performed a study in which samples with concentrations at -50% of the cutoff (0.5 ng/mL) and at -100% of the cutoff (0 ng/mL) were analyzed immediately after a sample with a concentration of 100 ng/mL (100 times the cutoff). The data was collected by three operators using three lots and three instruments (one lot per instrument). In all instances the samples at 0.5 and 0 ng/mL produced a negative result when run immediately after a sample with a concentration of 100 ng/mL

B Comparison Studies:

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1. Method Comparison with Predicate Device:

A comparison study between BioSieve™ Fentanyl Test Kit (FIA) and LC-MS/MS method was conducted in three different testing sites including two POC sites (physician’s offices).

This study was a randomized and blinded accuracy study.

Clinical samples included a total of 80 urine samples (40 Negative and 40 positive). The clinical samples were labeled using randomized numbers by the person who prepares samples and did not perform the actual testing. Sample concentrations of fentanyl were confirmed by LC-MS/MS prior to testing on the candidate device.

The study was performed using three reagent lots and three analyzers, and by three operators. Results are summarized in the tables below:

| Site | Positive/Negative | Negative | Low Negative by LC/MS (< -50%) < 0.5 ng/mL | Near Cutoff Negative by LC/MS (between -50% and cutoff) 0.5 - 0.9 | Near Cutoff Positive by LC/MS (between cutoff and +50%) 1.0 – 1.5 | High Positive by LC/MS (> +50%) > 1.5 ng/mL |
| --- | --- | --- | --- | --- | --- | --- |
| 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 |

2. Matrix Comparison:

Not applicable. The assay is intended to be used with urine samples only.

C Clinical Studies:

1. Clinical Sensitivity:

Not applicable.

2. Clinical Specificity:

Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

Not applicable.

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D Clinical Cut-Off:
Not applicable.

E Expected Values/Reference Range:
Not applicable.

F Other Supportive Instrument Performance Characteristics Data:
Not applicable.

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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