(25 days)
Not Found
No
The device description and performance studies detail a standard enzyme immunoassay based on chemical reactions and spectrophotometric measurement. There is no mention of AI, ML, or any computational algorithms used for data interpretation beyond basic qualitative analysis against a cutoff.
No.
This device is an in vitro diagnostic (IVD) device used for the qualitative determination of norfentanyl in human urine, providing a preliminary analytical result. It is not used to treat or prevent a disease or condition.
Yes
This device is intended for the qualitative determination of norfentanyl in human urine, which is a diagnostic purpose to detect the presence of a substance in the body.
No
The device is a homogeneous enzyme immunoassay kit comprised of liquid reagents, which are physical components, not software. While it is used with automated clinical chemistry analyzers (which contain software), the device itself is a chemical assay.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "for the qualitative determination of norfentanyl in human urine". This indicates the device is used to test a sample taken from the human body (urine) in vitro (outside the body) to provide information about a medical condition or state (presence of norfentanyl).
- Device Description: The description details a "homogeneous enzyme immunoassay with ready-to-use liquid reagents" that measures enzyme activity in the sample. This is a common method used in in vitro diagnostic tests.
- Sample Type: The device is designed to test "human urine".
- Performance Studies: The document describes performance studies conducted on "clinical samples" of human urine, comparing the results to a reference method (LC/MS). This is typical for the validation of an IVD.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K181159) strongly suggests that this device is being submitted for regulatory clearance as a medical device, specifically an IVD, by demonstrating substantial equivalence to a previously cleared device.
All these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
Product codes (comma separated list FDA assigned to the subject device)
DJG
Device Description
The LZI Fentanyl II Enzyme Immunoassay is a homogeneous enzyme immunoassay with readyto-use liguid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available fentanyl standard and referred to as fentanyl-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, fentanyl-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound fentanyllabeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Fentanyl II Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The LZI Fentanyl II Enzyme Immunoassay is traceable to a commercially available fentanyl standard.
The R1 solution contains mouse monoclonal anti-fentanyl antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with fentanyl in buffer with sodium azide (0.09 %) as a preservative.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
prescription use/professional use with a number of automated clinical chemistry analyzers.
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
The precision study used norfentanyl sample concentrations prepared by spiking a norfentanyl standard into a pool of negative human urine. Samples were tested in replicate of two, two runs a day (one in the morning and one in the afternoon) for 22 days on one Beckman Coulter® AU480 automated clinical analyzer for a total of 88 replicates.
For the method comparison, a total of one hundred (100) unaltered clinical samples were tested. All samples were tested in singlet. All samples were confirmed with LC/MS for norfentanyl concentrations. Samples were collected by Lin-Zhi International, Inc. and from various clinical labs including University of California, San Francisco (UCSF) (San Francisco, CA), Northwest Physicians Labs (NWPL) (Bellevue, Washington), Soloniuk Pain Clinic (Redding, CA), and Calgary Labs (Calgary, Canada).
For cross-reactivity studies, various potentially interfering drugs, structurally related compounds, structurally unrelated pharmacological compounds, and endogenous and preservative compounds were tested by spiking various concentrations of each substance into a pool of negative human urine. All samples were tested in duplicates.
For specific gravity interference, samples ranging from 1.000 to 1.027 were split into three portions each and either left un-spiked or further spiked to a final norfentanyl concentration of either 3.75 ng/mL or 6.25 ng/mL. These samples were then evaluated in qualitative mode.
For pH interference, negative urine and urine spiked with norfentanyl to the final norfentanyl concentration of either 3.75 ng/mL or 6.25 ng/mL were adjusted to various pH levels and tested. The pH adjusted solutions were evaluated in qualitative mode.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision Study:
Study Type: Qualitative Precision (AOD, mAU) based on a modified NCCLS-EP5 protocol.
Sample Size: 88 replicates for each concentration.
Key Results:
- Qualitative positive/negative results showed consistent negative determinations for concentrations up to 3.75 ng/mL (75.0 % of cutoff).
- At 5 ng/mL (100.0 % of cutoff), 59 Negative and 29 Positive results were observed across 88 determinations.
- For concentrations 6.25 ng/mL (125.0 %) and above, all 88 determinations were positive.
Method Comparison – Clinical Samples / Qualitative Accuracy Study:
Study Type: Qualitative Accuracy Study comparing LZI Fentanyl II Enzyme Immunoassay results with LC/MS analysis.
Sample Size: 100 unaltered clinical samples.
Key Results:
- 20 Negative by LC/MS analysis were Negative by EIA.
- 19 samples 50% of cutoff) were Positive by EIA.
- There were 9 discrepant samples (1 from 50% above cutoff): 40 samples. EIA Positive: 40 samples. (No False Negatives)
Total samples: 100
True Negatives (TN): 20 (from 0 ng/mL LC/MS) + 19 (from
§ 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). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 7, 2020
Lin-Zhi International, Inc. Bernice Lin VP Operations 2945 Oakmead Village Court Santa Clara, CA 95051
Re: K201938
Trade/Device Name: LZI Fentanyl II Enzyme Immunoassay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: DJG Dated: July 8, 2020 Received: July 13, 2020
Dear Bernice Lin:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. 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 located 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.
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
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to 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,
Marianela Perez-Torres, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K201938
Device Name LZI Fentanyl II Enzyme Immunoassay
Indications for Use (Describe)
The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) Summary of Safety and Effectiveness
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number
Prepared On
July 2, 2020
Introduction
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitter Name, Address, and Contact:
Lin-Zhi International, Inc. 2945 Oakmead Village Court Santa Clara, CA 95051 Phone: (408) 970-8811 (408) 970-9030 Fax: e-mail: bclin@lin-zhi.com
Contact: Bernice Lin, Ph.D. VP Operations
Device Name and Classification
| Classification Name: | Enzyme Immunoassay, Opiates
Class II, DJG (91 Toxicology),
21 CFR 862.3650 |
|----------------------|----------------------------------------------------------------------------------|
| Common Name: | Homogeneous Fentanyl Enzyme Immunoassay |
| Proprietary Name: | LZI Fentanyl II Enzyme Immunoassay |
4
Legally Marketed Predicate Device(s)
The LZI Fentanyl II Enzyme Immunoassay is substantially equivalent to the LZI Fentanyl Enzyme Immunoassay (K181159) manufactured by Lin-Zhi International, Inc. The LZI Fentanyl II Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.
Device Description
The LZI Fentanyl II Enzyme Immunoassay is a homogeneous enzyme immunoassay with readyto-use liguid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available fentanyl standard and referred to as fentanyl-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, fentanyl-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound fentanyllabeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Fentanyl II Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The LZI Fentanyl II Enzyme Immunoassay is traceable to a commercially available fentanyl standard.
The R1 solution contains mouse monoclonal anti-fentanyl antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with fentanyl in buffer with sodium azide (0.09 %) as a preservative.
5
Intended Use
The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatograpy and mass spectrometry) must be used in order to obtain a confirmed analytical result. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
6
Comparison to Predicate Device
The LZI Fentanyl II Enzyme Immunoassay is substantially equivalent to the LZI Fentanyl Enzyme Immunoassay which was cleared by the FDA under the premarket notification K181159 for its stated intended use.
The following table compares the LZI Fentanyl II Enzyme Immunoassay with the predicate device.
| Device
Characteristics | Subject Device | Predicate Device (K181159) |
---|---|---|
Intended Use | The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL when calibrated against norfentanyl. The assay is designed for professional use with a number of automated clinical chemistry analyzers. |
This assay provides a rapid screening procedure for determining the presence of norfentanyl in urine. The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive. | The LZI Fentanyl Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL when calibrated against norfentanyl. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
This assay provides a rapid screening procedure for determining the presence of norfentanyl in urine. The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive. |
| Analyte | norfentanyl | norfentanyl |
| Cutoff | 5 ng/mL | 5 ng/mL |
| Matrix | Urine | Urine |
| Calibrator
Level | 5 ng/mL | 5 ng/mL |
| Controls Level | 3.75 ng/mL and 6.25 ng/mL | 3.75 ng/mL and 6.25 ng/mL |
| Storage | 2-8 °C until expiration date | 2-8 °C until expiration date |
| Instrument
used for
performance | Beckman Coulter® AU480 automated
clinical analyzer | Beckman Coulter® AU680 automated
clinical analyzer |
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Performance Characteristics Summary:
All 510(k) studies below were conducted on the Beckman Coulter® AU480 Analyzer
Precision: 5 ng/mL Cutoff
The assay was tested in qualitative (AOD, mAU) mode using a modified NCCLS-EP5 protocol. Norfentanyl sample concentrations were prepared by spiking a norfentanyl standard into a pool of negative human urine at concentrations ±25 %, ±75 %, and ±100 % of the cutoff concentration.
Results shown below were obtained by testing all samples in replicate of two, two runs a day (one in the morning and one in the afternoon) for 22 days on one Beckman Coulter® AU480 automated clinical analyzer for a total of 88 replicates. Samples were evaluated against the cutoff calibrator in qualitative mode. One single lot of reagents, calibrators, and controls were used and stored at 2-8℃ when not in use.
| Norfentanyl
Concentration | Within Run (N=22) | Total Precision (N=88) | ||||
---|---|---|---|---|---|---|
Mean | SD | % | ||||
CV | Mean | SD | % CV | |||
0 ng/mL | 0.0 | 0.0 | N/A | 0.0 | 0.2 | N/A |
1.25 ng/mL | 15.5 | 3.0 | 20.2 % | 15.5 | 4.1 | 26.6 % |
2.5 ng/mL | 35.1 | 2.9 | 8.4 % | 35.1 | 3.5 | 10.0 % |
3.75 ng/mL | 58.8 | 3.0 | 5.1 % | 58.8 | 3.8 | 6.5 % |
5 ng/mL | 81.0 | 3.3 | 4.1 % | 81.0 | 3.7 | 4.6 % |
6.25 ng/mL | 105.5 | 2.7 | 2.5 % | 105.5 | 3.9 | 3.7 % |
7.5 ng/mL | 128.0 | 2.9 | 2.3 % | 128.0 | 3.5 | 2.8 % |
8.75 ng/mL | 150.1 | 3.2 | 2.2 % | 150.1 | 4.2 | 2.8 % |
10 ng/mL | 171.3 | 4.3 | 2.5 % | 171.3 | 5.2 | 3.0 % |
Precision: 5 ng/mL Cutoff Precision: Qualitative, results in ΔΟD (mAU)
Oualitative Positive/Negative Results:
5 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
---|---|---|---|---|---|
Norfentanyl | % of Cutoff | Number of | Immunoassay | Number of | Immunoassay |
Concentration | Determination | Result | Determination | Result | |
0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative |
1.25 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative |
2.5 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative |
3.75 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative |
5 ng/mL | 100.0 % | 22 | 13 Neg/9 Pos | 88 | 59 Neg/29 Pos |
6.25 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive |
7.5 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive |
8.75 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive |
10 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive |
8
Beckman Coulter® AU480 Analyzer
Method Comparison - Clinical Samples:
A total of one hundred (100) unaltered clinical samples were tested with the LZI Fentanyl II Enzyme Immunoassay on the Beckman Coulter® AU480 automated clinical analyzer. Samples were evaluated against the cutoff calibrator in qualitative mode. All samples were tested in singlet.
All samples were confirmed with LC/MS for norfentanyl concentrations. Samples were collected by Lin-Zhi International, Inc. and from various clinical labs including University of California, San Francisco (UCSF) (San Francisco, CA), Northwest Physicians Labs (NWPL) (Bellevue, Washington), Soloniuk Pain Clinic (Redding, CA), and Calgary Labs (Calgary, Canada).
Qualitative Accuracy Study:
| NFEN Results
5 ng/mL Cutoff | Negative
by LC/MS
analysis |