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 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.

Device Description

The LZI Fentanyl Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid 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. 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, norfentanyl-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 norfentanyl-labeled 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 Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

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.

The LZI Fentanyl Enzyme Immunoassay calibrators and controls are designated for use at the 5 ng/mL cutoff contain 0, 2.5, 3.75, 5, 6.25, 10, and 20 ng/mL of norfentanyl in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.

AI/ML Overview

Here's an analysis of the acceptance criteria and study findings for the LZI Fentanyl Enzyme Immunoassay, based on the provided document:

This document is a 510(k) summary for a diagnostic device, which typically focuses on demonstrating substantial equivalence to a predicate device rather than comprehensive clinical effectiveness. Therefore, some of the requested information (like multi-reader multi-case studies, effect size of AI, or detailed training set information for an AI algorithm) is not applicable or present in this type of submission. The device described is a traditional enzyme immunoassay, not an AI-based system.

1. Acceptance Criteria and Reported Device Performance

The document describes performance characteristics typically assessed for an immunoassay. The primary acceptance criteria are implied by the precision and method comparison studies. For qualitative drug tests, the key is the accuracy of positive and negative determinations around the cutoff.

Acceptance Criteria Category	Specific Metric (Implied)	Acceptance Criteria (Implied)	Reported Device Performance
Precision	% CV near cutoff	Low % CV (e.g., < 20%)	3.1% at 5 ng/mL cutoff (Within Run), 4.0% (Total Precision)
Qualitative Agreement	Agreement for positives	100% (or very high)	100.0 % agreement with positive samples
	Agreement for negatives	High (e.g., > 90%)	86.5 % agreement with negative samples
Interference	No significant interference	No significant interference	Interference observed with Boric Acid (1% w/v) and dextromethorphan; no other significant undesired cross-reactants or endogenous substance interference observed.

Note on Acceptance Criteria: For 510(k) submissions, the acceptance criteria are often benchmarked against the predicate device's performance or established standards for that device type. Explicit numerical acceptance criteria are not always stated directly in the summary document but are implicit in the study design and the finding of "substantial equivalence."

2. Sample Size and Data Provenance

Test Set Sample Size:
- Precision (Qualitative): 88 determinations per concentration (N=88) spread across different runs/days.
- Method Comparison - Clinical Samples: 101 clinical unaltered samples.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an in-vitro diagnostic, these studies are typically conducted by the manufacturer in a controlled environment, likely using a mix of spiked and anonymized clinical samples. The "unaltered clinical samples" suggests prospective or retrospective collection from a clinical setting, but further details are not provided.

3. Number of Experts used to establish Ground Truth & Qualifications

Number of Experts: Not applicable/not specified. For an immunoassay measuring a chemical compound, the "ground truth" is typically established by an independent, highly accurate analytical method, not human expert interpretation.
Qualifications of Experts: Not applicable.

4. Adjudication Method

Adjudication Method: Not applicable. The ground truth (confirmatory method) for chemical analysis in this context does not involve human adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Was it done?: No. This type of study is relevant for imaging or interpretation-based AI systems where human readers are involved. This device is an automated immunoassay.

6. Standalone (Algorithm Only) Performance Study

Was it done?: Yes, in a sense. The performance characteristics (precision, method comparison, interference) describe the standalone performance of the LZI Fentanyl Enzyme Immunoassay on an automated clinical chemistry analyzer (AU680 Analyzer), without human interpretation being part of the primary measurement process. The results are quantitative (ΔOD, mAU) or qualitative (positive/negative) based on predefined cutoff values.

7. Type of Ground Truth Used

Ground Truth: For the method comparison study with clinical samples, the ground truth was established by a "more specific alternative chemical method," specifically gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS). This is considered the gold standard for confirming the presence and concentration of chemical compounds in forensic and clinical toxicology.

8. Sample Size for the Training Set

Training Set Sample Size: Not applicable. This is a traditional immunoassay, not an AI/machine learning algorithm that requires a "training set" in that sense. The device's performance is based on its chemical and enzymatic reactions, which are inherent to its design and formulation, not learned from data. Development might involve optimizing reagents, but not "training" like an AI model.

9. How the Ground Truth for the Training Set was Established

Ground Truth for Training Set: Not applicable, as there is no "training set" in the AI sense. The development of such an immunoassay involves analytical chemistry principles and empirical testing to optimize sensitivity, specificity, and other performance parameters.

Summary

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December 3, 2018

Lin-Zhi International, Inc. Bernice Lin, VP Operations 2945 Oakmead Village Court Santa Clara. CA 95051

Re: K181159

Trade/Device Name: LZI Fentanyl Enzyme Immunoassay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: DJG Dated: October 25, 2018 Received: October 25, 2018

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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181159

Device Name LZI Fentanyl Enzyme Immunoassay

Indications for Use (Describe)

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 norfentany. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

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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K181159

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.

Submitted On

April 26, 2018

Last Updated On

November 27, 2018

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 Fax: (408) 970-9030 e-mail: bclin@lin-zhi.com

Bernice Lin. Ph.D. Contact: VP Operations

Device Name and Classification

Classification Name:	Enzyme Immunoassay, OpiatesClass II, DJG (91 Toxicology),21 CFR 862.3650
Common Name:	Homogeneous Fentanyl Enzyme Immunoassay
Proprietary Name:	LZI Fentanyl Enzyme Immunoassay

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Legally Marketed Predicate Device(s)

The LZI Fentanyl Enzyme Immunoassay is substantially equivalent to the Immunalysis SEFRIA Fentanyl Urine Enzyme Immunoassay (K161216) manufactured by Immunalysis Corporation. The LZI Fentanyl 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 Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-touse liquid 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. 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, norfentanyl-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 norfentanyl-labeled 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 Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

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Intended Use

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.

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Comparison to Predicate Device

Levels

Storage

Control Levels

The LZI Fentanyl Enzyme Immunoassay is substantially equivalent to the Immunalysis SEFRIA Fentanyl Urine Enzyme Immunoassay which was cleared by the FDA under the premarket notification K161216 for its stated intended use.

Predicate Device (K161216) Subject Device Device Immunalysis SEFRIA Fentanyl Urine LZI Fentanyl Enzyme Immunoassay, Characteristics Enzyme Immunoassay and Fentanyl Norfentanyl Calibrators and Controls Calibrators The LZI Fentanyl Enzyme Immunoassay, For the qualitative determination of Intended Use when used in conjunction with the AU680 the presence of Fentanyl in human automated clinical system analyzer, is urine at a cutoff of 1 ng/mL 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 prescription use with a number of automated clinical chemistry analyzers. 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. Absorbance change measured Absorbance change measured Detection spectrophotometrically at 340 nm spectrophotometrically at 570 nm Analyte Norfentanyl Fentanyl Cutoff 5 ng/mL 1 ng/mL Matrix Urine Urine Calibrator One negative and three levels (0, 1, 5 ng/mL

3.75 and 6.25 ng/mL

2-8 ℃ until expiration date

2 and 4 ng/mL

2-8 °C until expiration date

N/A

The following table compares the LZI Fentanyl Enzyme Immunoassay with the predicate device.

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Performance Characteristics Summary:

AU680 Analyzer

Precision: 5 ng/mL Cutoff

NorfentanylConcentration		Within Run (N=22)		Total Precision(N=88)
	Mean	SD	% CV	Mean	SD	% CV
0 ng/mL	0.1	0.1	N/A	0.1	0.3	N/A
1.25 ng/mL	17.2	2.9	16.5%	17.2	3.6	20.8%
2.5 ng/mL	38.4	2.7	7.2%	38.4	3.2	8.4%
3.75 ng/mL	62.5	2.3	3.8%	62.5	3.6	5.7%
5 ng/mL	84.4	2.7	3.1%	84.4	3.3	4.0%
6.25 ng/mL	107.3	2.8	2.6%	107.3	3.6	3.4%
7.5 ng/mL	128.9	3.0	2.3%	128.9	4.1	3.2%
8.75 ng/mL	151.5	3.0	2.0%	151.5	4.1	2.7%
10 ng/mL	169.2	3.8	2.3%	169.2	4.3	2.6%

Precision: Qualitative, results in ΔΟD, mAU

Qualitative Positive/Negative Results:

5 ng/mL Cutoff Result:		Within Run (N=22)		Total Precision (N=88)
NorfentanylConcentration	% of Cutoff	Number ofDetermination	EIA Result	Number ofDetermination	EIA Result
0 ng/mL	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	2 Pos/20 Neg	88	26 Pos/62 Neg
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

Method Comparison - Clinical Samples:

From a total of one-hundred and one (101) clinical unaltered samples, Qualitative Data: 100.0 % agreement with positive, 86.5 % agreement with negative samples

Endogenous Compound Interference, Specificity, and Cross-Reactivity:

Interference was observed with Boric Acid at 1% w/v and with dextromethorphan. No other significant undesired cross-reactants or endogenous substance interference was observed.

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Performance Characteristics Summary: (continued) AU680 Analyzer

Summary:

The information provided in this pre-market notification demonstrates that the LZI Fentanyl Enzyme Immunoassay is substantially equivalent to the legally marketed predicate device for its general intended use. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by chromatography/mass spectrometry (GC/MS or LC/MS), an independent analytical method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Fentanyl Enzyme Immunoassay is safe and effective for its stated intended use.

Regulation Number and Section

§ 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).