The Benzodiazepine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 200 ng/mL and/or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semi-quantitative analyses of benzodiazepines in human urine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The Benzodiazepine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when the preliminary positive results are used.

Device Description

LZI's Benzodiazepine Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibody that can detect benzodiazepines in human urine with minimal cross-reactivity to various, common prescription drugs and abused drugs.

The assay is based on competition between benzodiazepine labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme and free drug from the urine sample for a fixed amount of specific antibody. In the absence of free drug from the urine sample the specific antibody binds to the drug labeled G6PDH enzyme causing a decrease in enzyme activity. It is therefore the drug concentration is proportional to the enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to covert nicotinamide adenine dinucleotide (NAD) to NADH.

AI/ML Overview

The provided document describes the LZI's Benzodiazepine Enzyme Immunoassay and its performance evaluation against a predicate device (Syva EMIT® II Plus Benzodiazepine Assay) to establish substantial equivalence.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as a separate list with pass/fail thresholds. Instead, it presents performance characteristics of both the predicate device and the LZI device side-by-side, implying that performance comparable to or better than the predicate device constitutes acceptable performance for substantial equivalence.

Based on the "Performance Characteristics" table and the "Conclusion" section, here's a reconstructed table:

Performance Characteristic	Acceptance Criteria (Implied: Comparable to Predicate Device)	LZI's Benzodiazepine EIA Performance
Within Run Precision (Qualitative)	Coefficient of Variation (% CV) similar to or better than predicate.	Negative: 0.9% CV 100 ng/mL: 0.8% CV 200 ng/mL: 0.8% CV 300 ng/mL: 0.7% CV 400 ng/mL: 0.7% CV 1000 ng/mL: 0.7% CV
Within Run Precision (Semi-quantitative)	Coefficient of Variation (% CV) similar to or better than predicate.	100 ng/mL: 7.2% CV 200 ng/mL: 2.9% CV 300 ng/mL: 3.9% CV 400 ng/mL: 4.1% CV
Run-To-Run Precision (Qualitative)	Coefficient of Variation (% CV) similar to or better than predicate.	Negative: 0.7% CV 100 ng/mL: 0.6% CV 200 ng/mL: 0.4% CV 300 ng/mL: 0.5% CV 400 ng/mL: 0.6% CV 1000 ng/mL: 0.6% CV
Run-To-Run Precision (Semi-quantitative)	Coefficient of Variation (% CV) similar to or better than predicate.	100 ng/mL: 6.7% CV 200 ng/mL: 3.4% CV 300 ng/mL: 5.3% CV 400 ng/mL: 3.9% CV
Sensitivity	Functional sensitivity of 15 ng/mL (as per predicate).	15 ng/mL (functional)
Accuracy (Positive Samples)	Percentage agreement with commercial EIA similar to predicate (95.6%).	89.4% agreement with Syva
Accuracy (Negative Samples)	Percentage agreement with commercial EIA similar to predicate (99%).	100% agreement with Syva
Analytical Recovery (Qualitative)	100% accuracy on positive vs. negative tests.	100% accuracy on positive vs. negative tests.
Analytical Recovery (Semi-quantitative)	Quantitates within ±15% of nominal concentration between 40-900 ng/mL.	Quantitates within ±10% of nominal concentration between 20-800 ng/mL.
Specificity	Comparable to the predicate device.	Comparable to the predicate device.

Note on Accuracy: While LZI's positive sample agreement (89.4%) is lower than the predicate's (95.6%), the FDA's acceptance of the 510(k) suggests this was deemed "acceptable results when compared to the predicate device" in the context of substantial equivalence.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set:
- For Accuracy testing against the predicate device (Syva), a sample size of n=116 was used ("Vs. Syva (n=116)").
- For precision studies (Within Run and Run-To-Run), specific sample sizes are not explicitly stated, but the data includes Mean, SD, and %CV, which are derived from repeated measurements. The control levels used (e.g., Negative, 100 ng/mL, 200 ng/mL, etc.) represent different test points within the assay's range.
Data Provenance: The document does not specify the country of origin of the data or whether the data was retrospective or prospective. It is implied to be laboratory-generated data from Lin-Zhi International, Inc. for the purpose of demonstrating device performance.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

This type of information is not applicable to this device. This is an in vitro diagnostic device (immunoassay) for detecting benzodiazepines in urine. Ground truth for such assays is typically established by:

Using known concentrations of analytes (e.g., spiked samples, reference materials) for precision and analytical recovery.
Comparing results directly to a reference method (e.g., Gas Chromatography/mass spectrometry (GC/MS) mentioned as the preferred confirmatory method) or a legally marketed predicate device (which the Syva EMIT® II Plus Benzodiazepine Assay serves as in this submission).

There are no human "experts" in the traditional sense (e.g., radiologists interpreting images) establishing "ground truth" for individual test cases in this context.

4. Adjudication Method for the Test Set

Not applicable. As this is an in vitro diagnostic test, adjudication methods involving expert consensus (like 2+1 or 3+1) are not used to establish the "truth" for individual samples. Performance is assessed based on direct comparison to known values, a reference method, or a predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No. A Multi-Reader Multi-Case (MRMC) comparative effectiveness study is typically conducted for diagnostic imaging devices where multiple human readers interpret images. This document describes an in vitro diagnostic immunoassay, not an imaging device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, the performance data presented (precision, sensitivity, accuracy, analytical recovery, specificity) are all standalone performance data for the LZI's Benzodiazepine Enzyme Immunoassay. The device itself (the immunoassay) performs the measurement and provides a result (qualitative or semi-quantitative). Although a human performs the test and interprets the result in a clinical setting, the performance characteristics described directly relate to the analytical capabilities of the assay itself. The term "algorithm only" is more commonly associated with software-based AI, but in the context of an immunoassay, the "device only" performance is what's being evaluated.

7. The Type of Ground Truth Used

The ground truth used for this study appears to be a combination of:

Known concentrations: For precision, sensitivity, and analytical recovery studies, the results are compared against samples with pre-defined, known concentrations of benzodiazepines.
Comparison to a legally marketed predicate device: For accuracy, the LZI assay's results were compared against the Syva EMIT® II Plus Benzodiazepine Assay for n=116 samples. The predicate device's results serve as the "ground truth" or reference for this comparison.
Implied reference methods: While not explicitly used to establish ground truth for reported metrics, the document states that "Gas Chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method," indicating it's the gold standard for confirming results, especially preliminary positive ones.

8. The Sample Size for the Training Set

The document does not provide information regarding a "training set." This is an immunoassay, not a machine learning or AI model that requires a discrete training phase with data. The components of the assay (antibodies, enzyme conjugates, reagents) are developed through chemical and biochemical processes, not by "training" on a dataset in the way an AI algorithm is trained.

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

Not applicable. As a traditional immunoassay, there is no "training set" or "ground truth for the training set" in the context of machine learning. The assay's parameters (e.g., reagent concentrations, antibody specificity) are established through biochemical research and development, not data-driven training.

Summary

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K032365

SEP - 5 2003

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.

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. 687 North Pastoria Avenue Sunnyvale, CA 94085 Phone: (408) 732-3856 (408) 732-3849 Fax:

Contact:	Cheng-I Lin, Ph.D.President, R&D Director
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Device Name and Classification

Classification Name:	Benzodiazepine test system, Class II,JMX (91 Toxicology),21CFR 862.3170
Common Name:	Homogeneous enzyme immunoassay for the determination ofBenzodiazepines levels in urine.
Proprietary Name:	None

Legally Marketed Predicate Device(s)

Lin-Zhi International, Inc.' Benzodiazepine Enzyme Immunoassay is substantially equivalent to Syva EMIT® II Plus Benzodiazepine Assay (By Syva Company-Dade Behring Inc.), cleared under premarket notification K993985.

LZI's Benzodiazepine Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.

Device Description

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Intended Use

Comparison to Predicate Device

LZI's Benzodiazepine Enzyme Immunoassay is substantially equivalent to other products in commercially distribution intended for similar use. Most notably it is substantially equivalent to the currently, commercially marketed Emit® II Plus Benzodiazepine Assay (K993985) by Syva Company-Dade Behring Inc.

The following table compares LZI's Benzodiazepine Enzyme Immunoassav with the predicate device, Emit® II Plus Benzodiazepine Assay by Syva Company-Dade Behring Inc.

Similarities:

. Both assays are for qualitative and semi-quantitative determination of benzodiazepines in human urine.
Both have dual cutoff design (200 ng/mL or 300 ng/mL). ●
Both assays use 5 points calibration (0, 100, 200, 300, 1000 ng/ml) for semi-● quantitative determination.
Both assays use the same method principle, and device components. ●

Difference:

Syva's assay uses 150, 225, 250, 375 ng/mL for various control levels. LZI's . assay uses 100, 200, 300, 400 ng/mL for various control levels.
. Syva's assay uses lormetazepam as calibrator and control. LZI's assay uses oxazepam as calibrator and control.

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Performance Characteristics
Feature	Syva's Benzodiazepine EIA				LZI's Benzodiazepine EIA
Within Run Precision:
Qualitative:	(mA/min.)	Mean	SD	% CV	(mA/min.)	Mean	SD	% CV
	Negative	246.7	1.0	0.4	Negative	361.0	3.1	0.9
	150 ng/mL	294.7	1.2	0.4	100 ng/mL	417.8	3.5	0.8
	200 ng/mL	310.5	1.4	0.5	200 ng/mL	455.5	3.5	0.8
	225 ng/mL	319.3	1.3	0.4	300 ng/mL	483.3	3.5	0.7
	250 ng/mL	325.5	1.4	0.4	400 ng/mL	504.9	3.7	0.7
	300 ng/mL	336.1	1.4	0.4	1000 ng/mL	559.7	4.2	0.7
	375 ng/mL	349.7	2.4	0.7
Semi-quantitative:	(ng/mL)	Mean	SD	%CV	(ng/mL)	Mean	SD	%CV
	150 ng/mL	148.2	3.3	2.2	100 ng/mL	105.7	7.6	7.2
	200 ng/mL	196.7	10.2	5.2	200 ng/mL	203.6	5.9	2.9
	225 ng/mL	225.1	4.5	2.0	300 ng/mL	281.8	11.1	3.9
	250 ng/mL	247.3	5.3	2.1	400 ng/ml	373.9	15.3	4.1
	300 ng/mL	289.5	5.9	2.0
	375 ng/mL	353.8	6.2	1.8
Run-To-Run Precision:
Qualitative:	(mA/min.)	Mean	SD	% CV	(mA/min.)	Mean	SD	% CV
	Negative	246.7	1.7	0.7	Negative	360.0	2.5	0.7
	150 ng/mL	294.7	2.1	0.7	100 ng/mL	417.9	2.5	0.6
	200 ng/mL	310.5	2.2	0.7	200 ng/mL	457.0	1.9	0.4
	225 ng/mL	319.3	2.4	0.8	300 ng/mL	483.6	2.5	0.5
	250 ng/mL	325.5	2.3	0.7	400 ng/mL	504.4	2.8	0.6
	300 ng/mL	336.1	2.4	0.7	1000 ng/mL	561.8	3.3	0.6
	375 ng/mL	349.7	3.6	1.0
Semi-quantitative:	(ng/mL)	Mean	SD	%CV	(ng/mL)	Mean	SD	%CV
	150 ng/mL	148.2	4.2	2.8	100 ng/mL	95.8	6.4	6.7
	200 ng/mL	196.7	11.0	5.6	200 ng/mL	192.0	6.5	3.4
	225 ng/mL	225.1	5.7	2.5	300 ng/mL	294.8	15.5	5.3
	250 ng/mL	247.3	5.7	2.3	400 ng/ml	398.6	15.4	3.9
	300 ng/mL	289.5	7.4	2.6
	375 ng/mL	353.8	11.0	3.1
Sensitivity:	15 ng/mL			15 ng/mL (functional)
Accuracy:	Vs. a commercial EIA				Vs. Syva (n=116)
Positive Samples:	95.6 % agreement				89.4 % agreement
Negative Samples:	99% agreement				100 % agreement
Analytical Recovery:
	Qualitative: 100 % accuracy on positive vs.
	negative tests
	Semi-quantitative: Quantitates within ±15% of the				Quantitates within ±10% of the
	nominal concentration between 40				nominal concentration between 20
	ng/mL and 900 ng/mL.				ng/mL and 800 ng/mL.
Specificity:	See attached Syva's Benzodiazepine				Comparable to the predicate device.
	Assay package insert

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Conclusion

LZI's Benzodiazepine Enzyme Immunoassay was evaluated for several performance characteristics including precision, sensitivity, accuracy, analytical recovery, and specificity. All the studies showed acceptable results when compared to the predicate device.

We trust the information provided in this Premarket Notification [510(k)] submission will support a determination of substantial equivalence of the LZI's Benzodiazepine Enzyme Immunoassay to other Benzodiazepine test systems currently marketed in the United States.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes coiled around it. The symbol is enclosed in a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is written around the top half of the circle. The text is in all caps and is evenly spaced around the circle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP - 5 2003

Cheng-I Lin, Ph.D. President. R&D Director Lin-Zhi International, Inc. 687 North Pastroia Avenue Sunnyvale, CA 94085

Re: K032365

Trade/Device Name: Benzodiazepine Enzyme Immunoassay Regulation Number: 21 CFR 862.3170 Regulation Name: Benzodiazepine Test System Regulatory Class: Class II Product Code: JXM, DLJ, LAS Dated: July 31, 2003 Received: July 31, 2003

Dear Dr. 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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Premarket Notification

Indications for Use Statement

510(k) Number (if known): _

KO32368

Device Name: Benzodiazepine Enzyme Immunoassay

Indications for Use:

Alberts

Division Sign-Off for Jean Cooper

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K032365

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (per 21 CFR 801.109) OR

Over-The-Counter Use

(Optional Format 1-2-96)

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Premarket Notification Supplement

Indications for Use Statement

510(k) Number (if known):

Device Name: Benzodiazepine Drug of Abuse Calibrators and Controls

Indications for Use:

The Benzodiazepine Drug of Abuse Calibrators are intended for in vitro diagnostic use for the calibration of the Benzodiazepine enzyme immunoassay to detect benzodiazepines in human urine.

The Benzodiazepine Drug of Abuse Controls are intended for in vitro diagnostic use for the validation of the Benzodiazepine enzyme immunoassay to detect benzodiazepines in human urine.

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use(Per 21 CFR 801.109)	OR	Over-The-Counter Use
	(Optional Format 1-2-96)
	Office of In Vitro Diagnostic DeviceEvaluation and Safety

510(k) K032365

Page 2

Regulation Number and Section

§ 862.3170 Benzodiazepine test system.

(a)
Identification. A benzodiazepine test system is a device intended to measure any of the benzodiazepine compounds, sedative and hypnotic drugs, in blood, plasma, and urine. The benzodiazepine compounds include chlordiazepoxide, diazepam, oxazepam, chlorzepate, flurazepam, and nitrazepam. Measurements obtained by this device are used in the diagnosis and treatment of benzodiazepine use or overdose and in monitoring levels of benzodiazepines to ensure appropriate therapy.(b)
Classification. Class II (special controls). A benzodiazepine 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).