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

The Methadone Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatorv method. Clinical consideration and professional judgement should be applied to any drug-ofabuse test result, particularly when preliminary positive results are used.

Device Description

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

The assay is based on competition between methadone 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 with G6PDH enzyme causing a decrease in 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 text describes the Lin-Zhi International, Inc. Methadone Enzyme Immunoassay, a device for detecting methadone in human urine. Here's a breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implied by Predicate) / Target	Reported Device Performance (LZI Methadone EIA)
Within Run Precision:	- Low %CV for qualitative results	Qualitative:
Negative	(Predicate: SD 1.0, %CV 0.8)	Mean Rate: 209.4, SD: 1.0, %CV: 0.49
225 ng/mL	(Predicate: 300 ng/mL, SD 1.6, %CV 0.7)	Mean Rate: 272.8, SD: 1.1, %CV: 0.39
300 ng/mL	(Predicate: 1000 ng/mL, SD 1.5, %CV 0.5)	Mean Rate: 293.4, SD: 0.7, %CV: 0.25
375 ng/mL	(No direct predicate comparison)	Mean Rate: 308.2, SD: 0.9, %CV: 0.29
1000 ng/mL	(No direct predicate comparison)	Mean Rate: 344.9, SD: 1.1, %CV: 0.33
Semi-quantitative:	(Predicate: No data available)	Mean Conc. at 225 ng/mL: 229.2, SD: 2.5, %CV: 1.09
		Mean Conc. at 300 ng/mL: 308.5, SD: 3.5, %CV: 1.13
		Mean Conc. at 375 ng/mL: 391.4, SD: 5.4, %CV: 1.37
Run-To-Run Precision:	- Low %CV for qualitative results	Qualitative:
Negative	(Predicate: No data available)	Mean Rate: 209.5, SD: 1.1, %CV: 0.51
225 ng/mL	(Predicate: No data available)	Mean Rate: 271.4, SD: 2.0, %CV: 0.74
300 ng/mL	(Predicate: No data available)	Mean Rate: 292.3, SD: 1.9, %CV: 0.66
375 ng/mL	(Predicate: No data available)	Mean Rate: 307.2, SD: 2.6, %CV: 0.84
1000 ng/mL	(Predicate: No data available)	Mean Rate: 344.1, SD: 2.0, %CV: 0.58
Semi-quantitative:	(Predicate: No data available)	Mean Conc. at 225 ng/mL: 228.0, SD: 7.8, %CV: 3.42
		Mean Conc. at 300 ng/mL: 305.1, SD: 10.2, %CV: 3.36
		Mean Conc. at 375 ng/mL: 379.6, SD: 13.2, %CV: 3.47
Sensitivity:	Predicate: 10 ng/mL	15 ng/mL
Accuracy:	Predicate: Vs. a commercial EIA, 100% agreement	Vs. GC/MS: 100% agreement for Positive Samples, 100% agreement for Negative Samples
Analytical Recovery:	Predicate: No data available	Qualitative: 100% accuracy on positive vs. negative tests. Semi-quantitative: Quantitates within ±15% of the nominal concentration between 30 ng/mL and 750 ng/mL. Average 96.6% recovery at 225 ng/mL level (Cutoff -25%). Average 93.7% recovery at 375 ng/mL level (Cutoff + 25%).
Specificity:	Predicate: See attached DRI's Methadone EIA package	Comparable to the predicate device.

Note on Acceptance Criteria: The document primarily demonstrates substantial equivalence to the predicate device (Methadone Enzyme Immunoassay by DRI/Microgenics Corp., K972526). Therefore, the "acceptance criteria" are generally implied to be comparable performance to the predicate. Where the predicate had "No data available," the new device presents its own performance which is implicitly considered "acceptable" for the purposes of substantial equivalence.

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

The document does not explicitly state the sample size used for the test set for precision studies. For accuracy, it states "100% agreement" for positive and negative samples against GC/MS, but the number of samples is not provided. The data provenance is also not specified (e.g., country of origin, retrospective/prospective). It is implied that these are laboratory studies since the product is an in-vitro diagnostic.

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

Not applicable. This device is an immunoassay for methadone levels. The primary "ground truth" method cited for accuracy is GC/MS (Gas Chromatography/Mass Spectrometry), which is an analytical chemical method, not reliant on human expert adjudication in the same way imaging or clinical diagnosis might be.

4. Adjudication Method for the Test Set

Not applicable in the conventional sense. The "ground truth" for reported accuracy is comparison against GC/MS.

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

No, this is not an MRMC study. This device is an in vitro diagnostic assay, not an imaging or interpretive diagnostic system requiring human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply.

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

Yes, the studies presented (precision, sensitivity, accuracy, analytical recovery, specificity) describe the standalone performance of the Methadone Enzyme Immunoassay. It is an automated assay intended for professional use with clinical chemistry analyzers, meaning its performance is evaluated as the algorithm/reagent system working independently without real-time human interpretation within the assay measurement itself. The "human-in-the-loop" would be lab personnel running the test and interpreting the final quantitative or qualitative result.

7. The Type of Ground Truth Used

The primary ground truth used for the accuracy study is GC/MS (Gas Chromatography/Mass Spectrometry). This is a highly specific and sensitive analytical method considered the gold standard for confirming drug presence and concentration in toxicology.

8. The Sample Size for the Training Set

Not applicable. This document describes an enzyme immunoassay, which is a biochemical assay and not an Artificial Intelligence (AI) or machine learning device that requires a "training set" in the computational sense. The device's performance characteristics are inherent to its chemical and enzymatic reactions, not learned from data. Therefore, there is no "training set" for an algorithm.

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

Not applicable, as there is no "training set" for this type of device.

Summary

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)(623317

DEC 1 2 2002

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. 2391 Zanker Road, Suite 340 San Jose, CA 95131-1124 Phone: (408) 944-0360 Fax: (408) 944-0359

Chiu Chin Chang, Ph.D. Contact: VP, R&D

Device Name and Classification

Classification Name:	Methadone test system, Class II, DJR (91 Toxicology), 21CFR 862.3620
Common Name:	Homogeneous enzyme immunoassay for the determination of methadone levels in urine.
Proprietary Name:	None

Legally Marketed Predicate Device(s)

Lin-Zhi International, Inc.' Methadone Enzyme Immunoassay is substantially equivalent to the Methadone Enzyme Immunoassay (By DRI/Microgenics Corp.), cleared under premarket notification K972526.

LZI's Methadone 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 Methadone 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 Methadone Enzyme Immunoassay (K972526) by DRI/Microgenics Corporation.

The following table compares LZI's Methadone Enzyme Immunoassay with the predicate device. Methadone Enzyme Immunoassay by DRI/Microgenics Corp.

Similarities:

Both assays are for qualitative and semi-quantitative determination of methadone . in human urine.
Both assays use the same method principle, and device components. .
Both assays use 300 ng/mL as cutoff level. ●

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(Comparison to Predicate Device, continued)

Performance Characteristics

Feature	DRI's Methadone EIA			LZI's Methadone EIA
Within Run Precision:
Qualitative	Mean Rate	SD	% CV	Mean Rate	SD	% CV
	Negative	127	1.0	0.8	Negative	209.4	1.0	0.49
	300 ng/mL	217	1.6	0.7	225 ng/mL	272.8	1.1	0.39
	1000 ng/mL	289	1.5	0.5	300 ng/mL	293.4	0.7	0.25
					375 ng/mL	308.2	0.9	0.29
					1000 ng/mL	344.9	1.1	0.33
Semi-quantitative	No data available				Mean Conc.	SD	% CV
					225 ng/mL	229.2	2.5	1.09
					300 ng/mL	308.5	3.5	1.13
					375 ng/mL	391.4	5.4	1.37
Run-To-Run Precision:
	Qualitative: No data available				Mean Rate	SD	% CV
					Negative	209.5	1.1	0.51
					225 ng/mL	271.4	2.0	0.74
					300 ng/mL	292.3	1.9	0.66
					375 ng/mL	307.2	2.6	0.84
					1000 ng/mL	344.1	2.0	0.58
Semi-quantitative	No data available				Mean Conc.	SD	% CV
					225 ng/mL	228.0	7.8	3.42
					300 ng/mL	305.1	10.2	3.36
					375 ng/mL	379.6	13.2	3.47
Sensitivity:	10 ng/mL			15 ng/mL
Accuracy:	Vs. a commercial EIA			Vs. GC/MS
Positive Samples	100 % agreement (GC/MS confirmed)			100 % agreement
Negative Samples	100 % agreement			100 % agreement
Analytical Recovery:
	Qualitative No data available			100 % accuracy on positive vs. negative tests
	Semi-quantitative No data available				Quantitates within ±15% of the nominal
					concentration between 30 ng/mL and 750
					ng/mL
					Average 96.6 % recovery at 225 ng/mL level(Cutoff -25%)
					Average 93.7 % recovery at 375 ng/mL level
					(Cutoff + 25%)
Specificity:		See attached DRI's Methadone EIA			Comparable to the predicate device.
	package insert

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Conclusion

LZI's Methadone 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 Methadone Enzyme Immunoassay to other methadone 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 shows a logo for the Department of Health & Human Services. The logo consists of a symbol with three stylized, curved lines that resemble a human figure. The symbol is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Chiu Chin Chang, Ph.D. VP. R & D Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085-2917

DEC 1 2 2002

Re: K023317

Trade/Device Name: Methadone Enzyme Immunoassay Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: Class II Product Code: DJR Dated: September 30, 2002 Received: October 3, 2002

Dear Dr. Chang:

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. Iisting 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).

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

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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 Putman

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):

Device Name: Methadone Enzyme Immunoassay

Indications for Use:

Qlan Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K023317

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3620 Methadone test system.

(a)
Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.(b)
Classification. Class II (special controls). A methadone 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).