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

The Methadone Metabolite 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 confirmatory method. Clinical consideration and professional judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

Device Description

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

The assay is based on competition between Methadone Metabolite labeled with glucose-6phosphate 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

Here's an analysis of the acceptance criteria and study detailed in the provided document for the Lin-Zhi International, Inc.'s Methadone Metabolite Enzyme Immunoassay ({0}-{6}):

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal acceptance criteria with numerical targets. Instead, it demonstrates substantial equivalence by comparing the performance characteristics of the LZI device to its predicate device (DRI/Microgenics Corp.'s Methadone Metabolite Enzyme Immunoassay) and showing "acceptable results." The criteria are implied by the performance metrics measured.

Performance Characteristic	Implicit Acceptance Criterion	LZI's Methadone Metabolite EIA Reported Performance
Precision (Within Run)	Low %CV (indicating consistency)	Qualitative:
		Negative: %CV = 0.73
		225 ng/mL: %CV = 0.69
		300 ng/mL: %CV = 0.72
		375 ng/mL: %CV = 0.78
		1000 ng/mL: %CV = 0.75
		Semi-quantitative:
	Quantitates accurately	225 ng/mL: %CV = 3.88
		300 ng/mL: %CV = 4.50
		375 ng/mL: %CV = 3.40
Precision (Run-To-Run)	Low %CV (indicating consistency)	Qualitative:
		Negative: %CV = 0.74
		225 ng/mL: %CV = 0.81
		300 ng/mL: %CV = 0.47
		375 ng/mL: %CV = 0.63
		1000 ng/mL: %CV = 0.93
		Semi-quantitative:
	Quantitates accurately	225 ng/mL: %CV = 3.59
		300 ng/mL: %CV = 3.62
		375 ng/mL: %CV = 3.19
Sensitivity	Low detection limit	15 ng/mL
Accuracy (Qualitative)	High agreement with a reference method	Vs. GC/MS (n=139):
		Positive: 100 % agreement
		Negative: 100 % agreement
Analytical Recovery (Qualitative)	100% accuracy on positive vs. negative tests	100% accuracy
Analytical Recovery (Semi-quantitative)	Quantitation within a specified percentage of nominal concentration	Quantitates within ±15% of nominal concentration between 30 ng/mL and 900 ng/mL. Average 95.0 % recovery at 225 ng/mL, Average 105.4 % recovery at 375 ng/mL.
Specificity	Comparable to predicate device	Comparable to the predicate device.

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

Sample Size for Accuracy Study: The accuracy study against GC/MS involved n=139 samples.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is implied to be laboratory-based validation data.

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

The ground truth for the test set (specifically for the accuracy study) was established by Gas Chromatography/Mass Spectrometry (GC/MS). GC/MS is an analytical chemical method, not an expert human interpretation. Therefore, the concept of "number of experts" and their "qualifications" is not applicable in this context.

4. Adjudication Method for the Test Set

Since the ground truth was established by an objective analytical method (GC/MS), there was no human adjudication reported or necessary for the test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, If So, What was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

No MRMC study was performed. This device is an in-vitro diagnostic (immunoassay) for methadone metabolites, not an AI-based imaging or interpretive device that would typically involve human readers.

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

This device is a standalone algorithm/kit. The performance data presented (precision, sensitivity, accuracy, recovery, specificity) represents the performance of the immunoassay system itself, without direct human interpretive "in-the-loop" performance affecting the result generation, although human operators perform the test and interpret the final qualitative/semi-quantitative output.

7. The Type of Ground Truth Used

The primary ground truth used for accuracy comparison was Gas Chromatography/Mass Spectrometry (GC/MS). This is an objective, gold-standard analytical method for confirming drug presence and concentration.

8. The Sample Size for the Training Set

The document does not mention a training set in the context of machine learning or AI. This is a conventional immunoassay where the reagents are formulated and optimized, but not "trained" on data in the same way an AI algorithm is. The development and optimization of the assay likely involved numerous samples during its formulation, but this is distinct from "training data" for an algorithm.

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

Not applicable, as there is no "training set" in the context of an AI/ML algorithm mentioned for this immunoassay device.

Summary

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 2 1 2004

Cheng-I Lin, Ph.D. President Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085

Re: K031797

Trade/Device Name: Methadone Metabolite Enzyme Immunoassay Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: Class II Product Code: DJR; DLJ Dated: August 25, 2003 Received: August 25, 2003

Dear Dr. Lin:

This SE Letter corrects the letter stamp dated October 10, 2003. The letter had only one Product Code. This letter corrects that with the addition of second Product Code DLJ.

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, Dr to 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, ist in o f 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 Begister.

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 aff 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 not the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll the fire 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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OCT 1 0 2003

Image /page/2/Picture/1 description: The image shows a sequence of handwritten alphanumeric characters. The sequence reads 'K031797'. The characters are written in a simple, slightly irregular style, giving them a casual appearance.

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

Device Name and Classification

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

Legally Marketed Predicate Device(s)

Lin-Zhi International, Inc.' Methadone Metabolite Enzyme Immunoassay is substantially equivalent to the Methadone Metabolite Enzyme Immunoassay (By DRI/Microgenics Corp.), cleared under premarket notification K931780.

LZI's Methadone Metabolite 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 Metabolite 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 Metabolite Enzyme Immunoassay (K931780) by DRI/Microgenics Corporation.

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

Similarities:

. Both assays are for qualitative and semi-quantitative determination of Methadone Metabolite in human urine.
Both assays use the same method principle, and device components. .

Differences:

DRI/Microgenics assay uses 4 points calibration (0. 300, 1000, 2000 ng/ml) for . semi-quantitative determination. LZI assay uses 5 calibrator set (0, 150, 300, 600, and 1000 ng/ml) for semi-quantitative determination.
LZI assay uses 300 ng/ml calibrator as cut-off concentration. DRI/Microgenics ● assay uses 1000 ng/ml calibrator as cut-off concentration.

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(Comparison to Predicate Device, continued)

Performance Characteristics

Feature	DRI's Methadone Metabolite EIA				LZI's Methadone Metabolite EIA
Within Run Precision:
Qualitative:	Mean Rate	SD	% CV		Mean Rate	SD	% CV
Negative	620	4.1	0.7	Negative	297.9	2.16	0.73
300 ng/mL	776	4.4	0.6	225 ng/mL	354.0	2.43	0.69
1000 ng/mL	974	7.7	0.8	300 ng/mL	379.4	2.69	0.72
2000 ng/mL	1083	5.4	0.5	375 ng/mL	390.9	3.03	0.78
				1000 ng/mL	449.4	3.37	0.75
Semi-quantitative: No data available					Mean Conc.	SD	% CV
				225 ng/mL	227.9	8.84	3.88
				300 ng/mL	304.9	13.73	4.50
				375 ng/mL	382.8	13.0	3.40
Run-To-Run Precision:
Qualitative: No data available					Mean Rate	SD	% CV
				Negative	296.7	2.2	0.74
				225 ng/mL	357.3	2.9	0.81
				300 ng/mL	377.2	1.8	0.47
				375 ng/mL	390.6	2.5	0.63
				1000 ng/mL	452.5	4.2	0.93
Semi-quantitative: No data available					Mean Conc.	SD	% CV
				225 ng/mL	227.2	8.17	3.59
				300 ng/mL	298.4	10.8	3.62
				375 ng/mL	371.1	11.8	3.19
Sensitivity:	75 ng/mL			15 ng/mL
Accuracy:	Vs. a commercial EIA				Vs. GC/MS (n=139)
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 nominalconcentration between 30 ng/mL and 900 ng/mL.Average 95.0 % recovery at 225 ng/mL level(Cutoff -25%)Average 105.4 % recovery at 375 ng/mLlevel (Cutoff + 25%)
Specificity:	See attached DRI's MethadoneMetabolite EIA package insert			Comparable to the predicate device.

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Conclusion

LZI's Methadone Metabolite 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 Metabolite Enzyme Immunoassay to other Methadone Metabolite test systems currently marketed in the United States.

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Premarket Notification

Indications for Use Statement

510(k) Number (if known): ΚΟ3 1797

Device Name: Methadone Metabolite Enzyme Immunoassay

Indications for Use:

Alberto C.
Division Sign-Off for Jean Carrier

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k). K031797

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)

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).