The Cocaine 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 benzoylecgonine (cocaine metabolite) in human urine.

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

The assay is based on competition between benzoylecgonine 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 convert nicotinamide adenine dinucleotide (NAD) to NADH.

AI/ML Overview

Here's an analysis of the provided text regarding the Lin-Zhi International, Inc.'s Cocaine Metabolite Enzyme Immunoassay, broken down by your requested categories:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as pass/fail thresholds against which the new device was measured. Instead, it presents performance characteristics of the new device and compares them to a legally marketed predicate device (DRI's Cocaine Metabolite EIA). The implicit acceptance criterion is that the new device's performance should be "comparable" or "acceptable" relative to the predicate, demonstrating substantial equivalence.

Performance Characteristic	Acceptance Criteria (Implicit - based on predicate)	Reported Device Performance (LZI's Cocaine Metabolite EIA)
Within Run Precision (Qualitative)	Comparable to DRI's (e.g., %CV < 1.0)	Negative: 0.37 %CV
		225 ng/mL: 0.50 %CV
		300 ng/mL: 0.48 %CV
		375 ng/mL: 0.56 %CV
		3000 ng/mL: 0.36 %CV
Within Run Precision (Semi-quantitative)	N/A (DRI had no data)	225 ng/mL: 1.45 %CV
		300 ng/mL: 1.53 %CV
		375 ng/mL: 1.37 %CV
Run-To-Run Precision (Qualitative)	Comparable to DRI's (e.g., %CV < 1.5)	Negative: 0.36 %CV
		225 ng/mL: 0.67 %CV
		300 ng/mL: 0.93 %CV
		375 ng/mL: 0.53 %CV
		3000 ng/mL: 0.49 %CV
Run-To-Run Precision (Semi-quantitative)	N/A (DRI had no data)	225 ng/mL: 1.41 %CV
		300 ng/mL: 1.65 %CV
		375 ng/mL: 1.83 %CV
Sensitivity	Comparable to DRI's (40 ng/mL)	4 ng/mL
Accuracy (vs. Commercial EIA)	100% Sensitivity, 100% Specificity	100% Sensitivity, 100% Specificity
Analytical Recovery (Qualitative)	N/A (DRI had no data)	100% accuracy on positive vs. negative tests
Analytical Recovery (Semi-quantitative)	N/A (DRI had no data)	Quantitate within ±10% of nominal concentration between 30 ng/mL and 2100 ng/mL. Average 100.6% recovery at 225 ng/mL, 97.3% recovery at 375 ng/mL.
Specificity	Comparable to predicate device	Comparable to the predicate device
Cutoff Level	300 ng/mL	300 ng/mL
Assay Range	0 to 1000 ng/mL (DRI's current) / 0 to 3000 ng/mL (DRI's previous)	0 to 3000 ng/mL

Study Proving Acceptance Criteria (Substantial Equivalence):

The submission functions as the study report. It aims to demonstrate substantial equivalence to the predicate device (DRI/Microgenics Corp.'s Cocaine Metabolite Enzyme Immunoassay, K960187) by comparing various performance characteristics. The conclusion states: "LZI's Cocaine Metabolite Enzyme Immunoassay was evaluated for several performance characteristics including precision, sensitivity, accuracy, analytical recovery, and specificity. [These] showed acceptable results when compared to the predicate device."

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

Sample Size for Test Set: The sample sizes are not explicitly stated for individual tests beyond the "Mean Rate," "SD," and "%CV" values, which imply multiple runs or measurements. For precision studies, there are multiple data points for "Within Run" and "Run-To-Run" precision for different concentration levels (Negative, 225, 300, 375, 3000 ng/mL). The specific number of replicates or runs for each condition is not provided.
Data Provenance: Not specified. It's likely an internal study conducted by Lin-Zhi International, Inc. The document does not indicate country of origin for test data or whether it was retrospective or prospective. Given the nature of a 510(k) submission for a new in-vitro diagnostic, it would typically involve prospective testing to generate the performance data.

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

This information is not provided in the document. For an enzyme immunoassay testing for a drug metabolite, the "ground truth" would typically be established by preparing samples with known concentrations of the analyte (benzoylecgonine) or by confirming the presence/absence and concentration using a highly accurate reference method like GC/MS. The document mentions GC/MS as the preferred confirmatory method for preliminary positive results, but it doesn't detail how known concentrations were prepared or verified for the internal test set.

4. Adjudication Method for the Test Set

Not applicable/Not specified. This refers to consensus-building amongst experts for diagnostic ground truth. For this type of IVD, the ground truth is established through chemical analysis methods (e.g., preparing spiked samples with known concentrations, or using a reference method like GC/MS).

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for imaging devices or those requiring human interpretation. This device is an automated enzyme immunoassay, so human interpretation is not the primary measure of performance in the same way. The comparison is between the performance metrics of the new assay and the predicate assay.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)

Yes, the provided data represents standalone performance. The "device" is the enzyme immunoassay kit itself, which provides an analytical result (rate or concentration) without human intervention in the result generation process beyond operating the analyzer. The precision, sensitivity, accuracy, and recovery data are measures of the assay's performance on its own.

7. Type of Ground Truth Used

The ground truth for evaluating the device's performance (precision, sensitivity, analytical recovery) appears to be based on known concentrations of benzoylecgonine. This is achieved by either:
- Creating samples with precisely prepared, spiked concentrations of benzoylecgonine.
- Using samples previously characterized by a reference method (like the mentioned GC/MS).
For accuracy, the "ground truth" was established by comparing the LZI assay's results against a commercial EIA (presumably the predicate device or another established method) and reporting 100% sensitivity and specificity, indicating agreement with a widely accepted method.

8. Sample Size for the Training Set

This information is not provided. This device is an enzyme immunoassay, not a machine learning algorithm that typically requires a large "training set" in the same sense. The development of such an assay involves formulation and optimization, but the document doesn't detail the experimental scale of that development process. The term "training set" is more common in AI/ML contexts.

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

Since there's no explicitly mentioned "training set" in the AI/ML sense, this question isn't directly applicable. If interpreted as how the assay was developed and optimized, the ground truth would have been established through a series of experiments using known concentrations of benzoylecgonine in urine samples to optimize reaction conditions, antibody concentrations, and enzyme activity, ensuring accurate detection across the intended range. However, these specific details are not elaborated upon in the 510(k) summary.

Summary

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MAY 1 0 2002

1020763

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 (408) 944-0359 Fax:

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

Device Name and Classification

Classification Name:	Enzyme Immunoassay, Cocaine and Cocaine Metabolites,Class II, DIO (91 Toxicology), 21CFR 862.3250
Common Name:	Homogeneous enzyme immunoassay for the determination ofbenzoylecgonine (cocaine metabolite) level in urine.
Proprietary Name:	None

Legally Marketed Predicate Device(s)

Lin-Zhi International, Inc.' Cocaine Metabolite Enzyme Immunoassay is substantially equivalent to the Cocaine Metabolite Enzyme Immunoassay (By DRI/Microgenics Corp.), cleared under premarket notification K960187.

LZI's Cocaine 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 Cocaine 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 Cocaine Metabolite Enzyme Immunoassay (K960187) by Diagnostic Reagents, Inc. (DRI, now Microgenics Corporation)

The following table compares LZI's Cocaine Metabolite Enzyme Immunoassay with the predicate device, DRI's Cocaine Metabolite Enzyme Immunoassay. Specific data on the performance of the test have been incorporated into the proposed product insert (Attachment A). Product inserts for the predicate device and two other commercial products of similar intended use are provided in the Attachment C.

Similarities:

Both assays are for qualitative and semi-quantitative determination of . benzovlecgonine (cocaine metabolite) in human urine.
Both assays use the same method principle, and device components. .
Both assays use 300 ng/mL as cutoff level per recommendations of The Substance . Abuse and Metal Health Services Administration (SAMHSA).

Differences:

. Assay range for the DRI's assay is 0 to 1000* ng/mL; LZI's assay range is 0 to 3000 ng/mL.
LZI's Cocaine Metabolite Enzyme Immunoassay uses 5 calibrators for the semi-. quantitative analysis of benzovlecgonine (cocaine metabolite) concentration in urine. DRI's Cocaine Metabolite EIA used 3 calibrators previously. A total of 5 calibrators are available now from DRI.

Previously DRI assay range was also 0 to 3000 ng/mL as indicated in its product insert of 03/98.

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(Comparison to Predicate Device, continued)

Performance Characteristics

Feature	DRI's Cocaine Metabolite EIA				LZI's Cocaine Metabolite EIA
Within Run Precision:
Qualitative:	Negative	Mean Rate	SD	% CV	Negative	Mean Rate	SD	% CV
	Negative	302	2.0	0.7	Negative	243.7	0.9	0.37
	225 ng/mL	341	2.5	0.7	225 ng/mL	356.8	1.8	0.50
	300 ng/mL	354	3.4	0.9	300 ng/mL	380.2	1.8	0.48
	375 ng/mL	374	2.4	0.6	375 ng/mL	397.3	2.2	0.56
	*3000 ng/mL	442	3.6	0.8	3000 ng/mL	488.4	1.8	0.36
Semi-quantitative:	No data available.					Mean Conc.	SD	% CV
					225 ng/mL	226.2	3.3	1.45
					300 ng/mL	303.4	4.6	1.53
					375 ng/mL	370.7	5.1	1.37
Run-To-Run Precision:
Qualitative:	Negative	Mean Rate	SD	% CV	Negative	Mean Rate	SD	% CV
	Negative	302	3.9	1.3	Negative	243.1	0.9	0.36
	225 ng/mL	342	3.9	1.1	225 ng/mL	354.8	2.4	0.67
	300 ng/mL	354	4.9	1.4	300 ng/mL	377.0	3.5	0.93
	375 ng/mL	374	5.1	1.4	375 ng/mL	394.6	2.1	0.53
	*3000 ng/mL	443	5.2	1.2	3000 ng/mL	486.0	2.4	0.49
Semi-quantitative:	No data available.					Mean Conc.	SD	% CV
					225 ng/mL	226.7	3.2	1.41
					300 ng/mL	307.9	5.1	1.65
					375 ng/mL	376.8	6.9	1.83
Sensitivity:	40 ng/mL				4 ng/mL
Accuracy:	Vs. a commercial EIA				Vs. DRI s Cocaine Metabolite EIA
Sensitivity	100 %				100 %
Specificity	100 %				100 %
Analytical Recovery:
	Qualitative: No data available				100 % accuracy on positive vs. negative tests
	Semi-quantitative: No data available				Quantitate within ±10% of the nominalconcentration between 30 ng/mL and 2100ng/mL.Average 100.6 % recovery at 225 ng/mLlevel (Cutoff -25%)Average 97.3 % recovery at 375 ng/mL level(Cutoff + 25%)
Specificity:	See attached DRI's Cocaine MetaboliteEIA package insert				Comparable to the predicate device.

*Data from 03/98 package insert. The assay range for DRI assay now is 0 to 1000 ng/mL.

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Conclusion

LZI's Cocaine Metabolite Enzyme Immunoassay was evaluated for several performance characteristics including precision, sensitivity, accuracy, analytical recovery, and specificity. onatuelers 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 Cocaine Metabolite Enzyme Immunoassay to other cocaine metabolite test systems currently marketed in the United States.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes representing the department's mission. The eagle is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 1 0 2002

Chiu Chin Chang, Ph.D. VP. R&D Lin-Zhi International, Inc. 2391 Zanker Road, Suite 340 San Jose, CA 95131-1124

K020763 Re:

Trade/Device Name: Cocaine Metabolite Enzyme Immunoassay Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: Class II Product Code: DIO Dated: April 15, 2002 Received: April 24, 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 for abound in the 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 may or sabyeet to been to deeal 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 r rouse of a read a determination that your device complies with other requirements of the Act and in Drederal statutes and regulations administered by other Federal agencies. You must or any 1 with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set Of A rate 677) working (21 CFR Part 820); and if applicable, the electronic forth in the qualis) 35 would provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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 Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Premarket Notification

Indications for Use Statement

510(k) Number (if known): KO 20763

Device Name: Cocaine Metabolite Enzyme Immunoassay

Indications for Use:

Pan Coopy

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K020763

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3250 Cocaine and cocaine metabolite test system.

(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite 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).