The Cannabinoid Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 20 ng/mL, 50 ng/mL (SHAHSA recommended initial test cutoff concentration), or 100 ng/mL cutoff. The assay is intended for use in the qualitative and semi-quantitative analyses of cannabinoids (THC) in human urine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

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

The assay is based on competition between Δ - THC-labeled 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 convert nicotinamide adenine dinucleotide (NAD) to NADH.

AI/ML Overview

Acceptance Criteria and Device Performance for LZI's Cannabinoid Enzyme Immunoassay

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes the performance of Lin-Zhi International, Inc.'s Cannabinoid Enzyme Immunoassay against a legally marketed predicate device (K943998 from DRI, now Microgenics Corp.). The acceptance criteria are implicitly defined by demonstrating comparability or superiority to the predicate device's performance characteristics.

Performance Metric	Acceptance Criteria (Implicit: Comparable to Predicate)	Reported Device Performance (LZI's Cannabinoid EIA)
Precision
Within Run	Comparable to DRI's (given by SD and %CV)	Low SD and %CV across various THC levels (e.g., THC 50 assay: 0.39-0.87% CV for qualitative, 2.12-2.91% CV for semi-quantitative).
Run-To-Run	Comparable to DRI's (given by SD and %CV)	Low SD and %CV across various THC levels (e.g., THC 50 assay: 0.66-0.97% CV for qualitative, 2.41-3.59% CV for semi-quantitative).
Sensitivity	Comparable to DRI's (10 ng/mL)	5 ng/mL (THC 20 assay); 7.5 ng/mL (THC 50 assay); 15 ng/mL (THC 100 assay) - Improved/Lower than predicate
Accuracy	Equivalent to predicate's (100% agreement vs. GC/MS for positive/negative samples for 50/100 ng/mL cutoffs).	Vs. DRI's Cannabinoid EIA (n=216 samples): - THC 20 assay: 100% Agreement (Positive & Negative Samples) - THC 50 assay: 100% Agreement (Positive & Negative Samples) - THC 100 assay: 98.3% Agreement for Positive (1 marginal discrepant), 100% Agreement for Negative Samples.
Analytical Recovery	No data available for predicate (implies demonstrating acceptable recovery for LZI’s device).	Qualitative: 100% accuracy on positive vs. negative tests. Semi-quantitative: Quantitates within ±12% of nominal concentration between 10 ng/mL and 95 ng/mL. Average 98.7% recovery at 37.5 ng/mL (Cutoff - 25%); Average 93.2% recovery at 62.5 ng/mL (Cutoff + 25%).
Specificity	Comparable to the predicate device.	Comparable to the predicate device (referencing DRI's package insert).

2. Sample Size and Data Provenance

Test Set Sample Size:
- Accuracy:
  - For comparison against the predicate device (DRI's Cannabinoid EIA): n = 216 samples.
  - The predicate device's accuracy was stated as Vs. GC/MS* (n = 592). This implies the predicate was validated with 592 samples, but the new device's accuracy against the predicate used 216 samples.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). However, given it's a submission to the FDA, it is expected to be from controlled laboratory and/or clinical settings. It is likely prospective for the LZI device's testing, especially for precision and analytical recovery.

3. Number of Experts and Qualifications for Ground Truth

Number of Experts: Not applicable. The ground truth for the predicate device's accuracy was against GC/MS, and the LZI device's accuracy was primarily against the predicate device's results.
Qualifications of Experts: Not applicable.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The testing involves direct comparison of analytical results (e.g., enzyme immunoassay readings, concentration measurements, or qualitative positive/negative calls) against a reference method (predicate EIA or GC/MS), not human interpretation requiring adjudication.

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

MRMC Study Done: No. This is an in vitro diagnostic device for chemical analysis (enzyme immunoassay), not an imaging or diagnostic device that requires human interpretation of outputs. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant to this device.

6. Standalone Performance Study

Standalone Performance Study Done: Yes. The "Performance Characteristics" section details the standalone performance of the LZI Cannabinoid Enzyme Immunoassay, including precision, sensitivity, accuracy (against a predicate and implicitly compared to GC/MS via the predicate), analytical recovery, and specificity. This data represents the algorithm's (assay's) performance without human intervention in the result generation process, beyond operating the analyzer.

7. Type of Ground Truth Used

Type of Ground Truth:
- For the LZI device's accuracy study: The predicate device's results (DRI's Cannabinoid EIA) served as the primary reference standard for comparison (n=216).
- For the predicate device's accuracy (which guides the LZI device's equivalence): Gas Chromatography/Mass Spectrometry (GC/MS) was used as the confirmatory method, as indicated by "* A 15 ng/mL cutoff for GC/MS was used for comparison." and the predicate's mention of "Vs. GC/MS* (n = 592)". GC/MS is a very high-accuracy 'gold standard' for drug confirmation.
- For other performance metrics (Precision, Sensitivity, Analytical Recovery, Specificity): Ground truth was established through defined laboratory protocols, known concentrations of cannabinoids (for sensitivity and recovery), and reference panels for specificity.

8. Sample Size for the Training Set

Training Set Sample Size: Not applicable. This device is an enzyme immunoassay, not a machine learning or AI-driven algorithm that requires a "training set" in the conventional sense. The assay chemistry and parameters are developed and optimized through R&D, but there isn't a separate, quantifiable "training set" like there would be for an AI model.

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

Ground Truth for Training Set: Not applicable, as no conventional "training set" with associated ground truth is used for an enzyme immunoassay. The development and optimization of such assays rely on established biochemical principles, standard reference materials, and empirical testing to achieve desired performance characteristics.

Summary

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AUG 1 5 2002

KC21887

510(k) Summary of Safety and Effectiveness

This summary of 510(k) safetv 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:	Enzyme Immunoassay, Cannabinoids,Class II, LDJ (91 Toxicology), 21CFR 862.3870
Common Name:	Homogeneous enzyme immunoassay for the determinationof cannabinoids (THC) level in urine.
Proprietary Name:	None

Legally Marketed Predicate Device(s)

Lin-Zhi International, Inc.'s Cannabinoid Enzyme Immunoassay is substantially equivalent to the Cannabinoid (THC) Enzyme Immunoassay (By DRJMicrogenics Corp.), cleared under premarket notification K943998.

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

Device Description

The assay is based on competition between Δ - THC-labeled glucose-6-phosphate dehydrogenase (G6PDH) enzyme, and free drug from the urine sample for a fixed

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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.

Intended Use

The Cannabinoid Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 20 ng/mL, 50 ng/mL (SAMHSA recommended initial test cutoff concentration), or 100 ng/mL cutoff. The assay is intended for use in the qualitative and semi-quantitative analyses of cannabinoids (THC) in human urine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

Comparison to Predicate Device

LZI's Cannabinoid 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 Cannabinoid (THC) Enzyme Immunoassay (K943998) by Diagnostic Reagents, Inc. (DRI, now Microgenics Corporation)

The following table compares LZI's Cannabinoid Enzyme Immunoassay with the predicate device, DRI's Cannabinoid (THC) Enzyme Immunoassay.

Similarities:

. Both assays are for qualitative and semi-quantitative determination of cannabinoids in human urine.
Both assays use the same method principle, and device components. .
Both assays can be used with a 20 ng/mL, 50 ng/mL (Cutoff level per . recommendations of The Substance Abuse and Metal Health Services Administration, or SAMHSA), or 100 ng/mL cutoff.
The same 5 calibrators were used for qualitative analyses of the assay. .

Differences:

In the semi-quantitative analysis of cannabinoids concentration in urine. LZI's . Cannabinoid Enzyme Immunoassay uses a specified 5 calibrators set for each cutoff assay. DRI's Cannabinoid (THC) EIA used the same 5 calibrators for both qualitative analyses and the semi-quantitative analyses purposes.

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(Comparison to Predicate Device, continued)

Feature	DRI's Cannabinoid (THC) EIA			LZI's Cannabinoid EIA
Within Run Precision:				(Illustrated with THC 50 assay results)
Qualitative:	Mean Rate	SD	% CV	Mean Rate	SD	% CV
	Negative	287	1.0	Negative	318.7	2.2	0.68
	20 ng/mL	317	0.9	20 ng/mL	346.3	2.5	0.72
	50 ng/mL	387	0.9	50 ng/mL	398.7	3.5	0.87
	100 ng/mL	447	0.9	100 ng/mL	456.0	3.3	0.73
	200 ng/mL	472	0.5	200 ng/mL	475.1	1.9	0.39
Semi-quantitative:	No data available.			Mean Conc	SD	% CV
				37.5 ng/mL	38.3	0.8	2.12
				50 ng/mL	50.0	1.4	2.78
				62.5 ng/mL	65.1	1.9	2.91
Run-To-Run Precision:				(Illustrated with THC 50 assay results)
Qualitative:	Mean Rate	SD	% CV	Mean Rate	SD	% CV
	Negative	287	1.0	Negative	320.5	3.1	0.96
	20 ng/mL	319	0.7	20 ng/mL	347.6	2.3	0.66
	50 ng/mL	388	1.0	50 ng/mL	399.8	3.9	0.97
	100 ng/mL	449	1.2	100 ng/mL	457.6	4.0	0.88
	200 ng/mL	473	0.8	200 ng/mL	477.1	3.5	0.73
Semi-quantitative:	No data available.			Mean Conc	SD	% CV
				37.5 ng/mL	37.1	0.9	2.41
				50 ng/mL	48.4	1.5	3.02
				62.5 ng/mL	63.9	2.3	3.59
Sensitivity:	10 ng/mL			5 ng/mL	(THC 20 assay);
				7.5 ng/mL	(THC 50 assay);
				15 ng/mL	(THC 100 assay)
Accuracy:	Vs. GC/MS* (n = 592)			Vs. DRI s Cannabinoid EIA (n = 216)
	THC 20 assay	THC 50 assay	THC 100 assay	THC 20 assay	THC 50 assay	THC 100 assay
Positive Samples:	No data	100% Agreement	6 borderline negative found	100 % Agreement	100 % Agreement	98.3 % (1 marginal discrepant)
Negative Samples:	No data	100% Agreement	100% Agreement	100 % Agreement	100 % Agreement	100 % Agreement
Analytical Recovery:				(Illustrated with THC 50 assay)
	Qualitative: No data available			100 % accuracy on positive vs. negative tests
	Semi-quantitative: No data available			Quantitate within ±12% of the nominal concentration between 10 ng/mL and 95 ng/mL.
				Average 98.7 % recovery at 37.5 ng/mL level (Cutoff - 25%)
				Average 93.2 % recovery at 62.5 ng/mL level (Cutoff + 25%)
Specificity:				See attached DRI s Cannabinoid (THC) EIA package insert			Comparable to the predicate device.

Performance Characteristics

A 15 ng/mL cutoff for GC/MS was used for comparison.

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Conclusion

LZI's Cannabinoid 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 Cannabinoid Enzyme Immunoassay to other cannabinoid 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 the logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with three lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 1 5 2002

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

Re: K021887

Trade/Device Name: Cannabinoid Enzyme Immunoassay Regulation Number: 21 CFR 862. 3870 Regulation Name: Cannabinoid test system Regulatory Class: Class II Product Code: LDJ Dated: June 5, 2002 Received: June 7, 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, 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 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control 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 Sutman

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): K021887

Device Name: Cannabinoid Enzyme Immunoassay

Indications for Use:

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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

§ 862.3870 Cannabinoid test system.

(a)
Identification. A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds includedelta -9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.(b)
Classification. Class II (special controls). A cannabinoid 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).