CANNABINOID ENZYME IMMUNOASSAY, CATALOG 0070, 0071

K021887 · Lin-Zhi International, Inc. · LDJ · Aug 15, 2002 · Clinical Toxicology

Device Facts

• Record ID: K021887
• Device Name: CANNABINOID ENZYME IMMUNOASSAY, CATALOG 0070, 0071
• Applicant: Lin-Zhi International, Inc.
• Product Code: LDJ · Clinical Toxicology
• Decision Date: Aug 15, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3870
• Device Class: Class 2

Intended Use

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 Story

Ready-to-use liquid reagent homogeneous enzyme immunoassay; detects cannabinoids (THC) in human urine. Principle: competition between Δ9-THC-labeled G6PDH enzyme and free drug in urine sample for fixed amount of specific antibody. Absence of free drug allows antibody binding to labeled enzyme, decreasing enzyme activity. Activity measured spectrophotometrically at 340 nm via conversion of NAD to NADH. Used in clinical laboratories with automated chemistry analyzers; operated by laboratory professionals. Provides preliminary analytical results; requires confirmation by GC/MS. Assists clinicians in drug-of-abuse screening.

Clinical Evidence

Bench testing only. Evaluated precision (within-run and run-to-run), sensitivity, accuracy, analytical recovery, and specificity. Accuracy compared against predicate device (n=216) and GC/MS (n=592). Results showed 100% agreement for most samples; one marginal discrepancy noted in THC 100 assay. Analytical recovery demonstrated 98.7% at 37.5 ng/mL and 93.2% at 62.5 ng/mL. Precision CVs generally <3.6%.

Technological Characteristics

Homogeneous enzyme immunoassay; liquid reagent format. Sensing principle: spectrophotometric measurement of G6PDH enzyme activity at 340 nm. Compatible with automated clinical chemistry analyzers. No specific materials of construction or connectivity standards listed.

Indications for Use

Indicated for qualitative and semi-quantitative analysis of cannabinoids (THC) in human urine. Intended for professional use in clinical settings to provide preliminary analytical test results. Requires confirmatory testing via alternative methods like GC/MS.

Regulatory Classification

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 include delta-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.

Special Controls

*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).

Predicate Devices

• Cannabinoid (THC) Enzyme Immunoassay (K943998)

Submission Summary (Full Text)

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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: [phone] Fax: [phone]

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

#### Device Name and Classification

| Classification Name: | Enzyme Immunoassay, Cannabinoids,<br>Class II, LDJ (91 Toxicology), 21CFR 862.3870 |
|----------------------|-----------------------------------------------------------------------------------------------|
| Common Name: | Homogeneous enzyme immunoassay for the determination<br>of 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

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

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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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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 [phone]. Additionally, for questions on the promotion and advertising of your device. please contact the Office of Compliance at [phone]. 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 [phone] or [phone] 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:

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.

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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)