ORAL FLUID COCAINE METABOLITE HOMOGENEOUS ENZYME IMMUNOASSAYS, CALIBRATORS & CONTROLS

K050945 · Lin-Zhi International, Inc. · DIO · Mar 29, 2006 · Clinical Toxicology

Device Facts

• Record ID: K050945
• Device Name: ORAL FLUID COCAINE METABOLITE HOMOGENEOUS ENZYME IMMUNOASSAYS, CALIBRATORS & CONTROLS
• Applicant: Lin-Zhi International, Inc.
• Product Code: DIO · Clinical Toxicology
• Decision Date: Mar 29, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3250
• Device Class: Class 2

Intended Use

The Cocaine Metabolite (Benzoylecgonine) Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect benzoylecgonine in human saliva with a cutoff of 15 ng/mL when testing oral fluid specimen collected with Salivette collector (manufactured by Sarstedt ) and diluted with 1 mL of buffer. The calibrators and controls of the analyte (Benzoylecgonine) are prepared with oral fluid buffer so that it can be used to verify and validate the assay. The assay is intended for use in the qualitative determination for cocaine metabolite drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers. The Cocaine Metabolite (Benzoylecgonine) Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoassay system 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 judgment 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 benzoylecgonine in human saliva. Principle: competition between drug-labeled G6PDH enzyme and free drug from saliva sample for fixed antibody; in absence of free drug, antibody binds labeled enzyme, decreasing activity. Enzyme activity measured spectrophotometrically at 340 nm via conversion of NAD to NADH; drug concentration proportional to enzyme activity. Used in clinical laboratories by professionals on automated chemistry analyzers. Provides preliminary qualitative results; requires GC/MS confirmation. Assists clinicians in drug-of-abuse screening; supports professional judgment in clinical decision-making.

Clinical Evidence

Method comparison study using 118 clinical oral fluid specimens compared to GC/MS. Results showed 72 true positives, 41 true negatives, and 5 false positives (all containing trace parent cocaine). Overall agreement: 95.7%. Precision studies (within-run CV 0.71-0.81%; total CV 0.83-0.89%) and stability studies (22 days at 2-8°C or -20°C) were performed.

Technological Characteristics

Liquid reagent, homogeneous enzyme immunoassay. Analyte: benzoylecgonine. Detection: spectrophotometric measurement of G6PDH enzyme activity at 340 nm. Form factor: ready-to-use liquid reagents. Connectivity: designed for use on automated clinical chemistry analyzers. No specific materials of construction or software algorithm class (e.g., ML) specified beyond standard spectrophotometric quantification.

Indications for Use

Indicated for the qualitative detection of benzoylecgonine (cocaine metabolite) in human saliva specimens collected via Salivette collector. Intended for professional use on automated clinical chemistry analyzers to provide preliminary analytical results. Requires confirmatory testing via GC/MS. No specific age or gender restrictions stated.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• LZI Cocaine Metabolite EIA (k020763)
• Dade Behring Enzyme immunoassay, Cocaine and Cocaine Metabolites (k033713)
• OraSure Cocaine Metabolite Intercept Micro-plate oral fluid EIA (k001197)

Submission Summary (Full Text)

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K050945

# MAR 2 9 2006 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

March 20, 2006

Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085 Phone: [phone] Fax: [phone]

Contact: Marie Lin, Ph.D. President, R&D Director

#### Device Name and Classification

| Classification Name: | The Cocaine and Cocaine Metabolite test system has been<br>placed in Class II by the Bureau of Medical Devices.<br>Classification Number: DIO (21 CFR 862.3250)<br>Panel: 91Toxicology |
|----------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The “Drug Specific, Calibrators” has been placed in<br>Class II by the Bureau of Medical Devices.<br>Classification No.: DLJ, 21 CFR 862.3200<br>Panel: 91Toxicology |
| | The “Single (Specified) Analyte Controls” has been placed<br>in Class I by the Bureau of Medical Devices.<br>Classification No.: LAS, 21 CFR 862.3280<br>Panel: 91Toxicology |
| Common Name: | Cocaine Oral Fluid Homogeneous Enzyme Immunoassays |
| Proprietary Name: | None |

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#### Predicate Device(s)

The LZI Cocaine Metabolite (Benzoylecgonine) Oral Fluid Enzyme Immunoassay is substantially equivalent to the Cocaine Metabolite Intercept® Micro-plate EIA (K001197) manufactured by OraSure Technologies Inc. (formerly known as STC Technologies, Inc) for its general intended use.

## Device Description

LZI's Oral Fluid Cocaine Metabolite (Benzoylecgonine) Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect benzoylecgonine in oral fluid with minimal crossreactivity to various, common prescription drugs and abused drugs. The assay is based on competition between drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme and free drug from the saliva sample for a fixed amount of specific antibody. In the absence of free drug from the saliva sample the specific antibody binds to the drug labeled G6PDH enzyme causing a decrease in enzyme activity. It is therefore the drug concentration is proportional to the enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to covert nicotinamide adenine dinucleotide (NAD) to NADH.

### Intended Use

The Cocainc Metabolite (Benzoylecgonine) Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogencous enzyme immunoassay system to detect benzoylecgonine in human saliva with a cutoff of 15 ng/mL when testing oral fluid specimen collected with Salivette collector (manufactured by Sarstedt ) and diluted with 1 mL of buffer. The calibrators and controls of the analyte (Benzoylecgonine) are prepared with oral fluid buffer so that it can be used to verify and validate the assay. The assay is intended for use in the qualitative determination for cocaine metabolite drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The Cocaine Metabolite (Benzoylecgonine) Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoassay system 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 judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

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### Comparison to Predicate Device

The LZI Cocaine Metabolite (Benzoylecgonine) Oral Fluid Homogeneous Enzyme Immunoassay, including calibrators and controls, is substantially equivalent to OraSure's Cocaine Metabolite Intercept® Micro-plate EIA in its intended use and in for the qualitative determination of cocaine metabolite drugs in human oral fluid.

| Device | Subject Device | Predicate Device |
|-----------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Characteristics | (LZI Cocaine Metabolite | (OraSure Cocaine Metabolite |
| | (Benzoylecgonine) Oral Fluid | Intercept® Micro-plate EIA) |
| | Homogeneous EIA) | |
| Intended Use | The LZI Cocaine Metabolite | The OraSure Cocaine Metabolite |
| | (Benzoylecgonine) Oral Fluid | Intercept® Micro-plate EIA is |
| | Homogeneous EIA is a homogeneous | intended for use by clinical |
| | enzyme immunoassay system to detect | laboratories in the qualitative |
| | cocaine metabolite in human saliva | determination of cocaine and cocaine |
| | with a cutoff of 15 ng/mL when testing | metabolite in oral fluid collected with |
| | oral fluid specimen collected with | Intercept® DOA Oral Specimen |
| | Salivette collector (manufactured by | Collection Device using a 5.0 ng/mL |
| | Sarstedt ) and diluted with 1 mL of<br>buffer. The calibrators and controls of | cutoff. For In Vitro Diagnostic Use. |
| | the analyte (Benzoylecgonine) are | |
| | prepared with oral fluid buffer so that it | The OraSure Cocaine Metabolite |
| | can be used to verify and validate the | Intercept® Micro-plate EIA provides<br>only a preliminary analytical test |
| | assay. The assay is intended for use in | result. A more specific alternative |
| | the qualitative determination for | chemical method should be used in |
| | cocaine/cocaine metabolite drugs. | order to obtain a confirmed analytical |
| | The Cocaine Metabolite<br>(Benzoylecgonine) Oral Fluid Enzyme<br>Immunoassay is a homogeneous<br>enzyme immunoassay system provides<br>only a preliminary analytical test<br>result. A more specific alternative<br>chemical method must be used to<br>obtain a confirmed analytical result.<br>Gas chromatography/mass<br>spectrometry (GC/MS) is the preferred<br>confirmatory method. Clinical<br>consideration and professional<br>judgment should be applied to any<br>drug-of-abuse test result, particularly<br>when preliminary positive results are<br>used. | result. Gas chromatography/mass<br>spectrometry (GC/MS) is the<br>preferred confirmatory method.<br>Clinical consideration and<br>professional judgement should be<br>applied to any drugs of abuse test<br>result, particularly when a<br>preliminary, positive result is<br>observed. |
| Analyte | Benzoylecgonine | Benzoylecgonine |
| Matrix | Saliva | Saliva |
| Calibrators/ | 5 levels including a negative | 4 levels including a negative |
| Controls Level | | |

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| Feature | | Oral Fluid Cocaine Metabolite (Benzoylecgonine)<br>EIA | | |
|----------------------------------------------------------|-----------------------------------|--------------------------------------------------------|------|-------|
| Qualitative : (n=120) mA/min | | Mean. | SD | % CV |
| Within Run Precision: | Negative | 240.0 | 1.71 | 0.71% |
| | 5 ng/mL | 255.1 | 2.00 | 0.78% |
| | 10 ng/mL | 270.3 | 2.17 | 0.80% |
| | 20 ng/mL | 285.8 | 2.32 | 0.81% |
| | 50 ng/mL | 321.9 | 2.49 | 0.77% |
| Total Precision: | Negative | 240.0 | 2.10 | |
| | 5 ng/mL | 255.1 | 2.26 | 0.88% |
| | 10 ng/mL | 270.3 | 2.37 | 0.88% |
| | 20 ng/mL | 285.8 | 2.51 | 0.88% |
| | 50 ng/mL | 321.9 | 2.68 | 0.83% |
| Accuracy: Clinical patients samples<br>(n=118) vs. GC/MS | 95.8 % Agreement | | | |
| Specificity: | See attached Assay package insert | | | |

#### LZI Cocaine Metabolite (Benzoylecgonine) Oral Fluid Assay

#### OraSure Cocaine Metabolite Micro=Plate EIA

| Feature | Benzoylecgonine | % CV |
|----------------------------------------------------------|----------------------------|------|
| Precision | | |
| Intra-assay<br>N=64 | 0 ng/mL | 3.7 |
| | 2.5 ng/mL | 3.4 |
| | 5.0 ng/mL | 4.3 |
| | 7.5 ng/mL | 7.6 |
| Inter-assay<br>N=4/day, 20 days | 0 ng/mL | 8.0 |
| | 2.5 ng/mL | 9.0 |
| | 5.0 ng/mL | 9.6 |
| | 7.5 ng/mL | 10.5 |
| Accuracy: Clinical patients samples<br>(n=220) vs. GC/MS | 93.2 % Agreement | |
| Specificity | See OraSure product insert | |

#### Summary

The information provided in this pre-market notification demonstrates that the LZI Oral Fluid Cocaine Metabolite (Benzoylecgonine) Homogeneous EIA is substantially equivalent to the legally marketed predicated device for its general intended use. Data and results provided in this premarket notification were collected and propared in accordance with the NCCLS guidance. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by gas chromatography/mass spectrometry, an independent analytical method. The information supplied in this pre-market notification

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provides reasonable assurance that the LZI Oral Fluid Cocaine Metabolite provides reasonable assurates ous EIA is safe and effective for its stated intended use.

:

:

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three wing segments, representing the department's commitment to health, human services, and well-being. The eagle is positioned to the right of a circular text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 2 9 2006

Ms. Marie Lin, Ph.D. President, R&D Director Lin-Zhi International, Inc. 687 North Pastoria Ave Sunnyvale, CA 94085-2917

Re: k050945

Trade/Device Name: Oral Fluid Metabolite (Benzoylecgonine) Homogeneous Enzyme Immunoassay, Calibrators and Controls Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: Class II Product Code: DIO, DLJ, LAS Dated: March 08, 2006 Received: March 10, 2006

Dear Ms. Lin:

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 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).

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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 [phone]. Also, please note 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-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto G. A.

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known):_ k050945

Device Name: Oral Fluid Cocaine Metabolite (Benzoylecgonine) Homogeneous Enzyme Immunoassay, Calibrators and Controls.

Indications For Use:

The Cocaine Metabolite (Benzoylecgonine) Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect cocaine metabolite in human saliva with a cutoff of 15 ng/mL when testing oral fluid specimen collected with Salivette collector (manufactured by Sarstedt ) and diluted with 1 mL of buffer. The calibrators and controls of the analyte (Benzoylecgonine) are prepared with oral fluid buffer so that it can be used to verify and validate the assay. The assay is intended for use in the qualitative determination for cocaine/cocaine metabolite drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The Cocaine Metabolite (Benzoylecgonine) Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoasay system 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 judgment should be applied to any drug-ofabuse test result, particularly when preliminary positive results are used.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-or

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