METHADONE ORAL FLUID HOMOGENEOUS ENZYME IMMUNOASSAY, CALIBRATORS AND CONTROLS

K051058 · Lin-Zhi International, Inc. · DJR · Mar 29, 2006 · Clinical Toxicology

Device Facts

• Record ID: K051058
• Device Name: METHADONE ORAL FLUID HOMOGENEOUS ENZYME IMMUNOASSAY, CALIBRATORS AND CONTROLS
• Applicant: Lin-Zhi International, Inc.
• Product Code: DJR · Clinical Toxicology
• Decision Date: Mar 29, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3620
• Device Class: Class 2

Intended Use

The Methadone Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methadone in human saliva with a cutoff of 30 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 (Methadone) 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 of methadone drugs. The assay is designed for professional use with a number of automated clinical analyzers. The Methadone 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

Liquid reagent, homogeneous enzyme immunoassay; detects methadone in human saliva samples collected via Salivette. Principle: competition between drug-labeled G6PDH enzyme and free drug in saliva for fixed antibody binding sites; 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 identifying methadone presence; supports clinical decision-making regarding drug abuse.

Clinical Evidence

Method comparison study performed on 119 clinical oral fluid specimens comparing the LZI Oral Fluid Methadone Enzyme Immunoassay to GC/MS. Results showed 60 true positives, 58 true negatives, and 1 false positive, yielding 99.2% agreement. Precision studies (replicates of 6, twice daily for 10 days) showed within-run CV 0.54-0.62% and total precision CV 0.61-0.78%.

Technological Characteristics

Homogeneous enzyme immunoassay; liquid reagents (mouse monoclonal antibody, G6P, NAD, methadone-labeled G6PDH). Spectrophotometric detection at 340 nm. Designed for automated clinical chemistry analyzers. Qualitative cutoff 30 ng/mL. Stability: 18 months at 2-8 °C; oral fluid samples stable for 22 days at 2-8 °C or -20 °C.

Indications for Use

Indicated for the qualitative detection of methadone in human saliva for professional use in clinical chemistry laboratories. Not for point-of-care settings.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• OraSure Methadones Intercept Micro-Plate EIA (k002010)
• LZI Methadone EIA (k023317)
• Dade Behring Emit II Plus Methadone Assay (k010962)

Submission Summary (Full Text)

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K051058

# 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 Methadone test system has been placed in Class II by<br>the Bureau of Medical Devices.<br>Classification Number: DJR (21 CFR 862.3620)<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: | Methadone Oral Fluid Homogeneous Enzyme<br>Immunoassays |
| Proprietary Name: | None |

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## Predicate Device(s)

The LZI Methadone Oral Fluid Enzyme Immunoassay is substantially equivalent to the Methadones Intercept® Micro-plate EIA (K002010) manufactured by OraSure Technologies Inc. (formerly known as STC Technologies, Inc) for its general intended use.

## Device Description

LZI's Oral Fluid Methadone Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect methadone in oral fluid with minimal cross-reactivity 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 Methadone Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methadone in human saliva with a cutoff of 30 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 (Methadone) 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 Methadone drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The Methadone 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-ofabuse test result, particularly when preliminary positive results are used.

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## Comparison to Predicate Device

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

| Device<br>Characteristics | Subject Device<br>(LZI Methadone Oral Fluid<br>Homogeneous EIA) | Predicate Device<br>(OraSure Methadone Intercept®<br>Micro-plate EIA) |
|--------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The LZI Methadone Oral Fluid<br>Homogeneous EIA is a homogeneous<br>enzyme immunoassay system to detect<br>methadone in human saliva with a<br>cutoff of 30 ng/mL when testing oral<br>fluid specimen collected with Salivette<br>collector (manufactured by Sarstedt )<br>and diluted with 1 mL of buffer. The<br>calibrators and controls of the analyte<br>(Methadone) are prepared with oral<br>fluid buffer so that it can be used to<br>verify and validate the assay. The assay<br>is intended for use in the qualitative<br>determination for Methadone drugs.<br><br>The Methadone 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. | The OraSure Methadone Intercept®<br>Micro-plate EIA is intended for use by<br>clinical laboratories in the qualitative<br>determination of methadone in oral<br>fluid collected with Intercept® DOA<br>Oral Specimen Collection Device<br>using a 5.0 ng/mL cutoff. For <i>In Vitro</i><br>Diagnostic Use.<br><br>The OraSure Methadone Intercept®<br>Micro-plate EIA provides only a<br>preliminary analytical test result. A<br>more specific alternative chemical<br>method should be used in order to<br>obtain a confirmed analytical result.<br>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 | Methadone | Methadone |
| Matrix | Saliva | Saliva |
| Calibrators/<br>Controls Level | 5 levels including a negative | 4 levels including a negative |

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#### LZI Methadone Oral Fluid Assay

| Feature | Oral Fluid Methadone EIA | | | |
|----------------------------------------------------------|-----------------------------------|-------|-------|-------|
| Qualitative : (n=120) mA/min | Mean. | SD | % CV | |
| Within Run Precision: | Negative | 328.4 | 1.90 | 0.58% |
| | 10 ng/mL | 347.4 | 1.96 | 0.56% |
| | 20 ng/mL | 368.3 | 2.30 | 0.62% |
| | 30 ng/mL | 390.0 | 2.21 | 0.57% |
| | 50 ng/mL | 433.4 | 2.33 | 0.54% |
| | Mean. | SD | % CV | |
| Total Precision: | Negative | 328.4 | 2.30 | |
| | 10 ng/mL | 347.4 | 2.72 | 0.70% |
| | | | | 0.78% |
| | 20 ng/mL | 368.3 | 2.58 | 0.70% |
| | 30 ng/mL | 390.0 | 2.66 | 0.68% |
| 50 ng/mL | 433.4 | 2.65 | 0.61% | |
| Accuracy: Clinical patients samples<br>(n=119) vs. GC/MS | 99.2 % Agreement | | | |
| Specificity: | See attached Assay package insert | | | |

### OraSure Methadone Micro=Plate EIA

| Feature | | | |
|---------------------------------------------------------|----------------------------|------|----------|
| Precision | Methadone | % CV | Mean OD. |
| Intra-assay<br>N=64 | 0 ng/mL | 6.3 | 1.932 |
| | 2.5 ng/mL | 6.6 | 0.687 |
| | 5.0 ng/mL | 6.7 | 0.507 |
| | 7.5 ng/mL | 6.8 | 0.426 |
| Inter-assay<br>N=4/day, 20 days | 0 ng/mL | 9.9 | 1.932 |
| | 2.5 ng/mL | 12.3 | 0.687 |
| | 5.0 ng/mL | 12.9 | 0.507 |
| | 7.5 ng/mL | 13.6 | 0.426 |
| Accuracy: Clinical patients sample<br>(n=102) vs. GC/MS | 97.1 % Agreement | | |
| Specificity | See OraSure product insert | | |

#### Summary

The information provided in this pre-market notification demonstrates that the LZI Oral Fluid Methadone 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 prepared 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 provides reasonable assurance that the LZI Oral Fluid Methadone Homogeneous EIA is safe and effective for its stated intended use.

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows a circular logo with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with a more abstract and modern design. The logo is black and white, with the text and symbol in black against a white background.

#### 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: k051058

Trade/Device Name: Oral Fluid Methadone Homogeneous Enzyme Immunoassay, Calibrator and Controls Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: Class II Product Code: DJR, DLJ, LAS Dated: March 08, 2006 Received: March 13, 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 af 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 practic t 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 Guti

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): k051058

Device Name: Oral Fluid Methadone Homogeneous Enzyme Immunoassay, Calibrators and Controls.

Indications For Use:

The Methadone Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methadone in human saliva with a cutoff of 30 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 (Methadone) 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 Methadone drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The Methadone 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.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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

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

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

05/057-CFC

"" " " Vitro Diagnostic Device 11 200 Na

K051058