OPIATE ENZYME IMMUNOASSAY

K110298 · Lin-Zhi International, Inc. · DJG · Jul 15, 2011 · Clinical Toxicology

Device Facts

• Record ID: K110298
• Device Name: OPIATE ENZYME IMMUNOASSAY
• Applicant: Lin-Zhi International, Inc.
• Product Code: DJG · Clinical Toxicology
• Decision Date: Jul 15, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Intended Use

The Opiate Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of opiates in human urine, at a cutoff value of 300 ng/mL when calibrated against morphine. The assay is designed for professional use with a number of automated clinical chemistry analyzers. The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS or (2) permitting laboratories to establish quality control procedures. The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method). Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

Device Story

Opiate Enzyme Immunoassay is a homogeneous, ready-to-use liquid reagent for professional use on automated clinical chemistry analyzers. Input: human urine sample. Principle: competitive immunoassay between drug in sample and drug-labeled G6PDH enzyme for fixed antibody amount. Enzyme activity is inhibited when bound to antibody; free drug in sample displaces labeled drug, increasing enzyme activity. Active enzyme converts NAD to NADH, measured spectrophotometrically at 340 nm. Output: preliminary qualitative or semi-quantitative result indicating presence of opiates. Used in clinical laboratories to screen for drug abuse; results require confirmation by GC/MS or LC/MS. Benefits: rapid screening for clinical decision-making regarding patient drug use.

Clinical Evidence

Bench testing only. Precision evaluated with 88 determinations per concentration level (0-600 ng/mL). Linearity demonstrated on Hitachi 717 (0-1000 ng/mL, r2=0.9976). Method comparison with 130 clinical samples showed 98.3% positive agreement and 94.5-95.9% negative agreement compared to reference methods.

Technological Characteristics

Homogeneous enzyme immunoassay; liquid reagent. Sensing principle: spectrophotometric measurement of NADH production at 340 nm via G6PDH enzyme activity. Storage: 2-8 °C. Compatible with automated clinical chemistry analyzers. No specific materials or ASTM standards cited.

Indications for Use

Indicated for qualitative and semi-quantitative detection of opiates in human urine at 300 ng/mL cutoff. For professional use in clinical settings with automated chemistry analyzers. Not for self-testing.

Regulatory Classification

Identification

An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An opiate 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

• Lin-Zhi International, Inc. Opiate Enzyme Immunoassay for Hitachi 717 Systems (k020368)

Submission Summary (Full Text)

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K110298

# 510(k) Summary of Safety and Effectiveness

This summary of 510(k) safety and effectiveness information is being submitted is summary of 510(k) sujely and effectiveness information is being stommed
in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. JUL 1 5 2011

# 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. 670 Almanor Avenue Sunnyvale, CA 94085 Phone: [phone] [phone] Fax: e-mail: [e-mail]

Contact: Bernice Lin, Ph.D. VP Operations

## Device Name and Classification

| Classification Name: | Enzyme Immunoassay, Opiate<br>Class II, DJG (91 Toxicology),<br>21 CFR 862.3650 |
|----------------------|---------------------------------------------------------------------------------|
| Common Name: | Homogeneous Opiate Enzyme Immunoassay |
| Proprietary Name: | Opiate Enzyme Immunoassay, |

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#### Legally Marketed Predicate Device(s)

The Opiate Enzyme Immunoassay (EIA) is substantially equivalent to the Lin-Zhi International, Inc. Opiate Enzyme Immunoassay for Hitachi 717 Systems (k020368) manufactured by Lin-Zhi International, Inc. The Opiate Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.

### Device Description (Assay Principle)

The Opiate Enzyme Immunoasay is a homogeneous enzyme immunoassay ready-to-use liquid reagent. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent.

Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, morphine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound morphine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.

#### Intended Use

The Opiate Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of opiates in human urine, at a cutoff value of 300 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The Opiate Drugs of Abuse (DAU) Calibrators (from k020769) are for use as calibrators in the qualitative and semi-quantitative calibration of the Opiate Enzyme Immunoassay.

The Opiate Drugs of Abuse (DAU) Controls (from k020769) are for use as assayed quality control materials to monitor the precision of the Opiate Enzyme Immunoassay.

The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method). Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

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# Comparison to Predicate Device

The Opiate Enzyme Immunoassay is substantially equivalent to the Lin-Zhi International, Inc. Opiate Enzyme Immunoassay for Hitachi 717 Systems cleared by the FDA under the premarket notification k020368 for its stated intended use.

The following table compares the Opiate Enzyme Immunoassay with the predicate device.

| Device<br>Characteristics | Subject Device | Predicate Device (k020368) |
|---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The Opiate Enzyme Immunoassay, when<br>used in conjunction with Hitachi 717<br>automated clinical system analyzers, is<br>intended for the qualitative and semi-<br>quantitative determination of opiates in<br>human urine, at a cutoff value of 300<br>ng/mL. The assay is designed for<br>professional use with a number of<br>automated clinical chemistry analyzers.<br><br>This assay provides a rapid screening procedure<br>for determining the presence of Opiates in urine.<br>The assay provides only a preliminary analytical<br>result. A more specific alternative chemical<br>method must be used in order to obtain a<br>confirmed analytical result. Gas or liquid<br>chromatography/mass spectrometry (GC/MS or<br>LC/MS) is the preferred confirmatory method.<br>Clinical consideration and professional judgment<br>should be exercised with any drug of abuse test<br>result, particularly when the preliminary test result<br>is positive. | The Opiate Enzyme Immunoassay, when<br>used in conjunction with Hitachi 717<br>automated clinical system analyzers, is<br>intended for the qualitative and semi-<br>quantitative determination of opiates in<br>human urine, at a cutoff value of 300<br>ng/mL. The assay is designed for<br>professional use with a number of<br>automated clinical chemistry analyzers.<br><br>This assay provides a rapid screening procedure<br>for determining the presence of Opiates in urine.<br>The assay provides only a preliminary analytical<br>result. A more specific alternative chemical<br>method must be used in order to obtain a<br>confirmed analytical result. Gas or liquid<br>chromatography/mass spectrometry (GC/MS or<br>LC/MS) is the preferred confirmatory method.<br>Clinical consideration and professional judgment<br>should be exercised with any drug of abuse test<br>result, particularly when the preliminary test result<br>is positive. |
| Analyte | Opiates | Opiates |
| Cutoff | 300 ng/ml | 300 ng/mL |
| Matrix | Urine | Urine |
| Calibrators | 5 Levels | 5 Levels |
| Level | (0, 150, 300, 600, 1000 ng/mL) | (0, 150, 300, 600, 1000 ng/mL) |
| Controls Level | 2 Levels | 2 Levels |
| | (225 ng/mL, 375 ng/mL) | (225 ng/mL, 375 ng/mL) |
| Storage | 2-8 °C until expiration date | 2-8 °C until expiration date |

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# Performance Characteristics Summary: Hitachi 717 Analyzer

## Precision:

:

Precision: Semi-Quantitative, ng/mL

| N=88 | (ng/mL) | Within Run | | | | Total Precision | | | |
|------|-----------|------------|------|---------|--|-----------------|------|---------|--|
| | | Mean | SD | % CV | | Mean | SD | % CV | |
| | 0 ng/mL | 0.0 | 0.0 | #DIV/0! | | 0.0 | 0.0 | #DIV/0! | |
| | 75 ng/mL | 84.0 | 3.5 | 4.2% | | 84.0 | 4.5 | 5.4% | |
| | 150 ng/mL | 148.4 | 3.7 | 2.5% | | 148.4 | 4.2 | 2.8% | |
| | 225 ng/mL | 228.2 | 5.3 | 2.3% | | 228.2 | 6.4 | 2.8% | |
| | 300 ng/mL | 297.5 | 6.3 | 2.1% | | 297.5 | 7.3 | 2.4% | |
| | 375 ng/mL | 370.4 | 7.6 | 2.0% | | 370.4 | 8.2 | 2.2% | |
| | 450 ng/mL | 453.3 | 9.8 | 2.2% | | 453.3 | 10.1 | 2.2% | |
| | 525 ng/mL | 529.0 | 11.5 | 2.2% | | 529.0 | 12.7 | 2.4% | |
| | 600 ng/mL | 600.8 | 16.2 | 2.7% | | 600.8 | 17.5 | 2.9% | |

## Semi-Quantitative Precision Analysis Summary: Qualitative Results

| N=88<br>(ng/mL) | Mean | Within Run<br>Qualitative Response | Mean | Total Precision<br>Qualitative Response |
|-----------------|-------|------------------------------------|-------|-----------------------------------------|
| 0 ng/mL | 0.0 | - | 0.0 | - |
| 75 ng/mL | 84.0 | - | 84.0 | - |
| 150 ng/mL | 148.4 | - | 148.4 | - |
| 225 ng/mL | 228.2 | - | 228.2 | - |
| 300 ng/mL | 297.5 | - | 297.5 | - |
| 375 ng/mL | 370.4 | + | 370.4 | + |
| 450 ng/mL | 453.3 | + | 453.3 | + |
| 525 ng/mL | 529.0 | + | 529.0 | + |
| 600 ng/mL | 600.8 | + | 600.8 | + |

# Semi-Quantitative Positive/Negative Results:

| 300 ng/mL Cutoff Result: | | Within Run | | Total Precision | |
|--------------------------|-------------|----------------------------|-----------------------|----------------------------|-----------------------|
| Sample<br>Concentration | % of Cutoff | Number of<br>Determination | Immunoassay<br>Result | Number of<br>Determination | Immunoassay<br>Result |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0% | 22 | 6 Pos/16 Neg | 88 | 27 Pos/61 Neg |
| 375 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |

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#### Precision: Qualitative, mA/min

| N=88 | Within Run | | | Total Precision | | |
|-----------|------------|-----|------|-----------------|-----|------|
| (mA/min) | Mean | SD | % CV | Mean | SD | % CV |
| 0 ng/mL | 261.0 | 2.1 | 0.8% | 261.0 | 2.4 | 0.9% |
| 75 ng/mL | 310.4 | 1.8 | 0.6% | 310.4 | 2.4 | 0.8% |
| 150 ng/mL | 345.6 | 2.1 | 0.6% | 345.6 | 3.2 | 0.9% |
| 225 ng/mL | 383.6 | 2.4 | 0.6% | 383.6 | 3.7 | 1.0% |
| 300 ng/mL | 410.9 | 2.3 | 0.6% | 410.9 | 3.7 | 0.9% |
| 375 ng/mL | 432.1 | 2.5 | 0.6% | 432.1 | 3.6 | 0.8% |
| 450 ng/mL | 454.3 | 2.8 | 0.6% | 454.3 | 4.0 | 0.9% |
| 525 ng/mL | 471.0 | 2.5 | 0.5% | 471.0 | 4.4 | 0.9% |
| 600 ng/mL | 482.6 | 2.5 | 0.5% | 482.6 | 3.6 | 0.8% |

#### Qualitative Positive/Negative Results:

| 300 ng/mL Cutoff Result: | | Within Run | | Total Precision | |
|--------------------------|-------------|----------------------------|-----------------------|----------------------------|-----------------------|
| Sample<br>Concentration | % of Cutoff | Number of<br>Determination | Immunoassay<br>Result | Number of<br>Determination | Immunoassay<br>Result |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0% | 22 | 16 Pos/6 Neg | 88 | 51 Pos/37 Neg |
| 375 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |

#### Limit of Detection:

The lowest concentration that can be differentiated from the negative urine with 95% confidence is determined as 20 ng/mL.

#### Linearity:

Hitachi 717 Instrument: 0 - 1000 ng/mL When comparing the result (y) and target (x) value, using the least squares regression technique, the regression equation and correlation are as follow: y = 1.0619x - 2.3861, r2=0.9976

#### Method Comparison: Clinical Samples

From a total of One-hundred-thirty (130) clinical unaltered samples:

Semi-Quantitative Results: 98.3 % agreement with positive, 95.9 % agreement with negative samples

Qualitative Results: 98.3 % agreement with positive, 94.5 % agreement with negative samples

## Endogenous Compound Interference, Specific Gravity, & Specificity -Cross-Reactivity:

No significant undesired cross reactants or endogenous substance interference was observed. See product insert for list of compounds tested.

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# Summary:

The information provided in this pre-market notification demonstrates that the LZI Opiate Enzyme Immunoassay is substantially equivalent to the legally marketed predicate device for its general intended use. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS), an independent analytical method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Opiate Enzyme Immunoassay is safe and effective for its stated intended use.

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Image /page/6/Picture/1 description: The image shows a logo for the Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-GSA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or bird with outstretched wings, depicted in a minimalist, flowing design. The logo is presented in black and white.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

15 2011

Lin-Zhi International, Inc. c/o Dr. Bernice Lin VP Operations 670 Almanor Avenue Sunnyvale, CA 94085

Re: k110298 Trade name: Opiate Enzyme Immunoassay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Code: DJG Dated: June 17, 2011 Received: June 20, 2011

Dear Dr. 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at [phone]. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Signature

Courtney C. Harper, 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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# Premarket Notification

# Indications for Use Statement

510(k) Number (if known): k110298

Device Name: Opiate Enzyme Immunoassay

### Indications for Use:

The Opiate Enzyme Immunoassay is intended for the qualitative and semi-quantitative ' determination of opiates in human urine, at a cutoff value of 300 ng/mL when calibrated against morphine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS or (2) permitting laboratories to establish quality control procedures."

The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method). Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

Prescription Use V AND/OR (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 Subpart C)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) (Per 21 CFR 801.109)

Qur

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K110298