LZI ORAL FLUID METHAMPHETAMINE ENZYME IMMUNOASSAY, CALIBRATORS, CONTROLS

K131652 · Lin-Zhi International, Inc. · LAF · Mar 21, 2014 · Clinical Toxicology

Device Facts

• Record ID: K131652
• Device Name: LZI ORAL FLUID METHAMPHETAMINE ENZYME IMMUNOASSAY, CALIBRATORS, CONTROLS
• Applicant: Lin-Zhi International, Inc.
• Product Code: LAF · Clinical Toxicology
• Decision Date: Mar 21, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3610
• Device Class: Class 2

Intended Use

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is intended for the qualitative determination of dmethamphetanine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 50 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers. The assay provides only a preliminary analytical result. A more specific altemical method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GCMS or LC/MS) is the preferred confimatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive. 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 and LCMS or (2) permitting laboratories to establish quality control procedures. The LZI Oral Fluid Methamphetamine Calibrators are for use as calibrators in the qualitative calibration of the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL. The LZI Oral Fluid Methamphetamine Controls are for use as assayed quality control materials to monitor the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL.

Device Story

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is a homogeneous enzyme immunoassay for use on automated clinical chemistry analyzers. It utilizes a competitive binding principle: d-methamphetamine in the oral fluid sample competes with methamphetamine-labeled glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of anti-methamphetamine antibody. When drug is absent, the labeled enzyme binds to the antibody, inhibiting enzyme activity. When drug is present, it binds to the antibody, leaving the labeled enzyme free to exhibit maximal activity. The active enzyme converts NAD to NADH, producing an absorbance change measured spectrophotometrically at 340 nm. The device is used by laboratory professionals to screen for methamphetamine presence. Results are preliminary and require confirmation via GC/MS or LC/MS. The system includes reagents, calibrators, and controls, and utilizes a 50 mL polypropylene collection tube.

Clinical Evidence

No clinical studies performed. Performance validated via bench testing using 85 clinical samples compared against LC/MS confirmation. Qualitative and semi-quantitative modes showed 100% positive agreement and 95.2% negative agreement. Precision evaluated over 22 days (n=88) on Hitachi 717 analyzer. Analytical specificity tested against endogenous/exogenous compounds and structurally related drugs; no significant interference observed.

Technological Characteristics

Homogeneous enzyme immunoassay; competitive binding principle. Reagents: mouse monoclonal anti-methamphetamine antibody, G6PDH-labeled methamphetamine, NAD, G6P. Collection device: 50 mL polypropylene tube. Connectivity: designed for automated clinical chemistry analyzers. Storage: 2-8°C. Software: None (automated analyzer-based).

Indications for Use

Indicated for the qualitative and semi-quantitative detection of d-methamphetamine in neat human oral fluid at a 50 ng/mL cutoff. Intended for prescription use in clinical laboratory settings to provide preliminary analytical results requiring confirmation by GC/MS or LC/MS.

Regulatory Classification

Identification

A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.

Special Controls

*Classification.* Class II (special controls). A methamphetamine 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. Oral Fluid Methamphetamine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems (k062242)

Submission Summary (Full Text)

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K131652

# MAR 2 1 2014

# 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.

#### Preparation Date

March 19, 2014

#### 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] Fax: [phone] e-mail: [e-mail]

Bernice Lin, Ph.D. Contact: VP Operations

#### Device Name and Classification

| Classification Name: | Enzyme Immunoassay, Oral Fluid Methamphetamine<br>Class II, LAF (91 Toxicology),<br>21 CFR 862.3610<br><br>Drug Specific Calibrators,<br>Class II, DLJ (91 Toxicology),<br>21 CFR 862.3200<br><br>Drug Specific Controls,<br>Class I, LAS (91 Toxicology),<br>21 CFR 862.3280 |
|----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | Homogeneous Oral Fluid Methamphetamine Enzyme<br>Immunoassay |
| Proprietary Name: | LZI Oral Fluid Methamphetamine Enzyme Immunoassay,<br>LZI Oral Fluid Methamphetamine Calibrators<br>LZI Oral Fluid Methamphetamine Controls |

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### Legally Marketed Predicate Device(s)

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay (k131652) is substantially equivalent to the Lin-Zhi International, Inc. Oral Fluid Methamphetamine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems (k062242) manufactured by Lin-Zhi International, Inc. The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.

#### Device Description

The LZI Oral Fluid Methamphetamine assay is a homogeneous enzyme immunoassay with 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, methamphetamine-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 methamphetamine-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.

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

The R1 solution contains mouse monoclonal anti-methamphetamine antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09%) as a preservative. The R2 solution contains glucose-o-phosphate dehydrogenase (G6PDH) labeled with methamphetamine in buffer with sodium azide (0.09%) as preservative.

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay calibrators and controls designated for use at the 50 ng/mL cutoffs contain 0, 20, 37.5, 50, 62.5, 100, and 140 ng/mL of dmethamphetamine in human oral fluid with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.

The LZI Oral Fluid Collector is a 50 mL polypropylene collection tube. It is a non-sterile centrifuge tube with a screw-on cap and printed graduations (United Lab Plastics, Catalog#UP2262).

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#### Intended Use

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of d-methamphetamine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value 50 ng/mL. The assay is designed for prescription 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 and LCMS or (2) permitting laboratories to establish quality control procedures.

The LZI Oral Fluid Methamphetamine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value 50 ng/mL.

The LZI Oral Fluid Methamphetamine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL.

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 liquid 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 LZI Oral Fluid Methamphetamine Enzyme Immunoassay (k131652) is substantially equivalent to the Lin-Zhi International, Inc. Oral Fluid Methamphetamine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems cleared by the FDA under the premarket notification k062242 for its stated intended use.

The following table compares LZI's Oral Fluid Methamphetamine Enzyme Immunoassay (k131652) with the predicate device.

| Device<br>Characteristics | Subject Device (k131652)<br>LZI Oral Fluid Methamphetamine<br>Enzyme Immunoassay, Calibrators and<br>Controls | Predicate Device (k062242)<br>LZI Oral Fluid Methamphetamine<br>Enzyme Immunoassay, Calibrators and<br>Controls |
|---------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The LZI Oral Fluid Methamphetamine<br>Enzyme Immunoassay, is intended for the<br>qualitative and semi-quantitative<br>determination of d-methamphetamine in<br>neat human oral fluid, collected into the<br>LZI Oral Fluid Collector, at the cutoff<br>value 50 ng/mL. The assay is designed for<br>prescription use with a number of<br>automated clinical chemistry analyzers. | The Methamphetamine Enzyme<br>Immunoassays for Drugs of Abuse in Oral<br>Fluid is a homogeneous enzyme<br>immunoassay system to detect<br>methamphetamine in human saliva with a<br>cutoff of 45 ng/mL when testing oral fluid<br>specimen collected with Salivette<br>collector (manufactured by Sarstedt) and<br>diluted with 1 mL of buffer. The<br>calibrators and controls of the analyte (d-<br>methamphetamine) are prepared with oral<br>fluid buffer so that it can be used to verify<br>and validate the assay. The assay is<br>intended for use in the qualitative<br>determination for methamphetamine. The<br>assay is designed for professional use<br>with a number of automated clinical<br>chemistry analyzers. |
| | This assay provides a rapid screening procedure<br>for determining the presence of d-<br>methamphetamine in oral fluid. The assay<br>provides only a preliminary analytical result. A<br>more specific alternative chemical method must be<br>used in order to obtain a confirmed analytical<br>result. Gas or liquid chromatography/mass<br>spectrometry (GC/MS or LC/MS) is the preferred<br>confirmatory method. Clinical consideration and<br>professional judgment should be exercised with<br>any drug of abuse test result, particularly when the<br>preliminary test result is positive. | The Oral Fluid Methamphetamine Enzyme<br>Immunoassay is a homogeneous enzyme<br>immunoassay system provides only a preliminary<br>analytical test result. A more specific alternative<br>chemical method must be used to obtain a<br>confirmed analytical result. Gas<br>chromatography/mass spectrometry (GC/MS) is the<br>preferred confirmatory method. Clinical<br>consideration and professional judgment should be<br>applied to any drug-of-abuse test result,<br>particularly when preliminary positive results are<br>used. |
| Analyte | d-methamphetamine | d-methamphetamine |
| Cutoff | 50 ng/mL | 45 ng/mL |
| Matrix | Oral fluid | Oral fluid |
| Calibrator<br>Levels | 5 Levels<br>(0, 20, 50, 100, 140 ng/mL) | 5 Levels<br>(0, 15, 30, 45, 90 ng/mL) |
| Control Levels | 2 Levels<br>(37.5 ng/mL, 62.5 ng/mL) | 2 Levels<br>(15 ng/mL, 45 ng/mL) |
| Storage | 2-8 ℃ until expiration date | 2-8 ℃ until expiration date |

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# Performance Characteristics Summary:

Hitachi 717 Analyzer

| Sample<br>Concentration | Within Run | | Total Precision | |
|-------------------------|----------------------------|-----------------------|----------------------------|-----------------------|
| | Number of<br>Determination | Immunoassay<br>Result | Number of<br>Determination | Immunoassay<br>Result |
| 0 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 12.5 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 37.5 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 62.5 ng/mL | 22 | 22 Positive | 88 | 88 Positive |
| 75 ng/mL | 22 | 22 Positive | 88 | 88 Positive |
| 87.5 ng/mL | 22 | 22 Positive | 88 | 88 Positive |
| 100 ng/mL | 22 | 22 Positive | 88 | 88 Positive |

#### Semi-Quantitative Positive/Negative Results:

#### Qualitative Positive/Negative Results:

| Sample<br>Concentration | Within Run | | Total Precision | |
|-------------------------|----------------------------|-----------------------|----------------------------|-----------------------|
| | Number of<br>Determination | Immunoassay<br>Result | Number of<br>Determination | Immunoassay<br>Result |
| 0 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 12.5 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 37.5 ng/mL | 22 | 22 Negative | 88 | 88 Negative |
| 62.5 ng/mL | 22 | 22 Positive | 88 | 88 Positive |
| 75 ng/mL | 22 | 22 Positive | 88 | 88 Positive |
| 87.5 ng/mL | 22 | 22 Positive | 88 | 88 Positive |
| 100 ng/mL | 22 | 22 Positive | 88 | 88 Positive |

## Linearity:

Hitachi 717 Instrument: 5 - 140 ng/mL

When using drug-free samples spiked with known amounts of d-methamphetamine and comparing the result (y) and target (x) value, using the least squares regression technique, the regression equation and correlation are as follow:

y = 0.9834x -0.9874, r2 = 0.9993

#### Method Comparison: Clinical Samples

From a total of eighty-five (85) clinical unaltered samples For both Qualitative and Semi-Quantitative results: 100.0 % agreement with positive, 95.2 % agreement with negative samples

#### Endogenous Compound Interference and 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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#### Shipping/Recovery Stability Study:

No significant sample degradation occurred following real-time and accelerated stability studies up to 72 hours. All sample shipments are based on the assumption of a 24 hour priority overnight delivery.

#### Sample Storage Stability Study:

No significant sample degradation occurred following real-time and accelerated stability studies up to 13 Days. Based on real-time studies, samples can be stored at 2-8 ℃ for up to 15 Days. Based on the Arrhenius equation, accelerated stability data supports at least 18 months of shelflife storage at -20 ℃. Real-time stability studies are on-going.

#### Open (and re-capped) vial Stability for Calibrator/Control:

Real time (2 - 8 ℃) and accelerated stability studies (at room temperature and 30 ℃) were carried out for 17 months (508 Days) and results indicated degradation at all three conditions was minimal. Thermal stability data supports at least 18 months of shelf life storage at 2 - 8 ℃.

#### Summary:

The information provided in this pre-market notification demonstrates that the LZI Oral Fluid Methamphetamine Enzyme Immunoassay (k131652) 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 Oral Fluid Methamphetamine Enzyme Immunoassay is substantially equivalent to the predicate device in terms of safety and effectiveness for its stated intended use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle-like symbol with three trailing lines, positioned to the right of a circular emblem. The circular emblem contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter of the circle.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

March 21, 2014

LIN-ZHI INTERNATIONAL, INC. BERNICE LIN VP OF OPERATIONS 670 ALMANOR AVE SUNNYVALE CA 94085

Re: K131652

Trade/Device Name: LZI Oral Fluid Methamphetamine Enzyme Immunoassay, Calibrators, LZI Oral Fluid Methamphetamine Calibrators LZI Oral Fluid Methamphetamine Controls

Regulation Number: 21 CFR 862.3600 Regulation Name: Methamphetamine test system Regulatory Class: II Product Code: LAF, DLJ, LAS Dated: December 18, 2013 Received: December 23, 2013

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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Page 2-Dr. Lin

electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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/Reportal?roblem/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 [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

# Courtney H. Lias -S

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

#### Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

#### 510(k) Number (if known) k131652

#### Device Name

LZI Oral Fluid Methamphetamine Enzyme Immunossay LZI Oral Fluid Methamphetamine Calibrators LZI Oral Fluid Methamphami

#### Indications for Use (Describe)

The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is intended for the qualitative determination of dmethamphetanine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 50 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

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

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 and LCMS or (2) permitting laboratories to establish quality control procedures.

The LZI Oral Fluid Methamphetamine Calibrators are for use as calibrators in the qualitative calibration of the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL.

The LZI Oral Fluid Methamphetamine Controls are for use as assayed quality control materials to monitor the LZI Oral Fluid Methamphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL.

Type of Use (Select one or both, as applicable) | Over-The-Counter Use (21 CFR 801 Subpart C) [x] Prescription Use (Part 21 CFR 801 Subpart D)

# PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FOR FOR USE ONLY IN THE PHOTO CHANNER FE 的一个人 - 家居梅德 -

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)