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.

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).

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (LZI Oral Fluid Methamphetamine Enzyme Immunoassay)
Qualitative Positive Agreement	Excellent agreement	100.0% agreement with positive samples (compared to GC/MS or LC/MS)
Qualitative Negative Agreement	Excellent agreement	95.2% agreement with negative samples (compared to GC/MS or LC/MS)
Semi-Quantitative Linearity	High correlation	Regression equation: y = 0.9834x -0.9874, r² = 0.9993 (for 5 - 140 ng/mL)
Within-Run Precision (Negative)	100% Negative	0 ng/mL, 12.5 ng/mL, 25 ng/mL, 37.5 ng/mL all showed 22/22 Negative
Within-Run Precision (Positive)	100% Positive	62.5 ng/mL, 75 ng/mL, 87.5 ng/mL, 100 ng/mL all showed 22/22 Positive
Total Precision (Negative)	100% Negative	0 ng/mL, 12.5 ng/mL, 25 ng/mL, 37.5 ng/mL all showed 88/88 Negative
Total Precision (Positive)	100% Positive	62.5 ng/mL, 75 ng/mL, 87.5 ng/mL, 100 ng/mL all showed 88/88 Positive
Endogenous Compound Interference	No significant interference	No significant undesired cross reactants or endogenous substance interference
Shipping/Recovery Stability	No significant degradation	No significant sample degradation up to 72 hours (real-time & accelerated)
Sample Storage Stability	No significant degradation	Up to 15 days at 2-8°C (real-time); At least 18 months at -20°C (accelerated)
Open Vial Stability (Calibrator/Control)	Minimal degradation	Minimal degradation for 17 months (508 days) at 2-8°C, room temp, and 30°C

Note: The document does not explicitly state numerical acceptance criteria for qualitative agreement, but "100.0% agreement with positive" and "95.2% agreement with negative" are presented as favorable performance. The precision data indicates 100% concordance with expected results at various concentrations relative to the cutoff.

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: "a total of eighty-five (85) clinical unaltered samples" were used for method comparison.
Data Provenance: The text does not specify the country of origin. It indicates the samples were "clinical unaltered samples," implying they were collected from human subjects in a clinical setting, making them prospective or retrospective clinical samples. The exact nature (prospective vs. retrospective) is not explicitly stated.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of immunoassay device relies on a "confirmatory method" for establishing ground truth, not typically human expert consensus for individual results.

Number of Experts: Not applicable in the traditional sense of human consensus.
Qualifications of Experts: Not applicable. The ground truth is established by analytical methods.

4. Adjudication Method for the Test Set

Not applicable for this type of device where the ground truth is established by a specific analytical method. The device's results are compared directly to the results from the confirmatory method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically used for image-based diagnostic devices where human readers interpret images. This device is an in-vitro diagnostic assay.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies reported are standalone performance studies of the device (immunoassay) itself. The "Immunoassay Result" tables directly show the device's output (Positive/Negative) for given sample concentrations. The method comparison directly evaluates the device against a gold standard analytical method without human interpretation of the device's output other than reading the final result.

7. The Type of Ground Truth Used

The type of ground truth used is an alternative chemical method, specifically Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS). These are considered the "preferred confirmatory method[s]" for drug detection in oral fluid.

8. The Sample Size for the Training Set

The document does not report a specific sample size for a training set. Immunoassays like this are developed through a different process involving reagent formulation and optimization rather than machine learning training on a large dataset in the way a software algorithm would be. The "within run" and "total precision" studies use 22 and 88 determinations per concentration, respectively, but these are for performance evaluation, not a "training set."

9. How the Ground Truth for the Training Set Was Established

Since a "training set" in the context of machine learning is not explicitly mentioned or relevant for this type of device, the method for establishing ground truth for such a set is not described. The device's performance is demonstrated by comparing its results to established analytical methods for clinical samples and spiked samples with known concentrations.

Summary

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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: (408) 732-3856 Fax: (408) 732-3849 e-mail: bclin@lin-zhi.com

Bernice Lin, Ph.D. Contact: VP Operations

Device Name and Classification

Classification Name:	Enzyme Immunoassay, Oral Fluid MethamphetamineClass II, LAF (91 Toxicology),21 CFR 862.3610Drug Specific Calibrators,Class II, DLJ (91 Toxicology),21 CFR 862.3200Drug Specific Controls,Class I, LAS (91 Toxicology),21 CFR 862.3280
Common Name:	Homogeneous Oral Fluid Methamphetamine EnzymeImmunoassay
Proprietary Name:	LZI Oral Fluid Methamphetamine Enzyme Immunoassay,LZI Oral Fluid Methamphetamine CalibratorsLZI 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 Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

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

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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.

DeviceCharacteristics	Subject Device (K131652)LZI Oral Fluid MethamphetamineEnzyme Immunoassay, Calibrators andControls	Predicate Device (K062242)LZI Oral Fluid MethamphetamineEnzyme Immunoassay, Calibrators andControls
Intended Use	The LZI Oral Fluid MethamphetamineEnzyme Immunoassay, is intended for thequalitative and semi-quantitativedetermination of d-methamphetamine inneat human oral fluid, collected into theLZI Oral Fluid Collector, at the cutoffvalue 50 ng/mL. The assay is designed forprescription use with a number ofautomated clinical chemistry analyzers.	The Methamphetamine EnzymeImmunoassays for Drugs of Abuse in OralFluid is a homogeneous enzymeimmunoassay system to detectmethamphetamine in human saliva with acutoff of 45 ng/mL when testing oral fluidspecimen collected with Salivettecollector (manufactured by Sarstedt) anddiluted with 1 mL of buffer. Thecalibrators and controls of the analyte (d-methamphetamine) are prepared with oralfluid buffer so that it can be used to verifyand validate the assay. The assay isintended for use in the qualitativedetermination for methamphetamine. Theassay is designed for professional usewith a number of automated clinicalchemistry analyzers.
	This assay provides a rapid screening procedurefor determining the presence of d-methamphetamine in oral fluid. The assayprovides only a preliminary analytical result. Amore specific alternative chemical method must beused in order to obtain a confirmed analyticalresult. Gas or liquid chromatography/massspectrometry (GC/MS or LC/MS) is the preferredconfirmatory method. Clinical consideration andprofessional judgment should be exercised withany drug of abuse test result, particularly when thepreliminary test result is positive.	The Oral Fluid Methamphetamine EnzymeImmunoassay is a homogeneous enzymeimmunoassay system provides only a preliminaryanalytical test result. A more specific alternativechemical method must be used to obtain aconfirmed analytical result. Gaschromatography/mass spectrometry (GC/MS) is thepreferred confirmatory method. Clinicalconsideration and professional judgment should beapplied to any drug-of-abuse test result,particularly when preliminary positive results areused.
Analyte	d-methamphetamine	d-methamphetamine
Cutoff	50 ng/mL	45 ng/mL
Matrix	Oral fluid	Oral fluid
CalibratorLevels	5 Levels(0, 20, 50, 100, 140 ng/mL)	5 Levels(0, 15, 30, 45, 90 ng/mL)
Control Levels	2 Levels(37.5 ng/mL, 62.5 ng/mL)	2 Levels(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

SampleConcentration	Within Run		Total Precision
	Number ofDetermination	ImmunoassayResult	Number ofDetermination	ImmunoassayResult
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:

SampleConcentration	Within Run		Total Precision
	Number ofDetermination	ImmunoassayResult	Number ofDetermination	ImmunoassayResult
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 (800) 638 2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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)

Regulation Number and Section

§ 862.3610 Methamphetamine test system.

(a)
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.(b)
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).