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

The Cocaine Metabolite (Benzoylecgonine) Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoasay system provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-ofabuse test result, particularly when preliminary positive results are used.

Device Description

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

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the LZI Cocaine Metabolite (Benzoylecgonine) Oral Fluid Homogeneous Enzyme Immunoassay, Calibrators and Controls:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on demonstrating substantial equivalence to a predicate device and provides performance characteristics rather than explicit "acceptance criteria" in the sense of predefined thresholds. However, we can infer some criteria from the presented data, particularly in comparison to the predicate device. The key performance metrics reported are accuracy, within-run precision, and total precision.

Acceptance Criteria (Inferred from Predicate and Study Design)	Reported Device Performance (LZI Cocaine Metabolite (Benzoylecgonine) Oral Fluid EIA)
Accuracy (Agreement with Confirmatory Method):	95.8% Agreement with GC/MS for clinical patient samples.
Predicate Device Accuracy for Comparison:	93.2% Agreement with GC/MS for clinical patient samples.
Within Run Precision (%CV):	- Negative: 0.71%
	- 5 ng/mL: 0.78%
	- 10 ng/mL: 0.80%
	- 20 ng/mL: 0.81%
	- 50 ng/mL: 0.77%
Total Precision (%CV):	- 5 ng/mL: 0.88%
	- 10 ng/mL: 0.88%
	- 20 ng/mL: 0.88%
	- 50 ng/mL: 0.83%
Predicate Device Precision:	Intra-assay: 0 ng/mL (3.7%), 2.5 ng/mL (3.4%), 5.0 ng/mL (4.3%), 7.5 ng/mL (7.6%)
	Inter-assay: 0 ng/mL (8.0%), 2.5 ng/mL (9.0%), 5.0 ng/mL (9.6%), 7.5 ng/mL (10.5%)
Specificity:	"See attached Assay package insert." (The document states comparability to the predicate's specificity.)

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

Accuracy Test (Clinical Patients Samples):
- Sample Size: 118 samples (n=118)
- Data Provenance: Not explicitly stated, but clinical patient samples are used, implying real-world data. The country of origin is not specified, but the submission is to the US FDA. The study appears to be prospective since it's providing data for pre-market notification.
Qualitative (Precision) Test:
- Sample Size: 120 samples (n=120) for "Qualitative : (n=120) mA/min". This likely refers to the number of measurements rather than distinct individuals.
- Data Provenance: Not specified, but likely laboratory-controlled samples, not clinical patient data. Presumably prospective.

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

Number of Experts: Not applicable in this context.
Qualifications of Experts: Not applicable.

For this type of in-vitro diagnostic device, the "ground truth" for drug detection is established by a more definitive analytical method, not by expert consensus in the human interpretation sense.

4. Adjudication Method for the Test Set:

Adjudication Method: Not applicable. The "adjudication" is done by comparing the device's results directly against the quantitative results of the GC/MS method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

MRMC Study: No, an MRMC comparative effectiveness study was not done. This is an in-vitro diagnostic device, not an imaging device or one that involves human interpretation of complex data where "readers" are involved in the traditional sense.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Standalone Performance: Yes, the described studies represent standalone performance. The device is an automated immunoassay system that provides a preliminary analytical result. Its accuracy and precision are evaluated independently against a gold standard (GC/MS) or against internal measures. There isn't a "human-in-the-loop" component for the device's direct output. Human professional judgment is still required for interpreting the results in a clinical context, but this is separate from the device's technical performance.

7. The Type of Ground Truth Used:

Ground Truth: For the accuracy study, the ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS). The document explicitly states: "Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method." and "Accuracy: Clinical patients samples (n=118) vs. GC/MS".

8. The Sample Size for the Training Set:

Training Set Sample Size: The document does not provide details on a specific "training set" size. For laboratory developed immunoassays like this, the development and optimization process (which could be considered analogous to "training") involves various reagent formulations, calibration curves, and testing. However, a distinct, quantifiable "training set" as understood in machine learning is not described. The provided data focuses on the validation of the final product.

9. How the Ground Truth for the Training Set was Established:

Ground Truth for Training Set: Since a distinct training set and its ground truth are not explicitly described in the context of this traditional immunoassay, this information is not available in the provided text. The overall method development and validation would rely on established analytical chemistry principles and comparison to reference methods like GC/MS at various stages.

Summary

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K050945

MAR 2 9 2006 510(k) Summary of Safety and Effectiveness

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

Introduction

According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Submitter name, Address, and Contact

March 20, 2006

Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085 Phone: (408) 732-3856 Fax: (408) 732-3849

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

Device Name and Classification

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

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Predicate Device(s)

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

Device Description

Intended Use

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

The Cocaine Metabolite (Benzoylecgonine) Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoassay system provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

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Comparison to Predicate Device

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

Device	Subject Device	Predicate Device
Characteristics	(LZI Cocaine Metabolite	(OraSure Cocaine Metabolite
	(Benzoylecgonine) Oral Fluid	Intercept® Micro-plate EIA)
	Homogeneous EIA)
Intended Use	The LZI Cocaine Metabolite	The OraSure Cocaine Metabolite
	(Benzoylecgonine) Oral Fluid	Intercept® Micro-plate EIA is
	Homogeneous EIA is a homogeneous	intended for use by clinical
	enzyme immunoassay system to detect	laboratories in the qualitative
	cocaine metabolite in human saliva	determination of cocaine and cocaine
	with a cutoff of 15 ng/mL when testing	metabolite in oral fluid collected with
	oral fluid specimen collected with	Intercept® DOA Oral Specimen
	Salivette collector (manufactured by	Collection Device using a 5.0 ng/mL
	Sarstedt ) and diluted with 1 mL ofbuffer. The calibrators and controls of	cutoff. For In Vitro Diagnostic Use.
	the analyte (Benzoylecgonine) are
	prepared with oral fluid buffer so that it	The OraSure Cocaine Metabolite
	can be used to verify and validate the	Intercept® Micro-plate EIA providesonly a preliminary analytical test
	assay. The assay is intended for use in	result. A more specific alternative
	the qualitative determination for	chemical method should be used in
	cocaine/cocaine metabolite drugs.	order to obtain a confirmed analytical
	The Cocaine Metabolite(Benzoylecgonine) Oral Fluid EnzymeImmunoassay is a homogeneousenzyme immunoassay system providesonly a preliminary analytical testresult. A more specific alternativechemical method must be used toobtain a confirmed analytical result.Gas chromatography/massspectrometry (GC/MS) is the preferredconfirmatory method. Clinicalconsideration and professionaljudgment should be applied to anydrug-of-abuse test result, particularlywhen preliminary positive results areused.	result. Gas chromatography/massspectrometry (GC/MS) is thepreferred confirmatory method.Clinical consideration andprofessional judgement should beapplied to any drugs of abuse testresult, particularly when apreliminary, positive result isobserved.
Analyte	Benzoylecgonine	Benzoylecgonine
Matrix	Saliva	Saliva
Calibrators/	5 levels including a negative	4 levels including a negative
Controls Level

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

LZI Cocaine Metabolite (Benzoylecgonine) Oral Fluid Assay

OraSure Cocaine Metabolite Micro=Plate EIA

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

Summary

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

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

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 2 9 2006

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

Re: K050945

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

Dear Ms. Lin:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 –

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. 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 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto G. A.

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

Enclosure

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Indications for Use

510(k) Number (if known):_ K050945

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

Indications For Use:

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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

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

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

Division Sign-or

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୍ରିୟିତ of In View Diagnostic Device Evaluation and Safe

Regulation Number and Section

§ 862.3250 Cocaine and cocaine metabolite test system.

(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).