(58 days)
The Methamphetamine Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methamphetamine in human saliva with a cutoff of 45 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 (d-methamphetamine) 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 methamphetamine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Oral Fluid Methamphetamine 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.
LZI's Oral Fluid Methamphetamine Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect methamphetamine in oral fluid with minimal cross-reactivity to various, common prescription drugs and abused drugs. The assay is based on competition between drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme and free drug from the saliva sample for a fixed amount of specific antibody. In the absence of free drug from the saliva sample the specific antibody binds to the drug labeled G6PDH enzyme causing a decrease in enzyme activity. It is therefore the drug concentration is proportional to the enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to covert nicotinamide adenine dinucleotide (NAD) to NADH.
Here's a breakdown of the acceptance criteria and study information for the LZI Oral Fluid Methamphetamine Homogeneous Enzyme Immunoassay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied by Predicate/General Benchmarks) | Reported Device Performance (LZI Oral Fluid Methamphetamine Assay) |
|---|---|---|
| Accuracy (Clinical Samples) | Similar to Predicate (98% Agreement vs. GC/MS) | 98.2 % Agreement (vs. GC/MS) |
| Matrix | Saliva | Saliva |
| Analyte | d-methamphetamine | d-methamphetamine |
| Cutoff | 45 ng/mL | 45 ng/mL |
| Total Precision: | Negative: 284.8 (Mean), 2.27 (SD), 0.80% (CV) | |
| 15 ng/mL: 332.0 (Mean), 2.13 (SD), 0.64% (CV) | ||
| 30 ng/mL: 351.9 (Mean), 2.13 (SD), 0.60% (CV) | ||
| 45 ng/mL: 373.2 (Mean), 2.50 (SD), 0.67% (CV) | ||
| 90 ng/mL: 400.4 (Mean), 2.33 (SD), 0.58% (CV) |
Explanation of "Acceptance Criteria (Implied)": The document doesn't explicitly state quantitative acceptance criteria for the LZI device. Instead, it demonstrates substantial equivalence to a predicate device (OraSure Methamphetamine Intercept® Micro-plate EIA) and other LZI test systems by showing comparable performance. Therefore, the predicate's reported performance (e.g., 98% accuracy agreement) serves as the de-facto benchmark for acceptance of the new device. The precision data for the LZI device is presented without an explicit "criteria" column, but the low %CV values indicate good precision, which is generally expected for such devices.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Patients): 112 for the LZI Oral Fluid Methamphetamine Assay. (The predicate device study used n=50 clinical samples).
- Data Provenance: The document does not explicitly state the country of origin. It is a retrospective study, as it uses collected clinical patient samples and compares the assay results to a confirmatory method (GC/MS).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- This information is not provided in the document.
- The ground truth was established using an analytical method (GC/MS), not through expert interpretation of images or clinical assessments by a panel of human experts. Therefore, the concept of "number of experts" or their qualifications is not relevant here.
4. Adjudication Method for the Test Set
- None. The primary method for ground truth establishment was Gas Chromatography/Mass Spectrometry (GC/MS), which is an objective chemical analysis method, not requiring adjudication by human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
- No. This is an in vitro diagnostic device (immunoassay) designed to provide an analytical result based on a chemical reaction, not an imaging or diagnostic AI tool that assists human readers. Therefore, an MRMC study is not applicable or mentioned.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) was Done
- Yes. The performance data presented (accuracy vs. GC/MS, precision) are for the LZI Oral Fluid Methamphetamine Enzyme Immunoassay operating as a standalone analytical device. The "algorithm" in this context is the biochemical reaction of the immunoassay itself, and its performance is evaluated independently of human interpretation, beyond the professional use and judgment required in applying the results.
7. The Type of Ground Truth Used
- Analytical Confirmation: Gas Chromatography/Mass Spectrometry (GC/MS). This is explicitly stated as the "preferred confirmatory method" and the method against which the device's accuracy was compared.
8. The Sample Size for the Training Set
- This information is not applicable/provided for this type of device. The LZI Oral Fluid Methamphetamine Homogeneous Enzyme Immunoassay is an immunoassay, not a machine learning or AI algorithm that undergoes "training" on a data set in the conventional sense. Its performance is based on its chemical design and validation against known standards and clinical samples.
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, the concept of a "training set" with established ground truth is not applicable for this immunoassay device. The device's underlying chemical principles and components are developed and optimized (not "trained") according to biochemical and analytical chemistry principles. Its performance is then validated using calibrators, controls, and clinical samples, with GC/MS as the gold standard for confirmation.
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SEP 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
Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085 Phone: (408) 732-3856 Fax: (408) 732-3849 Email: mtlin@lin-zhi.com
Contact: Marie Lin, Ph.D. President, R&D Director
Device Name and Classification
| Classification Name: | The Methamphetamine test systems have been placed in Class II by the Bureau of Medical Devices. |
|---|---|
| Classification Number: LAF (21 CFR 862.3600) | |
| Panel: 91 Toxicology 862.3610 | |
| The “Drug Specific, Calibrators” has been placed in Class II by the Bureau of Medical Devices. | |
| Classification No.: DLJ, 21 CFR 862.3200 | |
| Panel: 91Toxicology | |
| The “Single (Specified) Analyte Controls” has been placed in Class I by the Bureau of Medical Devices. | |
| Classification No.: LAS, 21 CFR 862.3280 | |
| Panel: 91Toxicology | |
| Common Name: | Oral Fluid Methamphetamine Homogeneous Enzyme Immunoassays |
Proprietary Name:
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Legally Marketed Predicate Device(s)
The LZI Oral Fluid Methamphetamine Enzyme Immunoassay is substantially equivalent . to the Methamphetamine Intercept® Micro-plate EIA (K993208) manufactured by OraSure Technologies Inc. (formerly known as STC Technologies, Inc) for its general intended use. The current subject device is also substantially equivalent to other LZI test systems cleared by FDA, e.g., the Oral Fluid Cocaine (K0509045), Opiate (K050988), and Methadone (K051058) Homogeneous Enzyme Immunoassay for its stated intended use.
Device Description
LZI's Oral Fluid Methamphetamine Enzyme Immunoassay is a ready-to-use, Iiquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect methamphetamine in oral fluid with minimal cross-reactivity to various, common prescription drugs and abused drugs. The assay is based on competition between drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme and free drug from the saliva sample for a fixed amount of specific antibody. In the absence of free drug from the saliva sample the specific antibody binds to the drug labeled G6PDH enzyme causing a decrease in enzyme activity. It is therefore the drug concentration is proportional to the enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to covert nicotinamide adenine dinucleotide (NAD) to NADH.
Intended Use
The Methamphetamine Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methamphetamine in human saliva with a cutoff of 45 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 (d-methamphetamine) 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 methamphetamine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Oral Fluid Methamphetamine Enzyme Immunoassay is a homogeneous enzyme immunoassay system provides only a preliminary analytical test result. A more specific atternative 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(s)
The LZI Oral Fluid Methamphetamine Homogeneous Enzyme Immunoassay, including calibrators and controls, is substantially equivalent to OraSure's Methamphetamine Intercept® Micro-plate EIA in its intended use and in for the qualitative determination of methamphetamine in human oral fluid.
| DeviceCharacteristics | Subject Device(LZI Oral Fluid MethamphetamineHomogeneous EIA) | Predicate Device(OraSure MethamphetamineIntercept® Micro-plate EIA) | Feature | Oral Fluid Methamphetamine EIA | ||||
|---|---|---|---|---|---|---|---|---|
| Intended Use | The Methamphetamine EnzymeImmunoassays for Drugs of Abuse inOral Fluid is a homogeneous enzymeimmunoassay system to detectmethamphetamine in human saliva witha cutoff of 45 ng/mL when testing oralfluid specimen collected with Salivettecollector (manufactured by Sarstedt)and diluted with 1 mL of buffer. Thecalibrators and controls of the analyte(d-methamphetamine) are preparedwith oral fluid buffer so that it can beused to verify and validate the assay.The assay is intended for use in thequalitative determination formethamphetamine. The assay isdesigned for professional use with anumber of automated clinical chemistryanalyzers.The Oral Fluid MethamphetamineEnzyme Immunoassay is ahomogeneous enzyme immunoassaysystem provides only a preliminaryanalytical test result. A more specificalternative chemical method must beused to obtain a confirmed analyticalresult. 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. | The OraSure MethamphetamineIntercept® Micro-plate EIA isintended for use by clinicallaboratories in the qualitativedetermination of methamphetamine inoral fluid collected with the InterceptⓇDOA Oral Specimen CollectionDevice using a 40 ng/mL cutoff. ForIn Vitro Diagnostic Use.The OraSure MethamphetamineIntercept® Micro-plate EIA providesonly a preliminary analytical testresult. A more specific alternativechemical method should be used inorder to obtain a confirmed analyticalresult. 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. | Qualitative : (n=120) mA/min | Mean. | SD | % CV | ||
| Analyte | d-methamphetamine | d-methamphetamine | Within Run Precision: | Negative | 284.8 | 1.83 | 0.64 % | |
| Matrix | Saliva | Saliva | 15 ng/mL | 332.0 | 1.82 | 0.55 % | ||
| Calibrators/Controls Level | 5 levels including a negative | 4 levels including a negative | 30 ng/mL | 351.9 | 1.84 | 0.52 % | ||
| DeviceCharacteristics | Predicate Device(K0509045) | Predicate Device(K0509088) | Predicate Device(K051058) | 45 ng/mL | 373.2 | 1.97 | 0.53 % | |
| Intended Use | The LZI Cocaine Metabolite(Benzoylecgonine) OralFluid Homogeneous EIA is ahomogeneous enzymeimmunoassay system todetect cocaine metabolite inhuman saliva with a cutoff of15 ng/mL when testing oralfluid specimen collected withSalivette collector(manufactured by Sarstedt )and diluted with 1 mL ofbuffer. The calibrators andcontrols of the analyte(Benzoylecgonine) areprepared with oral fluidbuffer so that it can be usedto verify and validate theassay. The assay is intendedfor use in the qualitativedetermination forcocaine/cocaine metabolitedrugs. | The LZI Opiate OralFluid Homogeneous EIAis a homogeneousenzyme immunoassaysystem to detect opiatesin human saliva with acutoff of 30 ng/mL whentesting oral fluidspecimen collected withSalivette collector(manufactured bySarstedt ) and dilutedwith 1 mL of buffer. Thecalibrators and controlsof the analyte (Opiate)are prepared with oralfluid buffer so that it canbe used to verify andvalidate the assay. Theassay is intended for usein the qualitativedetermination for Opiatedrugs. | The LZI Methadone OralFluid Homogeneous EIAis a homogeneous enzymeimmunoassay system todetect methadone inhuman saliva with acutoff of 30 ng/mL whentesting oral fluidspecimen collected withSalivette collector(manufactured bySarstedt) and diluted with1 mL of buffer. Thecalibrators and controls ofthe analyte (Methadone)are prepared with oralfluid buffer so that it canbe used to verify andvalidate the assay. Theassay is intended for usein the qualitativedetermination forMethadone drugs. | 90 ng/mL | 400.4 | 1.54 | 0.39 % | |
| The Cocaine Metabolite(Benzoylecgonine) Oral FluidEnzyme Immunoassay is ahomogeneous enzyme immunoassaysystem provides only a preliminaryanalytical test result. A morespecific alternative chemicalmethod must be used to obtain aconfirmed analytical result. Gaschromatography/mass spectrometry(GC/MS) is the preferredconfirmatory method. Clinicalconsideration and professionaljudgment should be applied to anydrug-of-abuse test result.particularly when preliminarypositive results are used. | The Opiate Oral FluidEnzyme Immunoassay is ahomogeneous enzymeimmunoassay system providesonly a preliminary analyticaltest result. A more specificalternative chemical methodmust be used to obtain aconfirmed analytical result.Gas chromatography/massspectrometry (GC/MS) is thepreferred confirmatorymethod. Clinicalconsideration andprofessional judgement shouldbe applied to any drug-of-abuse test result, particularlywhen preliminary positiveresults are used. | The Methadone Oral FluidEnzyme Immunoassay is ahomogeneous enzymeimmunoassay system providesonly a preliminary analyticaltest result. A more specificalternative chemical methodmust be used to obtain aconfirmed analytical result. Gaschromatography/massspectrometry (GC/MS) is thepreferred confirmatory method.Clinical consideration andprofessional judgement shouldbe applied to any drug-of-abusetest result, particularly whenpreliminary positive results areused. | Mean. | SD | % CV | |||
| Analyte | Benzoylecgonine | Morphine | Methadone | Total Precision: | Negative | 284.8 | 2.27 | 0.80 % |
| Matrix | Saliva | Saliva | Saliva | 15 ng/mL | 332.0 | 2.13 | 0.64 % | |
| Calibrators/Controls Level | 5 levels including a negative | 5 levels including anegative | 5 levels including anegative | 30 ng/mL | 351.9 | 2.13 | 0.60 % | |
| 45 ng/mL | 373.2 | 2.50 | 0.67 % | |||||
| 90 ng/mL | 400.4 | 2.33 | 0.58 % | |||||
| Accuracy: Clinical patients samples(n=112) vs. GC/MS | 98.2 % Agreement | |||||||
| Specificity: | See attached Assay package insert |
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The LZI Oral Fluid Methamphetamine Homogeneous Enzyme Immunoassay, including calibrators and controls, is also substantially equivalent to other LZI test systems cleared by FDA, e.g., the Oral Fluid Cocaine (K0509045), Opiate (K050988), and Methadone (K051058) Homogeneous Enzyme Immunoassay for its stated intended use.
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Performance Characteristics
LZI Oral Fluid Methamphetamine Assay
OraSure Methamphetamine Micro=Plate EIA
| Feature | Methamphetamine | Mean O.D. | % CV |
|---|---|---|---|
| PrecisionIntra-assayN=64 | 0 ng/mL | 2.056 | 7.8 |
| 20 ng/mL | 0.978 | 7.0 | |
| 40 ng/mL | 0.710 | 6.2 | |
| 60 ng/mL | 0.554 | 7.8 | |
| 80 ng/mL | 0.480 | 6.4 | |
| Inter-assayN=4/day, 20 days | 0 ng/mL | 2.056 | 7.5 |
| 20 ng/mL | 0.978 | 7.7 | |
| 40 ng/mL | 0.710 | 7.9 | |
| 60 ng/mL | 0.554 | 7.5 | |
| 80 ng/mL | 0.480 | 8.4 | |
| Accuracy: Clinical patients sample (n=50)vs. GC/MS | 98 % Agreement | ||
| Specificity | See OraSure product insert |
Summary
The information provided in this pre-market notification demonstrates that the LZI Oral Fluid Methamphetamine Homogeneous ELA is substantially equivalent to the legally marketed predicated device for its general intended use. Data and results provided in this premarket notification were collected and prepared in accordance with the NCCLS guidance. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by gas chromatography/mass spectrometry, an independent analytical method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Oral Fluid Methamphetamine Homogeneous 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 caduceus, a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
SEP 2 9 2006
Marie Lin. Ph.D. President, R&D Director Lin-Zhi International, Inc. 687 North Pastoria Avenue Sunnyvale, CA 94085
K062242 Re:
Oral Eluid Methamphetamine Homogeneous Enzyme ्
Immunoassay, Calibrators and Controls Regulation Number: 21 CFR 862.3610 Regulation Name: Methamphetamine test system Regulatory Class: Class II Product Code: LAF, DLJ, LAS Dated: July 31, 2006 Received: August 2, 2006
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); 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 catitied, "Misteranding by reserves to promarket notification" (21 CFR 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 Gutierrez
Alberto Guticarez, 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
510(k) Number (if known): K062242
Device Name: Oral Fluid Methamphetamine Homogeneous Enzyme Immunoassay, Calibrators and Controls.
Indications For Use:
The Methamphetamine Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methamphetamine in human saliva with a cutoff of 45 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 (d-methamphetamine) 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 methamphetamine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Oral Fluid Methamphetamine Enzyme Immunoassay is a homogeneous enzyme immunoassay system provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(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-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
Page 1 of 1
§ 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).