(28 days)
The Amphetamine-Specific Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect amphetamine 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-amphetamine) 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 amphetamine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Oral Fluid Amphetamine-Specific 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 Amphetamine-Specific Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect amphetamine 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 summary of the acceptance criteria and study details for the LZI Oral Fluid Amphetamine-Specific Homogeneous Enzyme Immunoassay based on the provided 510(k) summary:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to the predicate device and the reported performance characteristics. The primary acceptance criterion appears to be achieving a high agreement rate with the Gas Chromatography/Mass Spectrometry (GC/MS) confirmatory method for clinical samples, along with acceptable precision.
| Acceptance Criterion (Implied) | Reported Device Performance (LZI Oral Fluid Amphetamine-Specific EIA) | Predicate Device Performance (OraSure Amphetamine-Specific Micro-Plate EIA) |
|---|---|---|
| Accuracy (Agreement with GC/MS) | 97.1 % Agreement | 89 % Agreement |
| Within Run Precision (%CV) | Negative: 0.63% | 0 ng/mL: 3.9% |
| 15 ng/mL: 0.56% | 50 ng/mL: 3.5% | |
| 30 ng/mL: 0.49% | 100 ng/mL: 4.0% | |
| 45 ng/mL: 0.46% | 150 ng/mL: 4.5% | |
| 90 ng/mL: 0.50% | 200 ng/mL: 6.4% | |
| Total Precision (%CV) | Negative: 1.02 % | 0 ng/mL: 6.7% |
| 15 ng/mL: 0.85 % | 50 ng/mL: 6.7% | |
| 30 ng/mL: 0.70 % | 100 ng/mL: 7.5% | |
| 45 ng/mL: 0.70 % | 150 ng/mL: 7.7% | |
| 90 ng/mL: 0.76 % | 200 ng/mL: 7.9% | |
| Specificity | See attached Assay package insert | See OraSure product insert |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Accuracy: n=120 clinical patient samples for the LZI device.
- Precision: Not explicitly stated as a separate "test set" for precision, rather it seems to be part of the overall performance characterization. For "Within Run Precision", 120 (unspecified units) are mentioned. For "Total Precision", no sample size is given directly.
- Data Provenance: Not explicitly stated (e.g., country of origin). The samples are referred to as "Clinical patients samples," implying they are real-world human samples. The study appears to be prospective in nature for these performance characteristics, as it describes the testing of the newly developed device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. The ground truth for this device is established through a laboratory method (GC/MS), not by human expert interpretation of images or other subjective data.
4. Adjudication Method for the Test Set
Not applicable. The ground truth is established by a definitive analytical method (GC/MS), not by expert consensus or adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic assay for detecting amphetamine, not an imaging device or AI-assisted diagnostic tool that would involve human readers interpreting cases.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance presented for the LZI Oral Fluid Amphetamine-Specific Homogeneous Enzyme Immunoassay is a standalone performance. It measures the analytical performance of the assay itself using clinical samples, without human intervention in the interpretation of the initial assay result. The assay provides a "preliminary analytical test result," and it is noted that a "more specific alternative chemical method must be used to obtain a confirmed analytical result" (GC/MS). This implies the device operates independently to provide the preliminary result.
7. The Type of Ground Truth Used
The type of ground truth used for the accuracy study is 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
Not applicable. This is an immunoassay, not a machine learning or AI-based device that typically requires a distinct "training set" in the computational sense. The device's performance is based on its chemical and enzymatic reactions.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there isn't a "training set" in the context of this type of in-vitro diagnostic device. The assay development would involve optimizing the reagents and reaction conditions, but not "training" on a dataset with established ground truth in the way an AI algorithm is trained.
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Kα63024
OCT 3 0 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 Amphetamine test systems have been placed in ClassII by the Bureau of Medical Devices.Classification Number: DKZ (21 CFR 862.3100)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: | Oral Fluid Amphetamine Homogeneous EnzymeImmunoassays |
| Proprietary Name: |
12
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Legally Marketed Predicate Device(s)
The LZI Oral Fluid Amphetamine-Specific Enzyme Immunoassay is substantially equivalent to the Amphetamine-Specific Intercept® Micro-plate EIA (K992918) 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 (K050945). Opiate (K050988), and Methadone (K051058) Homogeneous Enzyme Immunoassay for its stated intended use.
Device Description
LZI's Oral Fluid Amphetamine-Specific Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect amphetamine 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 Amphetamine-Specific Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect amphetamine 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-amphetamine) 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 amphetamine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Oral Fluid Amphetamine-Specific 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 Amphetamine-Specific Homogeneous Enzyme Immunoassay, including calibrators and controls, is substantially equivalent to OraSure's Amphetamine-Specific Intercept® Micro-plate EIA in its intended use and in for the qualitative determination of amphetamine in human oral fluid.
| DeviceCharacteristics | Subject Device(LZI Oral Fluid Amphetamine-SpecificHomogeneous EIA) | Predicate Device(OraSure Amphetamine-SpecificIntercept® Micro-plate EIA) | DeviceCharacteristics | Predicate Device(K050945) | Predicate Device(K050988) | Predicate Device(K051058) |
|---|---|---|---|---|---|---|
| Intended Use | The Amphetamine-Specific EnzymeImmunoassays for Drugs of Abuse inOral Fluid is a homogeneous enzymeimmunoassay system to detectamphetamine in human saliva with acutoff 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-amphetamine) are prepared with oralfluid buffer so that it can be used toverify and validate the assay. The assayis intended for use in the qualitativedetermination for amphetamine. Theassay is designed for professional usewith a number of automated clinicalchemistry analyzers.The Oral Fluid Amphetamine-SpecificEnzyme 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 Amphetamine-SpecificIntercept® Micro-plate EIA isintended for use by clinicallaboratories in the qualitativedetermination of amphetamine in oralfluid collected with the Intercept®DOA Oral Specimen CollectionDevice using a 100 ng/mL cutoff. ForIn Vitro Diagnostic Use.The OraSure Amphetamine-SpecificIntercept® 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. | 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. |
| Analyte | d-amphetamine | d-amphetamine | 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. | |
| Matrix | Saliva | Saliva | Analyte | Benzoylecgonine | Morphine | Methadone |
| Calibrators/Controls Level | 5 levels including a negative | 4 levels including a negative | Matrix | Saliva | Saliva | Saliva |
| Calibrators/Controls Level | 5 levels including a negative | 5 levels including anegative | 5 levels including anegative |
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The LZI Oral Fluid Amphetamine-Specific 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 (K050945), Opiate (K050988), and Methadone (K051058) Homogeneous Enzyme Immunoassay for its stated intended use.
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Performance Characteristics
LZI Oral Fluid Amphetamine-Specific Assay
| Feature | Oral Fluid Amphetamine-Specific EIA | |||
|---|---|---|---|---|
| Qualitative : (n=120) mA/min | Mean. | SD | % CV | |
| Within Run Precision: | Negative | 250.9 | 1.58 | 0.63% |
| 15 ng/mL | 284.6 | 1.60 | 0.56% | |
| 30 ng/mL | 297.9 | 1.46 | 0.49% | |
| 45 ng/mL | 309.6 | 1.44 | 0.46% | |
| 90 ng/mL | 331.2 | 1.67 | 0.50% | |
| Mean. | SD | % CV | ||
| Total Precision: | Negative | 250.9 | 2.57 | 1.02 % |
| 15 ng/mL | 284.6 | 2.43 | 0.85 % | |
| 30 ng/mL | 297.9 | 2.07 | 0.70 % | |
| 45 ng/mL | 309.6 | 2.15 | 0.70 % | |
| 90 ng/mL | 331.2 | 2.51 | 0.76 % | |
| Accuracy: Clinical patients samples(n=) vs. GC/MS | 97.1 % Agreement | |||
| Specificity: | See attached Assay package insert |
OraSure Amphetamine-Specific Micro-Plate EIA
| Feature | Amphetamine | Mean O.D. | % CV |
|---|---|---|---|
| PrecisionIntra-assayN=64 | 0 ng/mL | 1.905 | 3.9 |
| 50 ng/mL | 1.005 | 3.5 | |
| 100 ng/mL | 0.709 | 4.0 | |
| 150 ng/mL | 0.563 | 4.5 | |
| 200 ng/mL | 0.438 | 6.4 | |
| Inter-assayN=4/day, 20 days | 0 ng/mL | 1.905 | 6.7 |
| 50 ng/mL | 1.005 | 6.7 | |
| 100 ng/mL | 0.709 | 7.5 | |
| 150 ng/mL | 0.563 | 7.7 | |
| 200 ng/mL | 0.438 | 7.9 | |
| Accuracy: Clinical patients sample (n=53)vs. GC/MS | 89 % Agreement | ||
| Specificity | See OraSure product insert |
Summary
The information provided in this pre-market notification demonstrates that the LZI Oral Fluid Amphetamine-Specific 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 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 Amphetamine-Specific Homogeneous EIA is safe and effective for its stated intended use.
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Image /page/5/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle. The eagle is composed of three curved lines that form the shape of the bird's body and wings. The seal is black and white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Marie Lin, Ph.D. President, R&D Director Lin-Zhi International, Inc. 687 North Pastoria Ave Sunnyvale, CA 94085
OCT 3 0 2006
Re: K063024 Trade/Device Name: Oral Fluid Amphetamine-Specific Enzyme Immunoassay, Calibrators and Controls Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ, DLJ, LAS Dated: September 27, 2006
Received: October 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. Iisting 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 Gutierrez
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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Premarket Notification
Indications for Use
510(k) Number (if known): K063024
Device Name: Oral Fluid Amphetamine-Specific Homogeneous Enzyme Immunoassay, Calibrators and Controls.
Indications For Use:
The Amphetamine-Specific Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect amphetamine 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-amphetamine) 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 amphetamine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Oral Fluid Amphetamine-Specific 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)
Page 1 of 1
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
5106(K) k06,3024
11
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).