(337 days)
The Methadone Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methadone in human saliva with a cutoff of 30 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 (Methadone) 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 Methadone drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Methadone 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.
LZI's Oral Fluid Methadone Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect methadone 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 the study details for the LZI Methadone Oral Fluid Homogeneous Enzyme Immunoassay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Criteria | Acceptance Value (LZI Methadone Oral Fluid Homogeneous EIA) | Reported Performance (LZI Methadone Oral Fluid Homogeneous EIA) |
|---|---|---|
| Accuracy (Agreement vs. GC/MS) | Not explicitly stated as an "acceptance criteria" but implied to be high agreement. | 99.2% Agreement (Clinical patient samples, n=119) |
| Precision | Not explicitly stated as numerical acceptance criteria, but implied to be low %CV. | Within Run Precision (%CV): - Negative: 0.58% - 10 ng/mL: 0.56% - 20 ng/mL: 0.62% - 30 ng/mL: 0.57% - 50 ng/mL: 0.54% Total Precision (%CV): - Negative: 0.70% - 10 ng/mL: 0.78% - 20 ng/mL: 0.70% - 30 ng/mL: 0.68% - 50 ng/mL: 0.61% |
| Cutoff | 30 ng/mL (for qualitative detection) | Device designed to detect at this cutoff. |
| Intended Use | Qualitative determination of methadone in human saliva. | Meets this intended use. |
| Specimen Collection | Oral fluid collected with Salivette collector and diluted with 1 mL of buffer. | Designed for use with this collection method. |
| Confirmatory Method | A more specific alternative chemical method (GC/MS preferred) must be used for confirmation. | Device provides preliminary results; GC/MS is preferred confirmatory method. |
| Specificity | Not explicitly stated, but implied to have minimal cross-reactivity. | "See attached Assay package insert" (not detailed in this document) |
2. Sample Size Used for the Test Set and Data Provenance
- Accuracy Test Set: n=119 clinical patient samples.
- Precision Test Set: n=120 for qualitative (mA/min) and used to calculate precision (%CV).
- Data Provenance: The document does not explicitly state the country of origin. It refers to "Clinical patients samples" without specifying if they are retrospective or prospective. Given the context of a 510(k) submission for an in vitro diagnostic, these are typically clinical samples collected and tested for validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Not Applicable. This device is an in vitro diagnostic (immunoassay) for drug detection. The ground truth is established by a more definitive laboratory method, not by human expert opinion or interpretation of images.
4. Adjudication Method for the Test Set
- Not Applicable. Adjudication methods like 2+1 or 3+1 are typically used for studies where human readers interpret data (e.g., medical images) and their agreement is critical. For this immunoassay, comparison is made against a definitive analytical method (GC/MS).
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
- Not Applicable. This is an automated immunoassay for detecting methadone in oral fluid. It does not involve human readers interpreting data or AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, effectively. The "LZI Methadone Oral Fluid Homogeneous Enzyme Immunoassay" is an automated, standalone assay. Its performance is evaluated independently against a reference method (GC/MS) without human intervention in the interpretation of the initial assay result. The assay provides a "preliminary analytical test result" on its own.
7. The Type of Ground Truth Used
- Confirmatory Analytical Method: Gas Chromatography/Mass Spectrometry (GC/MS). The document explicitly states: "Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method." and "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."
8. The Sample Size for the Training Set
- The document describes the validation of the device but does not specify a "training set" or its size. Immunoassays are developed through iterative refinement and validation, but the concept of a distinct 'training set' in the machine learning sense is not typically applied or documented in this type of 510(k) submission. The data provided are for performance evaluation.
9. How the Ground Truth for the Training Set was Established
- Not Applicable. As no specific "training set" is mentioned in the context of machine learning, the establishment of its ground truth is not detailed. For the overall development of an immunoassay, the "ground truth" (i.e., accurate concentrations of methadone) would be established using validated reference materials and analytical methods (like GC/MS) during the assay's development and optimization phases.
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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 Methadone test system has been placed in Class II bythe Bureau of Medical Devices.Classification Number: DJR (21 CFR 862.3620)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: | Methadone Oral Fluid Homogeneous EnzymeImmunoassays |
| Proprietary Name: | None |
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Predicate Device(s)
The LZI Methadone Oral Fluid Enzyme Immunoassay is substantially equivalent to the Methadones Intercept® Micro-plate EIA (K002010) manufactured by OraSure Technologies Inc. (formerly known as STC Technologies, Inc) for its general intended use.
Device Description
LZI's Oral Fluid Methadone Enzyme Immunoassay is a ready-to-use, liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect methadone 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 Methadone Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methadone in human saliva with a cutoff of 30 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 (Methadone) 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 Methadone drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Methadone 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-ofabuse test result, particularly when preliminary positive results are used.
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Comparison to Predicate Device
The LZI Methadone Oral Fluid Homogeneous Enzyme Immunoassay, including calibrators and controls, is substantially equivalent to OraSure's Methadone Intercept® Micro-plate EIA in its intended use and in for the qualitative determination of Methadone in human oral fluid.
| DeviceCharacteristics | Subject Device(LZI Methadone Oral FluidHomogeneous EIA) | Predicate Device(OraSure Methadone Intercept®Micro-plate EIA) |
|---|---|---|
| Intended Use | The LZI Methadone Oral FluidHomogeneous EIA is a homogeneousenzyme immunoassay system to detectmethadone in human saliva with acutoff of 30 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(Methadone) 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 Methadone drugs.The Methadone 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. | The OraSure Methadone Intercept®Micro-plate EIA is intended for use byclinical laboratories in the qualitativedetermination of methadone in oralfluid collected with Intercept® DOAOral Specimen Collection Deviceusing a 5.0 ng/mL cutoff. For In VitroDiagnostic Use.The OraSure Methadone Intercept®Micro-plate EIA provides only apreliminary analytical test result. Amore specific alternative chemicalmethod should be used in order toobtain a confirmed analytical 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 | Methadone | Methadone |
| Matrix | Saliva | Saliva |
| Calibrators/Controls Level | 5 levels including a negative | 4 levels including a negative |
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LZI Methadone Oral Fluid Assay
| Feature | Oral Fluid Methadone EIA | |||
|---|---|---|---|---|
| Qualitative : (n=120) mA/min | Mean. | SD | % CV | |
| Within Run Precision: | Negative | 328.4 | 1.90 | 0.58% |
| 10 ng/mL | 347.4 | 1.96 | 0.56% | |
| 20 ng/mL | 368.3 | 2.30 | 0.62% | |
| 30 ng/mL | 390.0 | 2.21 | 0.57% | |
| 50 ng/mL | 433.4 | 2.33 | 0.54% | |
| Mean. | SD | % CV | ||
| Total Precision: | Negative | 328.4 | 2.30 | |
| 10 ng/mL | 347.4 | 2.72 | 0.70% | |
| 0.78% | ||||
| 20 ng/mL | 368.3 | 2.58 | 0.70% | |
| 30 ng/mL | 390.0 | 2.66 | 0.68% | |
| 50 ng/mL | 433.4 | 2.65 | 0.61% | |
| Accuracy: Clinical patients samples(n=119) vs. GC/MS | 99.2 % Agreement | |||
| Specificity: | See attached Assay package insert |
OraSure Methadone Micro=Plate EIA
| Feature | |||
|---|---|---|---|
| Precision | Methadone | % CV | Mean OD. |
| Intra-assayN=64 | 0 ng/mL | 6.3 | 1.932 |
| 2.5 ng/mL | 6.6 | 0.687 | |
| 5.0 ng/mL | 6.7 | 0.507 | |
| 7.5 ng/mL | 6.8 | 0.426 | |
| Inter-assayN=4/day, 20 days | 0 ng/mL | 9.9 | 1.932 |
| 2.5 ng/mL | 12.3 | 0.687 | |
| 5.0 ng/mL | 12.9 | 0.507 | |
| 7.5 ng/mL | 13.6 | 0.426 | |
| Accuracy: Clinical patients sample(n=102) vs. GC/MS | 97.1 % Agreement | ||
| Specificity | See OraSure product insert |
Summary
The information provided in this pre-market notification demonstrates that the LZI Oral Fluid Methadone 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 Methadone Homogeneous EIA is safe and effective for its stated intended use.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image shows a circular logo with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with a more abstract and modern design. The logo is black and white, with the text and symbol in black against a white background.
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: K051058
Trade/Device Name: Oral Fluid Methadone Homogeneous Enzyme Immunoassay, Calibrator and Controls Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: Class II Product Code: DJR, DLJ, LAS Dated: March 08, 2006 Received: March 13, 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 af 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 practic t 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 Guti
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): K051058
Device Name: Oral Fluid Methadone Homogeneous Enzyme Immunoassay, Calibrators and Controls.
Indications For Use:
The Methadone Enzyme Immunoassays for Drugs of Abuse in Oral Fluid is a homogeneous enzyme immunoassay system to detect methadone in human saliva with a cutoff of 30 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 (Methadone) 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 Methadone drugs. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Methadone 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.
Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
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Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
05/057-CFC
"" " " Vitro Diagnostic Device 11 200 Na
§ 862.3620 Methadone test system.
(a)
Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.(b)
Classification. Class II (special controls). A methadone 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).