(136 days)
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the qualitative and semi-quantitative modes of the assay are 100 ng/mL and 300 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GCMS or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between EDDP in the sample and EDDP labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the EDDP concentration in the sample is measured in terms of enzyme activity. In the absence of EDDP in the sample, EDDP-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free EDDP is present in the sample, antibody would bind to free EDDP; the unbound EDDP-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The Ri solution contains mouse monoclonal anti-methadone metabolite antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with methadone metabolite in buffer with sodium azide (0.09 %) as a preservative.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 100 ng/mL cutoff contain 0, 50, 75, 100, 125, 250, 500 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 300 ng/mL cutoff contain 0, 150, 225, 300, 375, 600, and 1000 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.
The provided document is a 510(k) premarket notification for the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and Calibrators. It focuses on demonstrating substantial equivalence to a predicate device, rather than establishing acceptance criteria and proving conformance to them in the same way a de novo or PMA submission might.
Therefore, the acceptance criteria are largely implied by the comparison to the predicate device and the analytical performance data presented. The study aims to show that the new device performs comparably to the predicate and provides accurate results for methadone metabolite detection.
Here's an attempt to extract the requested information based on the provided text, with notable limitations due to the nature of the document:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (100 ng/mL Cutoff) | Consistency in qualitative results (Negative/Positive) at various concentrations, particularly near the cutoff, demonstrating minimal variation within and between runs. For concentrations <75 ng/mL, results should be consistently negative. For concentrations >125 ng/mL, results should be consistently positive. At the 100 ng/mL cutoff, a mix of positive and negative results is expected due to inherent variability, but overall agreement with expected ranges should be demonstrated. | Semi-Quantitative Results:- 0, 25, 50, 75 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 100 ng/mL (Cutoff): Within Run: 11 Neg/11 Pos (50%); Total: 40 Pos/48 Neg (45.5% Pos)- 125, 150, 175, 200 ng/mL: 100% Positive (Within Run N=22, Total N=88)Qualitative Results:- 0, 25, 50, 75 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 100 ng/mL (Cutoff): Within Run: 13 Neg/9 Pos (40.9% Pos); Total: 34 Pos/54 Neg (38.6% Pos)- 125, 150, 175, 200 ng/mL: 100% Positive (Within Run N=22, Total N=88) |
| Precision (300 ng/mL Cutoff) | Consistency in qualitative results (Negative/Positive) at various concentrations, particularly near the cutoff, demonstrating minimal variation within and between runs. For concentrations <225 ng/mL, results should be consistently negative. For concentrations >375 ng/mL, results should be consistently positive. At the 300 ng/mL cutoff, a mix of positive and negative results is expected due to inherent variability, but overall agreement with expected ranges should be demonstrated. | Semi-Quantitative Results:- 0, 75, 150, 225 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 300 ng/mL (Cutoff): Within Run: 6 Neg/16 Pos (72.7% Pos); Total: 52 Pos/36 Neg (59.1% Pos)- 375, 450, 525, 600 ng/mL: 100% Positive (Within Run N=22, Total N=88)Qualitative Results:- 0, 75, 150, 225 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 300 ng/mL (Cutoff): Within Run: 7 Neg/15 Pos (68.2% Pos); Total: 55 Pos/33 Neg (62.5% Pos)- 375, 450, 525, 600 ng/mL: 100% Positive (Within Run N=22, Total N=88) |
| Method Comparison - Clinical Samples (100 ng/mL Cutoff) | High concordance with LC/MS results, especially for samples clearly positive or negative relative to the cutoff. Discrepancies should be understood and ideally minimal, particularly for samples significantly above/below the cutoff. The device should demonstrate appropriate sensitivity and specificity compared to a confirmatory method. | Qualitative/Semi-Quantitative Accuracy Study (N=87):- Agreement for 23 Negative, 11 <50% of cutoff, 9 Near Cutoff Neg, 40 High Pos.- 2 discordant samples: Sample #45 (LC/MS 103.1 ng/mL, EIA Negative); Sample #46 (LC/MS 126.0 ng/mL, EIA Negative). These were "Near Cutoff Pos" by LC/MS but negative by EIA. This indicates the EIA may be less sensitive for results very close to the cutoff, which is acceptable for a screening assay requiring confirmation. |
| Method Comparison - Clinical Samples (300 ng/mL Cutoff) | High concordance with LC/MS results, especially for samples clearly positive or negative relative to the cutoff. Discrepancies should be understood and ideally minimal, particularly for samples significantly above/below the cutoff. The device should demonstrate appropriate sensitivity and specificity compared to a confirmatory method. | Qualitative/Semi-Quantitative Accuracy Study (N=84):- Agreement for 21 Negative, 15 <50% of cutoff, 6 Near Cutoff Neg, 38 High Pos.- 4 discordant samples: These were "Near Cutoff Pos" by LC/MS but positive by EIA (no specific concentrations provided, but implies the EIA correctly identified them as positive, while LC/MS categorized them differently near the cutoff based on the table structure). The table indicates 4 samples were "Near Cutoff Pos" by LC/MS and "Positive" by EIA. No 'Negative' results for these 'Near Cutoff Pos' samples are shown as in the 100ng/mL cutoff. |
| Cross-reactivity | Minimal or no cross-reactivity with structurally related compounds that are not the target analyte, ensuring specificity of the assay. | 100 ng/mL Cutoff:- EDDP: 100% Cross Reactivity- EMDP, Methadone, LAAM HCl, (±)-α-Methadol, (-)-Isomethadone HCl, (-)-α-Noracetylmethadol (Nor-LAAM) HCl: <0.1% or <0.2% Cross Reactivity (i.e., consistently Negative at high spiked concentrations).300 ng/mL Cutoff:- EDDP: 100% Cross Reactivity- EMDP, Methadone, LAAM HCl, (±)-α-Methadol, (-)-Isomethadone HCl, (-)-α-Noracetylmethadol (Nor-LAAM) HCl: <0.1% Cross Reactivity (i.e., consistently Negative at high spiked concentrations). |
| Endogenous Compound Interference & Specific Gravity | No significant undesired interference from common endogenous compounds or variations in specific gravity. | "No significant undesired cross-reactants or endogenous substance interference was observed." |
| Intended Use | The device should be reliably used for qualitative and semi-quantitative determination of Methadone Metabolite in human urine at specified cutoffs (100 ng/mL and 300 ng/mL) on automated clinical chemistry analyzers for prescription use, providing preliminary analytical results requiring confirmatory methods. | The performance data supports the claims for qualitative and semi-quantitative determination at both 100 ng/mL and 300 ng/mL cutoffs, indicating it functions as intended for preliminary screening. |
2. Sample Size Used for the Test Set and Data Provenance
-
Precision Studies:
- For each concentration level tested (e.g., 0, 25, 50, 75, 100, 125, 150, 175, 200 ng/mL for 100 ng/mL cutoff, and similarly for 300 ng/mL cutoff), there were N=22 samples for "Within Run" analysis and N=88 samples for "Total Precision" analysis. This suggests 4 runs (88/22).
- Total number of unique samples for precision is not explicitly stated as distinct samples across all concentrations, but it's at least 9 concentrations x 22 samples for within-run and 9 concentrations x 88 for total precision for each cutoff. These are likely replicates of specific concentrations rather than 88 unique patient samples.
- Data Provenance: Not specified (e.g., country of origin). Likely laboratory-prepared spiked samples for precision. Retrospective or Prospective is not stated but typically spiked samples are prepared for the study.
-
Method Comparison - Clinical Samples:
- 100 ng/mL Cutoff: N=87 clinical unaltered samples.
- 300 ng/mL Cutoff: N=84 clinical unaltered samples.
- Data Provenance: "clinical unaltered samples." Not specified (e.g., country of origin, retrospective or prospective), but implies real patient samples.
-
Cross-reactivity: The sample sizes are implied by the "Spiked []" concentrations for each cross-reactant. Each cross-reactant was tested at a specific concentration. This is generally a set of controlled laboratory-prepared samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Ground Truth Method: The primary ground truth for the clinical sample method comparison and for validating the calibrators/controls is Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS).
- Number/Qualifications of Experts: The document does not specify the number of experts or their qualifications involved in establishing the GC/MS or LC/MS ground truth. This is a common characteristic of device submissions where a recognized "gold standard" analytical method (like GC/MS or LC/MS for drug testing) is used, and the expertise is assumed to be inherent in the execution of that method by a qualified laboratory.
4. Adjudication Method for the Test Set
- The document does not describe an adjudication method involving multiple human readers or a formal adjudication process beyond using GC/MS/LC/MS as the confirmatory method. The presented data primarily compares the EIA results directly to LC/MS results. For the two discordant samples at the 100 ng/mL cutoff, their LC/MS concentrations are noted, but no further "adjudication" is detailed in the text beyond acknowledging the discrepancy.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done as described in the document. This type of study typically assesses human reader performance with and without AI assistance for tasks like image interpretation. This submission is for an in vitro diagnostic (IVD) immunoassay, not an AI-powered diagnostic imaging device.
6. Standalone Performance Study (Algorithm Only)
- Yes, this entire submission is essentially a standalone performance study of the "algorithm" (the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay). The performance characteristics (precision, method comparison, cross-reactivity) demonstrate the device's analytical performance without human intervention in the interpretation of the raw assay signal, as it's designed for automated clinical chemistry analyzers. The "EIA Result" is the output of the device itself.
7. Type of Ground Truth Used
- The primary ground truth used is confirmatory analytical chemistry methods, specifically Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These are considered highly accurate and specific "gold standards" for drug quantification.
8. Sample Size for the Training Set
- The document does not explicitly describe a "training set" in the context of an AI/machine learning model. This is an IVD device, where performance is established through analytical validation studies (precision, accuracy, interference, cross-reactivity) using predefined reagents and methods. The device's "algorithm" is the enzymatic reaction and spectrophotometric measurement, which is inherently deterministic, not a learned model in the AI sense.
- The calibrators are used for the calibration of the assay (0, 50, 100, 250, 500 ng/mL for 100 ng/mL cutoff; 0, 150, 300, 600, 1000 ng/mL for 300 ng/mL cutoff), which is analogous to "setting up" the device for accurate measurement.
9. How the Ground Truth for the Training Set Was Established
- As there is no "training set" in the AI/ML context, this question is not directly applicable. For the calibrators, their concentrations are precisely defined (e.g., 100 ng/mL or 300 ng/mL of methadone metabolite (EDDP)). These are manufactured with known concentrations in a human urine matrix. The "ground truth" for calibrators is therefore their known, manufactured concentration.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 26, 2017
LIN-ZHI INTERNATIONAL, INC. BERNICE LIN VP OPERATIONS 2945 OAKMEAD VILLAGE COURT SANTA CLARA CA 95051
Re: K170416
Trade/Device Name: LZI Methadone Metabolite (EDDP) Enzyme Immunoassay, LZI Methadone Metabolite (EDDP) (100 And 300) Calibrators Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: II Product Code: DJR, DJR, DLJ Dated: May 24, 2017 Received: May 25, 2017
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K170416
Device Name
LZI Methadone Metabolite (EDDP) Enzyme Immunoassay The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators
Indications for Use (Describe)
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the and semi-quantitative modes of the assay are 100 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternistry method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semiquantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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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.
Submitted On
February 9, 2017
Last Updated On
June 26, 2017
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. 2945 Oakmead Village Court Santa Clara, CA 95051 Phone: (408) 970-8811 (408) 970-9030 Fax: e-mail: bclin@lin-zhi.com
Bernice Lin, Ph.D. Contact: VP Operations
Device Name and Classification
| Classification Name: | Enzyme Immunoassay, Methadone MetaboliteClass II, DJR (91 Toxicology),21 CFR 862.3620 | |
|---|---|---|
| Drug Specific Calibrators,Class II, DLJ (91 Toxicology),21 CFR 862.3200 | ||
| Common Name:Proprietary Name: | Homogeneous Methadone Metabolite Enzyme ImmunoassayLZI Methadone Metabolite (EDDP) Enzyme Immunoassay,LZI Methadone Metabolite (EDDP) (100 and 300) Calibrator |
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Legally Marketed Predicate Device(s)
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay (EIA) is substantially equivalent to the Lin-Zhi International, Inc. Methadone Metabolite (EDDP) Enzyme Immunoassay (K031797) manufactured by Lin-Zhi International, Inc. The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.
Device Description
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between EDDP in the sample and EDDP labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the EDDP concentration in the sample is measured in terms of enzyme activity. In the absence of EDDP in the sample, EDDP-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free EDDP is present in the sample, antibody would bind to free EDDP; the unbound EDDP-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The Ri solution contains mouse monoclonal anti-methadone metabolite antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with methadone metabolite in buffer with sodium azide (0.09 %) as a preservative.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 100 ng/mL cutoff contain 0, 50, 75, 100, 125, 250, 500 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 300 ng/mL cutoff contain 0, 150, 225, 300, 375, 600, and 1000 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.
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Intended Use
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the qualitative and semi-quantitative modes of the assay are 100 ng/mL and 300 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GCMS or (2) permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL.
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Comparison to Predicate Device
The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is substantially equivalent to the Lin-Zhi International, Inc. Methadone Metabolite Enzyme Immunoassay, Calibrators and Controls cleared by the FDA under the premarket notification K031797 for its stated intended use.
The following table compares LZI's Methadone Metabolite (EDDP) Enzyme Immunoassay with the predicate device.
| DeviceCharacteristics | Subject Device (K170416)LZI Methadone Metabolite (EDDP)Enzyme Immunoassay and MethadoneMetabolite (EDDP) (100 and 300)Calibrators | Predicate Device (K031797)LZI Methadone Metabolite (EDDP)Enzyme Immunoassay, Calibrators andControls |
|---|---|---|
| Intended Use | The LZI Methadone Metabolite (EDDP)Enzyme Immunoassay is an in vitrodiagnostic test intended for the qualitativeand semi-quantitative determination ofMethadone Metabolite in human urine.The cutoff for the qualitative and semi-quantitative modes of the assay are 100ng/mL and 300 ng/mL for methadonemetabolite. The assay is designed forprescription use on automated clinicalchemistry analyzers.The assay provides only a preliminary analytical | The Lin-Zhi International, Inc. (LZI)Methadone Metabolite (EDDP) EnzymeImmunoassay is intended for thequalitative and semi-quantitativedetermination of methadone metabolite inhuman urine at a cutoff value of 300ng/mL. The assay is designed forprofessional use with a number ofautomated clinical chemistry analyzers.This assay provides a rapid screening procedurefor determining the presence of methadonemetabolite in urine. The assay provides only a |
| result. A more specific alternative analyticalchemistry method must be used in order to obtain aconfirmed analytical result. Gas or liquidchromatography/mass spectrometry (GC/MS orLC/MS) is the preferred confirmatory method.Clinical consideration and professional judgmentshould be exercised with any drug of abuse testresult, particularly when the preliminary test resultis positive. | preliminary analytical result. A more specificalternative chemical method must be used in orderto obtain a confirmed analytical result. Gas orliquid chromatography/mass spectrometry (GC/MSor LC/MS) is the preferred confirmatory method.Clinical consideration and professional judgmentshould be exercised with any drug of abuse testresult, particularly when the preliminary test resultis positive. | |
| Analyte | Methadone Metabolite (EDDP) | Methadone Metabolite (EDDP) |
| Cutoff | 100 and 300 ng/ml | 300 ng/mL |
| Matrix | Urine | Urine |
| CalibratorsLevel | 100 ng/mL Cutoff: 5 Levels0, 50, 100, 250, and 500 ng/mL300 ng/mL Cutoff: 5 Levels0, 150, 300, 600, and 1000 ng/mL | 0, 150, 300, 600, and 1000 ng/mL |
| Storage | 2-8°C until expiration date | 2-8°C until expiration date |
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Performance Characteristics Summary:
Beckman Coulter AU480 Analyzer
Precision: 100 ng/mL Cutoff
Semi-Quantitative Precision Analysis Summary: Qualitative Results
| MethadoneMetabolite(EDDP)Concentration | Within Run(N=22) | Total Precision(N=88) |
|---|---|---|
| 0 ng/mL | - | - |
| 25 ng/mL | - | - |
| 50 ng/mL | - | - |
| 75 ng/mL | - | - |
| 100 ng/mL | - | - |
| 125 ng/mL | + | + |
| 150 ng/mL | + | + |
| 175 ng/mL | + | + |
| 200 ng/mL | + | + |
Semi-Quantitative Positive/Negative Results:
| 100 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| MethadoneMetabolite(EDDP)Concentration | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result |
| 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100.0 % | 22 | 11 Neg/11 Pos | 88 | 40 Pos/48 Neg |
| 125 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive |
Qualitative Positive/Negative Results:
| 100 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| MethadoneMetabolite(EDDP)Concentration | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result |
| 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100.0 % | 22 | 13 Neg/ 9 Pos | 88 | 54 Neg/34 Pos |
| 125 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive |
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Performance Characteristics Summary, continued: Beckman Coulter AU480 Analyzer
Precision: 300 ng/mL Cutoff
Semi-Quantitative Precision Analysis Summary: Qualitative Results
| MethadoneMetabolite(EDDP)Concentration | Within Run(N=22) | Total Precision(N=88) |
|---|---|---|
| 0 ng/mL | - | - |
| 75 ng/mL | - | - |
| 150 ng/mL | - | - |
| 225 ng/mL | - | - |
| 300 ng/mL | + | + |
| 375 ng/mL | + | + |
| 450 ng/mL | + | + |
| 525 ng/mL | + | + |
| 600 ng/mL | + | + |
Semi-Quantitative Positive/Negative Results:
| 300 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| MethadoneMetabolite(EDDP)Concentration | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result |
| 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0 % | 22 | 6 Neg/ 16 Pos | 88 | 36 Neg/ 52 Pos |
| 375 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive |
Qualitative Positive/Negative Results:
| 300 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| MethadoneMetabolite(EDDP) | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result |
| Concentration | |||||
| 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0 % | 22 | 7 Neg/15 Pos | 88 | 33 Neg/55 Pos |
| 375 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive |
{9}------------------------------------------------
Performance Characteristics Summary, continued: Beckman Coulter AU480 Analyzer
Method Comparison - Clinical Samples: 100 ng/mL Cutoff
From a total of eighty-seven (87) clinical unaltered samples, Semi-Quantitative & Qualitative Data:
| 100 ng/mLCutoff | Neg | < 50 % ofthe cutoff | NearCutoffNeg | NearCutoffPos | HighPos |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 2 | 40 |
| Negative | 23 | 11 | 9 | 2* | 0 |
Qualitative Accuracy Study:
The following table summarizes the result for the two discordant samples:
| 100 ng/mLCutoff | Assay Result: | LC/MS (ng/mL) | |
|---|---|---|---|
| LC/MS | LZI EIA | ||
| Sample #45 | + | - | 103.1 |
| Sample #46 | + | - | 126.0 |
Concentration for the discrepant samples are based on the absorbance rate from a single point calibration.
Semi-Quantitative Accuracy Study:
| 100 ng/mLCutoff | Neg | < 50 % ofthe cutoff | NearCutoffNeg | NearCutoffPos | HighPos |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 2 | 40 |
| Negative | 23 | 11 | 9 | 2* | 0 |
The following table summarizes the result for the two discordant samples:
| 100 ng/mLCutoff | Assay Result: | LC/MS (ng/mL) | |
|---|---|---|---|
| LC/MS | LZI EIA | ||
| Sample #45 | + | - | 103.1 |
| Sample #46 | + | - | 126.0 |
{10}------------------------------------------------
Method Comparison - Clinical Samples: 300 ng/mL Cutoff
From a total of eighty-four (84) clinical unaltered samples, Semi-Quantitative & Qualitative Qualitative Accuracy Study:
| 300 ng/mLCutoff | Neg | < 50 % ofthe cutoff | NearCutoffNeg | NearCutoffPos | HighPos |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 4 | 38 |
| Negative | 21 | 15 | 6 | 0 | 0 |
Semi-Quantitative Accuracy Study:
| 300 ng/mLCutoff | Neg | < 50 % ofthe cutoff | NearCutoffNeg | NearCutoffPos | HighPos |
|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 4 | 38 |
| Negative | 21 | 15 | 6 | 0 | 0 |
Cross-reactivity: 100 ng/mL Cutoff
Methadone Metabolite and Structurally Related Compounds for 100 ng/mL Cutoff:
| Cross-reactant | Spiked [](ng/mL) | EIA [](ng/mL) | % CrossReactivity |
|---|---|---|---|
| EDDP | 100 | Pos | 100 % |
| EMDP | 100,000 | Neg | <0.1 % |
| Methadone | 300,000 | Neg | <0.1 % |
| LAAM HCl | 500,000 | Neg | <0.1 % |
| (±)-α-Methadol | 300,000 | Neg | <0.1 % |
| (-)-Isomethadone HCl | 60,000 | Neg | <0.2 % |
| (-)-α-Noracetylmethadol(Nor-LAAM) HCl | 300,000 | Neg | <0.1 % |
Cross-reactivity: 300 ng/mL Cutoff
Methadone Metabolite and Structurally Related Compounds for 100 ng/mL Cutoff:
{11}------------------------------------------------
Endogenous Compound Interference & Specific Gravity:
No significant undesired cross-reactants or endogenous substance interference was observed.
Performance Characteristics Summary, continued:
Beckman Coulter AU480 Analyzer
Summary:
The information provided in this pre-market notification demonstrates that the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are substantially equivalent to the legally marketed predicate device for its general intended use. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by chromatography/mass spectrometry (LC/MS), an independent analytical chemistry method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are safe and effective for its stated intended use.
§ 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).