← Product Code [DJR](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJR) · K031797 # METHADONE METABOLITE (EDDP) ENZIME IMMUNOASSAY, CAT. NO. 190 (500 TEST KIT), NO. 191 (5000 TEST KIT) (K031797) _Lin-Zhi International, Inc. · DJR · Oct 10, 2003 · Clinical Toxicology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJR/K031797 ## Device Facts - **Applicant:** Lin-Zhi International, Inc. - **Product Code:** [DJR](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJR.md) - **Decision Date:** Oct 10, 2003 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 862.3620 - **Device Class:** Class 2 - **Review Panel:** Clinical Toxicology ## Indications for Use The Methadone Metabolite Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 300 ng/ml cutoff. The assay is intended for use in the qualitative and semi-quantitative analyses of methadone metabolite in human urine. The assay is designed for professional use with automated clinical chemistry analyzers. ## Device Story Ready-to-use liquid reagent homogeneous enzyme immunoassay; detects Methadone Metabolite (EDDP) in human urine. Principle: competition between G6PDH-labeled Methadone Metabolite and free drug in urine for fixed antibody; absence of free drug allows antibody binding to labeled drug, decreasing enzyme activity. Enzyme activity measured spectrophotometrically at 340 nm via NAD to NADH conversion. Used in clinical laboratories with automated chemistry analyzers; operated by laboratory technicians/professionals. Provides preliminary analytical results; requires GC/MS confirmation. Assists clinicians in drug-of-abuse screening; supports clinical decision-making regarding patient drug status. ## Clinical Evidence Bench testing only. Performance evaluated on Hitachi 717 analyzer. Precision studies (within-run and 3-week reproducibility) showed %CVs < 5%. Linearity/recovery evaluated across 30-900 ng/ml range. Analytical sensitivity (LOD) is 15 ng/ml. Method comparison against GC/MS using 139 clinical specimens showed 100% agreement (48/48 positive, 91/91 negative). Accuracy near cutoff confirmed with 20 clinical specimens. ## Technological Characteristics Homogeneous enzyme immunoassay; liquid reagent. Sensing principle: spectrophotometric measurement of G6PDH enzyme activity at 340 nm. Cutoff: 300 ng/mL. Designed for use on automated clinical chemistry analyzers. No specific materials or connectivity standards listed. ## Regulatory 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. ## Special Controls *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). ## Predicate Devices - Methadone Metabolite Enzyme Immunoassay ([K931780](/device/K931780.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY DEVICE ONLY TEMPLATE A. 510(k) Number: K031797 B. Analyte: methadone C. Type of Test: qualitative and semi-quantitative homogeneous enzyme immunoassay D. Applicant: Lin-Zhi International Inc E. Proprietary and Established Names: Methadone Metabolite Enzyme Immunoassay F. Regulatory Information: 1. Regulation section: 21CFR862.3620, Methadone Test System. 2. Classification: Class II 3. Product Code: DJR 4. Panel: Toxicology (91) G. Intended Use: 1. Indication(s) for use: The Methadone Metabolite Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 300 ng/ml cutoff. The assay is intended for use in the qualitative and semi-quantitative analyses of methadone metabolite in human urine. The assay is designed for professional use with automated clinical chemistry analyzers. 2. Special condition for use statement(s): The assay 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 is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are used. For prescription use. 3. Special instrument Requirements: The device is designed for use on automated clinical chemistry analyzers. H. Device Description: The device consists of an antibody/substrate reagent and an enzyme-drug conjugate reagent containing all components of the immunoassay. {1} Page 2 of 5 # I. Substantial Equivalence Information: 1. Predicate device name(s): DRI Microgenics Methadone Metabolite Enzyme Immunoassay. 2. Predicate K number(s): K931780 3. Comparison with predicate: Operating principle and reagent composition are similar to the predicate device. The cutoff concentration for this device (300 ng/ml) is lower than that of the predicate device (1000 ng/ml). # J. Standard/Guidance Document Referenced (if applicable): K. Test Principle: The test is a homogeneous enzyme immunoassay for use on automated clinical chemistry analyzers. # L. Performance Characteristics (if/when applicable): Performance was evaluated on the Hitachi 717 analyzer. 1. Analytical performance: a. Precision/Reproducibility: Qualitative assay: Precision within one run was evaluated by assaying 21 replicates each of calibrators and control material at the concentrations indicated below, during one run. The mean and standard deviation of the 21 replicates are shown below: | concentrations (ng/ml) | 225 | 300 | 375 | 1000 | | | --- | --- | --- | --- | --- | --- | | average reading (mA/min) | | 354.0 | 374.9 | 390.9 | 449.4 | | standard deviation (mA/min) | 2.4 | 2.7 | 3.0 | 3.4 | | | %cv | | 0.7 | 0.7 | 0.8 | 0.8 | Precision was evaluated using calibrator and control material for 12 runs over a 3 week period. The mean and standard deviations over all readings are shown below: | concentrations (ng/ml) | 225 | 300 | 375 | 1000 | | | --- | --- | --- | --- | --- | --- | | average reading (mA/min) | | 357.3 | 377.2 | 390.6 | 452.5 | | standard deviation (mA/min) | 2.9 | 1.8 | 2.5 | 4.2 | | | %cv | | 0.8 | 0.5 | 0.6 | 0.9 | Semi-Quantitative Assay: Using 5 calibrators as reference, precision within one run was determined by assaying 21 replicates each of calibrators and control material at the concentrations indicated below, during one run. The mean and standard deviation of the 21 replicates are shown below: | concentrations (ng/ml) | 225 | 300 | 375 | | | --- | --- | --- | --- | --- | | average reading (ng/ml) | 227.9 | 304.9 | 382.8 | | | standard deviation (ng/ml) | | 8.8 | 13.7 | 13.0 | | %cv | | 3.9 | 4.5 | 3.4 | {2} Page 3 of 5 Using 5 calibrators as reference, precision was evaluated for 12 runs over a 3 week period. The mean and standard deviations over all readings are shown below: | concentrations (ng/ml) | 225 | 300 | 375 | | --- | --- | --- | --- | | average reading (ng/ml) | 227.2 | 298.4 | 371.1 | | standard deviation (ng/ml) | | 8.2 | 10.8 | | %cv | | 3.6 | 3.6 | b. Linearity/assay reportable range Semiquantitation of positive results enables the laboratory to determine an appropriate dilution of the specimen for confirmation by GC/MS. The semiquantitative mode also permits the laboratory to establish quality control procedures and assess control performance. Percent recovery was evaluated using spiked negative urine samples (5 replicates per level) between the range of 30-900. Average % recoveries for each level and standard deviations are shown below: | Target concentration | Measured concentration | % recovery | STDEV | %CV | | --- | --- | --- | --- | --- | | 30 | 33 | 109 | 3.0 | 9.2 | | 60 | 61 | 102 | 5.7 | 9.3 | | 120 | 124 | 104 | 6.7 | 5.4 | | 180 | 172 | 95 | 15.5 | 9.1 | | 225 | 214 | 95 | 16.1 | 7.5 | | 375 | 395 | 105 | 12.7 | 3.2 | | 400 | 477 | 95 | 6.2 | 1.3 | | 600 | 569 | 95 | 15.1 | 3.7 | | 750 | 699 | 93 | 38.8 | 5.5 | | 900 | 863 | 96 | 35.0 | 4.3 | c. Traceability (controls, calibrators, or method): Calibrators are prepared as spiked methadone metabolite in a processed drug-free human urine matrix. Value assignments for calibrator and control lots are based on dilutions of known stock solutions and are confirmed by GCMS (to target concentrations of 0, 150, 300, 600 and 1000 ng/ml). Observed recoveries ranged from 96-103%. The material used to prepare the solutions is a commercial material, reported to be traceable to NIST standards. Calibrators stability was evaluated at room temperature and 2-8 degrees C over 10 months. The recoveries in terms of absolute reading (mA/min) were greater than 97% over this time. The ratios of recoveries for the room temperature calibrators relative to the cold calibrators were greater than 99% over this time. {3} Page 4 of 5 d. Detection limit: Sensitivity was determined by evaluating ten replicates of zero calibrators and serial dilutions of calibrators of low concentration. A concentration of 15 ng/ml can be differentiated from negative urine with 95% confidence. e. Analytical specificity: Test compounds were spiked into the drug-free urine calibrator matrix to various concentrations and evaluated against the cutoff calibrator. The following results were obtained for potential cross-reacting compounds. Values represent concentration of each test compound giving a response approximately equal to the cutoff calibrator (for positives) or the highest concentration tested (for negatives). EDDP positive at 300 ng/ml Methadone positive at 200 ug/ml EMDP positive at 550 ug/ml (-) alpha-Methadol positive at 60 ug/ml LAAM negative at 100 ug/ml nor-LAAM negative at 10 ug/ml A variety of over-the-counter and prescription drugs were tested for interference by spiking into negative urine. The drugs and levels in the samples tested are listed in the package insert. These compounds are listed in the package insert. No unusual interference was observed. f. Assay cut-off: The assay cutoff is 300 ng/ml 2. Comparison studies: a. Method comparison with predicate device: Comparison to GCMS was evaluated at the manufacturer's site for 139 randomly selected banked clinical urine specimens, previously analyzed by GCMS. Sample concentrations ranged up to 22,000 ng/ml included two positive near-cutoff samples). Reported results were similar for the qualitative and semi-quantitative modes. Results are shown below: Method Comparison Tables 300 ng/ml cutoff, qualitative GCMS | + | - | | --- | --- | | 48 | 0 | | 0 | 91 | To evaluate accuracy around the cutoff concentration, 20 positive clinical specimens that were diluted to near cutoff concentrations were tested by {4} Page 5 of 5 GCMS and the Lin-Zhi Methadone Metabolite Assay. Sample concentrations ranged between 125-1360 g/ml and included 11 samples within +/- 25% of the cutoff). Results, which were similar for the qualitative and semi-quantitative mode are shown below. 300 ng/ml cutoff, qualitative mode, near cutoff samples: GCMS | + | - | | --- | --- | | + | | | Lin-Zhi | | | Methadone | | | metabolite | | | - | | b. Matrix comparison: Not applicable. The device is indicated only for urine specimens. 3. Clinical studies: a. Clinical sensitivity: Not applicable. Clinical studies are not typically submitted for this device type. b. Clinical specificity: Not applicable. Clinical studies are not typically submitted for this device type. c. Other clinical supportive data (when a and b are not applicable): 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: Not applicable M. Conclusion: I recommend that the Lin-Zhi Methadone Metabolite Enzyme Immunoassay is substantially equivalent to the predicate device. --- **Source:** [https://fda.innolitics.com/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJR/K031797](https://fda.innolitics.com/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DJR/K031797) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. 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