(70 days)
The Methadone Enzyme Immunoassav 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 in human urine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Methadone Enzyme Immunoassay 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 confirmatorv method. Clinical consideration and professional judgement should be applied to any drug-ofabuse test result, particularly when preliminary positive results are used.
LZI's Methadone Enzyme Immunoassav is a ready-to-use. liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibody that can detect methadone in human urine with minimal cross-reactivity to various, common prescription drugs and abused drugs.
The assay is based on competition between methadone labeled with glucose-6-phosphate dehydrogenase (G6PDH) enzyme and free drug from the urine sample for a fixed amount of specific antibody. In the absence of free drug from the urine sample the specific antibody binds to the drug labeled with G6PDH enzyme causing a decrease in enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to covert nicotinamide adenine dinucleotide (NAD) to NADH.
The provided text describes the Lin-Zhi International, Inc. Methadone Enzyme Immunoassay, a device for detecting methadone in human urine. Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
| Feature | Acceptance Criteria (Implied by Predicate) / Target | Reported Device Performance (LZI Methadone EIA) |
|---|---|---|
| Within Run Precision: | - Low %CV for qualitative results | Qualitative: |
| Negative | (Predicate: SD 1.0, %CV 0.8) | Mean Rate: 209.4, SD: 1.0, %CV: 0.49 |
| 225 ng/mL | (Predicate: 300 ng/mL, SD 1.6, %CV 0.7) | Mean Rate: 272.8, SD: 1.1, %CV: 0.39 |
| 300 ng/mL | (Predicate: 1000 ng/mL, SD 1.5, %CV 0.5) | Mean Rate: 293.4, SD: 0.7, %CV: 0.25 |
| 375 ng/mL | (No direct predicate comparison) | Mean Rate: 308.2, SD: 0.9, %CV: 0.29 |
| 1000 ng/mL | (No direct predicate comparison) | Mean Rate: 344.9, SD: 1.1, %CV: 0.33 |
| Semi-quantitative: | (Predicate: No data available) | Mean Conc. at 225 ng/mL: 229.2, SD: 2.5, %CV: 1.09 |
| Mean Conc. at 300 ng/mL: 308.5, SD: 3.5, %CV: 1.13 | ||
| Mean Conc. at 375 ng/mL: 391.4, SD: 5.4, %CV: 1.37 | ||
| Run-To-Run Precision: | - Low %CV for qualitative results | Qualitative: |
| Negative | (Predicate: No data available) | Mean Rate: 209.5, SD: 1.1, %CV: 0.51 |
| 225 ng/mL | (Predicate: No data available) | Mean Rate: 271.4, SD: 2.0, %CV: 0.74 |
| 300 ng/mL | (Predicate: No data available) | Mean Rate: 292.3, SD: 1.9, %CV: 0.66 |
| 375 ng/mL | (Predicate: No data available) | Mean Rate: 307.2, SD: 2.6, %CV: 0.84 |
| 1000 ng/mL | (Predicate: No data available) | Mean Rate: 344.1, SD: 2.0, %CV: 0.58 |
| Semi-quantitative: | (Predicate: No data available) | Mean Conc. at 225 ng/mL: 228.0, SD: 7.8, %CV: 3.42 |
| Mean Conc. at 300 ng/mL: 305.1, SD: 10.2, %CV: 3.36 | ||
| Mean Conc. at 375 ng/mL: 379.6, SD: 13.2, %CV: 3.47 | ||
| Sensitivity: | Predicate: 10 ng/mL | 15 ng/mL |
| Accuracy: | Predicate: Vs. a commercial EIA, 100% agreement | Vs. GC/MS: 100% agreement for Positive Samples, 100% agreement for Negative Samples |
| Analytical Recovery: | Predicate: No data available | Qualitative: 100% accuracy on positive vs. negative tests. |
| Semi-quantitative: Quantitates within ±15% of the nominal concentration between 30 ng/mL and 750 ng/mL. | ||
| Average 96.6% recovery at 225 ng/mL level (Cutoff -25%). | ||
| Average 93.7% recovery at 375 ng/mL level (Cutoff + 25%). | ||
| Specificity: | Predicate: See attached DRI's Methadone EIA package | Comparable to the predicate device. |
Note on Acceptance Criteria: The document primarily demonstrates substantial equivalence to the predicate device (Methadone Enzyme Immunoassay by DRI/Microgenics Corp., K972526). Therefore, the "acceptance criteria" are generally implied to be comparable performance to the predicate. Where the predicate had "No data available," the new device presents its own performance which is implicitly considered "acceptable" for the purposes of substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size used for the test set for precision studies. For accuracy, it states "100% agreement" for positive and negative samples against GC/MS, but the number of samples is not provided. The data provenance is also not specified (e.g., country of origin, retrospective/prospective). It is implied that these are laboratory studies since the product is an in-vitro diagnostic.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
Not applicable. This device is an immunoassay for methadone levels. The primary "ground truth" method cited for accuracy is GC/MS (Gas Chromatography/Mass Spectrometry), which is an analytical chemical method, not reliant on human expert adjudication in the same way imaging or clinical diagnosis might be.
4. Adjudication Method for the Test Set
Not applicable in the conventional sense. The "ground truth" for reported accuracy is comparison against GC/MS.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, this is not an MRMC study. This device is an in vitro diagnostic assay, not an imaging or interpretive diagnostic system requiring human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented (precision, sensitivity, accuracy, analytical recovery, specificity) describe the standalone performance of the Methadone Enzyme Immunoassay. It is an automated assay intended for professional use with clinical chemistry analyzers, meaning its performance is evaluated as the algorithm/reagent system working independently without real-time human interpretation within the assay measurement itself. The "human-in-the-loop" would be lab personnel running the test and interpreting the final quantitative or qualitative result.
7. The Type of Ground Truth Used
The primary ground truth used for the accuracy study is GC/MS (Gas Chromatography/Mass Spectrometry). This is a highly specific and sensitive analytical method considered the gold standard for confirming drug presence and concentration in toxicology.
8. The Sample Size for the Training Set
Not applicable. This document describes an enzyme immunoassay, which is a biochemical assay and not an Artificial Intelligence (AI) or machine learning device that requires a "training set" in the computational sense. The device's performance characteristics are inherent to its chemical and enzymatic reactions, not learned from data. Therefore, there is no "training set" for an algorithm.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device.
§ 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).