(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.
§ 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).