(216 days)
The LZI Fentanyl Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL when calibrated against norfentanyl. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result.
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 Fentanyl Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between drug in the sample and drug 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 drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, norfentanyl-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound norfentanyl-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 Fentanyl Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The R1 solution contains mouse monoclonal anti-fentanyl antibody, glucose-6-phosphate (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 fentanyl in buffer with sodium azide (0.09 %) as a preservative.
The LZI Fentanyl Enzyme Immunoassay calibrators and controls are designated for use at the 5 ng/mL cutoff contain 0, 2.5, 3.75, 5, 6.25, 10, and 20 ng/mL of norfentanyl in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.
Here's an analysis of the acceptance criteria and study findings for the LZI Fentanyl Enzyme Immunoassay, based on the provided document:
This document is a 510(k) summary for a diagnostic device, which typically focuses on demonstrating substantial equivalence to a predicate device rather than comprehensive clinical effectiveness. Therefore, some of the requested information (like multi-reader multi-case studies, effect size of AI, or detailed training set information for an AI algorithm) is not applicable or present in this type of submission. The device described is a traditional enzyme immunoassay, not an AI-based system.
1. Acceptance Criteria and Reported Device Performance
The document describes performance characteristics typically assessed for an immunoassay. The primary acceptance criteria are implied by the precision and method comparison studies. For qualitative drug tests, the key is the accuracy of positive and negative determinations around the cutoff.
| Acceptance Criteria Category | Specific Metric (Implied) | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|---|
| Precision | % CV near cutoff | Low % CV (e.g., 90%) | 86.5 % agreement with negative samples |
| Interference | No significant interference | No significant interference | Interference observed with Boric Acid (1% w/v) and dextromethorphan; no other significant undesired cross-reactants or endogenous substance interference observed. |
Note on Acceptance Criteria: For 510(k) submissions, the acceptance criteria are often benchmarked against the predicate device's performance or established standards for that device type. Explicit numerical acceptance criteria are not always stated directly in the summary document but are implicit in the study design and the finding of "substantial equivalence."
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Precision (Qualitative): 88 determinations per concentration (N=88) spread across different runs/days.
- Method Comparison - Clinical Samples: 101 clinical unaltered samples.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an in-vitro diagnostic, these studies are typically conducted by the manufacturer in a controlled environment, likely using a mix of spiked and anonymized clinical samples. The "unaltered clinical samples" suggests prospective or retrospective collection from a clinical setting, but further details are not provided.
3. Number of Experts used to establish Ground Truth & Qualifications
- Number of Experts: Not applicable/not specified. For an immunoassay measuring a chemical compound, the "ground truth" is typically established by an independent, highly accurate analytical method, not human expert interpretation.
- Qualifications of Experts: Not applicable.
4. Adjudication Method
- Adjudication Method: Not applicable. The ground truth (confirmatory method) for chemical analysis in this context does not involve human adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was it done?: No. This type of study is relevant for imaging or interpretation-based AI systems where human readers are involved. This device is an automated immunoassay.
6. Standalone (Algorithm Only) Performance Study
- Was it done?: Yes, in a sense. The performance characteristics (precision, method comparison, interference) describe the standalone performance of the LZI Fentanyl Enzyme Immunoassay on an automated clinical chemistry analyzer (AU680 Analyzer), without human interpretation being part of the primary measurement process. The results are quantitative (ΔOD, mAU) or qualitative (positive/negative) based on predefined cutoff values.
7. Type of Ground Truth Used
- Ground Truth: For the method comparison study with clinical samples, the ground truth was established by a "more specific alternative chemical method," specifically gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS). This is considered the gold standard for confirming the presence and concentration of chemical compounds in forensic and clinical toxicology.
8. Sample Size for the Training Set
- Training Set Sample Size: Not applicable. This is a traditional immunoassay, not an AI/machine learning algorithm that requires a "training set" in that sense. The device's performance is based on its chemical and enzymatic reactions, which are inherent to its design and formulation, not learned from data. Development might involve optimizing reagents, but not "training" like an AI model.
9. How the Ground Truth for the Training Set was Established
- Ground Truth for Training Set: Not applicable, as there is no "training set" in the AI sense. The development of such an immunoassay involves analytical chemistry principles and empirical testing to optimize sensitivity, specificity, and other performance parameters.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).