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510(k) Data Aggregation
(25 days)
The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL. 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 II Enzyme Immunoassay is a homogeneous enzyme immunoassay with readyto-use liguid 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. The drug-labeled G6PDH conjugate is traceable to a commercially available fentanyl standard and referred to as fentanyl-labeled G6PDH conjugate. 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, fentanyl-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 fentanyllabeled 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 II Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The LZI Fentanyl II Enzyme Immunoassay is traceable to a commercially available fentanyl standard.
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 II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at a cutoff value of 5 ng/mL. The device provides a preliminary analytical result, and a more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used for a confirmed analytical result.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance:
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Precision | Ability to consistently produce correct qualitative results (Negative/Positive) for samples with concentrations at various percentages around the 5 ng/mL cutoff (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200%). | Within Run (N=22): All 0%, 25%, 50%, 75% negative samples were Negative. All 125%, 150%, 175%, 200% positive samples were Positive. 100% cutoff samples were 13 Neg/9 Pos (indicating some variability around the cutoff, which is expected for qualitative assays at the cutoff). Total Precision (N=88): All 0%, 25%, 50%, 75% negative samples were Negative. All 125%, 150%, 175%, 200% positive samples were Positive. 100% cutoff samples were 59 Neg/29 Pos. |
| Method Comparison (Qualitative Accuracy) | Comparison of EIA results with LC/MS confirmation for clinical samples, especially focusing on false positives and false negatives within different concentration ranges relative to the cutoff. Acceptable levels of agreement and defined explanations for discrepancies. | Overall Accuracy: 20/20 negative samples (by LC/MS) were EIA Negative. 19/19 samples <50% of cutoff (by LC/MS) were EIA Negative. 2/10 samples Near Cutoff Negative (by LC/MS) were EIA Negative, while 8 were EIA Positive. 10/10 Near Cutoff Positive samples (by LC/MS) were EIA Positive. 40/40 High Positive samples (by LC/MS) were EIA Positive. Discrepant Samples: 9 samples with LC/MS norfentanyl concentrations between 1.5 ng/mL and 4.2 ng/mL (below the 5 ng/mL cutoff) were reported as EIA Positive. These were attributed to "levels of fentanyl that contributed to the false positive result" (cross-reactivity from fentanyl itself). |
| Cross-reactivity | Identification of compounds (structurally related, unrelated pharmacological, endogenous, preservatives) that might interfere with the assay, and quantification of their cross-reactivity. Acceptable cross-reactivity levels (e.g., "Not Detected" or specific percentage) for various substances. | Fentanyl and Metabolites: Fentanyl showed 131.58% cross-reactivity at 3.8 ng/mL. Norfentanyl showed 100.00% cross-reactivity at 5 ng/mL (as expected). Many other fentanyl analogs and metabolites showed significant cross-reactivity (e.g., Cyclopropyl Fentanyl 156.25% at 3.2 ng/mL). Structurally Unrelated Compounds: Most tested at 100,000 ng/mL showed "ND" (Not Detected). Dextromethorphan interfered at 40,000 ng/mL, showing 0.01% cross-reactivity and causing a positive result at the -25% Norfentanyl Cutoff (3.75 ng/mL). Endogenous & Preservative Compounds: Most showed no interference. Boric Acid showed interference at 1000 mg/dL, causing a negative result even at the +50% Norfentanyl Cutoff (7.5 ng/mL). |
| Specific Gravity Interference | No qualitative result interference across a range of specific gravity values (1.000 to 1.027) for negative, -25% cutoff, and +25% cutoff samples. | No interference was observed across the tested specific gravity range (1.000 to 1.027) for negative, -25% cutoff, and +25% cutoff samples. |
| pH Interference | No qualitative result interference across a range of pH values (pH 3 to pH 11) for negative, -25% cutoff, and +25% cutoff samples. | No major interference was observed between pH 3 to pH 11 for negative, -25% cutoff, and +25% cutoff samples. |
Important Note: The document focuses on demonstrating substantial equivalence to the predicate device and does not explicitly state numerical "acceptance criteria" for precision or accuracy, but rather reports the performance of the device against established test designs (e.g., NCCLS-EP5 for precision) and confirms qualitative results against a gold standard (LC/MS). The tables demonstrate the device's performance characteristics.
2. Sample size used for the test set and the data provenance:
- Precision Test Set (Qualitative): 88 replicates per concentration level (for 9 concentration levels from 0 to 200% of cutoff), making a total of 792 individual tests. These were prepared by spiking known norfentanyl standards into a pool of negative human urine.
- Method Comparison - Clinical Samples (Qualitative Accuracy): 100 unaltered clinical samples.
- Data Provenance: Samples were collected by Lin-Zhi International, Inc. and from various clinical labs: University of California, San Francisco (UCSF) (San Francisco, CA), Northwest Physicians Labs (NWPL) (Bellevue, Washington), Soloniuk Pain Clinic (Redding, CA), and Calgary Labs (Calgary, Canada). The study represents a retrospective analysis of these collected samples.
- Cross-reactivity, Endogenous, Preservative, Specific Gravity, and pH Interference Tests: Samples were prepared by spiking various compounds into pooled negative human urine or by adjusting the urine's properties. These were not external clinical samples in the same way as the method comparison set.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):
The ground truth for clinical samples (method comparison) was established using LC/MS (Liquid Chromatography/Mass Spectrometry) analysis. LC/MS is a highly specific and sensitive analytical technique, often considered the gold standard for drug quantification in toxicology. This method does not typically involve human experts establishing a subjective "ground truth" but rather relies on the analytical results of the instrument. The document does not specify the qualifications of the personnel performing the LC/MS analysis.
For the other test sets (precision, cross-reactivity, interference), the ground truth was established by the known concentrations of spiked compounds or the known properties of the prepared urine samples.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
There was no adjudication method involving multiple human readers described for establishing the ground truth or interpreting the results.
- For the precision study, the qualitative results (Negative/Positive) were derived directly from the automated clinical analyzer's response compared to the cutoff calibrator.
- For the method comparison (clinical samples), the ground truth was solely determined by the LC/MS reference method.
- For interference studies, the outcomes were based on the instrument's qualitative determination relative to the cutoff.
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:
No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic (IVD) immunoassay performed on an automated clinical chemistry analyzer, not an AI-assisted diagnostic imaging or interpretative tool that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
Yes, the performance studies described are essentially standalone (algorithm/device-only performance). The LZI Fentanyl II Enzyme Immunoassay operates on an automated clinical analyzer (Beckman Coulter AU480), and its performance metrics (precision, qualitative accuracy against LC/MS, cross-reactivity, interference) are determined directly from the instrument's output based on its chemical reactions and detection system, without human interpretation in the diagnostic process.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The primary ground truth used was analytical reference methods, specifically:
- LC/MS (Liquid Chromatography/Mass Spectrometry) for confirming the concentration of norfentanyl in clinical urine samples. This is considered an objective gold standard for drug testing.
- Known concentrations/properties for prepared spiked samples (for precision, cross-reactivity, and interference studies).
8. The sample size for the training set:
This document describes a premarket notification for an immunoassay kit, which is a chemical and enzymatic assay, not a machine learning or AI algorithm. Therefore, there is no "training set" in the context of data used to train an AI model. The device's performance is based on its reagents' chemical properties and reaction kinetics.
9. How the ground truth for the training set was established:
As there is no training set for an AI model, this question is not applicable. The device's performance is intrinsically linked to the validated formulation of its reagents and the instrument's analytical capabilities, which are established through general scientific and manufacturing practices, not data-driven AI training.
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