(244 days)
The LZI Oral Fluid Amphetamine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of d-amphetamine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value 50 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS and LCMS or (2) permitting laboratories to establish quality control procedures.
The LZI Oral Fluid Amphetamine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid Amphetamine Enzyme Immunoassay at the cutoff value 50 ng/mL.
The LZI Oral Fluid Amphetamine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid Amphetamine Enzyme Immunoassay at the cutoff value of 50 ng/mL.
The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method). 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 Oral Fluid Amphetamine assay is a homogeneous enzyme immunoassay with ready-touse liquid reagent. 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, amphetamine-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 amphetamine-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 Oral Fluid Amphetamine Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The R solution contains mouse monoclonal anti-amphetamine 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 amphetamine in buffer with sodium azide (0.09%) as preservative.
The LZI Oral Fluid Amphetamine Enzyme Immunoassay calibrators and controls designated for use at the 50 ng/mL cutoffs contain 0, 25, 37.5, 50, 62.5, 100, and 140 ng/mL of d-amphetamine in human oral fluid with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
The LZI Oral Fluid Collector is a 50 mL polypropylene collection tube. It is a non-sterile centrifuge tube with a screw-on cap and printed graduations (United Lab Plastics, Catalog#UP2262).
Here's a breakdown of the acceptance criteria and study information for the LZI Oral Fluid Amphetamine Enzyme Immunoassay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are implied through the comparison to the predicate device and the presented performance data, particularly in the context of precision and method agreement. Explicit numerical "acceptance criteria" are not stated as clear, pre-defined thresholds in the provided summary, but rather performance results are reported for evaluation against accepted scientific principles for such assays.
Here's an interpretation based on the provided data:
| Performance Metric | Acceptance Criteria (Implied/Expected) | Reported Device Performance (LZI Oral Fluid Amphetamine Enzyme Immunoassay) |
|---|---|---|
| Qualitative Detection (Precision) | Accurate classification of samples below cutoff as negative and above cutoff as positive (with expected variability at cutoff). | |
| - Negative Samples ( 50 ng/mL) | 100% Positive | 100% Positive (for 62.5, 75, 87.5, 100 ng/mL - 88 determinations each) |
| - Around Cutoff (50 ng/mL) | Expected variability in classification (some positive, some negative) | 46 Positive / 42 Negative (out of 88 total determinations) |
| Semi-Quantitative Detection (Precision) | Similar to qualitative, with expected variability around the cutoff. | |
| - Negative Samples ( 50 ng/mL) | 100% Positive | 100% Positive (for 62.5, 75, 87.5, 100 ng/mL - 88 determinations each) |
| - Around Cutoff (50 ng/mL) | Expected variability in classification | 36 Positive / 52 Negative (out of 88 total determinations) |
| Method Comparison (Clinical Samples) | High agreement with a confirmed analytical method (e.g., GC/MS or LC/MS). | 100.0% agreement with negative samples; 97.7% agreement with positive samples |
| Linearity | Strong linear correlation across the analytical range. | R² = 0.9945 (y = 1.0555x - 0.7832) for range 0-140 ng/mL |
| Interference/Specificity | No significant undesired cross-reactivity or endogenous substance interference. | Reported as "No significant undesired cross reactants or endogenous substance interference was observed." |
| Stability (Shipping/Recovery) | No significant degradation of samples. | No significant sample degradation up to 72 hours. |
| Stability (Sample Storage) | No significant degradation of samples. | No significant sample degradation up to 13 days (2-8°C). Accelerated data supports 18 months at -20°C. |
| Stability (Open Vial Calibrator/Control) | Minimal degradation. | Minimal degradation for 17 months (568 days) at 2-8°C, RT, and 30°C. |
| Stability (Closed Reagent Shelf-life) | Minimal degradation. | Minimal degradation for 17 months (568 days) at 2-8°C. |
2. Sample Size and Data Provenance for Test Set (Clinical Samples)
- Sample Size: A total of eighty-five (85) clinical unaltered samples were used for the method comparison study.
- Data Provenance: The document does not explicitly state the country of origin. It indicates they were "clinical unaltered samples," suggesting a prospective or retrospective collection from a clinical setting, but further details are not provided. Given the US FDA submission, it's highly probable the data was generated or collected in the US or under US regulatory standards.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
- The document does not mention the use of human experts to establish ground truth for the test set.
- Instead, the ground truth for the clinical samples used in the "Method Comparison" was established by confirmatory analytical methods such as Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These are considered highly accurate and specific methods in toxicology testing.
4. Adjudication Method for the Test Set
- None in the context of expert adjudication. The ground truth was established by independent, highly specific analytical methods (GC/MS or LC/MS), which are the gold standard for confirming drug presence. There was no need for expert consensus or adjudication in this type of analytical validation.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) enzyme immunoassay. Such assays are designed to produce a direct analytical result (positive/negative based on a cutoff, or semi-quantitative value) rather than interpreted by multiple human readers in the way, for example, a medical imaging AI would be. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply to this type of device.
6. Standalone (Algorithm Only) Performance
- Yes, a standalone performance study was done. The entire performance characterization section (Precision, Linearity, Method Comparison, Interference, Stability) describes the performance of the LZI Oral Fluid Amphetamine Enzyme Immunoassay as an analytical device, operating independently to produce results. There is no human-in-the-loop component for the initial diagnostic output of this specific immunoassay. It reports a direct result based on its enzymatic reaction and spectrophotometric measurement on an automated analyzer.
7. Type of Ground Truth Used
- Confirmatory Analytical Methods: The ground truth for the clinical samples tested was established by Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These are the accepted gold standard methods for definitive drug confirmation in toxicology.
8. Sample Size for the Training Set
- The document does not specify a separate "training set" or its size in the context of a machine learning algorithm. This device is an enzyme immunoassay, which is a biochemical reaction-based test, not a machine learning or AI-driven diagnostic.
- The "training" of such a system typically refers to the calibration process. The immunoassay calibrators contain d-amphetamine at 0, 25, 37.5, 50, 62.5, 100, and 140 ng/mL. These are used to establish the standard curve for the assay on the automated analyzer.
9. How the Ground Truth for the Training Set was Established
- As this is not a machine learning/AI device, there isn't a traditional "training set" with independent ground truth.
- The "ground truth" for the calibrators (which are analogous to what might be used to define assay response) is established by their precisely manufactured and quantified d-amphetamine concentrations (e.g., 0 ng/mL, 25 ng/mL, 50 ng/mL, etc.) in human oral fluid matrix. These concentrations are analytically verified during the manufacturing process of the calibrators.
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).