(41 days)
The LZI Methamphetamine Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of d-methamphetamine in human urine, at a cutoff value of 500 ng/mL. The assay is designed for professional 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 Methamphetamine Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the Methamphetamine Enzyme Immunoassay at a cutoff value of 500 ng/mL.
The LZI Methamphetamine Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the Methamphetamine Enzyme Immunoassay at a cutoff value of 500 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 liquid 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 Methamphetamine Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use 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, methamphetamine-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 methamphetamine-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 Methamphetamine 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-methamphetamine 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 d-methamphetamine in buffer with sodium azide (0.09%) as a preservative.
The LZI Methamphetamine Enzyme Immunoassay calibrators and controls designated for use at the 500 ng/mL cutoff contain 0, 250, 375, 500, 625, 1000, and 2000 ng/mL of d-methamphetamine in human urine with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
The LZI Methamphetamine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of d-methamphetamine in human urine, at a cutoff value of 500 ng/mL. The assay provides only a preliminary analytical result, and a more specific alternative chemical method (e.g., GC/MS or LC/MS) is required for confirmation.
Here's a breakdown of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as separate targets in the document. However, the performance characteristics demonstrated serve as the basis for establishing substantial equivalence. The document primarily focuses on precision (intra-run and total precision) and method comparison (agreement with GC/MS or LC/MS). Based on the provided data, we can infer the expected performance.
| Performance Metric | Acceptance Criteria (Inferred from Predicate Equivalence) | Reported Device Performance (LZI Methamphetamine EIA) |
|---|---|---|
| Precision (Semi-Quantitative, % CV) | Low %CV, indicating good reproducibility. | Ranges from 1.1% to 1.7% (Total Precision) |
| Precision (Qualitative, Qualitative Response Agreement for samples at 500 ng/mL cutoff) | High agreement (e.g., 95% or higher) with expected positive/negative results. | Total Precision: 85 Positive / 3 Negative at 500 ng/mL (96.6% positive agreement expected to be positive for the 500 ng/mL samples) |
| Agreement with Confirmatory Method (Clinical Samples - Semi-Quantitative) | High agreement (e.g., 95% or higher) with GC/MS or LC/MS. | 97.87% agreement with positive samples, 100% agreement with negative samples. |
| Agreement with Confirmatory Method (Clinical Samples - Qualitative) | High agreement (e.g., 95% or higher) with GC/MS or LC/MS. | 97.87% agreement with positive samples, 100% agreement with negative samples. |
| Limit of Detection | Ability to differentiate from negative urine with 95% confidence. | 25 ng/mL |
| Linearity (0 - 2000 ng/mL) | High correlation (r²) close to 1.0. | y = 0.9791x - 2.8289, r² = 0.9996 |
| Endogenous Compound Interference & Specificity & Cross-Reactivity | No significant undesired interference or cross-reactants. | No significant undesired cross reactants or endogenous substance interference was observed. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set: The number of determinations (N) for precision studies was 88 (for total precision) and 22 (for within-run precision) for each concentration level tested (0, 125, 250, 375, 500, 625, 750, 875, 1000 ng/mL).
- Method Comparison - Clinical Samples Test Set: 95 clinical unaltered samples were used.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective for either the precision studies or clinical sample method comparison. It is implied to be prospective testing for device validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
There were no human experts validating the test set for this device in the traditional sense of image or clinical interpretation. The ground truth for the test set (e.g., actual methamphetamine concentration in urine) would have been established by a validated reference method, referred to as Gas or Liquid Chromatography/Mass Spectrometry (GC/MS or LC/MS). The qualifications of individuals performing these confirmatory tests are not specified but would typically be trained laboratory personnel.
4. Adjudication Method for the Test Set
Not applicable. This is a laboratory immunoassay device, and "adjudication" in the context of expert consensus is not relevant. The ground truth is determined by the reference analytical method (GC/MS or LC/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 immunoassay device, not a device involving human readers or AI assistance in interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics presented (Precision, Limit of Detection, Linearity, Method Comparison) represent the standalone performance of the LZI Methamphetamine Enzyme Immunoassay system on the Hitachi 717 Analyzer, without human intervention in result interpretation beyond routine laboratory operations.
7. The Type of Ground Truth Used
The ground truth used for establishing the performance of the device, particularly for method comparison, is a confirmatory chemical analytical method, specifically Gas or Liquid Chromatography/Mass Spectrometry (GC/MS or LC/MS). This is a highly accurate and specific method for determining drug concentrations.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an algorithm or machine learning. This is a traditional immunoassay device. The described performance studies are for validation of the device. If the question implicitly refers to samples used during assay development and optimization, that information is not provided in this summary.
9. How the Ground Truth for the Training Set was Established
As this is a traditional immunoassay and not an AI/ML device, the concept of a "training set" with ground truth established for it in the same way is not directly applicable. If one were to interpret "training" as the development and optimization of the assay itself, the internal standards and reference materials used for assay development would have had their concentrations established through precise chemical methods, likely including GC/MS or LC/MS, to ensure accuracy.
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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).