(69 days)
The Cannabinoid Enzyme Immunoassay is a homogeneous enzyme immunoassay with a 20 ng/mL, 50 ng/mL (SHAHSA recommended initial test cutoff concentration), or 100 ng/mL cutoff. The assay is intended for use in the qualitative and semi-quantitative analyses of cannabinoids (THC) in human urine. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The Cannabinoid Enzyme Immunoassay 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 judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
LZI's Cannabinoid Enzyme Immunoassay is a ready-to-use liquid reagent, homogeneous enzyme immunoassay. The assay uses specific antibody that can detect cannabinoids (THC) in human urine with minimal cross-reactivity to various, common prescription drugs and abused drugs.
The assay is based on competition between Δ - THC-labeled glucose-6-phosphate dehydrogenase (G6PDH) enzyme, and free drug from the urine sample for a fixed amount of specific antibody. In the absence of free drug from the urine sample the specific antibody binds to the drug labeled with G6PDH enzyme causing a decrease in enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
Acceptance Criteria and Device Performance for LZI's Cannabinoid Enzyme Immunoassay
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes the performance of Lin-Zhi International, Inc.'s Cannabinoid Enzyme Immunoassay against a legally marketed predicate device (K943998 from DRI, now Microgenics Corp.). The acceptance criteria are implicitly defined by demonstrating comparability or superiority to the predicate device's performance characteristics.
| Performance Metric | Acceptance Criteria (Implicit: Comparable to Predicate) | Reported Device Performance (LZI's Cannabinoid EIA) |
|---|---|---|
| Precision | ||
| Within Run | Comparable to DRI's (given by SD and %CV) | Low SD and %CV across various THC levels (e.g., THC 50 assay: 0.39-0.87% CV for qualitative, 2.12-2.91% CV for semi-quantitative). |
| Run-To-Run | Comparable to DRI's (given by SD and %CV) | Low SD and %CV across various THC levels (e.g., THC 50 assay: 0.66-0.97% CV for qualitative, 2.41-3.59% CV for semi-quantitative). |
| Sensitivity | Comparable to DRI's (10 ng/mL) | 5 ng/mL (THC 20 assay); 7.5 ng/mL (THC 50 assay); 15 ng/mL (THC 100 assay) - Improved/Lower than predicate |
| Accuracy | Equivalent to predicate's (100% agreement vs. GC/MS for positive/negative samples for 50/100 ng/mL cutoffs). | Vs. DRI's Cannabinoid EIA (n=216 samples): |
- THC 20 assay: 100% Agreement (Positive & Negative Samples)
- THC 50 assay: 100% Agreement (Positive & Negative Samples)
- THC 100 assay: 98.3% Agreement for Positive (1 marginal discrepant), 100% Agreement for Negative Samples. |
| Analytical Recovery | No data available for predicate (implies demonstrating acceptable recovery for LZI’s device). | Qualitative: 100% accuracy on positive vs. negative tests.
Semi-quantitative: Quantitates within ±12% of nominal concentration between 10 ng/mL and 95 ng/mL. Average 98.7% recovery at 37.5 ng/mL (Cutoff - 25%); Average 93.2% recovery at 62.5 ng/mL (Cutoff + 25%). |
| Specificity | Comparable to the predicate device. | Comparable to the predicate device (referencing DRI's package insert). |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Accuracy:
- For comparison against the predicate device (DRI's Cannabinoid EIA): n = 216 samples.
- The predicate device's accuracy was stated as
Vs. GC/MS* (n = 592). This implies the predicate was validated with 592 samples, but the new device's accuracy against the predicate used 216 samples.
- Accuracy:
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). However, given it's a submission to the FDA, it is expected to be from controlled laboratory and/or clinical settings. It is likely prospective for the LZI device's testing, especially for precision and analytical recovery.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not applicable. The ground truth for the predicate device's accuracy was against GC/MS, and the LZI device's accuracy was primarily against the predicate device's results.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The testing involves direct comparison of analytical results (e.g., enzyme immunoassay readings, concentration measurements, or qualitative positive/negative calls) against a reference method (predicate EIA or GC/MS), not human interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- MRMC Study Done: No. This is an in vitro diagnostic device for chemical analysis (enzyme immunoassay), not an imaging or diagnostic device that requires human interpretation of outputs. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant to this device.
6. Standalone Performance Study
- Standalone Performance Study Done: Yes. The "Performance Characteristics" section details the standalone performance of the LZI Cannabinoid Enzyme Immunoassay, including precision, sensitivity, accuracy (against a predicate and implicitly compared to GC/MS via the predicate), analytical recovery, and specificity. This data represents the algorithm's (assay's) performance without human intervention in the result generation process, beyond operating the analyzer.
7. Type of Ground Truth Used
- Type of Ground Truth:
- For the LZI device's accuracy study: The predicate device's results (DRI's Cannabinoid EIA) served as the primary reference standard for comparison (n=216).
- For the predicate device's accuracy (which guides the LZI device's equivalence): Gas Chromatography/Mass Spectrometry (GC/MS) was used as the confirmatory method, as indicated by "* A 15 ng/mL cutoff for GC/MS was used for comparison." and the predicate's mention of "Vs. GC/MS* (n = 592)". GC/MS is a very high-accuracy 'gold standard' for drug confirmation.
- For other performance metrics (Precision, Sensitivity, Analytical Recovery, Specificity): Ground truth was established through defined laboratory protocols, known concentrations of cannabinoids (for sensitivity and recovery), and reference panels for specificity.
8. Sample Size for the Training Set
- Training Set Sample Size: Not applicable. This device is an enzyme immunoassay, not a machine learning or AI-driven algorithm that requires a "training set" in the conventional sense. The assay chemistry and parameters are developed and optimized through R&D, but there isn't a separate, quantifiable "training set" like there would be for an AI model.
9. How the Ground Truth for the Training Set was Established
- Ground Truth for Training Set: Not applicable, as no conventional "training set" with associated ground truth is used for an enzyme immunoassay. The development and optimization of such assays rely on established biochemical principles, standard reference materials, and empirical testing to achieve desired performance characteristics.
§ 862.3870 Cannabinoid test system.
(a)
Identification. A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds includedelta -9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.(b)
Classification. Class II (special controls). A cannabinoid 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).