(256 days)
The Lin-Zhi International (LZI) Buprenorphine Enzyme Immunoassay, when used in conjunction with Beckman Coulter® Synchron LX®, CX®, and UniCel® DxC automated clinical system analyzers, is intended for the qualitative and semi-quantitative determination of norbuprenorphine (buprenorphine metabolite) in human urine, at a cutoff value of 10 ng/mL.
The Norbuprenorphine Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the Lin-Zhi International (LZI) Buprenorphine Enzyme Immunoassay with Beckman Coulter® Synchron LX®, CX®, and UniCel® DxC automated clinical system analyzers.
The Norbuprenorphine Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the Lin-Zhi International (LZI) Buprenorphine Enzyme Immunoassay with Beckman Coulter® Synchron LX®, CX®, and UniCel® DxC automated clinical system analyzers.
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. Chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method (1,2). Clinical consideration and professional judgement should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Buprenorphine assay 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, buprenorphine-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 buprenorphine-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
Here's an analysis of the provided text regarding the Lin-Zhi International (LZI) Buprenorphine Enzyme Immunoassay, Calibrators and Controls:
1. Table of Acceptance Criteria and Reported Device Performance
For an in vitro diagnostic (IVD) device like this immunoassay, acceptance criteria typically revolve around precision (reproducibility) and method comparison (agreement with a gold standard). The provided document presents detailed precision data. While explicit "acceptance criteria" for these values aren't stated as pass/fail thresholds in the summary, the detailed data demonstrates the device's performance characteristics.
The "Method comparison against GC/MS confirmation device" section provides the most direct performance against a ground truth.
Acceptance Criteria (Implied) and Reported Device Performance:
| Performance Metric | Implied Acceptance Criterion (Typical for IVD) | Reported Device Performance (LZI Buprenorphine Enzyme Immunoassay) |
|---|---|---|
| Precision (Semi-Quantitative) | ||
| Within-Run CV% (various concentrations) | Low coefficient of variation (CV%) to indicate high reproducibility within a single run. (e.g., typically 90-95%) | CX4CE Instrument: 93.0% agreement with positive results. |
| LX20 Pro Instrument: 97.4% agreement with positive results. | ||
| DxC Instrument: 97.4% agreement with positive results. | ||
| Negative Agreement | High percentage of agreement for samples confirmed negative by GC/MS. (e.g., typically >90-95%) | CX4CE Instrument: 97.5% agreement with negative results. |
| LX20 Pro Instrument: 95.3% agreement with negative results. | ||
| DxC Instrument: 95.3% agreement with negative results. | ||
| Detection Limit | Low detection limit for clinical relevance and to ensure identification of drug presence at therapeutically relevant or abuse levels. | Determined as 3 ng/mL on all three platforms of instruments with 95% confidence. |
| Linearity Range | A broad and clinically relevant range over which the assay provides accurate quantitative results. | CX4CE Instrument: 3-90 ng/mL. |
| LX20 Pro Instrument: 3-70 ng/mL. | ||
| DxC Instrument: 3-70 ng/mL. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Studies:
- Semi-Quantitative and Qualitative Precision (Within-Run): n=21 determinations for each concentration level (0 ng/mL to 20 ng/mL) on each of the three analyzer types (CX4CE, LX20 Pro, DxC600).
- Semi-Quantitative and Qualitative Precision (Run-to-Run): n=20 determinations over 2 weeks for each concentration level (0 ng/mL to 20 ng/mL) on each of the three analyzer types.
- Method Comparison (against GC/MS):
- CX4CE Instrument: 83 clinical unaltered samples.
- LX20 Pro Instrument: 82 clinical unaltered samples.
- DxC Instrument: 83 clinical unaltered samples.
- Data Provenance: The document states "clinical unaltered samples" for the method comparison, implying human urine samples. There is no information provided about the country of origin or whether the data was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay device does not typically involve human "experts" establishing ground truth in the way medical imaging AI might.
- For the precision studies, the ground truth (sample concentration) was established by preparing samples to specific known concentrations (e.g., 0, 2.5, 5.0 ng/mL, etc.).
- For the method comparison study, the ground truth was established by a confirmatory analytical method: Chromatography/mass spectrometry (GC/MS). This is a highly accurate and widely accepted gold standard for drug detection and quantification in biological samples. The expertise implicitly lies in the validated GC/MS method and trained laboratory personnel performing these analyses, rather than individual "experts" reviewing cases.
4. Adjudication Method for the Test Set
Not applicable for this type of IVD device study. The ground truth (GC/MS results or known sample concentration) is determined analytically, not through human consensus or adjudication. Discrepancies between the device and GC/MS would be analyzed statistically rather than adjudicated by experts.
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 in vitro diagnostic device, not an AI or human-in-the-loop diagnostic imaging system. It performs a standalone analytical measurement.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this entire study is a standalone performance assessment of the LZI Buprenorphine Enzyme Immunoassay. It's an "algorithm only" in the sense that the device itself performs the chemical reaction and measurement, yielding a result without direct human intervention in the interpretation of that primary result for a given sample. Humans operate the instrument and interpret the final quantitative or qualitative output, but the core analytical performance is standalone.
7. The Type of Ground Truth Used
- Precision Studies: The ground truth was based on known, spiked concentrations of norbuprenorphine in samples.
- Method Comparison Study: The ground truth was established using Chromatography/mass spectrometry (GC/MS), which is considered the gold standard for confirmatory drug testing.
8. The Sample Size for the Training Set
No information about a "training set" is provided. This is typical for traditional IVD devices. The device's performance characteristics (e.g., standard curves, reagent formulations) are developed and optimized by the manufacturer, but the regulatory submission focuses on the validation or test set performance. There isn't a "machine learning" training phase in the context of this immunoassay.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as no training set (in the machine learning sense) is explicitly described for this traditional IVD device. The underlying chemical principles and instrument calibration guide its function, rather than data-driven machine learning.
§ 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).