(68 days)
The 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of 6-Acetylmorphine in human urine, at a cutoff value of 10 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers.
The 6-Acetylmorphine Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the 6-Acetylmorphine Enzyme Immunoassay.
The 6-Acetylmorphine Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the 6-AcetyImorphine Enzyme Immunoassay.
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 6-Acetylmorphine 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. In the absence of drug in the sample, 6-Acetylmorphine-labeled G6PDH activity is maximal. When free drug is present in the sample, and both enzyme-labeled and free drug would bind to antibody, the unbound 6-Acetylmorphine-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 acceptance criteria and study for the Lin-Zhi International, Inc. 6-Acetylmorphine Enzyme Immunoassay:
1. Table of Acceptance Criteria and Reported Device Performance:
The document focuses on precision and linearity as key performance characteristics. The acceptance criteria aren't explicitly stated as "acceptance criteria," but rather implied targets based on the precision and linearity results presented.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance (LZI 6-Acetylmorphine Enzyme Immunoassay) |
|---|---|---|
| Precision (Semi-Quantitative, ng/mL): | ||
| Within Run %CV | Low (e.g., 0.98) | y = x (Implied, typically ideal for perfect linearity) |
| Linearity (Correlation Coefficient) | High (e.g., >0.99) | r = 0.9961 |
| Method Comparison (Clinical Samples - 10 ng/mL Cutoff) | High agreement with a confirmed method | 100% agreement with positive, 93% agreement with negative samples |
| Interference/Specificity | No significant undesired cross-reactivity | No significant undesired cross-reactivity observed. |
Note on Acceptance Criteria: The document directly presents performance results rather than explicit, pre-defined acceptance criteria. The "Implied Acceptance Criteria" are based on common industry standards for such assays to be considered acceptable for their intended use. For instance, low CVs indicate good precision, a high correlation coefficient indicates good linearity, and high agreement in method comparison is crucial for clinical utility.
2. Sample Size Used for the Test Set and Data Provenance:
- Precision and Qualitative Positive/Negative Results: N=88 for total precision.
- Method Comparison: Clinical Samples: 80 clinical unaltered samples.
- Data Provenance: Not explicitly stated. The document is submitted by Lin-Zhi International, Inc. from Sunnyvale, CA, USA. It does not mention the country of origin for the samples or if they are retrospective or prospective. Given it's a 510(k) submission to the FDA, it's highly probable the studies were conducted in the US. The nature of the samples (clinical unaltered samples) suggests they are real-world samples, but whether they were collected specifically for this study (prospective) or were existing samples (retrospective) is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The document does not mention the number or qualifications of experts used to establish ground truth for the test set.
- For the Method Comparison: Clinical Samples, the ground truth is established by an "independent analytical method," specifically "liquid chromatography/mass spectrometry (LC/MS)." LC/MS is a highly precise and preferred confirmatory method for drug testing, often considered the gold standard. However, no human "experts" are explicitly named as establishing this ground truth; it's an instrumental analytical result.
4. Adjudication Method for the Test Set:
No adjudication method (e.g., 2+1, 3+1, none) is described for the test set. The clinical sample comparison relies on the LC/MS result as the definitive truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay, not an imaging or diagnostic device that typically involves human readers interpreting results in the same way an AI might. The primary performance evaluation here is against analytical standards and a gold-standard confirmatory method.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:
Yes, the performance data presented (precision, linearity, limit of detection, method comparison) are all "standalone" algorithm performance metrics. This is an automated enzyme immunoassay (EIA) intended for use with automated clinical chemistry analyzers. The results are generated directly by the device/reagent system. While human operators load samples and interpret the final quantitative/qualitative readouts, the core measurement and determination are done entirely by the system itself before any human interpretation of the final result.
7. The Type of Ground Truth Used:
- Precision, Limit of Detection, Linearity: Ground truth for these studies would typically be established by preparing samples with known, precise concentrations of 6-Acetylmorphine. These are highly controlled, spiked samples.
- Method Comparison: Clinical Samples: The ground truth was established by liquid chromatography/mass spectrometry (LC/MS), which is referred to as the "preferred confirmatory method" and an "independent analytical method."
8. The Sample Size for the Training Set:
The document does not provide information about a "training set" in the context of machine learning or AI. This device is an enzyme immunoassay, which is a biochemical analytical test, not an AI/ML algorithm that requires a training phase with a distinct dataset.
9. How the Ground Truth for the Training Set Was Established:
As mentioned above, there is no "training set" in the context of AI/ML for this device. The development of such an immunoassay involves optimizing reagent concentrations, reaction conditions, and calibration curves through laboratory experimentation, but this is distinct from training an AI model with a labeled dataset.
§ 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).