(160 days)
The Opiates assay is used for the qualitative analysis of opiates in human urine with a cutoff of 300 ng/mL or 2,000 ng/mL for use in clinical laboratories. Measurements obtained by this device are used in the diagnosis and treatment of opiates use or overdose. The Opiates assay is calibrated with morphine and will detect a variety of opiates and their metabolites. The Opiates assay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GCMS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
Opiates is an in vitro diagnostic assay for the qualitative analysis of opiates in human urine. The assay is a homogeneous enzyme immunoassay with a 300 ng/mL cutoff. The assay is based on competition between drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity.
The provided text describes the acceptance criteria and the study demonstrating the performance of the Opiates assay.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Implicit) | Reported Device Performance (300 ng/mL cutoff) | Reported Device Performance (2,000 ng/mL cutoff) |
|---|---|---|
| Substantial equivalence to Emit II Opiates assay on SYVA-30R Analyzer | 100% agreement (compared to Emit II) | 98.3% agreement (compared to Emit II) |
| Acceptable concordance with GC/MS | 99% agreement (compared to GC/MS) | 83% agreement (compared to GC/MS) |
| Acceptable precision (Total %CV) for Control Materials | Verifier 1: 0.63%, Cutoff Calibrator: 1.44%, Verifier II: 0.62%, -25% Control: 1.00%, +25% Control: 1.41% | Verifier 1: 0.50%, Cutoff Calibrator: 0.63%, Verifier II: 0.65%, -25% Control: 0.95%, +25% Control: 0.62% |
| Limit of Detection (Sensitivity) | 20 ng/mL | 140 ng/mL |
Note on Acceptance Criteria: The document primarily focuses on demonstrating "substantial equivalence" to a predicate device (Emit II Opiates assay) and acceptable performance against a confirmatory method (GC/MS). The specific numerical acceptance criteria (e.g., minimum concordance percentages) are not explicitly stated as "acceptance criteria" but are implied by the reported results being deemed "acceptable concordance."
2. Sample Size and Data Provenance for Test Set
- Sample Size (AEROSET vs. Emit II): Not explicitly stated, however, the concordance tables provide a combined percentage for both cutoffs.
- Sample Size (AEROSET vs. GC/MS): Not explicitly stated, however, the concordance tables provide a combined percentage for both cutoffs. For the 300 ng/mL cutoff, clinical specimens ranged from 189.0 to 3,063.0 ng/mL, and for the 2,000 ng/mL cutoff, they ranged from 575.0 to 34,980.0 ng/mL.
- Data Provenance: Not explicitly stated (e.g., country of origin). The data appears to be retrospective as it involves comparative performance studies on existing clinical specimens.
3. Number of Experts used to establish ground truth for the test set and their qualifications
This information is not provided in the document. For an immunoassay device, the "ground truth" is typically established by a gold standard laboratory method like GC/MS, rather than human experts.
4. Adjudication method for the test set
This information is not applicable and therefore not provided, as the ground truth was established by laboratory methods (GC/MS and the predicate device), not through human expert review requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for imaging or interpretation-based diagnostic devices where human readers play a significant role. The Opiates assay is an in vitro diagnostic immunoassay, and its performance is assessed against other laboratory methods.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance studies described are essentially standalone studies. The Opiates assay is an automated in vitro diagnostic assay, and its performance is evaluated directly through its own analytical output compared to reference methods (Emit II and GC/MS), without direct human-in-the-loop interpretation being part of the primary performance evaluation.
7. The type of ground truth used
The ground truth used for the performance comparison studies was:
- Predicate Device Performance: The Emit II Opiates assay on the SYVA® 30R Analyzer.
- Confirmatory Analytical Method: Gas Chromatography/Mass Spectrometry (GC/MS).
8. The sample size for the training set
This information is not provided in the document. For an in vitro diagnostic assay, a "training set" in the context of machine learning for an algorithm is generally not relevant. The device is likely calibrated using known standards and controls, but a distinct "training set" like in AI/ML model development is not mentioned.
9. How the ground truth for the training set was established
This information is not provided. As noted above, the concept of a "training set" and associated ground truth establishment (as typically understood in AI/ML) is not applicable or described for this type of in vitro diagnostic device. The assay uses known calibrators (morphine) and controls, which serve as reference points for its proper function and measurement.
§ 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).