(254 days)
The Rapid Fentanyl (FYL) Test Strip is a rapid, screening test for the qualitative detection of Fentanyl (FYL) in human urine at the cut-off concentration of 1 ng/mL.
The tests is intended for in vitro diagnostics use. It is intended for prescription use including point of care sites. This assay provides only a preliminary analytical test result. To obtain a confirmed analytical result, a more specific alternative chemical method must be used. Gas Chromatography/ Mass spectrometry (GC/MS) or Liquid chromatography/Mass spectrometry (LC/MS) 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 indicated.
The Rapid Fentanyl (FYL) Test Dipcard is a rapid, screening test for the qualitative detection of Fentanyl (FYL) in human urine at the cut-off concentration of 1 ng/mL.
The tests is intended for in vitro diagnostics use. It is intended for prescription use including point of care sites. This assay provides only a preliminary analytical test result. To obtain a confirmed analytical result, a more specific alternative chemical method must be used. Gas Chromatography/ Mass spectrometry (GC/MS) or Liquid chromatography/Mass spectrometry (LC/MS) 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 indicated.
Rapid Fentanyl (FYL) Test Strip and Rapid Fentanyl (FYL) Test Dipcard are competitive binding, lateral flow immunochromatographic assays for qualitatively the detection of fentanyl at or above the cut-off concentration of 1 ng/mL. The tests can be performed without the use of an instrument. Test Strip and Test Dipcard use identical test strips made with same chemical formulation and manufacturing procedures.
The provided document describes the Co-Innovation Biotech Co.,Ltd. Rapid Fentanyl (FYL) Test Strip and Rapid Fentanyl (FYL) Test Dipcard, which are rapid screening tests for the qualitative detection of Fentanyl (FYL) in human urine at a cut-off concentration of 1 ng/mL. The document includes performance data to demonstrate substantial equivalence to a predicate device (K220046 Superbio Fentanyl Urine Detection Kit).
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" with numerical targets for accuracy, sensitivity, or specificity. However, the precision study and accuracy study demonstrate performance relative to the cut-off concentration. The implied acceptance criteria are that the device should accurately detect fentanyl around the 1 ng/mL cut-off and exhibit minimal interference and cross-reactivity. The precision study illustrates the device's ability to classify samples correctly relative to the cut-off, and the accuracy study compares device results to LC/MS reference results.
| Performance Metric | Implied Acceptance Criteria (Based on typical drug screening test expectations) | Reported Device Performance (Rapid Fentanyl (FYL) Test Strip and Dipcard - data presented is identical for both) |
|---|---|---|
| Precision | Consistent results for samples below, at, and above the cut-off. | Rapid Fentanyl (FYL) Test Strip: |
- 0 ng/mL, 0.25 ng/mL, 0.5 ng/mL: 100% negative (60/60 for each lot).
- 0.75 ng/mL (-25% cutoff): 4/60 (Lot 1), 4/60 (Lot 2), 2/60 (Lot 3) positive results (majority negative).
- 1 ng/mL (cutoff): 34/60 (Lot 1), 34/60 (Lot 2), 36/60 (Lot 3) positive results (near 50% positive/negative as expected at cutoff).
- 1.25 ng/mL (+25% cutoff): 56/60 (Lot 1), 58/60 (Lot 2), 56/60 (Lot 3) positive results (majority positive).
- 1.5 ng/mL, 1.75 ng/mL, 2 ng/mL: 100% positive (60/60 for each lot).
Rapid Fentanyl (FYL) Test Dipcard:
- 0 ng/mL, 0.25 ng/mL, 0.5 ng/mL: 100% negative (60/60 for each lot).
- 0.75 ng/mL (-25% cutoff): 4/60 (Lot 1), 2/60 (Lot 2), 6/60 (Lot 3) positive results (majority negative).
- 1 ng/mL (cutoff): 36/60 (Lot 1), 34/60 (Lot 2), 32/60 (Lot 3) positive results (near 50% positive/negative as expected at cutoff).
- 1.25 ng/mL (+25% cutoff): 54/60 (Lot 1), 56/60 (Lot 2), 56/60 (Lot 3) positive results (majority positive).
- 1.5 ng/mL, 1.75 ng/mL, 2 ng/mL: 100% positive (60/60 for each lot). |
| Accuracy (Agreement with Reference Method) | High agreement with a confirmed analytical method (LC/MS). | Rapid Fentanyl (FYL) Test Strip & Dipcard: - Discordant results for both devices and all sites: One positive at 0.76 ng/mL (LC/MS result, below cutoff) and one negative at 1.04 ng/mL (LC/MS result, above cutoff).
- Drug-free: 27/27 negative calls by device.
- Less than half cutoff: 5/5 negative calls by device.
- Near Cutoff Negative (0.5-1 ng/mL): 7/8 negative calls by device, 1/8 positive call (at 0.76ng/mL).
- Near Cutoff Positive (1-1.5 ng/mL): 8/9 positive calls by device, 1/9 negative call (at 1.04ng/mL).
- High Positive (>1.5 ng/mL): 31/31 positive calls by device. |
| Cross-reactivity | Minimal cross-reactivity with structurally similar compounds. | Fentanyl analogs showed varying degrees of cross-reactivity, some as low as 1.2 ng/mL (Acetyl fentanyl), while Norfentanyl and Acetyl norfentanyl showed very low (0.01%) cross-reactivity at 10,000 ng/mL. This indicates the device can detect some fentanyl analogs at relevant concentrations. |
| Interference | No interference from common opioids, medications, or endogenous substances. | None of the tested opioids, commonly ingested medications, or substances (at specified concentrations) were shown to interfere with the test. |
| Effect of urinary pH | Consistent results across a range of urinary pH. | Varying ranges of pH (3 to 9) did not interfere with performance. |
| Effect of urinary specific gravity | Consistent results across a range of urinary specific gravity. | Varying ranges of urinary specific gravity (1.000 to 1.040) did not affect the test result. |
2. Sample Size and Data Provenance for the Test Set:
- Precision Study (Test Set):
- Sample Size: 1620 observations in total (3 lots x 9 concentrations x 60 determinations/lot for each device type). Each concentration tested in 3 replicates daily for 10 non-consecutive days with 3 aliquots per location (2 operators per location, 3 locations).
- Data Provenance: Drug-free human urine spiked with target fentanyl at various concentrations. The document does not specify the country of origin but implies laboratory-controlled samples, not patient data. Retrospective, as urine samples were collected and then spiked.
- Accuracy Study (Test Set):
- Sample Size: 80 clinical urine specimens.
- Data Provenance: Clinical urine specimens. The country of origin is not specified. Retrospective.
3. Number of Experts (or Reference Method) and Qualifications to Establish Ground Truth for the Test Set:
- Precision Study: Ground truth was established by precise spiking of fentanyl into drug-free urine at known concentrations, confirmed by LC/MS. No human experts were involved in establishing the ground truth for these spiked samples, as the concentration was analytically determined.
- Accuracy Study: Ground truth was established by LC/MS (Gas Chromatography/ Mass spectrometry or Liquid chromatography/Mass spectrometry) analysis of the clinical urine specimens. LC/MS is the "preferred confirmatory method" and considered the gold standard for quantitative drug testing. The qualifications of the LC/MS operators or analysts are not specified.
4. Adjudication Method for the Test Set:
Not applicable in the conventional sense of expert adjudication.
- In the precision study, known concentrations (LC/MS confirmed) served as the reference.
- In the accuracy study, LC/MS served as the reference method. Discordant results were analyzed by comparing the device's reading to the objective LC/MS concentration around the cutoff.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No MRMC comparative effectiveness study was done in the context of human readers improving with AI vs. without AI assistance. This device is a rapid, screening test (immunochromatographic assay) and is not an AI-powered diagnostic imaging or interpretative device that augments human reader performance.
- However, the precision study did involve multiple operators (6 operators at 3 Point-of-Care sites) reading the results, although it wasn't designed as a comparative effectiveness study of human reader improvement. Each operator independently read the samples.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance):
- Yes, this device is a standalone test. The "Rapid Fentanyl (FYL) Test Strip and Rapid Fentanyl (FYL) Test Dipcard are competitive binding, lateral flow immunochromatographic assays for qualitatively the detection of fentanyl... The tests can be performed without the use of an instrument." The results are visually interpreted by a human operator, but the device itself does not involve an algorithm or AI. It functions as a direct chemical/immunological reaction.
7. Type of Ground Truth Used:
- Precision Study: Known concentrations of Fentanyl in urine, confirmed by LC/MS.
- Accuracy Study: Quantitative results from LC/MS analysis of clinical urine specimens.
8. Sample Size for the Training Set:
This information is typically not applicable or explicitly stated for rapid, immunoassay-based tests like the one described. These devices are developed through chemical and biological formulation and optimization rather than machine learning training on a "training set" of data. The document describes analytical validation studies, which are performance evaluations, not algorithm training.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no "training set" in the context of an AI/ML algorithm for this type of immunochromatographic device. The development process would involve optimizing reagent concentrations, membrane properties, and other manufacturing parameters to achieve the desired sensitivity and specificity, typically guided by analytical testing against known standards.
§ 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).