(52 days)
The CLUNGENE Fentanyl Home Test Cassette is competitive binding, lateral flow immunochromatographic assay for the qualitative detection of Fentany] in human urine at the cut off concentration of 1.0 ng/mL. This test provides only a preliminary result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas Chromatography-Mass Spectrometry (GC-MS) or Liquid Chromatography-Mass Spectrometry (LC-MS) is the preferred confirmatory method. Evaluate preliminary positive results carefully. For in vitro diagnostic use only.
The CLUNGENE Fentanyl Test Cassette is competitive binding, lateral flow immunochromatographic assay for the qualitative detection of Fentanyl in human urine at the cut off concentration of 1.0 ng/mL.
This test provides only a preliminary result. A more specific alternative chemical must be used to obtain a confirmed presumptive positive result. Gas Chromatography-Mass Spectrometry (GC-MS). Liquid Chromatography-Mass Spectrometry (LC-MS), and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results. For in vitro diagnostic use only.
The CLUNGENE Fentanyl Tests are immunoassays intended for the qualitative detection of fentanyl in human urine. Each CLUNGENE Fentanyl Test device consists of a Test Cassette, a Dropper and a package insert. Each Test Cassette is sealed with sachets of desiccant in an aluminum pouch.
Here's a breakdown of the acceptance criteria and study information for the CLUNGENE Fentanyl Home Test Cassette and CLUNGENE Fentanyl Test Cassette, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly list "acceptance criteria" in a structured table. However, based on the performance characteristics presented, we can infer the criteria considered for demonstrating substantial equivalence. The reported performance is presented in the context of these implied criteria.
For qualitative detection of Fentanyl in human urine at a cut-off concentration of 1.0 ng/mL, the key performance characteristics evaluated were:
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Precision (agreement around cutoff) | Lot 1: |
| -100%, -75%, -50% cut off: 100% negative (60-/0+) | |
| -25% cut off: 96.7% negative (58-/2+) | |
| Cut off: 55% negative, 45% positive (33-/27+) | |
| +25%, +50%, +75%, +100% cut off: 100% positive (60+/0-) |
Lot 2:
-100%, -75%, -50%, -25% cut off: 100% negative (60-/0+)
Cut off: 43.3% negative, 56.7% positive (26-/34+)
+25%, +50%, +75%, +100% cut off: 100% positive (60+/0-)
Lot 3:
-100%, -75%, -50% cut off: 100% negative (60-/0+)
-25% cut off: 96.7% negative (58-/2+)
Cut off: 53.3% negative, 46.7% positive (32-/28+)
+25%, +50%, +75%, +100% cut off: 100% positive (60+/0-) |
| Stability | Stable at 39-86º F for 24 months (based on accelerated stability study). |
| Interference (no impact from common substances) | No interference observed at 100µg/mL (or specified concentrations) for a wide range of physiological, pathological, and common drug substances listed. This includes substances like Acetone (1000 mg/dL), Ethanol (1%), Glucose (3000 mg/dL), Ibuprofen, Caffeine, etc. |
| Specificity (cross-reactivity with similar compounds) | Demonstrated defined cross-reactivity profiles for Fentanyl analogs and related substances (e.g., Acetyl fentanyl (100%), Isobutyryl fentanyl (40%), Carfentanil (2%), Sufentanil (4%)). No cross-reactivity for a list of 27 other opioid compounds tested at 100 µg/mL. |
| Effect of Urine Specific Gravity and pH (robustness to urine variability) | All samples at and above +50% Cut-Off were positive; all samples at and below -50% Cut-Off were negative for urine specific gravities from 1.000 to 1.035 and pH from 4 to 9. |
| Method Comparison (agreement with confirmatory method) | Overall agreement near cutoff: For samples near the cutoff (between -50% and +50% of cutoff), there were a few discordant results, indicating expected variability around the cutoff.
- Example: 1 positive result for a true negative sample (0.953 ng/mL) by Operator 1.
- Example: 2 negative results for true positive samples (1.073 ng/mL, 1.083 ng/mL) by Operator 1 and 2.
Key finding: Generally high agreement for samples significantly below or above the cutoff. |
| Lay-User Performance (ease of use and accuracy by target users) | - 100% correct results for -100%, -75%, -50%, +25%, +50%, +75% of cutoff concentrations. - 95% correct results for -25% of cutoff (1 positive result out of 20 samples).
- All lay users indicated the instructions were easy to follow.
- Package insert has a Flesch-Kincaid reading grade level less than 7. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study: For each of 9 fentanyl concentrations (-100% to +100% cut off), 60 tests were performed per lot (2 tests/day/operator for 10 days, across 3 lots).
- Interference Study: Urine samples were prepared with various interfering substances, with target fentanyl at 50% below and 50% above Cut-Off levels. Tested using three batches of each device. Specific sample sizes per substance are not given, but refers to "compounds that showed no interference at a concentration of 100µg/mL or specified concentrations".
- Specificity Study: Drug metabolites and other components were tested. Not explicitly stated as "test set" samples, but these are part of the analytical validation.
- Effect of Urine Specific Gravity and pH: Urine samples with varying specific gravity and pH were spiked with fentanyl at 50% below and 50% above cut-off levels. Tested using three lots of devices.
- Method Comparison Studies (Clinical Samples): 80 unaltered clinical urine samples (40 negative and 40 positive) were used.
- Lay-user Study: 140 lay persons tested samples. 20 samples were prepared per concentration level spanning -100% to +75% of the cutoff.
Data Provenance:
The document does not explicitly state the country of origin for the clinical samples or for the samples used in the precision and lay-user studies. The method comparison study used "unaltered clinical samples." The precision and lay-user studies used "spiked fentanyl in negative samples" or "spiked fentanyl into drug free-pooled urine specimens," which implies these were lab-prepared samples. The overall study appears to be retrospective in terms of sample collection for clinical samples, but the testing itself would be prospective for evaluating the device.
3. Number of Experts and Qualifications for Ground Truth for Test Set
- Method Comparison Studies (Clinical Samples): The ground truth was established by LC/MS (Liquid Chromatography-Mass Spectrometry). This is a highly accurate analytical method and is stated as the "preferred confirmatory method" in the Indications for Use. No human experts are listed for establishing this ground truth, as it is an instrumental analysis.
- Precision Study, Lay-user Study, Interference, Specificity, Effect of Urine Specific Gravity and pH: The fentanyl concentrations in spiked samples were "confirmed by LC/MS". Again, LC/MS served as the ground truth.
4. Adjudication Method for the Test Set
- Method Comparison Studies (Clinical Samples): Samples were "blind labeled" and compared to LC/MS results. This suggests a direct comparison method. Discrepancies (discordant results) were noted, but there's no mention of an adjudication process by human experts to resolve these. The LC/MS result is considered the definitive truth.
- Precision, Interference, Specificity, Effect of Urine Specific Gravity and pH, Lay-user Study: The ground truth was based on the known spiked concentrations confirmed by LC/MS. No human adjudication method is described or necessary for these types of analytical validation studies.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. The study compares the device's performance against LC/MS (a gold standard analytical method) and evaluates lay-user performance, but not in a comparative effectiveness study with human readers with and without AI assistance. This device is a rapid diagnostic test cassette, not an AI-assisted diagnostic tool.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
Yes, this is essentially a standalone (device-only) performance assessment. The "CLUNGENE Fentanyl Test Cassette" is a lateral flow immunoassay. Its performance is read visually from the lines on the cassette. While human interpretation is involved in reading the result, the core "performance" (sensitivity, specificity, precision, etc.) is inherent to the chemical reactions and design of the device itself. The lay-user study evaluates the human interpretation aspect too.
7. Type of Ground Truth Used
The ground truth used throughout the studies was analytical confirmation by LC/MS (Liquid Chromatography-Mass Spectrometry). This is considered a highly reliable and quantitative method for determining the presence and concentration of fentanyl.
8. Sample Size for the Training Set
The document does not describe a "training set" in the context of machine learning or AI. This is a traditional immunoassay device, which typically does not involve machine learning models that require training sets. The studies described are for analytical and clinical validation of the device's inherent performance characteristics.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a "training set" for a machine learning algorithm, this question is not applicable to the provided document.
§ 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).