(102 days)
The RapidFRET Oral Fluid Assay for THC is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Tetrahydrocannabinol at 4 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid THC Calibrator Set and RapidFRET Oral Fluid THC Control Set are intended for use only with theRapidFRET Oral Fluid Assay for THC and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid Assay for THC is an In Vitro Diagnostic competitive immunoassay used to detect THC in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.
Here's a breakdown of the acceptance criteria and study information for the RapidFRET Oral Fluid Assay for THC, based on the provided text:
Acceptance Criteria and Device Performance
| Criteria Category | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity | Achieve expected results (>97% frequency) between 75% and 125% of the 4 ng/mL cutoff level (i.e., between 3 ng/mL and 5 ng/mL). | >97% frequency of expected results between 75% and 125% of cutoff. |
| Correlation with MS | High agreement with confirmatory methods (GC/MS or LC/MS/MS). | 98% agreement for MS POS; 99% agreement for MS NEG. |
| Cross-Reactivity | Limited or no cross-reactivity with common compounds and structurally related substances, or cross-reactivity clearly defined. | Identified 6 structurally related compounds with cross-reactivity below 10,000 ng/mL in the absence of THC. |
| Analytical Specificity | No interference from common substances (foods, dental products) and pH variations at specified THC levels (2 ng/mL and 6 ng/mL). | All tested compounds and pH variations gave expected results (NEG at 2 ng/mL THC, POS at 6 ng/mL THC). |
Study Information
2. Sample size used for the test set and the data provenance:
- Analytical Sensitivity: 275 samples (spiked oral fluid pools) were tested per THC concentration level (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200% of cutoff). Total samples for this study were 275 x 9 = 2475 measurements, though the table shows slight variations in 'N' for some percentages due to rounding or reporting.
- Data Provenance: The oral fluid pools were "Negative oral fluid pools" spiked with THC, suggesting laboratory-prepared samples. No specific country of origin is mentioned, but typically such studies are conducted domestically. The study is prospective in nature as samples were specifically prepared and tested for this evaluation.
- Correlation with MS: 236 neat oral fluid samples from volunteers.
- Data Provenance: "Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for THC." This indicates prospective collection from human volunteers. No specific country of origin is mentioned.
- Cross-Reactivity: 167 different compounds were tested. The number of aliquots tested for each compound is not explicitly stated but implies multiple tests (0%, 50%, 150% THC levels).
- Data Provenance: Laboratory-prepared spiked oral fluid pool aliquots.
- Analytical Specificity: A range of common substances and pH variations were tested. Volunteers provided oral fluid samples after using certain items.
- Data Provenance: Laboratory-prepared spiked oral fluid pool aliquots for most common substances and pH levels. For certain items (e.g., mouthwash, chewing gum), oral fluid samples were collected prospectively from volunteers.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Analytical Sensitivity, Cross-Reactivity, Analytical Specificity: The ground truth for these studies was established by the known concentration of THC (and other compounds) in spiked samples. This does not involve human experts establishing ground truth in the same way as, for example, image interpretation.
- Correlation with MS: The ground truth was established by confirmatory testing using GC/MS or LC/MS/MS. These are highly precise and sensitive analytical chemistry techniques, considered the "gold standard" for drug confirmation. The document does not specify the number or qualifications of experts running these confirmatory tests, as the methods themselves are the standard.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable in the context of these analytical chemistry studies. The "adjudication" is inherent in the analytical methods used for ground truth (GC/MS or LC/MS/MS) and the pre-defined spiking concentrations. Discrepancies would be resolved by re-testing or reviewing analytical data, not by expert consensus in the typical sense.
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:
- No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an AI-based system designed to assist human readers in, for instance, image interpretation. Its performance is measured directly against analytical standards.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies described are all standalone (algorithm only). The RapidFRET Oral Fluid Assay for THC operates as an automated (or semi-automated) analytical system on the RapidFRET Integrated Workstation. Its performance is evaluated based on its ability to correctly identify THC concentrations in samples, independent of human interpretation or "human-in-the-loop" interaction for result generation. Professional judgment is applied to the test result (as stated in the Intended Use), but the device itself generates a preliminary positive or negative result without human interpretation of the primary signal.
7. The type of ground truth used:
- Known concentrations: For analytical sensitivity, cross-reactivity, and analytical specificity studies, the ground truth was the known concentration of THC or other compounds in the spiked oral fluid samples.
- Confirmatory analytical methods: For the correlation study, the ground truth was established by GC/MS or LC/MS/MS analysis of the neat oral fluid samples.
8. The sample size for the training set:
- The document describes performance validation studies, not development/training of a machine learning algorithm. Therefore, there is no explicit "training set" mentioned in the context of machine learning. The device is a "homogeneous time-resolved fluorescence assay" based on competitive immunoassay principles, a well-established biochemical method, not an AI algorithm that undergoes a training phase with a dataset. Any internal development or calibration within Biophor Diagnostics would not typically be referred to as a "training set" in the context of FDA submissions for such assays.
9. How the ground truth for the training set was established:
- As there is no explicit "training set" for an AI algorithm, this question is not applicable. The underlying biochemical principles and internal calibration methods for the assay would rely on precisely prepared standards and controls to establish its performance characteristics.
§ 862.3870 Cannabinoid test system.
(a)
Identification. A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds includedelta -9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.(b)
Classification. Class II (special controls). A cannabinoid 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).