(290 days)
The CEDIA® Methamphetamine OFT Assay is intended for use in the qualitative detection of methamphetamine at a cutoff concentration of 120.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against d-methamphetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Calibrators are intended for use in the calibration of d-Methamphetamine when used with the CEDIA Methamphetamine OFT Assay for human oral fluid samples collected with the Oral-Eze™ Saliva Collection System. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used.
The CEDIA® Methamphetamine OFT Assay uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments i.e., enzyme acceptor (EA) and enzyme donor (ED). These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically.
In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of drug present in the sample.
The Oral-Eze™ Saliva Collection System consists of Oral-Eze™ saliva collector and collection tube with preservative buffer. Oral-Eze™ saliva collector consists of an absorbent pad attached to a plastic handle. The saliva collector is provided with a volume adequacy indicator. The plastic handle has a round window where blue color will appear when sufficient volume of oral fluid is collected. Samples are collected by placing the collector pad and plastic shield between lower cheek and gum with the plastic shield facing the cheek. Oral fluid collection is done when blue color appears in the window of the handle. The pad is ejected in to the collection tube by placing thumb on the ridges on the handle and pushing the thumb forward. The collection tube is capped and sent to the laboratory for processing and testing.
Here's an analysis of the acceptance criteria and study details for the CEDIA® Methamphetamine OFT Assay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary doesn't explicitly state "acceptance criteria" in a quantitative format as might be found for imaging devices. Instead, it presents performance characteristics that implicitly serve as the basis for demonstrating substantial equivalence. The key performance metrics are related to accuracy (concordance, sensitivity, specificity) against a reference method (GC/MS).
| Acceptance Criteria (Implied) | Reported Device Performance (CEDIA® Methamphetamine OFT Assay) |
|---|---|
| High overall concordance with GC/MS | 98.8% overall concordance with GC/MS |
| High sensitivity compared to GC/MS | 97.6% sensitivity compared to GC/MS |
| High specificity compared to GC/MS | 100.0% specificity compared to GC/MS |
| Accurate classification of samples below cutoff (negative) | Samples below cutoff read as negative |
| Accurate classification of samples above cutoff (positive) | Samples above cutoff read as positive |
| Low control samples classified as negative | Low control samples recovered as negative |
| High control samples classified as positive | High control samples recovered as positive |
| No significant interference from endogenous/exogenous substances | No significant interference observed |
| No significant cross-reactivity with unrelated compounds | No significant cross-reactivity observed |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The document does not explicitly state the total number of individual patient samples used in the "Method Comparison" study that determined concordance, sensitivity, and specificity. It only states "The overall concordance between the CEDIA® Methamphetamine OFT Assay and GC/MS is 98.8%." Without the raw numbers of true positives, true negatives, false positives, and false negatives, the exact sample size cannot be determined from this summary.
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It implies the data was collected for the purpose of this submission (likely prospective data collection in a laboratory setting).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- This device is an in vitro diagnostic (IVD) assay, not an imaging AI device that relies on human interpretation for ground truth.
- The ground truth in this context is established by the Gas Chromatography/Mass Spectrometry (GC/MS) method. This is an objective, analytical gold standard for substance identification and quantification. Therefore, human experts are not directly involved in establishing the "ground truth" for individual test samples, though expert technicians operate and validate the GC/MS instruments.
4. Adjudication Method for the Test Set
- Not applicable. As noted above, the ground truth is established by an objective analytical method (GC/MS), not by human interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a "Multi-Reader Multi-Case (MRMC)" comparative effectiveness study was not done. This type of study design is typically used for medical imaging devices where human readers interpret images, and the AI's effect on their performance is being evaluated. This device is an automated IVD assay, not an AI for image interpretation.
6. Standalone Performance
- Yes, a standalone performance study was done. The "Method Comparison" section directly evaluates the CEDIA® Methamphetamine OFT Assay's performance (concordance, sensitivity, specificity) against the GC/MS reference method. This is a measure of the algorithm's (assay's) performance without human-in-the-loop interaction for interpretation, beyond standard laboratory procedures for running the assay.
7. Type of Ground Truth Used
- The ground truth used is objective analytical data from Gas Chromatography/Mass Spectrometry (GC/MS). The summary also mentions Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) as another preferred confirmatory method. These methods are considered the gold standard for drug detection and quantification.
8. Sample Size for the Training Set
- The document does not explicitly state a "training set" size. For an IVD assay like this, the development process involves extensive analytical validation, including testing numerous samples to establish linearity, precision, interference, cross-reactivity, and cutoff optimization. However, it's not typically described in terms of a "training set" like a machine learning model. The various studies (Qualitative Precision, Qualitative Cutoff Characterization, Interference, Specificity and Cross-Reactivity, Method Comparison) collectively represent the data used to characterize and validate the assay's performance.
9. How Ground Truth for the Training Set Was Established
-
For the development and optimization of such an assay, ground truth would be established through:
- Known concentrations: Samples spiked with precise, known concentrations of methamphetamine and its metabolites.
- GC/MS or LC-MS/MS confirmation: Samples from real-world scenarios would be confirmed by gold-standard analytical methods (GC/MS or LC-MS/MS) to establish their true status (positive/negative and concentration).
- Reference materials: Use of certified reference materials and calibrators with established values.
The summary does not detail the specific methodology for establishing ground truth during the assay's development (what would functionally be analogous to a "training set" in AI development), but it implies standard IVD development practices involving these types of validated samples.
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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).