(120 days)
The Carolina Liquid Chemistries Cocaine Metabolite Enzyme Immunoassay (COCM) Test System is intended for the qualitative determination of benzoylecgonine (cocaine metabolite) in human urine at a cutoff value of 300 ng/mL. The assay is designed for professional use with a Carolina Liquid Chemistries CLC6410 automated clinical chemistry analyzer. For in vitro diagnostic use only. The assay provides a rapid screening procedure for determining the presence of benzoylecgonine in urine. The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas or Liquid Chromatography/Mass Spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical considerations and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The Carolina Liquid Chemistries Cocaine and Cocaine Metabolite Enzyme Immunoassay (COCM) Test System is a ready-to-use, liquid reagent homogeneous enzyme immunoassay for qualitatively determining the presence of cocaine metabolite (benzoylecgonine) in human urine. The assay uses specific antibody that can detect benzoylecgonine in human urine with minimal cross-reactivity to various, common prescription drugs and abused drugs. The assay is based on competition between benzoylecgonine labeled with the enzyme glucose-6phosphate dehydrogenase (G6PDH) and free drug from the urine sample, for a fixed amount of antibody. In the absence of free drug from the urine sample, the specific antibody binds to the drug labeled with G6PDH causing a decrease in enzyme activity. The G6PDH enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD+) to NADH.
Here's a breakdown 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
| Acceptance Criterion | Specifics from Study (Reported Device Performance) |
|---|---|
| Precision | Within Run: |
- 0 ng/mL, 75 ng/mL, 150 ng/mL, 225 ng/mL: 4/4 Negative results.
- 300 ng/mL (Cutoff): 3/1 Neg/Pos (3 Negative, 1 Positive).
- 375 ng/mL, 450 ng/mL, 525 ng/mL, 600 ng/mL: 4/4 Positive results.
Run-to-Run: - 0 ng/mL, 75 ng/mL, 150 ng/mL, 225 ng/mL: 88/88 Negative results.
- 300 ng/mL (Cutoff): 53/35 Neg/Pos (53 Negative, 35 Positive).
- 375 ng/mL, 450 ng/mL, 525 ng/mL: 88/88 Positive results. |
| Specificity | Supported by cross-reactivity studies that supported the predicate device (K020763). (No specific numerical data provided in this document, but stated as acceptable by reference to predicate) |
| Interference (pH) | No substantial interference noted. - 225 ng/mL Target: All samples from pH 3.1 to 11.1 tested Negative.
- 375 ng/mL Target: All samples from pH 3.1 to 11.1 tested Positive. |
| Interference (Specific Gravity) | No substantial interference noted. - 225 ng/mL Target: All samples from SG 1.000 to 1.029 tested Negative.
- 375 ng/mL Target: All samples from SG 1.001 to 1.028 tested Positive. |
| Carryover | No carryover was noted during testing with alternating high (1000 ng/mL) and low (0 ng/mL) samples. |
| Method Comparison and Accuracy | Agreement among positives: 100% (40/40 samples correctly identified).
Agreement among negatives: 100% (41/41 samples correctly identified).
No discordant samples identified. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision:
- Within Run: 4 replicates per concentration.
- Run-to-Run: 88 replicates per concentration (2 samples/day for 22 non-consecutive days).
- Interference (pH): 18 real human urine samples (9 pH pools, each split and spiked at two concentrations).
- Interference (Specific Gravity): 20 real human urine samples (10 SG pools, each split and spiked at two concentrations).
- Carryover: 21 samples (10 "High" at 1000 ng/mL, 11 "Low" at 0 ng/mL).
- Method Comparison and Accuracy: 81 samples total.
- 41 LC/MS Confirmed Negative Samples (20 drug-free, 21 between 0-300 ng/mL, with 8 between 150-300 ng/mL).
- 40 LC/MS Confirmed Positive Samples (at least 8 between 300-450 ng/mL, remaining >450 ng/mL).
Data Provenance: The document states "real human urine samples" for interference testing, and for precision and accuracy, samples were "drug free urine" or "spiked with benzoylecgonine." The document does not specify the country of origin of the data or whether the data was retrospective or prospective. It implies a controlled laboratory setting (spiking, adjusting pH/SG).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts to establish a ground truth. The ground truth for the test set (Method Comparison and Accuracy, Precision) was established through instrumental analysis: LC/MS (Liquid Chromatography/Mass Spectrometry), which is explicitly called the "confirmatory method" and "reference method."
4. Adjudication Method for the Test Set
No adjudication method (e.g., 2+1, 3+1) is mentioned, as the ground truth was established by instrumental methods (LC/MS) rather than human experts requiring consensus.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No MRMC study was done, as this device is an in vitro diagnostic (IVD) assay for laboratory use, not an AI-assisted diagnostic tool for human readers. Therefore, there is no mention of effect size for human readers improving with or without AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
This device is a standalone algorithm/assay in the sense that it performs the qualitative determination of benzoylecgonine without a human-in-the-loop for the primary result interpretation. The "professional use" mentioned refers to laboratory professionals operating the automated analyzer and interpreting the results within a clinical context, not interacting with AI for improved diagnostic performance. The performance data presented (precision, accuracy, etc.) represents the standalone performance of the assay.
7. The Type of Ground Truth Used
The primary ground truth used for performance evaluation (especially for accuracy and precision) is Gas or Liquid Chromatography/Mass Spectrometry (GC/MS or LC/MS). For the precision study, it states: "All sample concentrations were verified by a confirmatory method (LCMS)." For method comparison and accuracy, it states: "Qualitative Mode Accuracy study with LC-MS/MS as reference method." This is an instrumental, objective laboratory method.
8. The Sample Size for the Training Set
The document describes performance studies for a developed immunoassay. It does not mention a "training set" in the context of machine learning, as this is a chemical assay, not an AI/ML algorithm that requires training data in that sense. The reagents and parameters are developed through R&D, not trained on a dataset like a deep learning model.
9. How the Ground Truth for the Training Set Was Established
As no training set (in the ML sense) is relevant for this type of immunoassay, this question is not applicable. The assay's analytical characteristics are determined by its chemical and biological components and detection principles, which are optimized during development and validated through the studies described.
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite 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).