(267 days)
The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.
This assay provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
The Cocaine Metabolite Enzyme Immunoassay consists of ready-to-use liquid reagents:
- . Reagent 1 contains a mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide (0.09%) as a preservative.
- Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with . benzoylecgonine in buffer with sodium azide (0.09%) as a preservative.
The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, benzoylecgonine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when drug is present in the sample, antibody binds to the free drug; the unbound benzovlecgonine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at a 340 nm primary wavelength.
The assay has a cutoff of 150 ng/mL benzoylecqonine.
Here's an analysis of the provided text to extract the acceptance criteria and study information, formatted as requested:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a numerical or categorical format for overall device performance (e.g., "sensitivity must be >X%"). Instead, it presents performance data for several metrics that implicitly represent the device's ability to perform as intended and demonstrate substantial equivalence to the predicate device.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Mindray BS-480) | Reported Device Performance (Mindray BA-800M) |
|---|---|---|---|
| Method Comparison (Qualitative Agreement with LC/MS) | Device results should show good agreement with the LC/MS reference method. Exact thresholds not specified, but high percentages are expected for substantial equivalence. | ||
| % Agreement among positives | (Implicit: High agreement for positives) | 88.9% (40/45) | 93.3% (42/45) |
| % Agreement among negatives | (Implicit: High agreement for negatives) | 98.6% (68/69) | 98.6% (68/69) |
| Precision (Qualitative Results at Cutoff) | Low variability in qualitative results near the cutoff for both within-run and between-run testing, indicating consistent performance. | ||
| Within Run (150 ng/mL cutoff) | (Implicit: Consistent positive/negative results) | 19 Neg / 1 Pos | 7 Neg / 13 Pos |
| Between Run (150 ng/mL cutoff) | (Implicit: Consistent positive/negative results) | 68 Neg / 12 Pos | 41 Neg / 39 Pos |
| Interference (Endogenous Substances & pH/Specific Gravity) | No positive or negative interference at specified concentrations of endogenous substances, pH range, and specific gravity range. | Qualitative results identical for both analyzers (no interference observed). | Qualitative results identical for both analyzers (no interference observed). |
| Cross-Reactivity (Structurally Related Compounds) | Low percent cross-reactivity with non-benzoylecgonine cocaine-related compounds. | Cocaine: 1.52% (BA-800M), 1.62% (BS-480) | Cocaine: 1.50% (referenced) |
| Cross-Reactivity (Structurally Unrelated Pharmacological Compounds) | Negligible cross-reactivity with common pharmacological compounds. | Meperidine: 0.00% | Meperidine: 0.00% (referenced), and many others at 0.00% |
| Reference LC/MS Precision (for method comparison) | (Implicit: Good precision for the reference method to ensure reliability of comparison.) | Level 1: 5.3% CV, Level 2: 6.5% CV, Level 3: 5.3% CV | N/A |
| Reference LC/MS Accuracy (for method comparison) | (Implicit: Good accuracy for the reference method.) | % Recovery ranging from 93.2% to 109.7% for various levels | N/A |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Method Comparison: 114 unaltered clinical urine remnant samples.
- Data Provenance: The samples were obtained from a "third-party biorepository." The country of origin is not specified but is implied to be within the scope of the FDA's jurisdiction (likely the US). The data is retrospective as it uses remnant samples.
- Sample Size for Precision Studies: Drug-free urine was spiked at various concentrations (zero, -75%, -50%, -25% of cutoff, at cutoff, +25%, +50%, +75%, +100% of cutoff). For within-run studies, 20 observations were made for each concentration. For between-run studies, 80 observations were made for each concentration.
- Sample Size for Interference Studies: Specific numbers are not given for each interfering substance, but the study involved "various concentrations" for endogenous compounds, and urine samples at 9 different pH levels and 12 different specific gravity levels.
- Sample Size for Cross-Reactivity Studies: "Various concentrations" of structurally related and unrelated compounds were spiked into drug-free urine. Specific numbers of replicates are not provided, except for the referenced study which likely involved a larger set.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- The ground truth for the method comparison study was established by Agilent 6460 LC/MS. This is an analytical instrument, not human experts.
- For the precision, interference, and cross-reactivity studies, the ground truth was established by spiking known concentrations of benzoylecgonine or interfering substances into drug-free urine or using urine samples with known characteristics (e.g., pH, specific gravity). This is also an analytical assessment.
- Therefore, no human experts were used to establish the ground truth in the traditional sense of consensus or adjudication. The "ground truth" was determined by the highly precise and accurate analytical methods of LC/MS and controlled spiking.
4. Adjudication Method for the Test Set:
- None. The primary analytical reference method (LC/MS) is considered the gold standard for quantitative determination of benzoylecgonine in this context. The comparison is directly between the candidate device and this analytical gold standard. Discrepancies are reported as "discordant results" without further human adjudication in the provided summary.
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. This device is an in vitro diagnostic (IVD) assay designed for qualitative determination of a cocaine metabolite in urine. It does not involve human "readers" in the context of image interpretation or subjective diagnostic assessment. Therefore, an MRMC study or AI assistance is not applicable to this type of device.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is essentially a standalone algorithm/device performance study. The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay operates as an automated assay on clinical chemistry analyzers (Mindray BS-480 and BA-800M). Its performance is evaluated intrinsically against an analytical gold standard (LC/MS) and under controlled laboratory conditions (precision, interference, cross-reactivity). It does not involve a human in the loop for interpreting its primary result, which is a qualitative "positive" or "negative" determination based on a defined cutoff.
7. The Type of Ground Truth Used:
- Analytical Gold Standard / Spiked Samples:
- For the method comparison, the ground truth was established by a fully validated and qualified Agilent 6460 LC/MS (Liquid Chromatograph/Mass Spectrometry), which is considered a highly accurate and precise reference method for quantitative drug analysis.
- For precision, interference, and cross-reactivity studies, the ground truth was established by spiking known, confirmed concentrations of benzoylecgonine or other substances into drug-free urine, or by using urine samples with precisely measured characteristics (pH, specific gravity).
8. The Sample Size for the Training Set:
- The document describes a 510(k) submission for a diagnostic assay, not a machine learning or AI algorithm. Therefore, the concept of a "training set" for an algorithm to learn from does not apply in this context. The assay's performance is based on its chemical and enzymatic reactions, which are designed and validated, not "trained" on data.
9. How the Ground Truth for the Training Set was Established:
- As explained above, there is no "training set" in the context of this chemical immunoassay. The device's operational characteristics are fixed by its chemical and biological components.
§ 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).