(84 days)
The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150ng/mL and 300ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzoylecgonine. This in-vitro device is for prescription use only.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures.
The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
Immunalysis Benzoylecgonine Urine Calibrators
The Immunalysis Benzoylecgonine Urine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calbrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers.
Immunalysis Benzoylecgonine Urine Control Set
The Immunalysis Benzoylecgonine Urine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analyte currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers
- The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes polyclonal sheep antibodies to Benzoylecgonine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Benzoylecgonine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with Sodium Azide as a preservative.
- All of the Immunalysis Benzoylecgonine Urine Calibrators and Controls are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.
The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control 1, HIGH Control 1, LOW Control 2 and HIGH Control 2 are prepared by spiking known concentrations of benzoylecgonine into the negative calibrator matrix. These five calibrators and four controls are sold as individual bottles.
The provided document describes the acceptance criteria and the study results for the Immunalysis Benzoylecgonine Urine Enzyme Immunoassay.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a single table with performance targets. However, the performance studies implicitly define the criteria by demonstrating acceptable results across various tests. For the purpose of this response, I've inferred the acceptance criteria based on the reported "Result" and "Interference?" columns, where "No" interference or expected qualitative results (Positive/Negative) for varying concentrations are considered acceptable.
Qualitative Analysis (150ng/mL cutoff):
| Concentration (ng/mL) | % of cutoff | Acceptance Criteria (Expected Result) | Reported Device Performance (Result) |
|---|---|---|---|
| 0 | -100% | Negative | 80 Negative |
| 37.5 | -75% | Negative | 80 Negative |
| 75 | -50% | Negative | 80 Negative |
| 112.5 | -25% | Negative | 80 Negative |
| 150 | Cutoff | Mix of Negative/Positive (Boundary) | 36 Neg / 44 Pos |
| 187.5 | +25% | Positive | 80 Positive |
| 225 | +50% | Positive | 80 Positive |
| 262.5 | +75% | Positive | 80 Positive |
| 300 | +100% | Positive | 80 Positive |
Qualitative Analysis (300ng/mL cutoff):
| Concentration (ng/mL) | % of cutoff | Acceptance Criteria (Expected Result) | Reported Device Performance (Result) |
|---|---|---|---|
| 0 | -100% | Negative | 80 Negative |
| 75 | -75% | Negative | 80 Negative |
| 150 | -50% | Negative | 80 Negative |
| 225 | -25% | Negative | 80 Negative |
| 300 | Cutoff | Mix of Negative/Positive (Boundary) | 37 Neg / 43 Pos |
| 375 | +25% | Positive | 80 Positive |
| 450 | +50% | Positive | 80 Positive |
| 525 | +75% | Positive | 80 Positive |
| 600 | +100% | Positive | 80 Positive |
Semi-Quantitative Analysis (150ng/mL cutoff):
| Concentration (ng/mL) | % of cutoff | Acceptance Criteria (Expected Result) | Reported Device Performance (Result) |
|---|---|---|---|
| 0 | -100% | Negative | 80 Negative |
| 37.5 | -75% | Negative | 80 Negative |
| 75 | -50% | Negative | 80 Negative |
| 112.5 | -25% | Negative | 80 Negative |
| 150 | Cutoff | Mix of Negative/Positive (Boundary) | 25 Neg / 55 Pos |
| 187.5 | +25% | Positive | 80 Positive |
| 225 | +50% | Positive | 80 Positive |
| 262.5 | +75% | Positive | 80 Positive |
| 300 | +100% | Positive | 80 Positive |
Semi-Quantitative Analysis (300ng/mL cutoff):
| Concentration (ng/mL) | % of cutoff | Acceptance Criteria (Expected Result) | Reported Device Performance (Result) |
|---|---|---|---|
| 0 | -100% | Negative | 80 Negative |
| 75 | -75% | Negative | 80 Negative |
| 150 | -50% | Negative | 80 Negative |
| 225 | -25% | Negative | 80 Negative |
| 300 | Cutoff | Mix of Negative/Positive (Boundary) | 24 Neg / 56 Pos |
| 375 | +25% | Positive | 80 Positive |
| 450 | +50% | Positive | 80 Positive |
| 525 | +75% | Positive | 80 Positive |
| 600 | +100% | Positive | 80 Positive |
Specificity and Cross-Reactivity (150ng/mL cutoff - Qualitative & Semi-Quantitative): All listed "Structurally Related Compounds" except Ecgonine Methyl Ester, Cocaethylene, and Norcocaine should show positive results at the tested concentration, demonstrating cross-reactivity where expected, and negative otherwise. This is shown as "POS" or "NEG" in the tables, with corresponding Cross-Reactivity (%).
Specificity and Cross-Reactivity (300ng/mL cutoff - Qualitative & Semi-Quantitative): All listed "Structurally Related Compounds" except Benzoylecgonine and m-Hydroxybenzoylecgonine should show negative results at the tested concentration. This is shown as "POS" or "NEG" in the tables, with corresponding Cross-Reactivity (%).
Interference Study (Structurally Non-Similar Compounds, Endogenous Compounds, pH, Specific Gravity):
For all tested compounds and parameters (pH range 3.0-11.0, Specific Gravity range 1.000-1.030) and both cutoffs, the reported device performance indicates "No" interference, which is the implicit acceptance criterion, except for Boric Acid.
Linearity/Recovery:
The reported recovery percentages range from 91.2% to 108.6%, indicating generally good linearity and recovery. The implicit acceptance criterion would be that recovery falls within a generally accepted range (e.g., +/- 20% of expected, or tighter), which the data appears to satisfy for most points.
Method Comparison (Qualitative & Semi-Quantitative for both cutoffs):
The acceptance criterion is high agreement with LC/MS confirmation.
For 150ng/mL cutoff:
- Qualitative Positive Agreement: 98% (1 sample with 124ng/mL Benzoylecgonine by LC-MS/MS was positive by device but had a concentration below the 150ng/mL cutoff, leading to 1 false positive out of 40 true positives)
- Qualitative Negative Agreement: 100%
- Semi-Quantitative Positive Agreement: 98%
- Semi-Quantitative Negative Agreement: 100%
For 300ng/mL cutoff:
- Qualitative Positive Agreement: 100%
- Qualitative Negative Agreement: 100%
- Semi-Quantitative Positive Agreement: 100%
- Semi-Quantitative Negative Agreement: 100%
2. Sample size used for the test set and the data provenance
- Precision/Cutoff Characterization/Reproducibility: 80 determinations for each concentration level for both qualitative and semi-quantitative analyses, at both 150ng/mL and 300ng/mL cutoffs. This means a total of 80x9=720 determinations for each cutoff in qualitative mode, and 80x9=720 for semi-quantitative total determinations. The samples were generated specifically for the study at defined concentrations; their provenance is thus "prepared samples."
- Specificity and Cross-Reactivity: Structurally similar compounds were spiked into drug-free urine.
- Interference: Structurally non-similar compounds, endogenous compounds, effect of pH, and effect of specific gravity were evaluated by spiking potential interferents into drug-free urine containing the target analyte at ±25% of the cutoff.
- Linearity/Recovery: A drug-free urine pool was spiked with a high concentration of the target analyte, and serial dilutions were made.
- Method Comparison: Unaltered, anonymous, and discarded clinical urine samples were obtained from clinical testing laboratories. The number of samples for the method comparison was 40 positive and 40 negative for each cutoff (150ng/mL and 300ng/mL) based on LC/MS confirmation, for a total of 80 unique samples that were then compared against the device for qualitative and semi-quantitative results. The provenance is retrospective clinical samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not specify the number of experts or their qualifications for establishing ground truth. The ground truth for the test set (Method Comparison) was established using Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS), which are considered preferred confirmatory methods, rather than human expert interpretation. For other studies (Precision, Specificity, Interference, Linearity), the ground truth was established by preparing samples with known concentrations of analytes.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable, as the ground truth was established by objective analytical methods (GC-MS/LC-MS) or sample preparation with known concentrations, not by subjective human expert adjudication.
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
Not applicable. This device is an in-vitro diagnostic immunoassay for chemical analysis, not an AI-assisted diagnostic imaging device requiring human-in-the-loop performance evaluation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance studies (Precision, Specificity, Interference, Linearity, Method Comparison) represent the standalone performance of the Immunalysis Benzoylecgonine Urine Enzyme Immunoassay device. The device's results are generated by automated clinical chemistry analyzers (Beckman Coulter AU 400e) without human interpretation in the determination of the qualitative or semi-quantitative result. The document emphasizes that the EIA provides a "preliminary analytical test result" and "A more specific alternate chemical method must be used in order to obtain a confirmed analytical result."
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Precision/Cutoff Characterization/Reproducibility, Specificity/Cross-Reactivity, Interference, Linearity/Recovery: Known concentrations of Benzoylecgonine or other compounds spiked into drug-free urine were used as ground truth.
- Method Comparison: LC/MS (Liquid Chromatography/Mass Spectrometry) confirmation was used as the ground truth for clinical urine samples.
8. The sample size for the training set
This is not applicable as the device is a chemical immunoassay kit, not a machine learning or AI algorithm that requires a training set in that context. The "training" would refer to the development and optimization of the assay reagents and conditions.
9. How the ground truth for the training set was established
Not applicable for the same reason as point 8. The development process would involve analytical testing and optimization against known standards and characterized samples to establish the assay's performance characteristics.
§ 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).