(189 days)
The Immunalysis Benzodiazepines Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzodiazepines in human urine with automated clinical chemistry analyzers. This assay is calibrated against Oxazepam. 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 Gas Chromatography/ Mass Spectrometry (GC-MS) or permitting laboratories to establish quality control procedures.
The Immunalysis Benzodiazepines 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. 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.
The Immunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine, Morphine and Oxazepam. The calibrators are designed for prescription use with immunoassays.
The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes monoclonal antibodies to Benzodiazepine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Benzodiazepines derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with Sodium Azide as a preservative.
All of the Immunalysis Multi-Drug Calibrators 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 are prepared by spiking known concentrations of drug analyte into the negative calibrator matrix. These five calibrators (negative, Level 1, 2, 3 and 4) are sold as individual bottles.
Here's an analysis of the acceptance criteria and the studies performed for the Immunalysis Benzodiazepines Urine Enzyme Immunoassay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state acceptance criteria in a quantitative format for all aspects of the testing. However, we can infer the performance expectations from the study descriptions and reported results. The core acceptance for qualitative and semi-quantitative results (positive/negative determination around the cutoff) is that the device should accurately classify samples at various concentrations relative to the 200 ng/mL cutoff, and not be significantly affected by common interferents or physiological variations. For cross-reactivity, it's expected that related compounds will show a response, ideally correlating with their known activity, and unrelated compounds should not cause false positives.
| Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|
| Precision/Cutoff Characterization (Qualitative) | |
| - Samples ≤ 150 ng/mL (negative region) should be Negative. | Table 3: All 80 determinations at 0, 50, 100, 150 ng/mL were Negative. |
| - Samples ≥ 250 ng/mL (positive region) should be Positive. | Table 3: All 80 determinations at 250, 300, 350, 400 ng/mL were Positive. |
| - Samples at 200 ng/mL (cutoff) should show a mixed result, ideally around 50% positive/negative (reflecting assay variability). | Table 3: At 200 ng/mL, 37 Negative / 43 Positive (46.25% Negative / 53.75% Positive), indicating appropriate cutoff characterization. |
| Precision/Cutoff Characterization (Semi-Quantitative) | |
| - Samples ≤ 150 ng/mL (negative region) should be Negative. | Table 4: All 80 determinations at 0, 50, 100, 150 ng/mL were Negative. |
| - Samples ≥ 250 ng/mL (positive region) should be Positive. | Table 4: All 80 determinations at 250, 300, 350, 400 ng/mL were Positive. |
| - Samples at 200 ng/mL (cutoff) should show a mixed result, ideally around 50% positive/negative. | Table 4: At 200 ng/mL, 34 Negative / 46 Positive (42.5% Negative / 57.5% Positive), indicating appropriate cutoff characterization. |
| Specificity/Cross-Reactivity | |
| - Structurally similar compounds should show cross-reactivity at expected levels. | Tables 5 & 6: Shows varying cross-reactivity (e.g., Lorazepam 333.3%, Diazepam 200%, Clonazepam 111.1%), which is expected for benzodiazepines and their metabolites. Many compounds tested POS. |
| - Structurally unrelated compounds should not interfere (no false positives/negatives at ±25% cutoff). | Table 7: All 109 structurally unrelated compounds tested at 100,000 ng/mL (or 500,000 ng/mL for some) showed Negative results at -25% Cutoff (150 ng/mL) and Positive results at +25% Cutoff (250 ng/mL) for both qualitative and semi-quantitative modes, indicating no interference. |
| - Endogenous compounds should not interfere. | Table 8: All 15 endogenous compounds tested at high concentrations showed Negative results at -25% Cutoff (150 ng/mL) and Positive results at +25% Cutoff (250 ng/mL) for both qualitative and semi-quantitative modes, indicating no interference. |
| - Urine pH range (3.0-11.0) should not interfere. | Table 11: No positive or negative interference observed across the entire pH range of 3.0 to 11.0 at ±25% of the cutoff. |
| - Urine specific gravity range (1.000-1.030) should not interfere. | Table 12: No positive or negative interference observed across the entire specific gravity range of 1.000 to 1.030 at ±25% of the cutoff. |
| Linearity/Recovery | |
| - Device should show consistent recovery across a range of spiked concentrations (typically within ±20% of expected). | Table 13: Recovery ranged from 94.2% to 106.8% across expected concentrations from 100 ng/mL to 1100 ng/mL, demonstrating good linearity and recovery. |
| Method Comparison (Qualitative) vs. LC/MS | |
| - High agreement with LC/MS confirmation for positive and negative samples. | Table 14 & 15: 42 true positives, 0 false positives, 1 false negative, 43 true negatives. |
| Agreement for qualitative positive samples (≥200ng/mL by LC/MS results) was 100% (42/42 samples correctly identified as positive by the device). | |
| Agreement for qualitative negative samples ( |
§ 862.3170 Benzodiazepine test system.
(a)
Identification. A benzodiazepine test system is a device intended to measure any of the benzodiazepine compounds, sedative and hypnotic drugs, in blood, plasma, and urine. The benzodiazepine compounds include chlordiazepoxide, diazepam, oxazepam, chlorzepate, flurazepam, and nitrazepam. Measurements obtained by this device are used in the diagnosis and treatment of benzodiazepine use or overdose and in monitoring levels of benzodiazepines to ensure appropriate therapy.(b)
Classification. Class II (special controls). A benzodiazepine 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).