VITROS CHEMISTRY PRODUCTS BENZ REAGENT, CALIBRATOR KIT 26, FS CALIBRATOR 1 AND DAT PERFORMANCE VERIFIERS I, II, III, IV
Device Facts
| Record ID | K062285 |
|---|---|
| Device Name | VITROS CHEMISTRY PRODUCTS BENZ REAGENT, CALIBRATOR KIT 26, FS CALIBRATOR 1 AND DAT PERFORMANCE VERIFIERS I, II, III, IV |
| Applicant | Ortho-Clinical Diagnostics, Inc. |
| Product Code | JXM · Clinical Toxicology |
| Decision Date | Dec 22, 2006 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3170 |
| Device Class | Class 2 |
Indications for Use
VITROS Chemistry Products BENZ Reagent is used on VITROS 5.1 FS Chemistry Systems for the semi-quantitative or qualitative determination of benzodiazepines (BENZ) in human urine using a cutoff of either 200 ng/mL or 300 ng/mL. Measurements obtained with the VITROS BENZ method are used in the diagnosis and treatment of benzodiazepines use or overdose. The VITROS Chemistry Products BENZ assay is intended for use by professional laboratory personnel. It provides only a preliminary test result. A more specific alternative chemical method must be used to confirm a result obtained with this assay. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drugof-abuse test result, particularly when evaluating a preliminary positive result. VITROS Chemistry Products Calibrator Kit 26 is used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative or semi-quantitative measurement of drugs of abuse. VITROS Chemistry Products FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits to calibrate VITROS 5,1 FS Chemistry Systems. VITROS Chemistry Products DAT Performance Verifiers are assayed controls used to monitor performance of urine drugs of abuse screening assays on VITROS 5,1 FS Chemistry Systems.
Device Story
VITROS BENZ assay is a homogeneous enzyme immunoassay for detecting benzodiazepines in human urine. Performed on VITROS 5,1 FS Chemistry Systems by professional laboratory personnel. Input: urine sample; Reagent 1 (antibody to diazepam, G6P, NAD); Reagent 2 (diazepam labeled with G6P-DH). Principle: competition between benzodiazepines in sample and enzyme-labeled diazepam for antibody binding sites. Enzyme activity decreases upon binding; concentration of benzodiazepines is directly proportional to measured enzyme activity. Active enzyme converts NAD to NADH, causing absorbance change measured spectrophotometrically at 340 nm. Output: semi-quantitative or qualitative benzodiazepine concentration. Used for preliminary screening; results require GC/MS confirmation. Clinical decision-making relies on professional judgment and confirmatory testing. Benefits include rapid, automated screening for drug use or overdose.
Clinical Evidence
No clinical trials; performance validated via bench testing comparing VITROS BENZ assay on VITROS 5,1 FS Chemistry System against Syva® EMIT® II Plus Benzodiazepine assay on Syva® 30R Biochemical System. Results demonstrated good agreement between the two immunoassay methods.
Technological Characteristics
Homogeneous enzyme immunoassay; liquid ready-to-use reagents; sheep polyclonal antibodies reactive to diazepam; spectrophotometric detection at 340 nm. Calibrated against lormetazepam. Used on VITROS 5,1 FS Chemistry Systems (automated clinical chemistry analyzer).
Indications for Use
Indicated for professional laboratory use for the qualitative or semi-quantitative determination of benzodiazepines in human urine to aid in the diagnosis and treatment of benzodiazepine use or overdose. Provides preliminary results requiring confirmation by GC/MS.
Regulatory Classification
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.
Special Controls
*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).
Predicate Devices
- EMIT II Plus Benzodiazepine Assay (k993985)
- Liquicheck Urine Toxicology Controls (k022707)
Related Devices
- K173963 — DRI Benzodiazepine Assay · Microgenics Corporation · Feb 21, 2018
- K032365 — BENZODIAZEPINE ENZYME IMMUNOASSAY · Lin-Zhi International, Inc. · Sep 5, 2003
Submission Summary (Full Text)
{0}
1
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k062285
B. Purpose for Submission:
New product
C. Measurand:
Benzodiazepines
D. Type of Test:
Semi-quantitative and qualitative homogeneous enzyme immunoassay
E. Applicant:
Ortho-Clinical Diagnostic
F. Proprietary and Established Names:
VITROS Chemistry Products BENZ Reagent
VITROS Chemistry Products Calibrator Kit 26
VITROS Chemistry Products FS Calibrator 1
VITROS Chemistry Products DAT Performance Verifiers I. II, III, IV, and V
G. Regulatory Information:
1. Regulation section:
21 CFR §862.3170, Benzodiazepine Test System
21 CFR §862.3200, Clinical Toxicology Calibrator
21 CFR §862.3280, Clinical Toxicology Control Material
2. Classification:
Class II (Reagent, Calibrator)
Class I Reserved (Control)
3. Product code:
JXM; DKB; DIF
4. Panel:
Toxicology (91)
H. Intended Use:
1. Intended use(s):
See Indications for Use below.
2. Indication(s) for use:
VITROS Chemistry Products BENZ Reagent is used on VITROS 5,1 FS
Chemistry Systems for the semi-quantitative or qualitative determination of
benzodiazepines (BENZ) in human urine using a cutoff of either 200 ng/mL or
300 ng/mL. Measurements obtained with the VITROS BENZ method are used in
the diagnosis and treatment of benzodiazepines use or overdose.
{1}
The VITROS Chemistry Products BENZ assay is intended for use by professional laboratory personnel. It provides only a preliminary test result. A more specific alternative chemical method must be used to confirm a result obtained with this assay. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when evaluating a preliminary positive result.
VITROS Chemistry Products Calibrator Kit 26 is used to calibrate VITROS 5.1 FS Chemistry Systems for the qualitative or semi-quantitative measurement of the drugs of abuse.
VITROS Chemistry Products FS Calibrator 1: For in vitro diagnostic use only. VITROS Chemistry Products FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits to calibrate VITROS 5,1 FS Chemistry Systems
VITROS Chemistry Products DAT Performance Verifiers are assayed control used to monitor performance of urine drugs of abuse screening assays on VITROS 5,1 FS Chemistry Systems.
3. Special conditions for use statement(s):
This device is for use by professional laboratory personnel. For in vitro diagnostic use only.
4. Special instrument requirements:
Ortho-Clinical Diagnostics VITROS 5,1 FS Chemistry System
I. Device Description:
The VITROS BENZ Reagent is a dual-chambered package containing ready-to-use liquid reagents that are used to detect benzodiazepines in urine. Sample, calibrators, and controls are automatically treated with surfactant (DAT Diluent 2) prior to addition of reagents. Treated sample is added to Reagent 1 containing antibody reactive to diazepam, glucose-6-phosphate and nicotinamide adenine dinucleotide $(\mathrm{NAD}^{+})$, followed by Reagent 2 containing diazepam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6P-DH).
VITROS Chemistry Products Calibrator Kit 26 is prepared from human urine to which drugs of abuse, metabolites of drugs of abuse, organic salts, surfactants and preservative have been added.
VITROS Chemistry Products FS Calibrator 1 is prepared from sodium chloride and processed water. These products are used to calibrate VITROS 5,1 FS Chemistry Systems for the qualitative and semi-quantitative measurement of cocaine.
VITROS DAT Performance Verifiers I, II, III, IV & V are prepared from a human urine pool to which analytes, surfactant and preservative have been added. These are assayed controls used to monitor performance of the VITROS COCM Reagent on VITROS 5,1 FS Chemistry Systems.
The product labeling for the Calibrator Kit 26 and Performance Verifiers contain warnings regarding the presence of human sourced materials and recommend the use
{2}
of Universal Precautions when handling these products.
## J. Substantial Equivalence Information:
1. Predicate device name(s):
EMIT II Plus Benzodiazepine Assay
Liquicheck Urine Toxicology Controls
2. Predicate 510(k) number(s):
k993985; k022707
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | For use in the qualitative and semi-quantitative analysis of benzodiazepines in human urine. | Same |
| Reagent | Liquid, ready to use | Same |
| Principle | Homogeneous enzyme immunoassay | Same |
| Matrix | Urine | Same |
| Antibody | Sheep polyclonal | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Instrumentation | VITROS 5,1 FS Chemistry Systems | Multiple automated clinical chemistry analyzers |
| Calibrators: Number of level | Six | Qualitative: Three at each cutoff value
Semi-quantitative: Five |
| Controls: Number of levels | Five | Two |
## K. Standard/Guidance Document Referenced (if applicable):
CSLI EP9-A2: Method Comparison and Bias Estimation Using Patient Samples
CLSI EP5-A: Evaluation of Precision Performance of Clinical Chemistry Devices
CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures, A Statistical Approach
CLSI EP7-P: Interference Testing in Clinical Chemistry
CLSI EP17-A: Protocols for Demonstration, Verification and Evaluation of Limits of Detection and Quantitation
CLSI EP12-A: User Protocols for Evaluation of Qualitative Test Performance
## L. Test Principle:
The VITROS BENZ assay is a homogeneous enzyme immunoassay that is performed using the VITROS Chemistry Products BENZ Reagent with the VITROS Chemistry
{3}
Products Calibrator Kit 26, VITROS Chemistry Products FS Calibrator 1, and VITROS Chemistry Products FS Diluent Pack 4 (DAT Diluent/DAT Diluent 2) on VITROS 5,1 FS Chemistry Systems.
The assay is based on competition between benzodiazepines in the treated urine sample and diazepam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6P-DH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, therefore the concentration of benzodiazepines in the urine sample is directly proportional to measured enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide $(\mathrm{NAD}^{+})$ to NADH, resulting in an absorbance change that is measured spectrophotometrically at $340~\mathrm{nm}$ .
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
Imprecision was evaluated with human urine based quality control materials on the VITROS 5,1 FS Chemistry System following CLSI Protocol EP5 and CLSI protocol EP12.
Imprecision for BENZ: Semi-Quantitative
| System | Conventional Units (ng/mL) and SI Units (μg/L) | | | Within Lab CV%** | No. Observ. | No. Days |
| --- | --- | --- | --- | --- | --- | --- |
| | Mean Conc. | Within Day SD* | Within Lab SD** | | | |
| VITROS 5,1 FS | 157 | 8.3 | 15.1 | 9.6 | 84 | 22 |
| | 233 | 10.1 | 20.5 | 8.8 | 84 | 22 |
| | 264 | 12.8 | 19.1 | 7.2 | 82 | 22 |
| | 397 | 17.2 | 31.3 | 7.9 | 82 | 22 |
| | 626 | 37.2 | 58.0 | 9.3 | 84 | 22 |
* Within Day imprecision was determined using one or two runs per day with two replicates per run.
** Within Lab imprecision was determined using a single lot of reagents with one analyzer and four calibrations.
Qualitative imprecision was assessed using test fluids targeted at $\pm 25\%$ of each cutoff.
| System | Cutoff Level (ng/mL & g/L) | Test Fluid at ± 25% Cutoff | Number of Observations | Number of Correct Results |
| --- | --- | --- | --- | --- |
| VITROS 5,1 FS | 200 | -25% | 84 | 84 |
| | 200 | +25% | 82 | 82 |
| | 300 | -25% | 84 | 84 |
| | 300 | +25% | 82 | 82 |
#### b. Linearity/assay reportable range:
The sponsor followed CLSI EP6-A in determining the linear range of their device. The low and high concentration pools were mixed to give 13 admixtures of intermediate BENZ concentrations. Three determinations of all pools were made together with three determinations each of VITROS Chemistry Products
{4}
DAT Performance Verifiers I, II, III, IV, and V. This experiment was performed three times, once with each of three VITROS BENZ Reagent lots on the VITROS 5,1 FS Chemistry System. A linear regression was performed and the results indicated acceptable linearity across the range of 33 to 869 ng/mL. This linearity determination in conjunction with determination of the limit of quantitation was used to establish the reportable range of the VITROS BENZ assay to be 85 to 800 ng/mL.
## Analytical Recovery of Semi-Quantitative Results
Eight admixtures were prepared from two human urine pools. The BENZ values for the admixtures were verified by GC/MS. Percent recovery was calculated using the concentration obtained by the VITROS Chemistry Products BENZ Assay versus the GC/MS value.
Recovery of Lormetazepam
| GC/MS (ng/mL) | VITROS BENZ Assay (ng/mL) | % Recovery |
| --- | --- | --- |
| 661 | 642 | 97.1 |
| 557 | 539 | 96.7 |
| 465 | 454 | 97.6 |
| 364 | 378 | 103.9 |
| 281 | 288 | 102.4 |
| 190 | 199 | 104.9 |
| 142 | 158 | 111.0 |
| 101 | 99 | 97.8 |
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The assigned values for the calibrators and controls are traceable to the Cerilliant lormetazepam standard catalogue L-910 and are verified by GC/MS. Real time and accelerated stability studies were conducted; protocols and acceptance criteria were described and found to be acceptable. These studies support the manufacturer's stability claims. Real time studies are ongoing.
d. Detection limit:
The detection limit was determined according to protocol recommendations in CLSI EP-17 on three different lots of reagent and one instrument platform. The claimed lower limit for VITROS BENZ is 85 ng/mL.
e. Analytical specificity:
The specificity of the VITROS BENZ assay for various benzodiazepines and structurally similar compounds was estimated by generating a dose response curve for each of the compounds listed below. The quantity (ng/mL) of compound that produces a value equivalent to the lormetazepam quantity (ng/mL) at each cutoff value is listed below. The combined effects of more than one compound detected in a sample may cause levels lower than those listed below to produce a value approximately equivalent to or greater than the cutoff value.
5
{5}
Substances that Cross-react with BENZ
| Compound | Quantity (ng/mL) equivalent to 200 ng/mL of lormetazepam | % cross-reactivity * | Quantity (ng/mL) equivalent to 300 ng/mL of lormetazepam | % cross-reactivity * |
| --- | --- | --- | --- | --- |
| nordiazepam | 70 | 285.7 | 100 | 300.0 |
| prazepam | 90 | 222.2 | 120 | 250.0 |
| tetrazepam | 105 | 190.5 | 138 | 217.4 |
| ketazolam | 108 | 185.2 | 142 | 211.3 |
| diazepam | 118 | 169.5 | 160 | 187.5 |
| N-desalkyflurazepam | 120 | 166.7 | 182 | 164.8 |
| medazepam | 120 | 166.7 | 182 | 164.8 |
| a-hydroxyalprazolam | 120 | 166.7 | 155 | 193.5 |
| flurazepam | 130 | 153.8 | 171 | 175.4 |
| a-hydroxytriazolam | 140 | 142.9 | 185 | 162.2 |
| nitrazepam | 145 | 137.9 | 210 | 142.9 |
| flunitrazepam | 152 | 131.6 | 215 | 139.5 |
| alprazolam | 155 | 129.0 | 200 | 150.0 |
| temazepam | 165 | 121.2 | 230 | 130.4 |
| norfludiazepam | 195 | 102.6 | 260 | 115.4 |
| halazepam | 209 | 95.7 | 274 | 109.5 |
| clonazepam | 224 | 89.3 | 408 | 73.5 |
| clobazam | 240 | 83.3 | 440 | 68.2 |
| oxazepam | 270 | 74.1 | 380 | 78.9 |
| 7-aminoflunitrazepam | 300 | 66.7 | 650 | 46.2 |
| N-desmethyldiazepam | 300 | 66.7 | 490 | 61.2 |
| demoxepam | 400 | 50.0 | 550 | 54.5 |
| bromazepam | 422 | 47.4 | 749 | 40.1 |
| chlordiazepoxide | 1230 | 16.3 | 2900 | 10.3 |
| 7-aminoclonazepam | 1800 | 11.1 | 4000 | 7.5 |
| norchlordiazepoxide | 1900 | 10.5 | 3750 | 8.0 |
| oxazepam glucuronide | >10,000 | <2 | >10,000 | <3 |
| lorazepam glucuronide | >10,000 | <2 | >10,000 | <3 |
* The VITROS BENZ Assay cutoff value (ng/mL) divided by the amount of cross-reactant (ng/mL) that produces a value equivalent to the cutoff value, multiplied by 100.
Interfering Substances:
Known Interfering Substances for BENZ
| Cutoff Value (ng/mL) | Interferent* | Interferent Concentration | | Bias (ng/mL)** |
| --- | --- | --- | --- | --- |
| 200 | desipramine | 10 mg/dL | 330 μmol/L | +57 |
| | dextromethorphan | 10 mg/dL | 368 μmol/L | +47 |
| | dicyclomine | 10 mg/dL | 289 μmol/L | +47 |
| | diethylpropion | 10 mg/dL | 487 μmol/L | +61 |
| | ethacrynic acid | 10 mg/dL | 330 μmol/L | +73 |
| | imipramine | 10 mg/dL | 357 μmol/L | +88 |
| | indomethacin | 2.5 mg/dL | 70 μmol/L | +65 |
{6}
Known Interfering Substances for BENZ
| Cutoff Value (ng/mL) | Interferent* | Interferent Concentration | | Bias (ng/mL)** |
| --- | --- | --- | --- | --- |
| | phenyltoloxamine | 2.5 mg/dL | 98 μmol/L | +76 |
| | phenylbutazone | 0.5 mg/dL | 324 μmol/L | +56 |
| | promethazine | 2.5 mg/dL | 20 μmol/L | +49 |
| | sertraline | 0.5 mg/dL | 16 μmol/L | +51 |
| | tripelannamine | 1.0 mg/dL | 39 μmol/L | +68 |
| | tripolidine | 10 mg/dL | 359 μmol/L | +41 |
| | NaCl | 1500 mg/dL | 207 mmol/L | +46 |
| 300 | desipramine | 10 mg/dL | 330 μmol/L | +67 |
| | dextromethorphan | 10 mg/dL | 368 μmol/L | +61 |
| | dicyclomine | 10 mg/dL | 379 μmol/L | +75 |
| | diethylpropion | 10 mg/dL | 487 μmol/L | +61 |
| | doxylamine | 10 mg/dL | 370 μmol/L | +80 |
| | ethacrynic acid | 10 mg/dL | 330 μmol/L | +80 |
| | imipramine | 10 mg/dL | 357 μmol/L | +107 |
| | indomethacin | 5.0 mg/dL | 140 μmol/L | +72 |
| | phenyltoloxamine | 2.5 mg/dL | 98 μmol/L | +63 |
| | phenylbutazone | 10 mg/dL | 324 μmol/L | +70 |
| | sertraline | 10 mg/dL | 327 μmol/L | +152 |
| | tripelannamine | 1.0 mg/dL | 39 μmol/L | +64 |
* The degree of interference at concentrations other than those listed might not be predictable from these results. Other interfering substances may be encountered in the patient population.
** The bias is an estimate of the maximum difference observed.
f. Assay cut-off:
The stated cutoffs of this assay are either 200 ng/mL or 300 ng/mL.
2. Comparison studies:
a. Method comparison with predicate device:
A total of 115 human urine samples were assayed using the VITROS Chemistry Products BENZ Reagent and GC/MS or LC/MS reference method for lormetazepam. Percent agreement was evaluated at assay cutoff values of 200 ng/mL and 300 ng/mL.
GC/MS Reference Method Comparison for BENZ
| | | GC/MS or LC/MS Reference | | | | %Agreement | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Cutoff Value (ng/mL) | | Low Negative | Near Cutoff Negative | Near Cutoff Positive | High Positive | %Agreement Negative | %Agreement Positive | %Agreement Overall |
| 200 | | (<-50%) <100 ng/mL | (-50% to cutoff) 100-200 ng/mL | (cutoff to +50%) 200-300 ng/mL | (>+50%) >300 ng/mL | 76.8 | 93.7 | 83.5 |
| | VITROS Positive | 7 | 9 | 10 | 33 | | | |
| | VITROS Negative | 52 | 3 | 0 | 1 | | | |
{7}
GC/MS Reference Method Comparison for BENZ
| | | GC/MS or LC/MS Reference | | | | %Agreement | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Cutoff Value (ng/mL) | | Low Negative | Near Cutoff Negative | Near Cutoff Positive | High Positive | %Agreement Negative | %Agreement Positive | %Agreement Overall |
| 300 | | (<-50%) <150 ng/mL | (-50% to cutoff) 150-300 ng/mL | (cutoff to +50%) 300-450 ng/mL | (>+50%) >450 ng/mL | 86.1 | 88.9 | 87.0 |
| | VITROS Positive | 6 | 5 | 8 | 24 | | | |
| | VITROS Negative | 55 | 13 | 3 | 1 | | | |
Summary of Discordant Results: GC/MS or LC/MS
| Cutoff Value (ng/mL) | VITROS BENZ Assay (ng/mL) | Reference (ng/mL) |
| --- | --- | --- |
| 200 | 87 | 415 oxazepam & 26 temazepam on LC/MS |
| | 108 | 395 alprazolam, 21 alpha-OH-alprazolam, and 168 7-amino-clonazepam on LC/MS |
| | 173 | 184 alprazolam & 5 alpha-OH-alprazolam on LC/MS |
| | 209 | 237 oxazepam on LC/MS |
| | 210 | 284 7-amino-clonazepam on LC/MS |
| | 216 | 101 alpha-OH-alprazolam & 41 alprazolam on LC/MS |
| | 224 | 303 7-amino-clonazepam on LC/MS |
| | 243 | 90 oxazepam, 26 temazepam, & 4 nordiazepam on LC/MS |
| | 248 | 38 alprazolam and 64 alpha-OH-alprazolam on LC/MS |
| | 265 | 155 oxazepam, 23 temazepam, & 8 nordiazepam on LC/MS |
| | 303 | 284 7-amino-clonazepam on LC/MS |
| | 303 | 343 7-amino-clonazepam on LC/MS |
| | 319 | 106 alpha-OH-alprazolam on GC/MS |
| | 342 | 90 oxazepam, 20 temazepam, & 15 nordiazepam on LC/MS |
| | 422 | 26 oxazepam & 6 of alpha-OH-alprazolam on LC/MS |
| | >RR | 237 oxazepam on GC/MS |
| | >RR | 71 alprazolam and 51 alpha-OH-alprazolam on LC/MS |
| | >RR | < 75 on GC/MS |
| | >RR | 76 oxazepam on GC/MS |
Summary of Discordant Results: GC/MS or LC/MS
| Cutoff Value (ng/mL) | VITROS BENZ Assay (ng/mL) | Reference (ng/mL) |
| --- | --- | --- |
| 300 | 87 | 415 oxazepam &26 temazepam on LC/MS |
| | 108 | 395 alprazolam, 21 alpha-OH-alprazolam, and 168 7-amino-clonazepam on LC/MS |
| | 250 | 200 temazepam, 104 oxazepam, & 42 nordiazepam on LC/MS |
| | 277 | 169 oxazepam, 127 temazepam, & 50 nordiazepam on LC/MS |
| | 303 | 284 7-amino-clonazepam on LC/MS |
| | 303 | 343 7-amino-clonazepam on LC/MS |
| | 319 | 106 alpha-OH-alprazolam on GC/MS |
| | 342 | 211 oxazepam, 31 temazepam, & 15 nordiazepam on LC/MS |
| | 342 | 90 oxazepam, 20 temazepam, & 15 nordiazepam on LC/MS |
| | 422 | 26 oxazepam & 6 of alpha-OH-alprazolam on LC/MS |
| | 466 | 118 alpha-OH-alprazolam & 38 alprazolam on LC/MS |
| | >RR | < 75 on GC/MS |
| | >RR | 76 oxazepam on GC/MS |
| | >RR | 237 oxazepam on GC/MS |
| | >RR | 71 alprazolam and 51 alpha-OH-alprazolam on LC/MS |
{8}
A total of 115 human urine samples were assayed using the VITROS Chemistry Products BENZ Reagent and a commercially available immunoassay method, for benzodiazepine. Percent agreement was evaluated at assay cutoff values of 200 ng/mL and 300 ng/mL.
To challenge performance at the 200 ng/mL cutoff value, 44 of the 115 samples tested had concentrations within +/- 50% of the cutoff value, 27 samples below the cutoff value and 17 above the cutoff value.
To challenge performance at the 300 ng/mL cutoff value, 39 of the 115 samples tested had concentrations within +/- 50% of the cutoff value, 30 samples below the cutoff value and 9 above the cutoff value.
Commercial Method Comparison for BENZ
| | | Commercial Method** | | | | %Agreement | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Cutoff Value (ng/mL) | | Low Negative | Near Cutoff Negative | Near Cutoff Positive | High Positive | %Agreement Negative | %Agreement Positive | %Agreement Overall |
| 200 | | (<-50%) <100 ng/mL | (-50% to cutoff) 100-200 ng/mL | (cutoff to +50%) 200-300 ng/mL | (>+50%) >300 ng/mL | 100.0 | 95.2 | 97.4 |
| | VITROS Positive | 0 | 0 | 14 | 45 | | | |
| | VITROS Negative | 26 | 27 | 3* | 0 | | | |
| 300 | | (<-50%) <150 ng/mL | (-50% to cutoff) 150-300 ng/mL | (cutoff to +50%) 300-450 ng/mL | (>+50%) >450 ng/mL | 98.6 | 93.3 | 96.5 |
| | VITROS Positive | 0 | 1* | 6 | 36 | | | |
| | VITROS Negative | 40 | 29 | 3* | 0 | | | |
b. Matrix comparison:
Not applicable; this device is for use with urine only.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
Not applicable.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
{9}
10
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
