CEDIA DAU BENZODIAZEPINE ASSAY

K962734 · Boehringer Mannheim Corp. · JXM · Dec 10, 1996 · Clinical Toxicology

Device Facts

• Record ID: K962734
• Device Name: CEDIA DAU BENZODIAZEPINE ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: JXM · Clinical Toxicology
• Decision Date: Dec 10, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3170
• Device Class: Class 2

Indications for Use

The Modified CEDIA DAU Benzodiazepine Assay is a homogeneous enzyme immunoassay for the qualitative and semi-quantitative assay of benzodiazepines in human urine. Measurements are used as an aid in the diagnosis and treatment of benzodiazepine use or overdose.

Device Story

In-vitro homogeneous enzyme immunoassay for benzodiazepine detection in urine; utilizes competitive binding between sample benzodiazepines and benzodiazepine-derivative labeled enzyme fragments (β-galactosidase) for specific antibodies. Recombinant DNA-derived β-galactosidase subunits (enzyme acceptor and enzyme donor) reassociate to form active enzyme; antibody binding to labeled donor inhibits reassociation. Enzyme activity, proportional to benzodiazepine concentration, measured via hydrolysis of chlorophenol red-β-D-galactopyranoside (CPRG) substrate. Optional β-glucuronidase reagent hydrolyzes glucuronide metabolites to increase detection sensitivity. Used on BM/Hitachi 717 analyzer in clinical laboratory settings; results interpreted by healthcare providers to assist in clinical management of drug use or overdose.

Clinical Evidence

Bench testing only. Precision evaluated using modified NCCLS protocols (N=120 per concentration level); total %CV ranged 5.8-6.0%. Sensitivity (LOD) reported at 12.3 ng/mL. Accuracy compared against predicate CEDIA assay at 200 ng/mL cutoff showed 100.0% sensitivity and 95.1% specificity. Interfering substances (e.g., acetone, glucose, hemoglobin) tested with <10% error threshold.

Technological Characteristics

Homogeneous enzyme immunoassay; utilizes recombinant β-galactosidase fragments (enzyme acceptor/donor) and benzodiazepine-specific antibodies. Substrate: chlorophenol red-β-D-galactopyranoside (CPRG). Optional β-glucuronidase reagent for metabolite hydrolysis. Designed for use on BM/Hitachi 717 automated analyzers. Qualitative and semi-quantitative measurement.

Indications for Use

Indicated for qualitative and semi-quantitative measurement of benzodiazepines in human urine to aid in the diagnosis and treatment of benzodiazepine use or overdose in patients.

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

• CEDIA DAU Benzodiazepine Assay (K954626)

Reference Devices

• EMIT II Benzodiazepine Assay

Submission Summary (Full Text)

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K962734
DEC 10 1996
Diagnostics

# 510(k) Summary

| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| --- | --- |
| 1) Submitter name, address, contact | Boehringer Mannheim Corporation
2400 Bisso Lane
Concord, CA 94524
[phone]

Contact Person: Betsy Soares-Maddox

Date Prepared: July 11, 1996 |
| 2) Device name | Proprietary name: CEDIA DAU Benzodiazepine Assay

Common name: Homonogeneous enzyme immunoassay for the determination of benzodiazepine levels in urine.

Classification name: Benzodiazepine test system |
| 3) Predicate device | We claim substantial equivalence to the CEDIA DAU Benzodiazepine Assay (K954626) |

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11/25/96 12:54 510 674 8523 BMC CONCORD 010/011

# 510(k) Summary, Continued

## 4) Device Description

The modified CEDIA® DAU Benzodiazepine Assay is an in-vitro homogeneous enzyme immunoassay used for the qualitative and semiquantitative measurement of benzodiazepines in urine. It is based on competitive binding concepts employing benzodiazepine derivative labeled enzymatic fragments (β-galactosidase) competing with sample benzodiazepines for the benzodiazepine-specific antibody.

Using recombinant DNA techniques, the β-galactosidase molecule has been split into two totally inactive polypeptide subunits called enzyme acceptor and enzyme donor. A benzodiazepine derivative has been covalently linked to the enzyme donor in a manner that does not prevent spontaneous reassociation of the subunits to yield active β-galactosidase enzyme. Benzodiazepine-specific antibody, by binding to the benzodiazepine derivative on the enzyme donor will inhibit enzyme reassociation, thereby regulating the level of β-galactosidase formed. The amount of enzyme formed is proportional to the amount of benzodiazepines as monitored by the hydrolysis of the substrate chlorophenol red-β-D-galactopyranoside (CPRG).

The optional β-Glucuronidase reagent, when added to the Enzyme Acceptor reagent and mixed with sample on the analyzer, hydrolyzes glucuronide metabolates of benzodiazepines, thereby increasing the recognition of samples containing benzodiazepine metabolites.

## 5) Intended use

The Modified CEDIA DAU Benzodiazepine Assay is a homogeneous enzyme immunoassay for the qualitative and semi-quantitative assay of benzodiazepines in human urine. Measurements are used as an aid in the diagnosis and treatment of benzodiazepine use or overdose.

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Diagnostics

# 510(k) Summary, Continued

## 6) Comparison to predicate device

The Boehringer Mannheim modified CEDIA DAU Benzodiazepine Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Boehringer Mannheim CEDIA DAU Benzodiazepine Assay (K954626).

The following table compares the modified CEDIA DAU Benzodiazepine Assay with the predicate device, CEDIA DAU Benzodiazepine Assay. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device is provided in attachment 6.

### Similarities:

- Both Assays use the same kit
- Both assays are used on the BM/Hitachi 717 analyzer using the same chemistry parameters
- Both assays are for qualitative and semiquantitative determination of benzodiazepines in urine.

### Differences:

- Addition of β-Glucuronidase to the reconstituted Enzyme Acceptor reagent. (This component is sold separately.)
- Higher sensitivity to conjugated benzodiazepine compounds
- When β-Glucuronidase is utilized, only the 200 ng/mL cutoff is available.

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Diagnostics

# 510(k) Summary, Continued

6) Comparison to predicate device, (cont.)

Performance Characteristics: (note: data generated from modified CEDIA DAU Benzodiazepine assay used the $\beta$-Glucuronidase application.)

| Feature | Modified CEDIA DAU Benzodiazepine | | | CEDIA DAU Benzodiazepine | | |
| --- | --- | --- | --- | --- | --- | --- |
| Precision | Modified NCCLS (mA/min):
200 ng/mL Cutoff Protocol | | | Modified NCCLS (mA/min):
200 ng/mL Cutoff Protocol | | |
| Concentration | | | | | | |
| Level | 150 | 200 | 250 | 150 | 200 | 250 |
| N | 120 | 120 | 120 | 120 | 120 | 120 |
| Within-Run | 303.0 | 331.7 | 363.1 | 299.6 | 324.3 | 362.1 |
| %CV | 0.8 | 0.8 | 0.9 | 0.9 | 0.8 | 0.9 |
| Total | 303.0 | 331.7 | 363.1 | 299.6 | 324.3 | 362.1 |
| %CV | 5.9 | 6.0 | 5.8 | 3.5 | 3.5 | 3.5 |
| Sensitivity (LOD)
200 ng/mL Cutoff | 12.3 ng/mL | | | 10.8 ng/mL | | |
| Sensitivity (LOQ)
200 ng/mL Cutoff | 12.1 ng/mL | | | 10.7 ng/mL | | |
| Accuracy | Vs. CEDIA Benzodiazepine Assay | | | Vs. EMIT II Benzodiazepine Assay | | |
| 200 ng/mL Cutoff | | | | | | |
| Sensitivity | 100.0% | | | 98.2% | | |
| Specificity | 95.1% | | | 99.1% | | |

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Diagnostics

# 510(k) Summary, Continued

Comparison to predicate device (cont.)

| Feature | Modified CEDIA DAU Benzodiazepine | CEDIA DAU Benzodiazepine |
| --- | --- | --- |
| Interfering substances | Less than 10% error at: | Less than 10% error at: |
| Acetone | 1 g/dL | 1 g/dL |
| Ascorbic Acid | 0.15 g/dL | 0.15 g/dL |
| Creatinine | 0.5 g/dL | 0.5 g/dL |
| Ethanol | 1 g/dL | 1 g/dL |
| Galactose | 10 mg/dL | 10 mg/dL |
| γ-globulin | 0.5 g/dL | 0.3 g/dL |
| Glucose | 3 g/dL | 1.5 g/dL |
| Hemoglobin | 0.3 g/dL | 0.3 g/dL |
| Human Serum | 0.5 g/L | 0.5 g/L |
| Albumin | 0.1g/dL | 0.1g/dL |
| Oxalic Acid | 7.5 mg/dL | 7.5 mg/dL |
| Riboflavin | 6 g/dL | 6 g/dL |
| Sodium Chloride | 4 g/dL | 6 g/dL |
| Urea | | |
| Specificity | Multiple benzodiazepine compounds | Multiple benzodiazepine compounds |