CEDIA PHENYTOIN II ASSAY

K963840 · Boehringer Mannheim Corp. · DIP · Nov 20, 1996 · Clinical Toxicology

Device Facts

• Record ID: K963840
• Device Name: CEDIA PHENYTOIN II ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: DIP · Clinical Toxicology
• Decision Date: Nov 20, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3350
• Device Class: Class 2

Intended Use

Immunoassay for the in vitro quantitative determination of phenytoin in human serum and plasma.

Device Story

CEDIA® Phenytoin II Assay is a homogeneous enzyme immunoassay for measuring phenytoin levels in human serum and plasma. The device utilizes genetically engineered β-galactosidase fragments that reassociate to form an active enzyme. Phenytoin in the patient sample competes with analyte-conjugated enzyme fragments for antibody binding sites. If phenytoin is present, it binds to the antibody, allowing the enzyme fragments to reassociate and cleave a substrate (CPRG), resulting in a color change measured spectrophotometrically at 570 nm. The assay is performed on clinical chemistry analyzers (e.g., Hitachi 911). Healthcare providers use the quantitative output to monitor phenytoin concentrations, aiding in therapeutic drug management. The assay provides a linear range of 0.6–40.0 µg/mL.

Clinical Evidence

Bench testing only. Precision studies (N=120 per level) showed within-run %CV of 1.3-3.2% and total %CV of 2.3-5.1%. Method comparison against the predicate (N=114) yielded a correlation coefficient of r=0.998 (y=1.00x - 0.17). Linearity established from 0.6 to 40.0 µg/mL. Interference testing performed for bilirubin, hemoglobin, lipemia, total protein, and rheumatoid factor.

Technological Characteristics

Homogeneous enzyme immunoassay using genetically engineered β-galactosidase fragments. Substrate: Chlorophenol red-β-D-Galactopyranoside (CPRG). Detection: Spectrophotometric at 570 nm. Sample type: Serum and plasma. Analytical range: 0.6–40.0 µg/mL. Designed for use on automated clinical chemistry analyzers (e.g., Hitachi 911).

Indications for Use

Indicated for the in vitro quantitative determination of phenytoin in human serum and plasma for therapeutic drug monitoring.

Regulatory Classification

Identification

A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.

Predicate Devices

• CEDIA® Phenytoin Assay (K905689)

Reference Devices

• Abbott TDx® Phenytoin

Submission Summary (Full Text)

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K963840
NOV 20 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
P.O. Box 4117
Concord, CA 94524-4117
(510) 674 - 0690, extension 8413

Contact Person: Yvette Lloyd
Date Prepared: September 20, 1996

## 2. Device name

Proprietary name: CEDIA® Phenytoin II Assay

Common name: Homogeneous enzyme immunoassay for the determination of phenytoin.

Classification name: Enzyme immunoassay, Diphenylhydantoin

## 3. Predicate device

The Boehringer Mannheim CEDIA® Phenytoin II Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed CEDIA® Phenytoin Assay (K905689).

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Diagnostics

## 4. Device Description

The CEDIA® Phenytoin II Assay is based on the bacterial enzyme β-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. In the assay, phenytoin in the sample competes with analyte conjugated to one inactive fragment of β-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive β-galactosidase fragments, and no active enzyme is formed.

## 5. Intended use

Immunoassay for the in vitro quantitative determination of phenytoin in human serum and plasma.

## 6. Comparison to predicate device

The Boehringer Mannheim CEDIA® Phenytoin II Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed CEDIA® Phenytoin Assay (K905689).

The following table compares the CEDIA® Phenytoin II Assay with the predicate device, CEDIA® Phenytoin 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:

- Intended Use: Immunoassay for the in vitro quantitative determination of phenytoin
- Sample type: Serum and plasma
- Assay range: 0 - 40 µg/mL
- Same Antibody
- Same Conjugate

Continued on next page

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Diagnostics

# 510(k) Summary, Continued

## 6. Comparison to predicate device cont.

### Differences:

| Feature | CEDIA® Phenytoin II | CEDIA® Phenytoin |
| --- | --- | --- |
| Reaction test principle | Spectrophotometric 570 nm | Spectrophotometric 415 nm |
| Instrument required | Hitachi 911 | Hitachi 704 |
| Enzyme Substrate | CPRG (Chlorophenol red-β-D-Galactopyranoside) | m-CNPG (m-Cyano-p-nitrophenol-β-D-galactopyranoside) |

### Performance Characteristics:

| Feature | CEDIA® Phenytoin II | | | CEDIA® Phenytoin | | |
| --- | --- | --- | --- | --- | --- | --- |
| Precision | Modified NCCLS (μg/mL): | | | Modified NCCLS (μg/mL): | | |
| Level | Sample | Control 2 | Control 3 | Low | Mid | High |
| N | 120 | 120 | 120 | 120 | 120 | 119 |
| Within-Run | 6.30 | 14.80 | 26.75 | 10.7 | 17.7 | 35.4 |
| %CV | 3.2 | 2.0 | 1.3 | 3.6 | 2.0 | 1.5 |
| Total | 6.30 | 14.80 | 26.75 | 10.7 | 17.7 | 35.4 |
| %CV | 5.1 | 3.1 | 2.3 | 4.7 | 3.8 | 3.3 |

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Diagnostics

# 510(k) Summary, Continued

## 6. Comparison to predicate device, (cont.)

Performance Characteristics:

| Feature | CEDIA® Phenytoin II | TDx Phenytoin |
| --- | --- | --- |
| Lower Detection Limit | 0.6 μg/mL | 0.6 μg/mL |
| Linearity | 0.6 - 40.0 μg/mL | 0.6 - 40.0 μg/mL |
| Method Comparison | Vs CEDIA® Phenytoin
Least Squares
y =1.00x - 0.17
r=0.998
SEE =0.55
N=114

Deming's
y =1.00x - 0.19
r=0.998
SEE =0.39
N=114 | Vs Abbott TDx® Phenytoin
Least Squares
y =0.984x - 0.10
r=0.994
N=92 |

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Diagnostics

# 510(k) Summary, Continued

## 6. Comparison to predicate device, (cont.)

Performance Characteristics:

| Feature | CEDIA® Phenytoin II | CEDIA Phenytoin |
| --- | --- | --- |
| Interfering substances | No interference at: | No interference at: |
| Bilirubin | 66 mg/dL | 50 mg/dL |
| Hemoglobin | 1000 mg/dL | 1000 mg/dL |
| Lipemia | 1000 mg/dL | 1000 mg/dL |
| Total Protein | 12.0 g/dL | 13 g/dL |
| Rheumatoid Factor | 100 IU/mL | 180 IU/mL |
| Specificity | % Cross-reactivity | % Cross-reactivity |
| HPPH | 1.8% | 1.4% |
| 5-MPPH | 5.7% | 4.8% |

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