CEDIA THEOPHYLLINE ASSAY

K961462 · Boehringer Mannheim Corp. · KLS · Jun 27, 1996 · Clinical Toxicology

Device Facts

• Record ID: K961462
• Device Name: CEDIA THEOPHYLLINE ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: KLS · Clinical Toxicology
• Decision Date: Jun 27, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3880
• Device Class: Class 2

Intended Use

The CEDIA Theophylline Assay is a homogeneous enzyme immunoassay for the in vitro assay of theophylline in human serum and plasma. Measurements are used in the diagnosis and treatment of theophylline overdose and in monitoring levels of theophylline to ensure proper therapy.

Device Story

In-vitro homogeneous enzyme immunoassay; measures theophylline in human serum/plasma. Uses competitive binding: theophylline-labeled β-galactosidase fragments compete with sample theophylline for specific antibody. Recombinant DNA-derived enzyme subunits (acceptor/donor) reassociate to form active β-galactosidase; antibody binding to theophylline-labeled donor inhibits reassociation. Enzyme activity proportional to theophylline concentration; monitored via hydrolysis of substrate chlorophenol red-β-D-galactopyranoside (CPRG) using spectrophotometry at 570 nm. Used in clinical laboratory settings on BM/Hitachi 704 analyzers. Results assist clinicians in therapeutic drug monitoring and overdose management.

Clinical Evidence

Bench testing only. Precision evaluated with 120 replicates per level (Low, Mid, High); total CVs ranged from 2.5% to 6.4%. Method comparison performed on 126 serum samples against the predicate (BM/Hitachi 911), yielding a slope of 1.09, intercept of -0.60, and correlation coefficient of 0.996.

Technological Characteristics

Homogeneous enzyme immunoassay; competitive binding mechanism. Reagents: lyophilized enzyme acceptor/donor, monoclonal anti-theophylline antibody, substrate (CPRG). Detection: spectrophotometry at 570 nm. Analyzers: BM/Hitachi 704. No software/algorithm complexity described beyond standard photometric quantification.

Indications for Use

Indicated for patients requiring theophylline level monitoring for diagnosis and treatment of theophylline overdose or therapeutic drug management in human serum and plasma.

Regulatory Classification

Identification

A theophylline test system is a device intended to measure theophylline (a drug used for stimulation of the muscles in the cardiovascular, respiratory, and central nervous systems) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of theophylline overdose or in monitoring levels of theophylline to ensure appropriate therapy.

Predicate Devices

• CEDIA® Theophylline Assay: BM/Hitachi 911 (K961462)

Submission Summary (Full Text)

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K961462

510(k) SUMMARY JUN 27 1996

| Subject: | Premarket Notification, 510(k)
CEDIA® Theophylline Assay application: BM/Hitachi 704
Safety and Effectiveness Summary |
| --- | --- |
| Manufacturer: | A Boehringer Mannheim Corporation
2400 Bisso Lane
P.O. Box 4117
Concord CA 94524-4117
Phone (510) 674 - 0667
Fax [phone] |
| Contact: | Betsy Soares-Maddox, Manager of Regulatory Affairs and Quality Assurance |
| Date: | 14 June 1996 |
| Proprietary Name | CEDIA® Theophylline Assay |
| Common Name | Homogeneous Enzyme Immunoassay for the Determination of Theophylline Levels in Serum and Plasma. |
| Classification Name | Theophylline Test System |
| Predicate Device | CEDIA® Theophylline Assay: BM/Hitachi 911 |
| Device Description | CEDIA® Technology
The CEDIA® Theophylline Assay is an in-vitro homogeneous enzyme immunoassay used for the measurement of theophylline in serum and plasma. It is based on competitive binding concepts employing theophylline labeled enzymatic fragments (β-galactosidase) competing with sample theophylline for the theophylline -specific antibody. |

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510(k) SUMMARY cont.

| Device Description cont. | Using recombinant DNA techniques, the β-galactosidase molecule has been split into two totally inactive polypeptide subunits called enzyme acceptor and enzyme donor. Theophylline 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. Theophylline -specific antibody, by binding to the Theophylline 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 theophylline as monitored by the hydrolysis of the substrate chlorophenol red-β-D-galactopyranoside (CPRG). | |
| --- | --- | --- |
| Intended Use | The CEDIA Theophylline Assay is a homogeneous enzyme immunoassay for the in vitro assay of theophylline in human serum and plasma. Measurements are used in the diagnosis and treatment of theophylline overdose and in monitoring levels of theophylline to ensure proper therapy. | |
| Statement of Similarities and Differences | The following table outlines the similarities and differences between the CEDIA Theophylline Assay on the BM/Hitachi 911 to the BM/Hitachi 704. | |
| Parameter | BM/Hitachi 911 | BM/Hitachi 704 |
| Methodology | Homogeneous Enzyme Immunoassay | Homogeneous Enzyme Immunoassay |
| Intended Use | Quantitative Determination of Theophylline in human serum and plasma | Quantitative Determination of Theophylline in human serum and plasma |
| Detection Mechanism | Spectrophotometer at 570 nm | Spectrophotometer at 570 nm |
| Reaction Volumes | | |
| Sample | 3 μL | 4 μL |
| R1 | 130 μL | 185 μL |
| R2 | 130 μL | 170 μL |

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510(k) SUMMARY cont.

| Statement of Similarities and Differences, cont. | | | | | |
| --- | --- | --- | --- | --- | --- |
| Parameter | BM/Hitachi 911 | | BM/Hitachi 704 | | |
| Reagents | Enzyme Acceptor lyophilized with buffer salts, bulking agent, detergent and preservative.
Enzyme Donor lyophilized with substrate, stabilizer and preservative.
Enzyme Acceptor Reconstitution Buffer with primary antibody, buffer salts, monoclonal anti-Theophylline antibody, stabilizer and preservative.
Enzyme Donor Reconstitution Buffer with buffer salts and preservative. | | Same | | |
| Sensitivity (LDD) | 0.8 μg/mL | | 0.8 μg/mL | | |
| Precision | Dose, μg/mL: NCCLS modified | | Dose, μg/mL: NCCLS modified | | |
| Control Level | Low | Mid | High | Low | Mid |
| Within-Run | 5.1 | 15.1 | 29.3 | 4.7 | 15.1 |
| %CV | 3.3 | 1.9 | 1.3 | 5.5 | 2.8 |
| Total | 5.1 | 15.1 | 29.3 | 4.7 | 15.1 |
| %CV | 5.1 | 2.4 | 2.0 | 6.4 | 3.2 |

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510(k) SUMMARY cont.

| Statement of Similarities and Differences, cont. | | | |
| --- | --- | --- | --- |
| Parameter | BM/Hitachi 911 | BM/Hitachi 704 | |
| Method Comparison | | | |
| Versus: | Fluorescene Polarization Immunoassay | BM/Hitachi 911 | |
| Slope | 1.01 | 1.09 | |
| Intercept | -0.38 | -0.60 | |
| Correlation | 0.997 | 0.996 | |
| Performance Characteristics | | | |
| Within-run and total precision were analyzed and the following results were obtained: | | | |
| Within-run | Concentration Level | | |
| | Low | Mid | High |
| Mean, μg/mL | 4.7 | 15.1 | 29.2 |
| SD, μg/mL | 0.26 | 0.42 | 0.62 |
| CV, % | 5.5 | 2.8 | 2.1 |
| N | 120 | 120 | 120 |
| Total Precision | Concentration Level | | |
| | Low | Mid | High |
| Mean, μg/mL | 4.7 | 15.1 | 29.2 |
| SD, μg/mL | 0.30 | 0.48 | 0.72 |
| CV, % | 6.4 | 3.2 | 2.5 |
| N | 120 | 120 | 120 |
| Method Comparison: | | | |
| A total of 126 serum samples having theophylline values throughout the assay range were tested with new CEDIA Theophylline Assay on the BM/Hitachi 911 and the BM/Hitachi 704, and yielded the following results: | | | |
| Number of Observations | Slope | Intercept | Correlation Coefficient |
| 126 | 1.09 | -0.60 | 0.996 |
| The performance information establishes the basis for substantial equivalence to the predicate device. | | | |