CEDIA DIGOXIN

K970881 · Boehringer Mannheim Corp. · KXT · May 14, 1997 · Clinical Toxicology

Device Facts

• Record ID: K970881
• Device Name: CEDIA DIGOXIN
• Applicant: Boehringer Mannheim Corp.
• Product Code: KXT · Clinical Toxicology
• Decision Date: May 14, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3320
• Device Class: Class 2

Intended Use

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

Device Story

CEDIA® Digoxin Assay is a homogeneous enzyme immunoassay for measuring digoxin levels in human serum and plasma. The device utilizes genetically engineered β-galactosidase fragments; these fragments reassociate to form an active enzyme that cleaves a substrate, producing a color change measured spectrophotometrically. In the assay, digoxin in the patient sample competes with analyte-conjugated inactive enzyme fragments for antibody binding sites. Presence of digoxin in the sample allows inactive fragments to reassociate into active enzyme; absence of digoxin results in antibody binding to the conjugate, inhibiting reassociation. The assay is performed on clinical chemistry analyzers (e.g., Hitachi 911). Results are used by clinicians to monitor therapeutic drug levels in patients.

Clinical Evidence

Bench testing only. Performance evaluated via precision studies (N=120 per level), linearity (0.15–4 ng/mL), and method comparison against the predicate (N=99, r=0.9667). Interference testing performed for bilirubin (66 mg/dL), hemoglobin (1000 mg/dL), and triglycerides (100 mg/dL). Specificity evaluated via cross-reactivity testing against various digoxin metabolites.

Technological Characteristics

Homogeneous enzyme immunoassay using genetically engineered β-galactosidase fragments. Detection principle: spectrophotometric measurement at 570 nm. Designed for use on automated clinical chemistry analyzers (e.g., Hitachi 911).

Indications for Use

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

Regulatory Classification

Identification

A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.

Predicate Devices

• Abbott TDx® Digoxin II Assay (K882233)

Reference Devices

• Baxter Dade Stratus (no submission number provided)

Submission Summary (Full Text)

{0}

MAY 14 1997
K970881

# 510(k) Summary

## BOEHRINGER MANNHEIM CORPORATION

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 8240
Fax: [phone]
Contact Person: Yvette Lloyd
Date Prepared: March 6, 1997

2. Device name

Proprietary name: CEDIA® Digoxin Assay
Common name: Homogeneous enzyme immunoassay for the determination of Digoxin.
Classification name: Enzyme immunoassay, Digoxin

3. Predicate device

The Boehringer Mannheim CEDIA® Digoxin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Abbott TDx® Digoxin II Assay (K882233).

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510(k) Summary, Continued

BOEHRINGER
MANNHEIM
CORPORATION
4.
Device
Description

The CEDIA® Digoxin 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, digoxin 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.

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510(k) Summary, Continued

## BOEHRINGER MANNHEIM CORPORATION

Intended use

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

6. Comparison to predicate device

The Boehringer Mannheim CEDIA® Digoxin Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Abbott TDx® Digoxin II Assay (K882233).

The following table compares the CEDIA® Digoxin Assay with the predicate device, Abbott TDx® Digoxin II 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 Digoxin
- Sample type: Serum and plasma
- Assay range: 0.15 - 4 ng/mL

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510(k) Summary, Continued

BOEHRINGER
MANNHEIM
CORPORATION

Comparison
to predicate
device cont.

Differences:

| Feature | CEDIA® Digoxin | TDx Digoxin II |
| --- | --- | --- |
| Reaction test principle | Spectrophotometric 570 nm | Fluorescence Polarization |
| Instrument required | Hitachi 911 | Abbott TDx |

Performance Characteristics:

| Feature | CEDIA® Digoxin | | | TDx Digoxin II | | |
| --- | --- | --- | --- | --- | --- | --- |
| Precision | Modified NCCLS (ng/mL): | | | NCCLS (ng/mL): | | |
| Level | Level 1 | Level 2 | Level 3 | Low | Mid | High |
| N | 120 | 120 | 120 | 50 | 50 | 50 |
| Within run | 1.0 | 1.7 | 3.8 | 0.70 | 1.44 | 3.66 |
| %CV | 4.25 | 3.45 | 1.45 | 5.75 | 3.15 | 1.87 |
| Total | 1.0 | 1.7 | 3.8 | 0.70 | 1.44 | 3.66 |
| %CV | 6.71 | 4.17 | 2.01 | 7.67 | 3.98 | 1.91 |

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510(k) Summary, Continued

BOEHRINGER
MANNHEIM
CORPORATION
Comparison
to predicate
device, (cont.)

Performance Characteristics:

| Feature | CEDIA® Digoxin | TDx Digoxin II |
| --- | --- | --- |
| Lower Detection Limit | 0.15 ng/mL | 0.2 ng/mL |
| Linearity | 0.15 - 4 ng/mL | 0.0 - 4.0 ng/mL |
| Method Comparison | Vs Abbott TDx Digoxin | Vs Baxter Dade Stratus |
| | Least Squares
y =0.97x - 0.17
r=0.9667
N=99 | y =0.94x + 0.08
r=0.962
N=200 |
| | Deming's:
y=1.00x - 0.22
r=0.9667
N=99 | |

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510(k) Summary, Continued

BOEHRINGER
MANNHEIM
CORPORATION
Comparison
to predicate
device, (cont.)

Performance Characteristics:

| Feature | CEDIA® Digoxin | TDx Digoxin II |
| --- | --- | --- |
| Interfering substances | No interference at: (within ±10% of baseline)
15 | No interference at: |
| Bilirubin | 66 mg/dL | 20 mg/dL |
| Hemoglobin | 1000 mg/dL | 1000 mg/dL |
| Triglyceride | 100 mg/dL | 2500 mg/dL |
| Lipemia | 10 g/dL | N/A |
| Total Protein | 100 IU/mL | N/A |
| Rheumatoid Factor | | |
| Specificity | % Cross-reactivity | % Cross-reactivity |
| Digoxigenin | 59.3 | up to 200 |
| β-Acetyldigoxin | 71.3 | not tested |
| α-Acetyldigoxin | 67.5 | not tested |
| Gitalin | 3.7 | not tested |
| Digoxigenin-Mono-Digitoxiside | 100.5 | up to 200 |
| Digitoxin-Bis-Digitoxiside | 77.3 | up to 200 |
| Digitoxin | 17.6 | 4.8 |
| β-Methyldigoxin | 71.3 | not tested |
| 3-Epe-Digoxigenin | 37.5 | not tested |
| Dehydrodigoxigenin | 47.4 | not tested |
| Epi-Digoxigenin-Glucuronide | 40.5 | not tested |