BAYER ADVIA DIGOXIN ASSAY FOR THE INTEGRATED MODULE SYSTEM

K033007 · Bayer Diagnostics Corp. · KXT · Nov 14, 2003 · Clinical Toxicology

Device Facts

• Record ID: K033007
• Device Name: BAYER ADVIA DIGOXIN ASSAY FOR THE INTEGRATED MODULE SYSTEM
• Applicant: Bayer Diagnostics Corp.
• Product Code: KXT · Clinical Toxicology
• Decision Date: Nov 14, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3320
• Device Class: Class 2

Intended Use

The Bayer ADVIA® IMS™ Digoxin assay is for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. Measurements obtained are used as an aid in the diagnosis of digoxin overdose and in monitoring therapeutic levels of digoxin to ensure appropriate therapy.

Device Story

In vitro diagnostic assay for human serum; measures digoxin concentration. Uses heterogeneous competitive magnetic separation principle. Reagents (antibody conjugate, enzyme conjugate, magnetic particles) react with patient sample; alkaline phosphatase-labeled digoxin competes with patient digoxin for antibody binding sites. System incubates at 37°C; magnetic particles capture antibody-hapten complexes; unbound components washed away. pNPP substrate added; alkaline phosphatase activity produces para-nitrophenoxide, measured via absorbance at 405 nm. Dose-response curve inversely proportional to digoxin concentration. Operated on ADVIA IMS Analyzer by laboratory personnel. Output provides quantitative digoxin levels (ng/mL) to assist clinicians in therapeutic drug monitoring and overdose assessment.

Clinical Evidence

Bench testing only. Precision studies (n=76-100 per level) showed total CVs ranging from 2.0% to 9.1%. Analytical sensitivity is 0.04 ng/mL. Method comparison against predicate (n=72) yielded correlation: ADVIA IMS = 1.017 x Immuno 1 + 0.055 (r=0.985). Analytical specificity tested against nine potential cross-reactants; significant cross-reactivity observed for digoxigenin, digoxigenin bis-digitoxoside, digoxigenin mono-digitoxoside, and lanatoside C.

Technological Characteristics

Heterogeneous competitive magnetic separation assay. Two liquid reagents. Storage 2-8 °C. Analytical range 0.04-6 ng/mL. System-specific packaging for ADVIA IMS analyzer.

Indications for Use

Indicated for quantitative measurement of digoxin in human serum for patients requiring monitoring of therapeutic drug levels or diagnosis of digoxin overdose.

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

• Immuno 1 Digoxin Assay (K912616)

Submission Summary (Full Text)

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# NOV 1 4 2003

# 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Digoxin Assay for Bayer ADVIA® Integrated Modular System (IMS)

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K 033 D 07

### 1. Intended Use

The ADVIA IMS® Digoxin method is for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. Measurements obtained are used as an aid in the diagnosis of digoxin overdose and in monitoring therapeutic levels of digoxin to ensure appropriate therapy.

### 2. Predicate Device

| Product Name | Reagents & Calibrators | Controls |
|------------------------|------------------------|----------|
| Immuno 1 Digoxin Assay | K912616 | K885226 |

# 3. Device / Method

| Product Name |
|-------------------------|
| ADVIA IMS Digoxin Assay |

Imprecision

| ADVIA IMS | |
|------------------|----------------|
| Level<br>(ng/mL) | Total<br>CV(%) |
| 0.75 | 6.0 |
| 1.9 | 5.9 |
| 3.3 | 3.8 |

| Immuno 1 | |
|------------------|----------------|
| Level<br>(ng/mL) | Total<br>CV(%) |
| 0.7 | 8.2 |
| 2.2 | 4.2 |
| 3.4 | 3.6 |

#### Correlation (Y= ADVIA IMS, X=comparison system)

| Specimen type | Comparison System (X) | N | Regression Equation | Syx (ng/mL) | R | Sample Range (ng/mL) |
|---------------|-----------------------|----|---------------------|-------------|-------|----------------------|
| Serum | Immuno 1 | 72 | Y=1.017X+0.055 | 0.265 | 0.985 | 0.04 to 4.73 |

#### Interfering Substances

| Interferant | Spiked<br>Concentration<br>(mg/dL) | Expected<br>Concentration<br>(ng/mL) | Observed<br>Concentration<br>(ng/mL) | %<br>Deviation |
|---------------|------------------------------------|--------------------------------------|--------------------------------------|----------------|
| Bilirubin | 25.0 | 0.77 | 0.80 | 3.6 |
| Bilirubin | 25.0 | 2.03 | 2.05 | 0.7 |
| Bilirubin | 25.0 | 3.44 | 3.67 | 6.2 |
| Triglycerides | 1000.0 | 0.73 | 0.72 | -1.7 |
| Triglycerides | 1000.0 | 1.87 | 1.88 | 0.1 |
| Triglycerides | 1000.0 | 3.21 | 3.30 | 3.0 |
| Hemoglobin | 1000.0 | 0.67 | 0.64 | -4.0 |
| Hemoglobin | 1000.0 | 1.82 | 1.71 | -6.9 |
| Hemoglobin | 1000.0 | 3.18 | 3.07 | -3.6 |

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#### Analytical Range

0.04 - 6 ng/mL

## Minimum Detectable Concentration

| ADVIA IMS<br>(ng/mL) | Immuno 1<br>(ng/mL) |
|----------------------|---------------------|
| 0.04 | 0.04 |

# Table of Similarities and Differences between IMS Digoxin and Immuno 1 Digoxin assays:

| Package Insert Sections | ADVIA IMS Digoxin assay | Bayer Immuno 1 Digoxin assay<br>(predicate device) |
|---------------------------------|---------------------------------------------------------------|---------------------------------------------------------------|
| Intended Use | Similar | Similar |
| Summary | Similar | Similar |
| Principle | Heterogeneous Competitive<br>Magnetic Separation Assay | Heterogeneous Competitive<br>Magnetic Separation Assay |
| Reagents | Two liquid reagents contained in<br>system specific packaging | Two liquid reagents contained in<br>system specific packaging |
| Storage | 2-8 °C | 2-8 °C |
| Stability | Similar | Similar |
| Precautions | Similar | Similar |
| Indications of<br>Deterioration | Similar | Similar |
| Performance<br>Characteristics | Similar | Similar |
| Limitations | Similar | Similar |
| Parameters | Similar | Similar |

Clu ets tos

Kenneta T. Edds Manager, Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

9/29/03
Date

Date

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer HealthCare 511 Benedict Avenue Tarrytown, New York 10591-5097

NOV 1 4 2003

Re: k033007

> Trade/Device Name: Digoxin Assay on the Bayer ADVIA IMS® Analyzer Regulation Number: 21 CFR § 862.3320 Regulation Name: Digoxin Test System Regulatory Class: II Product Code: KXT Dated: September 26, 2003 Received: September 26, 2003

Dear Dr. Edds:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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ocid 11-13-200

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510(k) Number: K033007

Device Name: Digoxin Assay for the Advia IMS

Indications for Use:

The Bayer ADVIA® IMS™ Digoxin assay is for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. Measurements obtained are used as an aid in the diagnosis of digoxin overdose and in monitoring therapeutic levels of digoxin to ensure appropriate therapy.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

| Concurrence of CDRH, Office of Device Evaluation (ODE) |
|--------------------------------------------------------|
|--------------------------------------------------------|

*Carol Benson for Jean Cooper, DVM*

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

| 510(k) | K033007 |
|---------------------------------------|----------------------------|
| Prescription Use (Per 21 CFR 801.109) | <div> <span></span> </div> |
| | OR Over-The-CounterUse |

(Optional Format 1-2-96)