ELECSYS DIGOXIN

K973112 · Boehringer Mannheim Corp. · KXT · Oct 10, 1997 · Clinical Toxicology

Device Facts

• Record ID: K973112
• Device Name: ELECSYS DIGOXIN
• Applicant: Boehringer Mannheim Corp.
• Product Code: KXT · Clinical Toxicology
• Decision Date: Oct 10, 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. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.

Device Story

Elecsys Digoxin Assay is an in vitro diagnostic immunoassay for quantitative digoxin measurement in human serum and plasma. Used on the Elecsys 2010 analyzer, the device employs an electrochemiluminescence (ECLIA) competition principle. Sample (10 µL) is incubated with a digoxin-specific ruthenylated antibody; subsequently, streptavidin-coated microparticles and biotin-labeled digoxin derivative are added. The resulting complex binds to the microparticles, which are magnetically captured on an electrode surface. Application of voltage induces chemiluminescent emission, measured by a photomultiplier. Results are calculated via a 2-point calibration curve and a master curve provided by reagent bar codes. The assay assists clinicians in diagnosing digoxin overdose and monitoring therapeutic levels to ensure appropriate patient dosing.

Clinical Evidence

Bench testing only. Performance evaluated via precision studies (N=60 per level), linearity (0.15-5 ng/mL), and method comparison against the predicate (N=357, y=1.03x + 0.10, r=0.9847). Interference testing performed for bilirubin, hemoglobin, lipemia, rheumatoid factor, and biotin. Specificity evaluated against various cross-reactants including digoxigenin and digitoxin.

Technological Characteristics

Electrochemiluminescence immunoassay (ECLIA). Components: ruthenylated antibody, streptavidin-coated microparticles, biotin-labeled digoxin derivative. Instrument: Elecsys 2010 analyzer. Detection: photomultiplier measurement of chemiluminescent emission induced by electrode voltage. Assay range: 0.15-5 ng/mL. Calibration: 2-point calibration with master curve via reagent bar code.

Indications for Use

Indicated for the in vitro quantitative determination of digoxin in human serum and plasma to aid in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure proper therapy.

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)

Submission Summary (Full Text)

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K973112

OCT 1997

| | 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.<br>Submitter<br>name,<br>address,<br>contact | Boehringer Mannheim Corporation<br>2400 Bisso Lane<br>P.O. Box 4117<br>Concord, CA 94524-4117<br>(510) 674 - 0690, extension 8413<br>Fax: [phone]<br>Contact Person: Yvette Lloyd<br>Date Prepared: August 14, 1997 |
| 2.<br>Device name | Proprietary name: Elecsys® Digoxin Assay<br>Common name: Electrochemiluminescent immunoassay for the determination of Digoxin.<br>Classification name: System, Test, Digoxin |
| 3.<br>Predicate<br>device | The Boehringer Mannheim Elecsys® 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). |

Continued on next page

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4. Device Description

Competition principle. Total duration of assay: 18 minutes, 37 ℃. · 1st incubation (9 minutes): By incubating the sample (10 µL) with a digoxinspecific ruthenylated** antibody (80 uL), an immunocomplex is formed, the amount of which is dependent upon the analyte concentration in the sample. · 2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (30 uL) and a digoxin derivative labeled with biotin (80 uL), the still-vacant sites of the ruthenylated antibodies become occupied, with the formation of an antibody-hapten complex. The entire complex becomes bound to the solid phase via interaction of biotin and streptavidin.

·The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).

·Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.

**Tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)2+3)

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# 0(k) Summary, Continued

Image /page/2/Picture/1 description: The image shows the logo for Boehringer Mannheim. The logo consists of a black square with a white circle inside. The word "boehringer" is written in white inside the circle. The word "mannheim" is written vertically in white on the left side of the square.

| 5.<br>Intended use | Immunoassay for the in vitro quantitative determination of Digoxin in human<br>serum and plasma. |
|--------------------|--------------------------------------------------------------------------------------------------|
|--------------------|--------------------------------------------------------------------------------------------------|

6. Comparison to predicate device

The Boehringer Mannheim Elecsys® 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 Elecsys® 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 - 5 ng/mL

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## BOEHRINGENO(k) Summary, Continued MANNHEIM CORPORATION

Image /page/3/Picture/1 description: The image shows a logo with the text "mannheim" vertically aligned on the left side. To the right of this text is a black square containing a white circle. Inside the circle is the text "boehringer" in a stylized font. The logo appears to be for a company named Boehringer Mannheim.

6. Comparison
to predicate device cont.

#### Differences:

| Feature | Elecsys®<br>Digoxin | TDx<br>Digoxin II |
|----------------------------|--------------------------|---------------------------|
| Reaction test<br>principle | Electrochemiluminescence | Fluorescence Polarization |
| Instrument<br>required | Elecsys® 2010 | Abbott TDx |

## Performance Characteristics:

| Feature | Elecsys®<br>Digoxin | | | TDx<br>Digoxin II | | |
|------------|-------------------------|---------|--------|-------------------|------|------|
| Precision | Modified NCCLS (ng/mL): | | | NCCLS (ng/mL): | | |
| Level | Level 1 | Level 2 | Pool 1 | Low | Mid | High |
| N | 60 | 60 | 60 | 50 | 50 | 50 |
| Within run | 1.34 | 3.08 | 0.85 | 0.70 | 1.44 | 3.66 |
| %CV | 3.57 | 3.33 | 5.22 | 5.75 | 3.15 | 1.87 |
| Total | 1.34 | 3.08 | 0.85 | 0.70 | 1.44 | 3.66 |
| %CV | 5.24 | 4.09 | 7.69 | 7.67 | 3.98 | 1.91 |

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## BOEHRINGEA 0(k) Summary, Continued MANNHEIM CORPORATION

Image /page/4/Picture/1 description: The image shows a logo with the word "boehringer" inside of a circle. To the left of the circle is the word "mannheim" written vertically. The logo is black and white and has a horizontal line underneath it.

6. Comparison to predicate device, (cont.)

·

Performance Characteristics:

| Feature | Elecsys®<br>Digoxin | TDx<br>Digoxin II |
|------------------------------------|------------------------------------------------------------------------------------------------------------------------------|---------------------------------------|
| Lower<br>Detection<br>Limit | 0.15 ng/mL | 0.2 ng/mL |
| Linearity | 0.15 - 5 ng/mL | 0.0 - 5.0 ng/mL |
| Method<br>Comparison | Vs Abbott TDx<br>Digoxin | Vs Baxter Dade Stratus |
| | Least Squares:<br>$y =1.03X + 0.10$<br>r=0.9847<br>N=357 | $y =0.94x + 0.08$<br>r=0.962<br>N=200 |
| | Passing Bablock:<br>$y=1.06X + 0.06$<br>r=0.9847<br>N=357 | |
| Feature | Elecsys®<br>Digoxin | TDx<br>Digoxin II |
| Interfering substances | No interference at:<br>(within 0.15 ng/ml at<br>digoxin level <1.5 ng/ml or<br>within ±10% at digoxin<br>level > 1.5 ng/ml.) | No interference at: |
| Bilirubin | | |
| Hemoglobin | 65 mg/dL | 20 mg/dL |
| Lipemia | 1000 mg/dL | 1000 mg/dL |
| Rheumatoid Factor | 1500 mg/dL | 2500 mg/dL |
| Biotin | 1630 IU/mL | N/A |
| | 100 ng/ml | N/A |
| Specificity | % Cross-reactivity | % Cross-reactivity |
| Digoxigenin | 14.28 | up to 200 |
| Digoxingenin-Mono-<br>Digitoxiside | 55.31 | up to 200 |
| Digitoxin-Bis-<br>Digitoxiside | 74.64 | up to 200 |
| Digitoxin | 1.13 | 4.8 |
| Cortisol | <0.01 | <1.0 |
| Canrenone | <0.01 | <1.0 |
| DHEA | 0.01 | <1.0 |
| 16-β-DHEA | <0.01 | not tested |
| Furosemide | <0.01 | <1.0 |
| Ouabain | <0.01 | <1.0 |
| Prednisolone | <0.01 | <1.0 |
| Prednisone | <0.01 | <1.0 |
| Progesterone | <0.01 | <1.0 |
| 17-<br>Hydroxyprogesterone | <0.01 | <1.0 |
| Spironolactone | <0.01 | <1.0 |
| Testosterone | <0.01 | <1.0 |

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#### INGE 0(k) Summary, Continued 30 ANNHEIM CORPORATION

Image /page/5/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of the word "boehringer" inside of a circle. To the left of the circle, the word "mannheim" is written vertically.

6. Comparison
to predicate device, (cont.)

## Performance Characteristics:

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Image /page/6/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's symbol, which is a stylized representation of a human figure. The figure is composed of three curved lines that suggest a person in motion. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Yvette Lloyd Regulatory Affairs Specialist Boehringer Mannheim Corporation 4300 Hacienda Drive Pleasanton, California 94588-2722

OCT 1 0 1997

Re : K973112 Trade Name: Elecsys® Digoxin Assay Regulatory Class: II Product Code: KXT Dated: Auqust 14, 1997 Received: August 20, 1997

Dear Ms. Lloyd:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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, listing 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such Failure to comply with the GMP regulation may result in assumptions. regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): N/A

Device Name: Elecsys® Digoxin Assay

Indications For Use:

Immunoassay for the in vitro quantitative determination of digoxin in human serum and minutedssar for the in Are quarthe diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure proper therapy .

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.

| | | | Concurrence of CDRH, Office of Device Evaluation (ODE) |
|------------------------------------------|---------------------|-----------------------------------------|--------------------------------------------------------|
| Prescription Use<br>(Per 21 CFR 801.109) | | OR | Over-The-Counter Use |
| | | | (Optional Format 1-2-96) |
| | (Division Sign-Off) | Division of Clinical Laboratory Devices | |
| 510(k) Number | | | |