ELECSYS PROBNP IMMUNOASSAY

K032646 · Roche Diagnostics Corp. · NBC · Nov 12, 2003 · Clinical Chemistry

Device Facts

• Record ID: K032646
• Device Name: ELECSYS PROBNP IMMUNOASSAY
• Applicant: Roche Diagnostics Corp.
• Product Code: NBC · Clinical Chemistry
• Decision Date: Nov 12, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

Intended Use

For the in vitro quantitative determination of N-terminal proBrain natriuretic peptide in human serum and plasma. Elecsys proBNP is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome and congestive heart failure. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010, and Modular Analytics E170.

Device Story

Elecsys proBNP is an in vitro diagnostic immunoassay for quantitative measurement of NT-proBNP in human serum or plasma. It utilizes an electrochemiluminescence immunoassay (ECLIA) sandwich principle. Input samples are incubated with biotinylated polyclonal anti-NT-proBNP antibodies and ruthenium-labeled polyclonal anti-NT-proBNP antibodies. The resulting sandwich complex binds to streptavidin-coated microparticles. These microparticles are magnetically captured on an electrode surface within the Roche Elecsys 1010, 2010, or Modular Analytics E170 instruments. Application of voltage induces chemiluminescent emission, measured by a photomultiplier. Results are calculated via a calibration curve generated by a 2-point calibration and a master curve provided by reagent barcodes. The output provides quantitative NT-proBNP concentrations, aiding clinicians in diagnosing congestive heart failure and performing risk stratification for acute coronary syndrome and heart failure patients.

Clinical Evidence

Clinical evidence includes previously established analytical performance (precision, linearity, sensitivity, specificity) from K022516. Clinical sensitivity and specificity were previously established across age and gender cohorts. Additional clinical support for the new indication (risk stratification for acute coronary syndrome and congestive heart failure) is provided by three peer-reviewed literature references (James et al., 2003; Jernberg et al., 2002; Fisher et al., 2003) demonstrating the prognostic utility of the Elecsys proBNP assay.

Technological Characteristics

Electrochemiluminescence immunoassay (ECLIA). Analyte: NT-proBNP. Sample: serum/plasma. Calibration: Elecsys proBNP CalSet. Controls: Elecsys PreciControl proBNP/Cardiac. Analyzers: Elecsys 1010, 2010, MODULAR ANALYTICS E170. Traceability: purified synthetic NTG-proBNP (1-76) in human serum matrix.

Indications for Use

Indicated for individuals suspected of having congestive heart failure (CHF) as a diagnostic aid, and for risk stratification of patients with acute coronary syndrome (ACS) and CHF.

Regulatory Classification

Identification

The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.

Special Controls

*Classification.* Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”

Predicate Devices

• Roche Elecsys proBNP (K022516)
• Triage BNP test (K021317)

Submission Summary (Full Text)

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K032646

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Elecsys® proBNP Immunoassay

# NOV 1 2 2003

## 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. |
|----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitter name, address, contact | Roche Diagnostics Corporation<br>9115 Hague Road<br>Indianapolis, IN 46250<br>(317) 521 - 3544 |
| | Contact Person: Kay A. Taylor |
| | Date Prepared: August 26, 2003 |
| Device Name | Proprietary name: Elecsys® proBNP Immunoassay |
| | Common name: proBNP test |
| | Classification name: Test, Natriuretic Peptide |
| Device Description | A device for the measurement of human proBNP in serum or plasma. |
| Intended use | For the quantitative determination of N-terminal pro-Brain natriuretic peptide. |
| Indications for Use | Elecsys proBNP is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome and congestive heart failure. |

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#### 510(k) Summary, Continued

Substantial The device and test method contained within this premarket notification and described in the labeling is substantially equivalent to other devices legally equivalence marketed in the United States. We claim equivalence to the Roche Elecsys proBNP (K022516). Both products are intended for use in the quantitative determination of brain natriuretic peptides. The Triage BNP test (K021317) is used as predicate method for the conceptual description of how a biochemical marker can be used to provide prognostic information to a physician. Although this predicate method describes a different analyte, the description of how the test results should be interpreted with respect to the prognosis of the patient are substantially equivalent.

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Substantial equivalence comparison

The following table compares the Elecsys proBNP Immunoassay with the predicate devices.

| Feature | Elecsys proBNP<br>(K022516) | Elecsys proBNP<br>(add'l indication) | Triage BNP<br>(K021317) |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Immunoassay for the in vitro<br>quantitative determination of N-<br>terminal pro-Brain natriuretic<br>Peptide in human serum and<br>plasma. | Immunoassay for the in vitro<br>quantitative determination of N-<br>terminal pro-Brain natriuretic<br>peptide in human serum and<br>plasma. | The Triage BNP test is intended for<br>use with the Triage Meter for the<br>rapid in vitro quantitative<br>measurement of B-Type Natriuretic<br>Peptide (BNP) in human whole<br>blood or plasma specimens using<br>EDTA as the anticoagulant. |
| Indication for Use | The Elecsys proBNP is intended<br>for use as an aid in the diagnosis of<br>individuals suspected of having<br>congestive heart failure. | Elecsys proBNP is used as an aid<br>in the diagnosis of individuals<br>suspected of having congestive<br>heart failure. The test is further<br>indicated for the risk stratification<br>of patients with acute coronary<br>syndrome and congestive heart<br>failure. | The test is used as an aid in the<br>diagnosis and assessment of<br>severity of congestive heart failure.<br>The test also is used for the risk<br>stratification of patients with acute<br>coronary syndromes. |
| Assay Protocol | Electrochemiluminescent<br>Immunoassay | Same Elecsys proBNP (K022516) | Fluorescence immunoassay |
| Traceability /<br>Standardization | Reference standard - purified<br>synthetic NTG-proBNP (1-76) in<br>human serum matrix | Same Elecsys proBNP (K022516) | Not available |
| Feature | Elecsys proBNP<br>(K022516) | Elecsys proBNP<br>(add'l indication) | Triage BNP<br>(K021317) |
| Calibration Interval | E170/E2010 After 1 month when using the same reagent lot After 7 days when using the same reagent kit E1010 With every reagent kit After 7 days (20-25°C) After 3 days (25-32°C) | Same Elecsys proBNP (K022516) | Per lot |
| Sample Type | Human serum and plasma | Same Elecsys proBNP (K022516) | EDTA whole venous blood or plasma |
| Reagent Stability | Unopened Up to stated expiration date stored at 2-8°C Opened 12 weeks at 2-8° 8 weeks on E170 8 weeks on E2010 4 weeks on E1010 (20-25° ambient temp - up to 20 hours opened in total) | Same Elecsys proBNP (K022516) | In sealed pouch if stored refrigerated until the expiration date printed on the device if stored at room temperature for 14 days (w/I expiration) do not remove device from pouch until ready to use. |
| Calibrator | Elecsys proBNP CalSet | Same Elecsys proBNP (K022516) | Reagent Code Chip |
| Controls | Elecsys PreciControl proBNP | Elecsys PreciControl proBNP<br>Elecsys PreciControl Cardiac | Triage BNP Controls |
| Result Interpretation | 125 pg/ml for patients younger than 75 years and 450 pg/ml for patients 75 years and older. | Same Elecsys proBNP (K022516) | 100 pg/ml |
| Feature | Elecsys proBNP<br>(K022516) | Elecsys proBNP<br>(add'l indication) | Triage BNP<br>(K021317) |
| Instrument | Elecsys 1010, Elecsys 2010 and<br>MODULAR analytics E170 family<br>of analyzers | Same Elecsys proBNP (K022516) | Triage Meter |
| Measuring Range | 5-35,000 pg/mL | Same Elecsys proBNP (K022516) | 5 - 5000 ng/mL |

#### Table 3 - Comparison to Predicate Device

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Substantial The performance characteristics of the Elecsys proBNP Immunoassay and the predicate device are compared in the equivalence table below. performance characteristics

| Feature | Elecsys proBNP<br>(add'l indication) | Elecsys proBNP<br>(K022516) | Triage BNP<br>(K021317) |
|-----------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Precision | E170 - Within run<br>0.9%CV @ 474 pg/mL<br>1.1%CV @ 8005 pg/mL<br>0.9%CV @ 13682 pg/mL<br>E170 - Total<br>5.8%CV @ 494 pg/mL<br>4.1%CV @ 7827 pg/mL<br>3.7%CV @ 13143 pg/mL<br>E1010/2010 – Within run<br>2.7%CV @ 175 pg/mL<br>2.4%CV @ 355 pg/mL<br>1.9%CV @ 1068 pg/mL<br>1.8%CV @ 4962 pg/mL<br>E1010/2010 - Total<br>3.2%CV @ 175 pg/mL<br>2.9%CV @ 355 pg/mL<br>2.6%CV @ 1068 pg/mL<br>2.3%CV @ 4962 pg/mL | Same Elecsys proBNP (K022516) | Within Day<br>8.8%CV @ 71.3 pg/mL<br>11.0%CV @ 629.9 pg/mL<br>11.6%CV @ 4087.9 pg/mL<br>Total<br>9.9%CV @ 71.3 pg/mL<br>12.0%CV @ 629.9 pg/mL<br>12.2%CV @ 4087.9 pg/mL |

### Table 4 - Comparison to Predicate Device - Performance Characteristics

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| Feature | Elecsys proBNP<br>(add'l indication) | Elecsys proBNP<br>(K022516) | Triage BNP<br>(K021317) |
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Hook Effect | No effect up to 300,000 pg/ml | Same Elecsys proBNP (K022516) | Not available |
| Analytical Sensitvity | 5 pg/mL | Same Elecsys proBNP (K022516) | < 5 pg/ml |
| Limitations | No interference from bilirubin up to 35 mg/dL No interference from hemoglobin up to 1.4 g/dL No interference from triglycerides up to 4000 mg/dL No interference with biotin up to 30 ng/mL No interference from rheumatoid factor up to 1500 IU/mL In patients receiving high biotin doses > 5 mg/dL, sample should not be taken until 8 hours after administration. Rare occurrence of interference from high titers of anti-streptavidin and ruthenium Use in conjunction with patient medical history, clinical exam and other findings | Same Elecsys proBNP (K022516) | No interference from bilirubin up to 20 mg/dL No interference from hemoglobin up to 10,000 mg/dL No interference up to cholesterol up to 1,000 mg/dL No interference up to triglycerides up to 1,000 mg/dL No significant effect from hematocrit between 27% and 51%. |

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal features a stylized image of an eagle with three lines representing its wings. The eagle is positioned within a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged around the circumference of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Kay A. Taylor, MT (ASCP), RAC Regulatory Program Principal Centralized Diagnostic Submissions Roche Diagnostics Corporation 9115 Hague Road Indianapolis, Indiana 46256

NOV 1 2 2003

k032646 Re:

> Trade/Device Name: Elecsys® proBNP Immunoassay Regulation Number: 21 CFR § 862.1117 Regulation Name: B-type natriuretic peptide test system (BNP) Regulatory Class: II Product Code: NBC Dated: August 26, 2003 Received: August 27, 2003

Dear Ms. Taylor:

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, 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 (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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Page 2 -

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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Elecsys® proBNP Immunoassay

## Indications for Use Statement

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

Device Name:

Elecsys® proBNP Immunoassay

Indications For Use:

For the in vitro quantitative determination of N-terminal proBrain natriuretic peptide in human serum and plasma.

Elecsys proBNP is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome and congestive heart failure.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use ------

(Optional Format 1-2-96)

Alberto Suts

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**Division Sign-Off** for Jean Cooper

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K032446

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