ELECSYS PROBNP IMMUNOASSAY

K051382 · Roche Diagnostics Corp. · NBC · Dec 5, 2005 · Clinical Chemistry

Device Facts

• Record ID: K051382
• Device Name: ELECSYS PROBNP IMMUNOASSAY
• Applicant: Roche Diagnostics Corp.
• Product Code: NBC · Clinical Chemistry
• Decision Date: Dec 5, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

Intended Use

Immunoassay for the in vitro quantitative determination of N-terminal pro-Brain Natriuretic Peptide in human serum and plasma.

Device Story

Elecsys proBNP is an in vitro quantitative immunoassay; utilizes electrochemiluminescence (ECLIA) sandwich principle. Input: human serum or plasma samples. Process: sample incubated with biotinylated polyclonal NT-proBNP-specific antibody and ruthenium-labeled polyclonal NT-proBNP-specific antibody; complex captured on streptavidin-coated microparticles; microparticles magnetically captured on electrode surface; voltage application induces chemiluminescent emission measured by photomultiplier. Output: quantitative NT-proBNP concentration determined via calibration curve. Used in clinical laboratory settings on Roche Elecsys 1010, 2010, and MODULAR ANALYTICS E170 analyzers. Results assist clinicians in diagnosing congestive heart failure, stratifying risk in acute coronary syndrome/heart failure patients, and assessing cardiovascular event/mortality risk in stable coronary artery disease patients.

Clinical Evidence

No new clinical trials were conducted. Substantial equivalence for the expanded indication is supported by three peer-reviewed literature articles (Schnabel et al., 2005; Kragelund et al., 2005; Ndrepepa et al., 2005) demonstrating the prognostic value of NT-proBNP in patients with stable coronary artery disease. Analytical performance (precision, sensitivity, interference) was verified via bench testing.

Technological Characteristics

Electrochemiluminescent immunoassay (ECLIA). Analyzers: Elecsys 1010, 2010, and MODULAR analytics E170. Measuring range: 5-35,000 pg/mL. Analytical sensitivity: 5 pg/mL. Calibration: synthetic NTG-proBNP (1-76) in human serum matrix. Reagents: Elecsys proBNP CalSet and PreciControl Cardiac.

Indications for Use

Indicated for individuals suspected of having congestive heart failure, risk stratification of patients with acute coronary syndrome or congestive heart failure, and assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure who have stable coronary artery disease.

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 Diagnostics Elecsys® proBNP Immunoassay (k022516)
• Roche Diagnostics Elecsys® proBNP Immunoassay (k032646)

Submission Summary (Full Text)

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K05/382

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Elecsys® proBNP Immunoassay Expanded Intended Use Submission

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# 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: Theresa M. Ambrose |
| | Date Prepared: Nov 28, 2005 |
| Device Name | Proprietary name: Elecsys® proBNP Immunoassay |
| | Common name: proBNP test |
| | Classification name: Test, Natriuretic Peptide |
| Description | A device for the measurement of human proBNP in serum or plasma. |
| Intended use | Immunoassay for the in vitro quantitative determination of N-terminal pro-Brain Natriuretic Peptide in human serum and plasma. |
| 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 or congestive heart failure. The test may also serve as an aid in the assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure who have stable coronary artery disease. |
| Substantial equivalence | The device and test method contained within this premarket notification and described in the labeling is substantially equivalent to other devices legally marketed in the United States. We claim equivalence to the Roche Elecsys proBNP (K032646). |

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The following table compares the Elecsys proBNP Test System with the Substantial predicate device. equivalence comparison

| Feature | Elecsys proBNP<br>Expanded Intended Use | Elecsys proBNP<br>(K032646) Predicate |
|-----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 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. | same |
| Indication for Use | 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 or congestive heart<br>failure. The test may also serve as<br>an aid in the assessment of<br>increased risk of cardiovascular<br>events and mortality in patients at<br>risk for heart failure who have<br>stable coronary artery disease. | 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. |
| Assay Protocol | Electrochemiluminescent<br>Immunoassay | Same |
| Traceability /<br>Standardization | Reference standard - purified<br>synthetic NTG-proBNP (1-76) in<br>human serum matrix | Same |
| Calibration Interval | E170/E2010<br>• After 1 month when using the<br>same reagent lot<br>• After 7 days when using the<br>same reagent kit<br>E1010<br>• With every reagent kit<br>• After 7 days (20-25°C)<br>• After 3 days (25-32°C) | Same |
| Sample Type | Human serum and plasma | Same |

### Table 3 - Comparison to Predicate Device

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| Feature | Elecsys proBNP<br>Expanded Intended Use | Elecsys proBNP<br>(K032646) Predicate |
|-----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|
| Reagent Stability | Unopened<br>• Up to stated expiration date<br>stored at 2-8°C<br>Opened<br>• 12 weeks at 2-8°<br>• 8 weeks on E170<br>• 8 weeks on E2010<br>• 4 weeks on E1010 (20-25°<br>ambient temp - up to 20 hours<br>opened in total) | Same |
| Calibrator | Elecsys proBNP CalSet | Same |
| Controls | Elecsys PreciControl Cardiac | Elecsys PreciControl proBNP<br>Elecsys PreciControl Cardiac |
| Result Interpretation | 125 pg/ml for patients younger<br>than 75 years and 450 pg/ml for<br>patients 75 years and older. | Same |
| Instrument | Elecsys 1010, Elecsys 2010 and<br>MODULAR analytics E170 family<br>of analyzers | Same |
| Measuring Range | 5-35,000 pg/mL | Same |

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The performance characteristics of the Elecsys proBNP Immunoassay and the predicate Substantial equivalence table below. performance characteristics

| Feature | Elecsys proBNP<br>(add'l indication) | Elecsys proBNP<br>(K022516) |
|-----------|--------------------------------------|-----------------------------|
| Precision | E170 - Within run | Same |
| | 0.9%CV @ 474 pg/mL | |
| | 1.1%CV @ 8005 pg/mL | |
| | 0.9%CV @ 13682 pg/mL | |
| | E170 - Total | |
| | 5.8%CV @ 494 pg/mL | |
| | 4.1%CV @ 7827 pg/mL | |
| | 3.7%CV @ 13143 pg/mL | |
| | E1010/2010 – Within run | |
| | 2.7%CV @ 175 pg/mL | |
| | 2.4%CV @ 355 pg/mL | |
| | 1.9%CV @ 1068 pg/mL | |
| | 1.8%CV @ 4962 pg/mL | |
| | E1010/2010 – Total | |
| | 3.2%CV @ 175 pg/mL | |
| | 2.9%CV @ 355 pg/mL | |
| | 2.6%CV @ 1068 pg/mL | |
| | 2.3%CV @ 4962 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) |
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------|
| Hook Effect | No effect up to 300,000 pg/ml | Same |
| Analytical Sensitvity | 5 pg/mL | Same |
| 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 |

Three literature articles were provided in support of the expanded intended Support for claim use:

- 1. Schnabel R, Rupprecht HJ, Lackner KJ, Lubos E, Bickel C, et al. Analysis of N-Terminal-pro-Brain Natriuretic Peptide and C-Reactive Protein for Risk Stratification in Stable and Unstable Coronary Artery Disease: Results from the AtheroGene Study. European Heart Journal, 2005. 26(3):241-249.
- 2. Kragelund C, Groenning B, Kober L, Hildebrandt P and Steffensen R. N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease. The New England Journal of Medicine, 2005. 352(7):666-675.
- 3. Ndrepepa G, Braun S, Niemoller K, Mehilli J, von Beckerath N, et al. Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Chronic Stable Angina. Circulation, 2005. 112:2102-2107.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features three abstract shapes resembling birds in flight. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

2005 DEC 5

Theresa M. Ambrose, PhD, RAC Regulatory Affairs Principal Roche Diagnostics Corporation 9115 Hague Road Indianapolis, IN 46250

Re: k051382

Trade/Device Name: Elecsys proBNP Immunoassay Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC Dated: October 14, 2005 Received: October 17, 2005

Dear Dr. Ambrose:

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).

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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 promative results in a classification for your device and thus, permits your device to proceed to the market.

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/industry/support/index.html.

Sincerely vours,

Alberto Guez

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known): k051382

Elecsys proBNP Immunoassay Device Name:

Indications For Use:

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

peptial in hamall ver an aid in the diagnosis of individuals suspected of having Electy proDities is as a the test is further indicated for the risk stratification of contents with acute coronary syndrome or congestive heart failure . The test may patients with assessment of increased risk of cardiovascular events and anso ser re as an and and failure who have stable coronary artery disease.

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

Prescription Use XXX

AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

CHS

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