ELECSYS PROBNP II, PRECICONTROL CARDIAC II, PROBNP II CALSET

K072437 · Roche Diagnostics · NBC · Feb 5, 2008 · Clinical Chemistry

Device Facts

• Record ID: K072437
• Device Name: ELECSYS PROBNP II, PRECICONTROL CARDIAC II, PROBNP II CALSET
• Applicant: Roche Diagnostics
• Product Code: NBC · Clinical Chemistry
• Decision Date: Feb 5, 2008
• 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. Elecsys proBNP II assay 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. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers. The Elecsys PreciControl Cardiac II is used for quality control of specified immunoassays on the Elecsys and cobas e immunoassay analyzers. The Elecsys proBNP II CalSet is used for calibrating the quantitative Elecsys proBNP II assay on the Elecsys and cobas e immunoassay analyzers.

Device Story

Elecsys proBNP II is an electrochemiluminescence immunoassay (ECLIA) for quantitative measurement of NT-proBNP in human serum/plasma. Device uses sandwich principle: antigen in sample binds to biotinylated monoclonal anti-NT-proBNP antibody and ruthenium-labeled monoclonal anti-NT-proBNP antibody. Complex binds to streptavidin-coated microparticles; microparticles captured magnetically on electrode surface. Voltage application induces chemiluminescent emission measured by photomultiplier. Used on Roche Elecsys and cobas e analyzers in clinical laboratory settings. Results aid diagnosis of congestive heart failure, risk stratification for acute coronary syndrome/heart failure, and assessment of cardiovascular event risk in stable coronary artery disease. Output is quantitative concentration (pg/mL) used by clinicians to guide management.

Clinical Evidence

Clinical evidence relies on method comparison and concordance studies against the predicate. Comparison of 1551 clinical samples (range 5-32,627 pg/mL) showed high correlation (r=0.996). Concordance testing on reference and diseased groups (NYHA classes I-IV) demonstrated 97.6-100% agreement with the predicate. Clinical sensitivity and specificity data were previously established under k022516, showing sensitivity ranging from 81.6-94.3% and specificity from 57.8-95.7% across age/gender subgroups. No new clinical trials were required for this modification.

Technological Characteristics

Two-step sandwich immunoassay; streptavidin-coated microparticles; electrochemiluminescence detection. Reagents, calibrators, and controls are liquid or lyophilized serum-based products. Compatible with Elecsys and cobas e series analyzers. Measuring range: 5-35,000 pg/mL. No specific material standards or software algorithm class provided.

Indications for Use

Indicated for individuals suspected of having congestive heart failure, patients with acute coronary syndrome, and patients with stable coronary artery disease at risk for heart failure. Used for in vitro quantitative determination of NT-proBNP in human serum and plasma.

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

• Elecsys proBNP Immunoassay (k051382)
• Elecsys proBNP Immunoassay (k022516)
• Elecsys proBNP Immunoassay (k032646)

Submission Summary (Full Text)

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# K672437

# 510(k) Summary

FEB - 5 2008

| Introduction | According to the requirements of 21 CFR 807.92, the following information<br>provides sufficient detail to understand the basis for a determination of<br>substantial equivalence. | | |
|----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
| Submitter<br>name, address,<br>contact | Roche Diagnostics Corporation<br>9115 Hague Road<br>Indianapolis, IN 46250<br>[phone] | | |
| | Contact Person: Kay Taylor | | |
| | Date Prepared: January 28, 2008 | | |
| Device Name | Proprietary name: 1.) Elecsys® proBNP II Immunoassay<br>2.) Elecsys® PreciControl Cardiac II<br>3.) Elecsys® proBNP II CalSet<br><br>Common name:<br>1.) proBNP Assay<br>2.) PreciControl Cardiac<br>1.) proBNP CalSet<br><br>Classification name: 1.) Test, Natriuretic Peptide<br>2.) Multi-Analyte Controls, All Kinds (Assayed and<br>Unassayed)<br>3.) Calibrator, Secondary | | |

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| Description | 1.) The Elecsys proBNP II Assay is a two step sandwich immunoassay with<br>streptavidin microparticles and electrochemiluminescence detection.<br>Results are determined using a calibration curve that is generated<br>specifically on each instrument by a 2 point calibration and a master curve<br>provided with the reagent bar code.<br>2.) The Elecsys PreciControl Cardiac II is a lyophilized product consisting of<br>human serum with added CK-MB, Digitoxin (not for use in U.S),<br>Digoxin, Myoglobin, and NT-proBNP 1-76 in two concentration ranges.<br>During manufacture, the analytes are spiked into the matrix at the desired<br>concentration levels.<br>3.) The Elecsys proBNP II CalSet is a lyophilized product consisting of<br>equine serum with added NT-proBNP 1-76 in two concentration ranges.<br>During manufacture, the analyte is spiked into the matrix at the desired<br>concentration levels.<br>Note: The reagent, calibrator, and quality control material are all packaged<br>separately. |
|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use /<br>Indications for<br>Use | Elecsys proBNP II: Immunoassay for the in vitro quantitative determination<br>of N-terminal pro-Brain natriuretic peptide in human serum and plasma.<br>Elecsys proBNP II assay is used as an aid in the diagnosis of individuals<br>suspected of having congestive heart failure. The test is further indicated for<br>the risk stratification of patients with acute coronary syndrome and congestive<br>heart failure. The test may also serve as an aid in the assessment of increased<br>risk of cardiovascular events and mortality in patients at risk for heart failure<br>who have stable coronary artery disease.<br>The electrochemiluminescence immunoassay "ECLIA" is intended for use on<br>Elecsys and cobas e immunoassay analyzers.<br>The Elecsys PreciControl Cardiac II is used for quality control of specified<br>immunoassays on the Elecsys and cobas e immunoassay analyzers.<br>The Elecsys proBNP II CalSet is used for calibrating the quantitative<br>Elecsys proBNP II assay on the Elecsys and cobas e immunoassay analyzers. |

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| Substantial<br>equivalence | The Elecsys proBNP II Test System is substantially equivalent to other<br>devices legally marketed in the United States.<br>1.) Elecsys proBNP II Immunoassay is equivalent to the Elecsys proBNP<br>Immunoassay (K051382). |
|----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | 2.) Elecsys PreciControl Cardiac II is equivalent to Elecsys PreciControl<br>Cardiac (K032089).<br>3.) Elecsys proBNP II CalSet is equivalent to Elecsys proBNP CalSet<br>(K022516). |

| Device | The following table compares the Elecsys proBNP II test system with the |
|--------------|-------------------------------------------------------------------------|
| Comparison - | predicate device (K051382). |
| Immunoassay | |

| Immunoassay | | |
|----------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys proBNP II Assay | Elecsys proBNP Assay<br>(K051382)Predicate |
| Intended Use /<br>Indication for Use | Immunoassay for the <i>in vitro</i><br>quantitative determination of N-<br>terminal pro-Brain □atriuretic<br>peptide in human serum and<br>plasma. The Elecsys proBNP assay<br>is used as an aid in the diagnosis of<br>individuals suspected of having<br>congestive heart failure. The test is<br>further indicated for the risk<br>stratification of patients with acute<br>coronary syndrome and congestive<br>heart failure. The test may also<br>serve as 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.<br><br>The electrochemiluminescence<br>immunoassay “ECLIA” is intended<br>for use on Elecsys and cobas e<br>immunoassay analyzers. | Same<br><br>The electrochemiluminescence<br>immunoassay “ECLIA” is intended<br>for use on the Elecsys 1010/2010<br>and MODULAR ANALYTICS<br>E170 (Elecsys module)<br>immunoassay analyzers. |
| | Immunoassay | |
| Feature | Elecsys proBNP II Assay | Elecsys proBNP Assay<br>(K051382)Predicate |
| Analyzer Platforms | Elecsys 1010<br>Elecsys 2010 / cobas e 411<br>MODULAR ANALYTICS E170<br>(Elecsys module) / cobas e 601 | Elecsys 1010<br>Elecsys 2010<br>MODULAR ANALYTICS E170<br>(Elecsys module) |
| Assay Protocol | Sandwich Principle | Same |
| Detection Protocol | Electrochemiluminescent | Same |
| Traceability /<br>Standardization | Standardized against the Elecsys<br>proBNP assay. | Reference standard - purified<br>synthetic NT-proBNP (1-76) in<br>equine serum matrix |
| Calibration Interval | E170/E2010/ cobas e analyzers<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) | E170/E2010<br>• After 1 month (28 days) when<br>using the 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) |
| Sample Type | Human serum and plasma | Same |
| 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/cobas e<br>601<br>• 8 weeks on E2010/ cobas e<br>411<br>• 4 weeks on E1010 (20-25°<br>ambient temp, up to 20<br>hours opened in total) | 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<br>hours opened in total) |
| Calibrator | Elecsys proBNP II CalSet | Elecsys proBNP CalSet |
| Controls | Elecsys PreciControl Cardiac II | Elecsys PreciControl Cardiac |
| Result Interpretation | 125 pg/ml for patients younger than<br>75 years and 450 pg/ml for patients<br>75 years and older | Same |
| Feature | Elecsys proBNP II Assay | Elecsys proBNP Assay<br>(K051382)Predicate |
| Instrument | Elecsys 1010, Elecsys 2010, cobas<br>e 411, cobas e 601, and<br>MODULAR analytics E170 family<br>of analyzers | Elecsys 1010<br>Elecsys 2010<br>MODULAR ANALYTICS E170<br>(Elecsys module) |
| Measuring Range | 5-35,000 pg/mL | Same |
| Precision | E170 and cobas e601 – Within run | E170 - Within run |
| | 1.9% CV @ 64 pg/mL | 0.9% CV @ 474 pg/mL |
| | 1.5% CV @ 124 pg/mL | 1.1% CV @ 8005 pg/mL |
| | 1.3% CV @ 14142 pg/mL | 0.9% CV @ 13682 pg/mL |
| | 1.8% CV @ 77.0 pg/mL | 0.8% CV @ 208 pg/mL |
| | 1.2% CV @ 2105 pg/mL | 3.0% CV @ 3786 pg/mL |
| | E170 and cobas e601 - Total | E170 - Total |
| | 3.1% CV @ 46 pg/mL | 5.8% CV @ 494 pg/mL |
| | 2.7% CV @ 125 pg/mL | 4.1% CV @ 7827 pg/mL |
| | 1.7% CV @ 32930 pg/mL | 3.7% CV @ 13143 pg/mL |
| | 2.7% CV @ 77.0 pg/mL | 4.5% CV @ 200 pg/mL |
| | 2.7% CV @ 2170 pg/mL | 3.6% CV @ 4002 pg/mL |
| | E1010/2010 and cobas e 411 –<br>Within run | E1010/2010 - Within run |
| | 4.2%CV @ 44.0 pg/mL | 2.7% CV @ 175 pg/mL |
| | 2.4%CV @ 126 pg/mL | 2.4% CV @ 355 pg/mL |
| | 1.3%CV @ 2410 pg/mL | 1.9% CV @ 1068 pg/mL |
| | 2.7%CV @ 33606 pg/mL | 1.8% CV @ 4962 pg/mL |
| | 2.58% CV @ 82.0 pg/mL | 1.8% CV @ 434 pg/mL |
| | 1.18% CV @ 2318 pg/mL | 1.8% CV @ 6781 pg/mL |
| | | |
| | E1010/2010 and cobas e411 –<br>Total | E1010/2010 - Total |
| | 4.6%CV @ 44.0 pg/mL | 3.2% CV @ 175 pg/mL |
| | 2.6%CV @ 126 pg/mL | 2.9% CV @ 355 pg/mL |
| | 1.8%CV @ 2410 pg/mL | 2.6% CV @ 1068 pg/mL |
| | 3.8%CV @ 33606 pg/mL | 2.3% CV @ 4962 pg/mL |
| | 2.8% CV @ 82.0 pg/mL | 2.4% CV @ 434 pg/mL |
| | 1.6% CV @ 2318 pg/mL | 2.2% CV @ 6781 pg/mL |
| | | |
| Immunoassay, continued | | |
| Feature | Elecsys proBNP II Assay | Elecsys proBNP Assay<br>(K051382)Predicate |
| Hook Effect | No effect up to 300,000 pg/mL | same |
| Analytical Sensitivity | 5 pg/mL | same |
| Method Comparison | Elecsys proBNP II (y) compared to<br>Elecsys proBNP (x): linear<br>regression (y= 1.0x – 21.74);<br>Passing/Bablok (y= 0.98x – 0.31) | n.a. |
| Limit of Blank /<br>Analytical Sensitivity | 1.72 pg/mL…