ACS:180 AND ADVIA CENTAUR B-TYPE NATRIURETIC PEPTIDE (BNP) ASSAYS

K043228 · Bayer Healthcare, LLC · NBC · Apr 22, 2005 · Clinical Chemistry

Device Facts

• Record ID: K043228
• Device Name: ACS:180 AND ADVIA CENTAUR B-TYPE NATRIURETIC PEPTIDE (BNP) ASSAYS
• Applicant: Bayer Healthcare, LLC
• Product Code: NBC · Clinical Chemistry
• Decision Date: Apr 22, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

Intended Use

For in vitro diagnostic use in the quantitative determination of B-type natriuretic peptide (BNP) in human plasma using the ADVIA Centaur® System. This assay is indicated for the measurement of plasma BNP as an aid in the diagnosis and assessment of severity of heart failure. In patients with acute coronary syndromes (ACS), this test, in conjunction with other known risk factors, can also be used to predict survival as well as to predict the likelihood of future heart failure. This assay is not intended for use on any other system. For in vitro diagnostic use in the quantitative determination of B-type natriuretic peptide (BNP) in human plasma using the ACS:180® System. This assay is indicated for the measurement of plasma BNP as an aid in the diagnosis and assessment of severity of heart failure. In patients with acute coronary syndromes (ACS), this test, in conjunction with other known risk factors, can also be used to predict survival as well as to predict the likelihood of future heart failure. This assay is not intended for use on any other system.

Device Story

Fully automated two-site sandwich chemiluminescence immunoassay; uses acridinium ester-labeled monoclonal mouse anti-BNP and biotinylated monoclonal mouse anti-BNP coupled to streptavidin-coated paramagnetic particles. Sample incubated with reagents; unbound conjugates washed away; chemiluminescent signal measured in luminometer. Signal intensity proportional to BNP concentration. Used in clinical laboratories by technicians; results interpreted by physicians to aid heart failure diagnosis, severity assessment, and prognosis in ACS patients. Benefits include rapid, objective quantification of BNP levels to inform clinical decision-making.

Clinical Evidence

No clinical study data provided in the summary document; substantial equivalence based on analytical performance characteristics including precision (1.8-9.9% CV), analytical sensitivity, dilution recovery, and lack of interference from common substances (hemoglobin, triglycerides, cholesterol, urea, creatinine, bilirubin, IgG).

Technological Characteristics

Chemiluminescence immunoassay; two-site sandwich format. Reagents: monoclonal mouse anti-human BNP antibodies. Energy source: automated system-based chemiluminescence detection. Sample type: EDTA plasma. Connectivity: Integrated with ADVIA Centaur or ACS:180 systems. Sterilization: N/A (reagent-based).

Indications for Use

Indicated for quantitative determination of BNP in human plasma as an aid in diagnosis and severity assessment of heart failure. In patients with acute coronary syndromes (ACS), used with other risk factors to predict survival and likelihood of future heart failure.

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

• Bayer Diagnostics ADVIA® Centaur® BNP Assay (k031038)
• Bayer Diagnostics ACS:180® BNP Assay (k040425)

Submission Summary (Full Text)

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# Bayer Diagnostics ADVIA Centaur BNP Assay

APR 2 2 2005

## Summary of Safety and Effectiveness

This Summary of Safety and Effectiveness has been prepared in accordance with the Inis Summary of Sufey and "Effectives" has "Securition to understand the basis for a determination of substantial equivalence.

| 1. Submitter Information | |
|--------------------------|---------------------------------------------------------------------------------------|
| Contact Person: | Carol Bianca |
| Address: | Bayer Healthcare - Diagnostics Division<br>511 Benedict Ave.<br>Tarrytown, N.Y. 10591 |
| | Phone: [phone]<br>Fax: [phone]<br>e-mail: [e-mail] |
| Date Summary Prepared: | October 18, 2004 |
| 2. Device Information | |
| Propriety Name: | ACS:180® and ADVIA Centaur® B-Type Natriuretic<br>Peptide (BNP) Assays |
| Common Name: | BNP assays |
| Classification Name: | B-type natriuretic peptide test systems |
| Class: | -II |
| CFR: | 21 CFR 862.1117 |
| Product Code: | NBC |

# 3. Predicate Device Information

| Name: | ADVIA Centaur ® B-Type Natriuretic Peptide (BNP) Assay |
|-----------------|---------------------------------------------------------------------------------------|
| Manufacturer: | Bayer Healthcare - Diagnostics Division<br>511 Benedict Ave.<br>Tarrytown, N.Y. 10591 |
| 510(k) Numbers: | K031038; K040425 |

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### 4. Device Description

The ACS:180 and ADVIA Centaur BNP assays are fully automated two-site sandwich The ACS. Too and ADVIN Ochtair Dr. Which use constant amounts of Immundassays using direct chemich.noosent issume is in the Reagent, is an acridinium ester two monoclonal antioodies: The first artissoft in the ting structure labeled monoconal mouse and haman is a biotinylated monoclonal mouse antiof BNP. The second antibody, in the C-terminal portion of BNP, which is coupled to streptavidin numan antibody specific to the O terminal portion or control materials) is incubated for 5 mightene particles. Thaten comple (cambreton the tracer antibody conjugate. minutes at 37 0 with the ERS Reagent is added and incubated for 2.5 minutes at 37°C. An Subsequently, Solla Frase reagont to added in the sample and the two antibody infinuno-complex is Tormed bothern the unbound antibody conjugates are washed away. Confider . Following noducal in muno-complex signal is measured in a luminometer. The Gremiumninescents of the will have a minimum amount of bound AE label, while Samples with high levels of BNP will have maximum label complex bound. Thus, a direct Samples with light lovely the amount of BNP present in the patient sample and the relationing light units (RLUs) detected by the system.

### 5. Statement of Intended Use

#### ACS:180 BNP Assay

ACS.100 DNr ASSay
For in vitro diagnostic use in the quantitative determination of B-type Natriuretic Peptide (BNP) in human plasma using the ACS:180® Automated Chemiluminescence System. This (ONY / In harian plasma comp trurement of plasma BNP as an aid in the diagnosis and assay is indicated for the modularentailure. In patients with acute coronary syndromes (ACS), this test, in conjunction with other known risk factors, can also be used to predict (AGO), this test, in ochjarieter likelihood of future heart failure. This assay is not intended for use on any other system.

#### ADVIA Centaur BNP Assay

For in vitro diagnostic use in the quantitative determination of B-type Natriuretic Peptide I or in human plasma using the ADVIA Centaur® System. This assay is indicated for the (DNP) in haman plasma BNP as an aid in the diagnosis and assessment of the severity of measurement of plasma bry. "Co ar aronary syndromes (ACS), this test, in conjunction with other known risk factors, can also be used to predict survival as well as to predict the other known i how labor failure. This assay is not intended for use on any other system.

### 6. Substantial Equivalence

The Bayer B-type Natriuretic Peptide (BNP) assays on the ACS:180® and ADVIA The Bayer e substantially equivalent to ADVIA Centaur® BNP assay. The ADVIA Centaur® are Substantially oquiralerr K031038 on June 23, 2003, as an aid in diagnosis Centail bril Assay was sloured the version has followed the new Replacement Reagent of heart railure. The AOC.100 - BRICA of the same intended use. The ADVIA Centaur r only guidance to allow his were cleared under K040425 on June 14, 2004, for the and AOS: 100 En. as a for use, in conjunction with other known risk factors, to predict survival in patients after myocardial infarction.

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# (a) Technological Characteristics

The following table compares the technology features of the current and proposed Bayer ADVIA Centaur and ACS: 180 BNP assays:

| Feature | Current Bayer ADVIA<br>Centaur® and ACS:180® BNP<br>Immunoassays | Proposed Bayer ADVIA<br>Centaur® and ACS:180® BNP<br>Immunoassays |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Quantitative determination of B-<br>type Natriuretic Peptide | Same |
| Indication for Use | An aid in the diagnosis and<br>assessment of the severity of<br>heart failure. Can also be used,<br>in conjunction with other known<br>risk factors, to predict survival in<br>patients after myocardial<br>infarction. | An aid in the diagnosis and<br>assessment of the severity of<br>heart failure. Can also be used,<br>in conjunction with other known<br>risk factors, to predict survival as<br>well as to predict the likelihood of<br>future heart failure in patients<br>with acute coronary syndromes. |
| Assay Principle | Chemiluminescence<br>immunoassay | Same |
| Traceability/Standardization | Reference standard - synthetic<br>human BNP (amino acid 77 to<br>108) in buffer based matrix. | Same |
| Calibration Interval | • After 28 days (ADVIA<br>Centaur), or 42 days<br>(ACS:180), when using the<br>same reagent lot<br>• With every new primary<br>reagent lot | Same |
| Sample Type | Human plasma using EDTA as<br>anticoagulant | Same |
| Sample Volume | 100 µL | Same |
| Calibrator | BNP Calibrator set (2 levels) | Same |
| Controls | BNP 1,2,3 Quality Control set | Same |
| Reagent Stability | • Until the expiration date when<br>stored at 2-8°C<br>Onboard<br>• ADVIA Centaur: 41.6 days (or<br>60 days with the use of<br>version 3.0 software or<br>higher)<br>• ACS:180: 72 hours | Same |
| Instruments | ADVIA Centaur and ACS:180<br>Systems, fully automated,<br>random-access immunoassay<br>analyzers | Same |
| Measuring Range | • ADVIA Centaur: <2.0 – 5000<br>pg/mL<br>• ACS:180: <15 – 5000 pg/mL | Same |
| | Current Bayer ADVIA | Proposed Bayer ADVIA |
| Feature | Centaur® and ACS:180® BNP | Centaur® and ACS:180® BNP |
| | Immunoassays | Immunoassays |
| Expected Values | Age and gender-matched<br>descriptive statistics providedDecision threshold of<br>100 pg/mL recommended for<br>diagnosis of heart failure.Decision threshold of<br>80 pg/mL recommended for<br>prediction of survival after<br>myocardial infarction. | Age and gender-matched<br>descriptive statistics provided.Decision threshold of<br>100 pg/mL recommended for<br>diagnosis of heart failure.Decision threshold of<br>80 pg/mL recommended for<br>prediction of survival and<br>future heart failure in patients<br>with acute coronary<br>syndromes. |
| Precision | ADVIA Centaur:<br>Within-run 1.8 – 4.3 %CV<br>from 29.4 - 1736 pg/mLTotal 2.3 - 4.7 %CV from 29.4<br>- 1736 pg/mLACS:180:<br>Within-run 2.5 – 7.9%CV from<br>51.5 - 1783 pg/mLTotal 3.8 - 9.9%CV from 51.5<br>- 1783 pg/mL | Same |
| Hook Effect | No high dose effect up to<br>100,000 pg/mL | Same |
| Analytical Sensitivity | ADVIA Centaur: <2 pg/mL<br>ACS:180: <15 pg/mL | Same |
| Dilution Recovery | On-board dilution 1:2, 1:5 and<br>1:10 with average recovery of<br>97% on ADVIA Centaur and 98%<br>on ACS:180. | Same |
| Limitations/Warning/<br>Precautions | This test has been evaluated<br>with plasma using EDTA as<br>the anticoagulant. Serum,<br>sodium citrate, lithium<br>heparin and sodium fluoride<br>sample tubes have also<br>been tested and are not<br>recommended.No interference from<br>hemoglobin up to<br>1000 mg/dLNo interference from<br>triglycerides up to 800 mg/dLNo interference from<br>cholesterol up to 1000 mg/dLNo interference from urea up<br>to 200 mg/dL | Same |
| Feature | Current Bayer ADVIA<br>Centaur® and ACS:180® BNP<br>Immunoassays | Proposed Bayer ADVIA<br>Centaur® and ACS:180® BNP<br>Immunoassays |
| | creatinine up to 2.5 mg/dL No interference from<br>unconjugated bilirubin up to<br>25 mg/dL No interference from<br>conjugated bilirubin up to<br>25 mg/dL No interference from human<br>IgG up to 5.3 g/dL No interference from 55<br>commonly used<br>pharmaceutical drugs. Results should always be<br>assessed in conjunction with<br>the patient's medical history,<br>clinical evaluation and other<br>diagnostic procedures. | |

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# (b) Performance Characteristics

The following table compares the performance characteristics of the current and proposed Bayer ADVIA Centaur and ACS:180 BNP assays:

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three lines representing its wings. The eagle is facing to the left. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

APR 2 2 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Carol Bianca Manager, Regulatory Affairs Bayer HealthCare, LLC. Diagnostics Division 511 Benedict Ave Tarrytown, NY 10591

Re: k043228

R043226
Trade/Device Name: Bayer Diagnostics ADVIA Centaur® BNP Assay Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC Dated: April 8, 2005 Received: April 12, 2005

Dear Ms. Bianca:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your Section >10(t) prematics is substantially equivalent (for the indications felerenced above and nave determined and marketed predicate devices marketed in interstate for use stated in the cherosure) to regars actment date of the Medical Device Amendments, or to commence prof to May 20, 1978, the excordance with the provisions of the Federal Food, Drug, devices that have been recides in assee approval of a premarket approval application (PMA). alle Cosment Act (Act) that do not required to the general controls provisions of the Act. The Tou may, increrore, market the device, octorements for annual registration, listing of general controls provisions of the 110 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 n may be subject to such additional controllations (CFR), Parts 800 to 895. In addition, FDA can be found in Thee 21, Courseling your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Flease oe advised that I Dri of issualites wour device complies with other requirements of the Act that FDA has made a decemmanding administered by other Federal agencies. You must of any I cuchai statutes and regulations, but not limited to: registration and listing (21 Comply with the Are Free Frequirements 801 and 809); and good manufacturing practice CFR Part 807), fabening (21 CF RT + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

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#### Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) I his letter witi anow you to begin maining of substantial equivalence of your device to a legally premarket notification: "The PD's 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, If you desire specific infortion and advertising of your device, please contact the Office of In of quotions on the promie 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 Tou may other butter gear. 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 yours,

Sean M. Cooper MS, DUM

Jean M. Cooper, MS, D.V.M. 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):_____________________________________________________________________________________________________________________________________________________ K043228

Device Name: Bayer Diagnostics ADVIA Centaur® BNP Assay

Indications For Use:

For in vitro diagnostic use in the quantitative determination of B-type Natriuretic Peptide For in ville diagnostic use in the quantica. Contaur System. This assay is indicated for (BNP) in numan plasma doling the AIS AIS AIR PERSENTIAN as and assessment of the the measurement of plasma BNF acute coronary syndromes (ACS), this test, in sevelly of healt fallure. In pations with as a see to predict survival as well as well as well as well as conjunction with other known hist factors, can also assay is not intended for use on any other system.

Prescription Use _ × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

Carol C. Benson
Division Sign-Off

Office of in Vitro Diagnostic Device Evaluation and Safety Page 1 of 2 __________________________________________________________________________________________________________________________________________________________________

\$1000 K043228

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# Indications for Use

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________ K043228

Device Name: Bayer Diagnostics ACS:180® BNP Assay

Indications For Use:

For in vitro diagnostic use in the quantitative determination of B-type Natriuretic Peptide For in virro diagnostic use in the quantitative docommation on a promotive scence System. (BNP) in human plasma using the NOC. 100 - Altema BNP as an aid in the diagnosis This assay is Indicated for the mo mo mo and failure. In patients with acute coronary and assessment of the seventy of hourthaller known risk factors, can also be syndromes (ACO), this test, in onlyandlier will be likelihood of future heart failure. This assay is not intended for use on any other system.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

Carol C. Benson
Division Sign-Off

Office of In Vitro Diagnostic Døvice Evaluation and Safety

2 Page 2 of

K043228