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

K040425 · Bayer Healthcare, LLC · NBC · Jun 14, 2004 · Clinical Chemistry

Device Facts

• Record ID: K040425
• Device Name: ACS:180 AND ADVIA CENTAUR B-TYPE NATRIURETIC PEPTIDE (BNP) ASSAYS
• Applicant: Bayer Healthcare, LLC
• Product Code: NBC · Clinical Chemistry
• Decision Date: Jun 14, 2004
• 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. This test, in conjunction with other known risk factors, can also be used to predict survival in patients after myocardial infarction. 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. This test, in conjunction with other known risk factors, can also be used to predict survival in patients after myocardial infarction. This assay is not intended for use on any other system.

Device Story

Fully automated two-site sandwich immunoassay; uses direct chemiluminescent technology. Input: human plasma sample (EDTA anticoagulant). Process: sample incubated with acridinium ester-labeled monoclonal mouse anti-human BNP antibody (Lite Reagent) and biotinylated monoclonal mouse anti-human antibody coupled to streptavidin magnetic particles (Solid Phase). Immuno-complex forms; unbound conjugates washed away. Output: relative light units (RLUs) measured via luminometer; signal proportional to BNP concentration. Used in clinical laboratories; operated by trained technicians. Results assist clinicians in diagnosing heart failure, assessing severity, and predicting post-myocardial infarction survival.

Clinical Evidence

Retrospective analysis of 438 patients from ENTIRE-TIMI 23 study. Primary endpoint: 30-day mortality post-myocardial infarction. BNP >80 pg/mL associated with higher risk of death (17.4% vs 1.8%, p<0.0001). Odds ratio for death: 11.5 (unadjusted), 8.3 (adjusted). Sensitivity/specificity data provided across age/gender groups for heart failure diagnosis using 100 pg/mL threshold.

Technological Characteristics

Chemiluminescent immunoassay; uses acridinium ester-labeled monoclonal mouse anti-human BNP F(ab')2 fragment and biotinylated monoclonal mouse anti-human antibody on streptavidin magnetic particles. Fully automated, random-access analyzer. Sample volume 100 µL. EDTA plasma matrix. Measuring range <2 to 5000 pg/mL.

Indications for Use

Indicated for quantitative measurement of plasma BNP in patients to aid in diagnosis and severity assessment of heart failure and to predict survival post-myocardial infarction in conjunction with other risk factors.

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)

Submission Summary (Full Text)

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K0404-25

ACS:180® and ADVIA Centaur® BNP 510(k) ______________________________________________________________________________________________________________________________________________________________________________

#### Bayer Diagnostics JUN 1 4 2004 ADVIA Centaur BNP Assay

#### Summary of Safety and Effectiveness

This Summary of Safety and Effectiveness has been prepared in accordance with the requirements of 21 CFR 807.92, to provide sufficient information to understand the basis for a determination of substantial equivalence.

# 1. Submitter Information

2.

| Contact Person: | Kenneth T. Edds, Ph.D. | |
|---------------------------------------------------------|---------------------------------------------------------------------------------------|--|
| 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: | February 13, 2004 | |
| Device Information | | |
| Propriety Name: | ACS: 180® and ADVIA Centaur® B-Type Natriuretic<br>Peptide (BNP) Assays | |
| Common Name: | BNP assays | |
| Classification Name:<br>Class:<br>CFR:<br>Product Code: | B-type natriuretic peptide test systems<br>II<br>21 CFR 862.1117<br>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) Number: | K031038 |

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#### 4. Device Description

The ACS:180 and ADVIA Centaur BNP assays are fully automated two-site sandwich immunoassays using direct chemiluminescent technology, which use constant amounts of two monoclonal antibodies. The first antibody, in the Lite Reagent, is an acridinium ester labeled monoclonal mouse anti-human BNP F(ab')2 fragment specific to the ring structure of BNP. The second antibody, in the Solid Phase, is a biotinylated monoclonal mouse antihuman antibody specific to the C-terminal portion of BNP, which is coupled to streptavidin Patient sample (calibrator or control materials) is incubated for 5 magnetic particles. minutes at 37°C with the Reagent that contains the tracer antibody conjugate. Subsequently, Solid Phase reagent is added and incubated for 2.5 minutes at 37°C. An immuno-complex is formed between the BNP in the sample and the two antibody conjugates. Following incubation, the unbound antibody conjugates are washed away. The chemiluminescence of the immuno-complex signal is measured in a fuminometer. Samples with low BNP levels 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 relationship exists between the amount of BNP present in the patient sample and the amount of relative light units (RLUs) detected by the system.

#### 5. Statement of Intended Use

#### ACS:180 BNP Assay

For in vitro diagnostic use in the quantitative determination of B-type Natriuretic Peotide (BNP) in human plasma using the ACS:180® Automated Chemiluminescence System. This assay is indicated for the measurement of plasma BNP as an aid in the diagnosis and assessment of the severity of heart failure. This test, in conjunction with other known risk factors, can also be used to predict survival in patients after myocardial infarction. 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 Peotide (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 of and assessment of the severity of heart failure. This test, in coniunction with other known risk factors, can also be used to predict survival in patients after myocardial infarction. 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 Centaur® are substantially equivalent to ADVIA Centaur® BNP assay. The ADVIA Centaur BNP Assay was cleared under K031038 on June 23, 2003; the ACS:180® BNP version has followed the new Replacement Reagent Policy guidance to allow its marketing under the same intended use.

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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 of heart<br>failure. | An aid in the diagnosis and<br>assessment of severity of heart<br>failure. To predict survival in<br>patients after myocardial<br>infarction, in conjunction with<br>other know risk factors. |
| Assay Principle | Chemiluminescence<br>immunoassay | Same |
| Traceability/Standardization | Reference standard –<br>synthetic human BNP (amino<br>acid 77 to 108) in buffer<br>based matrix. | Same |
| Calibration Interval | • After 28 days (ADVIA<br>Centaur), or 14 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 | Unopened<br>• 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 |
| Feature | Current Bayer ADVIA<br>Centaur® and ACS:180® BNP<br>Immunoassays | Proposed Bayer ADVIA<br>Centaur® and ACS:180® BNP<br>Immunoassays |
| Expected Values | Age and gender-matched descriptive statistics provided Decision threshold of 100 pg/mL recommended | Age and gender-matched descriptive statistics provided. Decision threshold of 100 pg/mL recommended for diagnosis of heart failure. Decision threshold of 80 pg/mL recommended for prediction of survival after myocardial infarction. |
| Precision | ADVIA Centaur:<br>Within-run 1.8 – 4.3 %CV from 29.4 to 1736 pg/mL Total 2.3 - 4.7 %CV from 29.4 to 1736 pg/mL ACS:180:<br>Within-run 2.5 - 7.9%CV from 51.5 to 1783 pg/mL Total 3.8 - 9.9%CV from 51.5 to 1783 pg/mL | Same |
| Hook Effect | No high dose effect up to 100,000 pg/mL | Same |
| Analytical Sensitivity | ADVIA Centaur: <2 pg/mL ACS:180: <15 pg/mL | Same |
| Dilution Recovery | On-board dilution 1:2, 1:5 and 1:10 with average recovery of 97% on ADVIA Centaur and 98% on ACS: 180. | Same |
| Limitations/Warning/<br>Precautions | This test has been evaluated with plasma using EDTA as the anticoagulant. Serum, sodium citrate, lithium heparin and sodium fluoride sample tubes have also been tested and are not recommended. No interference from hemoglobin up to 1000 mg/dL No interference from triglycerides up to 800 mg/dL No interference from cholesterol up to 1000 mg/dL No interference from urea up to 200 mg/dL No interference from creatinine up to 2.5 mg/dL No interference from unconjugated bilirubin up to 25 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 |
| | • No interference from<br>conjugated bilirubin up to<br>25 mg/dL<br>• No interference from human<br>IgG up to 5.3 g/dL<br>• No interference from 55<br>commonly used<br>pharmaceutical drugs.<br>• Results should always be<br>assessed in conjunction with<br>the patient's medical history,<br>clinical evaluation and other<br>diagnostic procedures. | Same |

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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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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 is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The logo is black and white and has a simple, clean design.

Public Health Service

JUN 1 4 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Kenneth T. Edds, Ph.D Director, Regulatory Affairs Bayer HealthCare, LLC Diagnostics Division 511 Benedict Avenue Tarrytown, NY 10591

k040425 Re:

K040423
Trade/Device Name: ACS: 180 and ADVIA Centaur BNP Assays Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC Dated: May 21, 2004 Received: May 24, 2004

Dear Dr. Edds:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your bection of the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encrosule) to regars actment date of the Medical Device Amendments, or to comments prior to May 20, 1978, tive excordance with the provisions of the Federal Food, Drug, devices that have been reclassined in asse approval of a premarket approval application (PMA). allu Cosmetic Act (71ct) that do not requently of the general controls provisions of the Act. The I ou may, therefore, market the act include requirements for annual registration, listing of general Controls provisions of the revelopment of the same of any misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), If your device is elassified (650 abs re) incl. Existing major regulations affecting your device It may be subject to such additional controllar Distance of Colors 800 to 895. In addition, FDA can oc louits in Thio 21, South ents concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that I DA 3 issualles or our device complies with other requirements of the Act that I DA has made a determinations administered by other Federal agencies. You must 01 any I coccal statutes and reguirements, including, but not limited to: registration and listing (21 Comply with an the Tree STequirements 801 and 809); and good manufacturing practice and requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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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 will anow you'to obgen mailing of substantial equivalence of your device to a legally premits to the device 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, If you desire spooline mirrotion and advertising of your device, please contact the Office of of questions on the promotion 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 I ou may obum other generarers, 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,

Jean M. Cooper, MS, DVM.

Tean 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): K040425

Device Name: ACS:180 and ADVIA Centaur BNP Assays

Indications For Use:

#### For ACS:180 BNP 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 assay is indicated for the measurement of plasma BNP as an aid in the diagnosis and assessment of the severity of heart failure. This test, in conjunction with other known risk factors, can also be used to predict survival in patients after myocardial infarction. This assay is not intended for use on any other system.

### For ADVIA Centaur BNP Assay:

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 of and assessment of the severity of heart failure. This test, in conjunction with other known risk factors, can also be used to predict survival in patients after myocardial infarction. This 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 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)

Carol Benson
Division Sign-Off

510(k) K040425

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