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 the 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® 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. In patients with acute coronary syndromes (ACS), this test, in conjunction with other known risk factors, can also be used to predict the likelihood of future heart failure. This assay is not intended for use on any other system.

Device Description

The ACS:180 and ADVIA Centaur BNP assays are fully automated two-site sandwich immunoassays using direct chemiluminescent technology. The first antibody, in the Reagent, is an acridinium ester labeled monoclonal mouse anti-human antibody specific to the N-terminal portion of BNP. The second antibody, in the Solid Phase Reagent, is a biotinylated monoclonal mouse anti-human antibody specific to the C-terminal portion of BNP, which is coupled to streptavidin coated magnetic particles. Patient sample (calibrators or control materials) is incubated for 5 minutes at 37°C with the Solid Phase Reagent and 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 unbound antibody conjugates are washed away. Following incubation, the immuno-complex signal is measured in a luminometer. The chemiluminescent signal 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 relative light units (RLUs) detected by the system.

AI/ML Overview

Here's an analysis of the provided text regarding the Bayer Diagnostics ADVIA Centaur BNP Assay, broken down by your requested criteria:

The provided document is a Summary of Safety and Effectiveness for the Bayer Diagnostics ADVIA Centaur BNP Assay and ACS:180 BNP Assay, primarily focusing on its updated indications for use and substantial equivalence to previously cleared devices. It describes the technological and performance characteristics but does not contain detailed study results like typical acceptance criteria tables for accuracy or precision studies against a defined benchmark. Instead, it states that the characteristics (like precision, measuring range, analytical sensitivity, etc.) are "Same" as the predicate device.

Therefore, for aspects like "reported device performance" against acceptance criteria, "sample sizes used for the test set," "number of experts," "adjudication method," "MRMC study effect size," and "standalone performance," the provided document does not contain this information. It relies on the previously cleared predicate devices for establishing performance equivalency without re-presenting the detailed studies.

Here's what can be extracted based on the information available:

1. A table of acceptance criteria and the reported device performance

The provided document does not explicitly present a table of acceptance criteria with corresponding device performance from new studies following the format typically seen for a new device's primary validation. Instead, it compares the proposed device's characteristics to a predicate device, largely stating they are "Same."

However, we can infer some "performance characteristics" that are deemed acceptable by virtue of being equivalent to the predicate.

Characteristic	Acceptance Criteria (Implied from Predicate)	Reported Device Performance (Proposed Device)
Measuring Range	ADVIA Centaur: <2.0 – 5000 pg/mL ACS:180: <15 – 5000 pg/mL	Same as predicate (ADVIA Centaur: <2.0 – 5000 pg/mL, ACS:180: <15 – 5000 pg/mL)
Precision (ADVIA Centaur)	Within-run 1.8 – 4.3 %CV (29.4 - 1736 pg/mL) Total 2.3 - 4.7 %CV (29.4 - 1736 pg/mL)	Same as predicate
Precision (ACS:180)	Within-run 2.5 – 7.9%CV (51.5 - 1783 pg/mL) Total 3.8 - 9.9%CV (51.5 - 1783 pg/mL)	Same as predicate
Hook Effect	No high dose effect up to 100,000 pg/mL	Same as predicate
Analytical Sensitivity	ADVIA Centaur: <2 pg/mL ACS:180: <15 pg/mL	Same as predicate
Dilution Recovery	On-board dilution 1:2, 1:5, 1:10 with average recovery of 97% (ADVIA Centaur) and 98% (ACS:180)	Same as predicate
Interference (Hemoglobin)	No interference up to 1000 mg/dL	Same as predicate
Interference (Triglycerides)	No interference up to 800 mg/dL	Same as predicate
Interference (Cholesterol)	No interference up to 1000 mg/dL	Same as predicate
Interference (Urea)	No interference up to 200 mg/dL	Same as predicate
Interference (Creatinine)	No interference up to 2.5 mg/dL	Same as predicate
Interference (Unconjugated Bilirubin)	No interference up to 25 mg/dL	Same as predicate
Interference (Conjugated Bilirubin)	No interference up to 25 mg/dL	Same as predicate
Interference (Human IgG)	No interference up to 5.3 g/dL	Same as predicate
Interference (Pharm. Drugs)	No interference from 55 commonly used drugs	Same as predicate
Sample Type	Human plasma using EDTA as anticoagulant	Same as predicate (Other types not recommended)

The study that "proves the device meets the acceptance criteria" is implicitly the previous 510(k) clearances for the predicate devices (K031038 and K040425). The current submission (K043228) relies on substantial equivalence to these predicate devices for its performance characteristics. The document explicitly states: "The Bayer B-type Natriuretic Peptide (BNP) assays on the ACS:180® and ADVIA Centaur® are substantially equivalent to ADVIA Centaur® BNP assay." And for the technological and performance tables, it consistently lists "Same" for the proposed device's characteristics when compared to the current (predicate) one.

2. Sample size used for the test set and the data provenance

Sample size: Not specified in the provided document for the current submission's validation. The document states "Same" for all performance characteristics, implying reliance on the studies for the predicate devices (K031038 and K040425).
Data provenance: Not specified in the provided document. As the submission relies on substantial equivalence to predicate devices, the original data provenance would be from those prior submissions.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the document as it focuses on an in vitro diagnostic assay, not an imaging device requiring expert interpretation for ground truth.

4. Adjudication method for the test set

This information is not provided as it is not relevant to this type of IVD device submission.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This information is not provided. This type of study (MRMC for AI assistance) is not applicable to an in vitro diagnostic assay like a BNP test.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The device is an in vitro diagnostic assay. Its performance is inherently standalone in the sense that it measures BNP levels from a sample without human interpretive assistance for the measurement itself. The results are then used by clinicians. The performance characteristics described (precision, sensitivity, range, etc.) are its standalone performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For an in vitro diagnostic assay like BNP, the "ground truth" for accuracy and calibration would typically be established against:

A reference standard system (e.g., highly pure synthetic human BNP (amino acid 77 to 108) as mentioned for traceability).
Known concentrations of analytes (for linearity, sensitivity verification).
Clinical correlation (for assessing diagnostic utility against patient outcomes or established clinical diagnoses, such as heart failure diagnosis confirmed by other clinical methods or follow-up).
The document mentions "Reference standard - synthetic human BNP (amino acid 77 to 108) in buffer based matrix" for traceability.

8. The sample size for the training set

This information is not provided. Given that this is an immunoassay and the submission is for substantial equivalence, the concept of a "training set" in the context of machine learning/AI (which your question implies) is not applicable here. The assay development would involve extensive analytical validation, but not typically a machine learning "training set."

9. How the ground truth for the training set was established

As above, the concept of a "training set" for AI is not applicable to this immunoassay. The ground truth for analytical validation (e.g., establishing accurate measurement, precision) is based on reference materials, calibrators, and controlled experimental conditions.

Summary

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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 Division511 Benedict Ave.Tarrytown, N.Y. 10591
	Phone: (914) 524 2531Fax: (914) 524 2500e-mail: carol.bianca.b@bayer.com
Date Summary Prepared:	October 18, 2004
2. Device Information
Propriety Name:	ACS:180® and ADVIA Centaur® B-Type NatriureticPeptide (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 Division511 Benedict Ave.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 ADVIACentaur® and ACS:180® BNPImmunoassays	Proposed Bayer ADVIACentaur® and ACS:180® BNPImmunoassays
Intended Use	Quantitative determination of B-type Natriuretic Peptide	Same
Indication for Use	An aid in the diagnosis andassessment of the severity ofheart failure. Can also be used,in conjunction with other knownrisk factors, to predict survival inpatients after myocardialinfarction.	An aid in the diagnosis andassessment of the severity ofheart failure. Can also be used,in conjunction with other knownrisk factors, to predict survival aswell as to predict the likelihood offuture heart failure in patientswith acute coronary syndromes.
Assay Principle	Chemiluminescenceimmunoassay	Same
Traceability/Standardization	Reference standard - synthetichuman BNP (amino acid 77 to108) in buffer based matrix.	Same
Calibration Interval	• After 28 days (ADVIACentaur), or 42 days(ACS:180), when using thesame reagent lot• With every new primaryreagent lot	Same
Sample Type	Human plasma using EDTA asanticoagulant	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 whenstored at 2-8°COnboard• ADVIA Centaur: 41.6 days (or60 days with the use ofversion 3.0 software orhigher)• ACS:180: 72 hours	Same
Instruments	ADVIA Centaur and ACS:180Systems, fully automated,random-access immunoassayanalyzers	Same
Measuring Range	• ADVIA Centaur: <2.0 – 5000pg/mL• 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-matcheddescriptive statistics providedDecision threshold of100 pg/mL recommended fordiagnosis of heart failure.Decision threshold of80 pg/mL recommended forprediction of survival aftermyocardial infarction.	Age and gender-matcheddescriptive statistics provided.Decision threshold of100 pg/mL recommended fordiagnosis of heart failure.Decision threshold of80 pg/mL recommended forprediction of survival andfuture heart failure in patientswith acute coronarysyndromes.
Precision	ADVIA Centaur:Within-run 1.8 – 4.3 %CVfrom 29.4 - 1736 pg/mLTotal 2.3 - 4.7 %CV from 29.4- 1736 pg/mLACS:180:Within-run 2.5 – 7.9%CV from51.5 - 1783 pg/mLTotal 3.8 - 9.9%CV from 51.5- 1783 pg/mL	Same
Hook Effect	No high dose effect up to100,000 pg/mL	Same
Analytical Sensitivity	ADVIA Centaur: <2 pg/mLACS:180: <15 pg/mL	Same
Dilution Recovery	On-board dilution 1:2, 1:5 and1:10 with average recovery of97% on ADVIA Centaur and 98%on ACS:180.	Same
Limitations/Warning/Precautions	This test has been evaluatedwith plasma using EDTA asthe anticoagulant. Serum,sodium citrate, lithiumheparin and sodium fluoridesample tubes have alsobeen tested and are notrecommended.No interference fromhemoglobin up to1000 mg/dLNo interference fromtriglycerides up to 800 mg/dLNo interference fromcholesterol up to 1000 mg/dLNo interference from urea upto 200 mg/dL	Same
Feature	Current Bayer ADVIACentaur® and ACS:180® BNPImmunoassays	Proposed Bayer ADVIACentaur® and ACS:180® BNPImmunoassays
	creatinine up to 2.5 mg/dL No interference fromunconjugated bilirubin up to25 mg/dL No interference fromconjugated bilirubin up to25 mg/dL No interference from humanIgG up to 5.3 g/dL No interference from 55commonly usedpharmaceutical drugs. Results should always beassessed in conjunction withthe patient's medical history,clinical evaluation and otherdiagnostic 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 (240)276-0484. 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 (800) 638-2041 or (301) 443-6597 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

Regulation Number and Section

§ 862.1117 B-type natriuretic peptide test system.

(a)
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.(b)
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.”