(117 days)
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 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.
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 magnetic particles. Patient sample (calibrator or control materials) is incubated for 5 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.
The provided text describes a 510(k) premarket notification for the ACS:180® and ADVIA Centaur® BNP Assays by Bayer Diagnostics. The document establishes substantial equivalence to a predicate device (ADVIA Centaur® B-Type Natriuretic Peptide (BNP) Assay, K031038) and discusses the assays' technological and performance characteristics.
Here's an analysis of the acceptance criteria and study information provided, structured according to your request:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for performance metrics in a pass/fail format. However, it presents the "Performance Characteristics" of the proposed devices, which implicitly serve as the demonstrated performance that FDA found substantially equivalent to the predicate device. These performance characteristics cover various analytical aspects of the assay. Since the document states "The following table compares the performance characteristics of the current and proposed Bayer ADVIA Centaur and ACS:180 BNP assays," and the values listed under "Proposed Bayer ADVIA Centaur® and ACS:180® BNP Immunoassays" are identical to "Current Bayer ADVIA Centaur® and ACS:180® BNP Immunoassays," it implies that the new devices meet the established performance of the predicate device.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (Proposed Devices) |
|---|---|---|
| Precision (ADVIA Centaur) | Within-run: 1.8 – 4.3 %CV (29.4 to 1736 pg/mL) | Within-run: 1.8 – 4.3 %CV (29.4 to 1736 pg/mL) |
| Total: 2.3 - 4.7 %CV (29.4 to 1736 pg/mL) | Total: 2.3 - 4.7 %CV (29.4 to 1736 pg/mL) | |
| Precision (ACS:180) | Within-run: 2.5 - 7.9%CV (51.5 to 1783 pg/mL) | Within-run: 2.5 - 7.9%CV (51.5 to 1783 pg/mL) |
| Total: 3.8 - 9.9%CV (51.5 to 1783 pg/mL) | Total: 3.8 - 9.9%CV (51.5 to 1783 pg/mL) | |
| Hook Effect | No high dose effect up to 100,000 pg/mL | No high dose effect up to 100,000 pg/mL |
| Analytical Sensitivity (ADVIA Centaur) | <2 pg/mL | <2 pg/mL |
| Analytical Sensitivity (ACS:180) | <15 pg/mL | <15 pg/mL |
| Dilution Recovery | On-board dilution 1:2, 1:5, 1:10 with avg recovery of 97% (ADVIA Centaur) | On-board dilution 1:2, 1:5, 1:10 with avg recovery of 97% (ADVIA Centaur) |
| On-board dilution 1:2, 1:5, 1:10 with avg recovery of 98% (ACS:180) | On-board dilution 1:2, 1:5, 1:10 with avg recovery of 98% (ACS:180) | |
| Interference | No interference from various substances (hemoglobin, triglycerides, cholesterol, urea, creatinine, unconjugated bilirubin, conjugated bilirubin, human IgG, 55 pharmaceutical drugs) | No interference from various substances (hemoglobin, triglycerides, cholesterol, urea, creatinine, unconjugated bilirubin, conjugated bilirubin, human IgG, 55 pharmaceutical drugs) |
2. Sample Sizes Used for the Test Set and Data Provenance
The document does not specify the exact sample sizes for the test sets or the data provenance (country of origin, retrospective/prospective) for each stated performance characteristic. It only presents the summary results. For clinical diagnostic assays like this, it's common for studies to involve various patient samples to assess precision, analytical sensitivity, dilution recovery, and interference. However, these details are not provided in this summary.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This document describes an in vitro diagnostic (IVD) assay which measures a biomarker (BNP). The "ground truth" for such assays is typically the actual concentration of the analyte, established through highly accurate and precise analytical methods, not through expert human review in the same way an imaging AI would be reviewed. Therefore, the concept of "experts" establishing ground truth for evaluating the device's analytical performance (precision, sensitivity, etc.) is not directly applicable in this context. The "ground truth" here is determined by the reference analytical methods themselves.
4. Adjudication Method for the Test Set
As explained above, for analytical performance characteristics of an IVD assay, there isn't a direct "adjudication method" in the sense of reconciling disagreements among human experts evaluating data. The performance is assessed against established analytical standards and reference methods.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for medical devices that involve human interpretation (e.g., radiologists reading images and an AI assisting them). The ACS:180 and ADVIA Centaur BNP assays are entirely automated quantitative tests, so human interpretation of the assay's direct output (BNP concentration) is not the primary focus of performance evaluation in the same way. The device's output itself is a numerical value.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the performance characteristics presented are for the standalone algorithm/device (the automated immunoassay system). The device provides a quantitative measurement of BNP without human intervention in the measurement process itself. The "without human-in-the-loop" aspect is inherent to automated diagnostic assays.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth for evaluating the analytical performance of these BNP assays is based on:
- Reference Standards/Synthetic Materials: Used for calibration and establishing traceability (e.g., "synthetic human BNP (amino acid 77 to 108) in buffer-based matrix").
- Known Concentrations: Samples with precisely known BNP concentrations are used to assess accuracy, linearity, and recovery.
- Validated Analytical Methods: Comparison against established and validated laboratory methods or reference methods to verify analytical parameters like precision, sensitivity, and linearity.
- Controlled Interference Studies: Samples spiked with known interfering substances at controlled concentrations to determine the device's robustness to these interferences.
For the stated clinical indications for use (diagnosis and assessment of heart failure severity, prediction of survival after MI), the clinical utility of BNP levels is established through extensive medical literature and clinical studies that correlate BNP levels with patient outcomes, pathology (e.g., echocardiography, cardiac catheterization), and clinical diagnoses. The device's role is to accurately measure these established BNP levels. The document mentions "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," which are clinical ground truths, but not data used to directly evaluate the analytical performance of the device in this submission.
8. The Sample Size for the Training Set
The document does not provide details on specific "training sets" in the context of an algorithm that learns from data. This type of immunoassay is based on established biochemical principles and reagents, not a machine learning model that requires a distinct training phase with a dataset. The development and optimization of the assay would involve extensive R&D and testing with numerous samples, but these are not typically referred to as a "training set" in the sense of AI/ML.
9. How the Ground Truth for the Training Set Was Established
As this is an immunoassay and not an AI/ML device, the concept of a "training set" with associated ground truth for learning is not directly applicable. The "ground truth" for the development and validation of such an assay would be based on:
- Precise gravimetric/volumetric measurements for reagent preparation.
- Characterization of antibodies and their binding kinetics.
- Use of highly purified and characterized synthetic BNP standards.
- Comparative analysis with established reference methods during the assay development process to ensure analytical accuracy and reliability.
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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
| Contact Person: | Kenneth T. Edds, Ph.D. | |
|---|---|---|
| Address: | Bayer Healthcare - Diagnostics Division511 Benedict Ave.Tarrytown, N.Y. 10591 | |
| Phone: (914) 524 2446Fax: (914) 524 2500e-mail: ken.edds.b@bayer.com | ||
| Date Summary Prepared: | February 13, 2004 | |
| Device Information | ||
| Propriety Name: | ACS: 180® and ADVIA Centaur® B-Type NatriureticPeptide (BNP) Assays | |
| Common Name: | BNP assays | |
| Classification Name:Class:CFR:Product Code: | B-type natriuretic peptide test systemsII21 CFR 862.1117NBC |
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) 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 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 of heartfailure. | An aid in the diagnosis andassessment of severity of heartfailure. To predict survival inpatients after myocardialinfarction, in conjunction withother know risk factors. |
| Assay Principle | Chemiluminescenceimmunoassay | Same |
| Traceability/Standardization | Reference standard –synthetic human BNP (aminoacid 77 to 108) in bufferbased matrix. | Same |
| Calibration Interval | • After 28 days (ADVIACentaur), or 14 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 | Unopened• 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 |
| Feature | Current Bayer ADVIACentaur® and ACS:180® BNPImmunoassays | Proposed Bayer ADVIACentaur® and ACS:180® BNPImmunoassays |
| 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: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: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/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 ADVIACentaur® and ACS:180® BNPImmunoassays | Proposed Bayer ADVIACentaur® and ACS:180® BNPImmunoassays |
| • 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. | 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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 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
Page 1 of 1
§ 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.”