The PBNP method is an in vitro diagnostic assay for the quantitative measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma on the Dimension Vista® System. In individuals suspected of having congestive heart failure (CHF), measurements of NT-proBNP are used as an aid in the diagnosis and assessment of severity. The test is further indicated for the risk stratification of patients with acute coronary syndrome and heart failure.

The PBNP CAL is an in vitro diagnostic product for the calibration of the N-Terminal Pro-Brain Natriuretic Peptide (PBNP) method for the Dimension Vista® System.

Device Description

The PBNP method is a one-step sandwich chemiluminescent immunoassay based on LOCI® technology. LOCI® reagents include two synthetic bead reagents and a biotinylated monoclonal antibody fragment which recognize an epitope located in the N-terminal part of proBNP. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The second bead reagent (Chemibeads) is coated with a second antibody specific for a second independent epitope on NT-proBNP and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a particle/NT-proBNP/biotiny|ated antibody sandwich. Sensibeads then are added and bind to the biotin to form a bead-aggregated immunocomplex. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads, which diffuses to the Chemibeads and triggers a chemiluminescent reaction. The resulting chemiluminescent signal is measured at 612 nm and is directly proportional to the concentration of NT-proBNP in the sample.

AI/ML Overview

The provided 510(k) summary describes a re-submission for the Siemens Healthcare Diagnostics Inc. Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Flex® Reagent Cartridge and Calibrator (K080578). This submission claims substantial equivalence to a previously cleared device (K061795). Therefore, the "acceptance criteria" and "device performance" are primarily focused on demonstrating this substantial equivalence, rather than establishing new performance benchmarks for a novel device.

The document indicates that comparative testing was performed, but it does not provide the specific quantitative results of this testing. Instead, it lists the features of the new device and the predicate device, highlighting their similarities and differences. The conclusion states that "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance." However, the details of that protocol and its specific results are not included in the provided text.

Here's an attempt to answer the questions based only on the provided information, noting where details are explicitly missing:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a substantial equivalence submission, the "acceptance criteria" are implied to be that the new device's performance is comparable to the predicate device's performance across the listed features. The "reported device performance" is the specification of the current device.

Feature	Predicate Device Performance (K061795) (Implied Acceptance Criteria)	New Device Performance (K080578) (Reported Device Performance)
Method
Intended Use	Same as new device	Aid in diagnosis/assessment of severity of CHF, risk stratification for ACS/heart failure
Device Technology	Chemiluminescent	Chemiluminescent
Measuring Range	5 - 35,000 pg/mL	5 - 35,000 pg/mL
Antibody	Polyclonal Sheep Antibody	Monoclonal Sheep Antibody
Cut-off	125 pg/mL (<75 years), 450 pg/mL (≥75 years)	125 pg/mL (<75 years), 450 pg/mL (≥75 years)
Analytical Sensitivity	≤ 5 pg/mL	≤ 5 pg/mL
Functional Sensitivity	≤ 30 pg/mL	≤ 30 pg/mL
Analytical Specificity	No significant cross-reactivity with Natrecor® (0 or 125 pg/mL NT-PBNP); no significant cross-reactivity with sixteen other substances.	No significant cross-reactivity with Natrecor® (0 or 125 pg/mL NT-PBNP); no significant cross-reactivity with sixteen other substances.
Interferences	No significant interference from: Bilirubin conjugated up to 60 mg/dL; Bilirubin unconjugated up to 60 mg/dL; Hemoglobin up to 680 mg/dL; Triglyceride up to 3000 mg/dL	No significant interference from: Bilirubin conjugated up to 60 mg/dL; Bilirubin unconjugated up to 60 mg/dL; Hemoglobin up to 1000 mg/dL; Triglyceride up to 3000 mg/dL
Hook Effect	No effect up to 400,000 pg/mL	No effect up to 400,000 pg/mL
Calibration Interval	30 days, same reagent lot	30 days, same reagent lot
Sample Volume	8 µL	8 µL
Calibrator
Intended Use	Calibration of PBNP method for Dimension Vista® System	Calibration of PBNP method for Dimension Vista® System
Analyte	Synthetic PBNP	Synthetic PBNP
Matrix	Bovine Albumin	Bovine Albumin
Form	Liquid, frozen	Liquid, frozen
Volume	Twelve vials, two per level (A-F), 1.0 mL per vial	Ten vials, two per level (A-E), 1.0 mL per vial
Levels	Six levels (0, 125, 450, 1500, 12,000, and 36,750 pg/mL)	Five Levels (0, 250, 1500, 12,000, 36,750 pg/mL)

Note on Differences: The primary differences noted between the new device and the predicate device are:

Antibody type: The new device uses a monoclonal sheep antibody, while the predicate used a polyclonal sheep antibody.
Calibrator Volume & Levels: The new calibrator has 10 vials (5 levels) compared to the predicate's 12 vials (6 levels) and the specific levels differ.
Hemoglobin Interference Limit: The new device tolerates higher hemoglobin levels (1000 mg/dL) than the predicate (680 mg/dL).

The submission argues that despite these differences, "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance." The specific quantitative results of this comparative testing are not provided in the summary.

2. Sample Size Used for the Test Set and the Data Provenance

The provided document does not specify the sample size used for the test set or the data provenance (e.g., country of origin, retrospective or prospective). It simply states that "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

This information is not applicable and not provided. This device is an in vitro diagnostic assay for biomarker measurement, not an imaging AI device that would typically rely on expert human interpretation for ground truth. Ground truth for such a device would involve reference methods or confirmed clinical states.

4. Adjudication Method for the Test Set

This information is not applicable and not provided. As explained in point 3, the concept of "adjudication" by experts for image interpretation is not relevant here.

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 applicable and not provided. This is an in vitro diagnostic (IVD) assay for measuring a biomarker, not an AI-powered diagnostic imaging tool intended to assist human readers. Therefore, an MRMC study comparing human readers with and without AI assistance is irrelevant to this device.

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

Yes, the device operates as a standalone algorithm/assay. The method describes a "one-step sandwich chemiluminescent immunoassay" that quantitatively measures NT-proBNP. This is a laboratory-based test where the result is generated directly by the instrument based on the sample, without human interpretative input in the measurement itself, other than proper sample handling and instrument operation.

7. The Type of Ground Truth Used

The "ground truth" for an IVD device like this typically refers to a reference method or a definitively established clinical state. While the document doesn't explicitly state the "type of ground truth used" for the comparative testing, for a quantitative assay measuring a biomarker, it would generally involve:

Reference method/Comparative method: Comparing the device's results against a gold standard method or another established, cleared method for NT-proBNP measurement.
Clinical correlation: Demonstrating the assay's ability to differentiate between patient populations (e.g., CHF vs. non-CHF, or different severities of CHF) based on established clinical diagnostic criteria or outcomes data, as implied by its intended use "as an aid in the diagnosis and assessment of severity" and "risk stratification."

The specific details of how the ground truth was established for the comparative performance study are not provided in this summary.

8. The Sample Size for the Training Set

This information is not applicable and not provided. This device is a biomarker assay based on immunoassay technology, not a machine learning or AI model that requires a "training set" in the conventional sense. The "training" of an immunoassay system involves calibration and optimization of reagents and instrument parameters, rather than a data-driven machine learning process.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable and not provided, for the same reasons as in point 8.

Summary

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510(k) Summary of Safety and Effectiveness for the Dimension Vista® P-BNP Mono Flex® Reagent Cartridge (K6423A) and Dimension Vista® P-BNP Mono Calibrator (KC676A)

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

A. 510(k) Number: K080578

MAY 1 6 2008

B. Date of Preparation: February 27, 2008

C. Proprietary and Established Names:

Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Flex® Reagent Cartridge (K6423A)

Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Calibrator (KC676A)

D. Applicant:

Siemens Healthcare Diagnostics Inc., P.O. Box 6101, Newark, DE 19714-6101 Victor M. Carrio, Requlatory Affairs and Compliance Manager Office: (302) 631-0376 Fax: (302) 631-6299

E. Regulatory Information:

Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Flex® Reagent Cartridge (K6423A)

1. Regulation section: 21 CFR § 862.1117 B-type natriuretic peptide test system
1. Classification: Class II
1. Product Code: NBC, Test, Natriuretic Peptide
1. Panel: Clinical Chemistry

Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Calibrator (KC676A)

1. Requlation section: 21 CFR § 862.1150 Calibrator, Secondary
1. Classification: Class II
1. Product Code: JIT, Calibrator, Secondary
1. Panel: Clinical Chemistry

F. Predicate Device:

G. Device Description:

Method

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with Chemibeads and biotinylated antibody to form a particle/NT-proBNP/biotiny|ated antibody sandwich. Sensibeads then are added and bind to the biotin to form a bead-aggregated immunocomplex. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads, which diffuses to the Chemibeads and triggers a chemiluminescent reaction. The resulting chemiluminescent signal is measured at 612 nm and is directly proportional to the concentration of NT-proBNP in the sample.

Calibrator

The PBNP Calibrator is a frozen liquid product containing synthetic human Nterminal pro-brain natriuretic peptide in bovine albumin matrix with stabilizers and preservative. The kit consists of ten vials, two vials per level (A, B, C, D, and E), 1.0 mL per vial. Description of the manufacturing, value assignment and stability testing process are provided in this submission report.

H. Intended Use:

Method

Calibrator

The PBNP CAL is an in vitro diagnostic product for the calibration of the N-Terminal Pro-Brain Natriuretic Peptide (PBNP) method for the Dimension Vista® System.

I. Substantial Equivalence Information:

The Dimension Vista® PBNP Flex® reagent cartridge (K6423A) and the Dimension Vista® PBNP Calibrator (KC676A) and the predicate devices, the Dimension Vista® PBNP Flex® reagent cartridge (K6423) and the Dimension Vista® PBNP Calibrator (KC676) were compared. A comparison of the important similarities and differences between the devices and the predicates is provided in the following tables:

Method

Feature	Dimension Vista® PBNP Flex®reagent cartridge (K6423A)	Dimension Vista® PBNP Flex®reagent cartridge (K6423)
IntendedUse	The PBNP method is an in vitrodiagnostic assay for the quantitativemeasurement of N-terminal pro-brainnatriuretic peptide (NT-proBNP) inhuman serum and plasma on theDimension Vista® System. Inindividuals suspected of havingcongestive heart failure (CHF),measurements of NT-proBNP areused as an aid in the diagnosis andassessment of severity. The test isfurther indicated for the riskstratification of patients with acute	The PBNP method is an in vitrodiagnostic assay for the quantitativemeasurement of N-terminal pro-brainnatriuretic peptide (NT-proBNP) inhuman serum and plasma on theDimension Vista® System. Inindividuals suspected of havingcongestive heart failure (CHF),measurements of NT-proBNP are usedas an aid in the diagnosis andassessment of severity. The test isfurther indicated for the riskstratification of patients with acute

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	coronary syndrome and heart failure.	coronary syndrome and heart failure.
DeviceTechnology(detection)	Chemiluminescent	Chemiluminescent
MeasuringRange	5 - 35,000 pg/mL	5 - 35,000 pg/mL
Antibody	Monoclonal Sheep Antibody	Polyclonal Sheep Antibody
Cut-off	125 pg/mL for patients less than 75years old and 450 pg/mL for patients75 years and older.	125 pg/mL for patients less than 75years old and 450 pg/mL for patients75 years and older.
AnalyticalSensitivity	≤ 5 pg/mL	≤ 5 pg/mL
FunctionalSensitivity	≤ 30 pg/mL	≤ 30 pg/mL
AnalyticalSpecificity	Natrecor® shows no significant crossreactivity, 0 or 125 pg/mL NT-PBNP;sixteen other substances show nosignificant cross reactivity.	Natrecor® shows no significant crossreactivity, 0 or 125 pg/mL NT-PBNP;sixteen other substances show nosignificant cross reactivity.
Interferences	No significant interference from:Bilirubin conjugated up to 60 mg/dL;Bilirubin unconjugated up to 60 mg/dL;Hemoglobin up to 1000 mg/dL;Triglyceride up to 3000 mg/dL	No significant interference from:Bilirubin conjugated up to 60 mg/dL;Bilirubin unconjugated up to 60 mg/dL;Hemoglobin up to 680 mg/dL;Triglyceride up to 3000 mg/dL
Hook Effect	No effect up to 400,000 pg/mL	No effect up to 400,000 pg/mL
CalibrationInterval	30 days, same reagent lot	30 days, same reagent lot
SampleVolume	8 µL	8 µL

Calibrator

Feature	Dimension Vista® PBNP Flex®Calibrator (KC676A)	Dimension Vista® PBNP Flex®Calibrator (KC676)
IntendedUse	For the calibration of the N-TerminalPro-Brain Natriuretic Peptide (PBNP)method for the Dimension Vista®System.	For the calibration of the N-TerminalPro-Brain Natriuretic Peptide (PBNP)method for the Dimension Vista®System.
Analyte	Synthetic PBNP	Synthetic PBNP
Matrix	Bovine Albumin	Bovine Albumin
Form	Liquid, frozen	Liquid, frozen
Volume	Ten vials, two vials per level (A, B, C,D, and E), 1.0 mL per vial.	Twelve vials, two vials per level (A, B,C, D, E, and F), 1.0 mL per vial.
Levels	Five Levels, (0, 250, 1500, 12,000,36.750 pg/mL)	Six levels, (0,125, 450, 1500, 12,000and 36,750 pg/mL)

J. Conclusion:

The Dimension Vista® PBNP Flex® reagent cartridge (K6423A) and the Dimension Vista® PBNP Calibrator (KC676A) are substantially equivalent to the Dimension Vista® PBNP Flex® reagent cartridge (K6423) and the Dimension Vista® PBNP Calibrator (KC676) both cleared under K061795. Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure, with its wings spread and head facing to the left. Encircling the bird is text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The text is arranged in a circular fashion around the bird.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics Inc. c/o Mr. Victory M. Carrio RA/QS Compliance Manager P.O. Box 6101, Mailbox 514 Newark, DE 19714-6101

MAY 1 6 2008

Re: K080578

Trade/Device Name: Dimension Vista® N-Terminal Pro-Brain Natriuretic Peptide (PBNP) Flex® Reagent Cartridge Regulation Number: 21 CFR§ 862.1117 Regulation Name: B-Type Natriuretic Peptide Regulatory Class: Class II Product Code: NBC, JIT Dated: February 29, 2008 Received: March 03, 2008

Dear Mr. Carrio:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, 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 can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice 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) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate 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, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. 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 Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper. M.S., 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 Statement

510(k) Number (if known):

KD80578

Device Name:

Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Flex® Reagent Cartridge (K6423A)

Indications for Use:

The PBNP method is an in vitro diagnostic assay for the quantitative measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma on the Dimension Vista® System. In individuals suspected of having congestive heart failure (CHF), measurements of NTproBNP are used as an aid in the diagnosis and assessment of severity. The test is further indicated for the risk stratification of patients with acute coronary syndrome and heart failure.

Prescription Use X (Per 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 Benson

Sign-Off

ce of In Vitro Diagnostic Device Juation and Safety

Image /page/5/Picture/14 description: The image shows a sequence of handwritten characters, which appear to be a combination of letters and numbers. The sequence reads as 'KQ80578'. The characters are written in a simple, slightly uneven style, suggesting they were written quickly or without strict adherence to a specific font. The overall impression is that of a handwritten code or identifier.

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Indications For Use Statement

510(k) Number (if known): K

: K080578

Device Name:

Dimension Vista® N-terminal Pro-Brain Natriuretic Peptide (PBNP) Calibrator (KC676A)

Indications for Use:

The PBNP CAL is an in vitro diagnostic product for the calibration of the N-Terminal Pro-Brain Natriuretic Peptide (PBNP) method for the Dimension Vista® System.

Prescription Use X (Per 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 Benam

... In Sign-Off

ിന്ce of In Vitro Diagnostic Device "ration and Safety

K080578

Page 272

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.”