The PBNP assay used on the Dimension® clinical chemistry system with the heterogeneous immunoassay module is an in vitro diagnostic assay for the quantitative determination of Nterminal pro-brain natriuretic peptide (NT-proBNP) in human serum or plasma. 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.

Device Description

The PBNP method is a one-step enzyme immunoassay based on the "sandwich" principle. Sample is incubated with chromium dioxide particles coated with monoclonal antibodies, which recognize an epitope located in the N-terminal part of proBNP, and a conjugate reagent [alkaline phosphatase (ALP)} labeled monoclonal antibody specific for a second independent epitope on NT-proBNP, to form a particle/NT-proBNP/conjugate sandwich. Unbound conjugate is removed by magnetic separation and washing. After separation and washing, the particle/NT-proBNP/conjugate sandwich is transferred to the cuvette where the sandwich-bound ALP triggers an amplification cascade. ALP dephosphorylates synthetic flavin adenine dinucleotide (FADP) to produce FAD. FAD binds to apo D-amino acid oxidase and converts it to active holo D-amino acid oxidase. Each molecule of holo D-amino acid oxidase produces multiple molecules of hydrogen peroxide (H2O2). H2O2 in the presence of horseradish peroxidase (HRP), converts 3,5-dichloro-2-hydroxybenzenesulfonic acid (DCHBS) and 4-aminoantipyrine (4-AAP) to a colored product that absorbs at 510 nm. The color change measured is directly proportional to the concentration of NTproBNP present in the patient sample.

AI/ML Overview

The provided text describes a 510(k) summary for the Dade Behring Dimension® PBNP reagent cartridge, which is an in vitro diagnostic assay. The document aims to demonstrate substantial equivalence to a predicate device (K041417/K042347).

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" but rather presents a comparison of performance characteristics between the new device and the predicate device, implying that meeting these characteristics substantially equivalent to the predicate is the "acceptance criterion" for regulatory approval.

Feature / Performance Characteristic	Predicate Device (K041417/K042347) Reported Performance	New Device (Dimension® PBNP-mono) Reported Performance
Intended Use	Aid in diagnosis & assessment of CHF severity; risk stratification for ACS & heart failure, using human plasma.	Aid in diagnosis & assessment of CHF severity; risk stratification for ACS & heart failure, using human serum or plasma.
Assay Type (detection)	Immunoassay (chemiluminescent)	Immunoassay (chemiluminescent)
Reportable Range	10 - 30,000 pg/mL	10 - 30,000 pg/mL
Antibody	Polyclonal (sheep) antibody	Monoclonal (sheep) antibody
Cut-off	125 pg/mL for < 75 years, 450 pg/mL for ≥ 75 years	125 pg/mL for < 75 years, 450 pg/mL for ≥ 75 years
Analytical Sensitivity	≤ 10 pg/mL	≤ 10 pg/mL
Functional Sensitivity	≤ 30 pg/mL	≤ 30 pg/mL
Analytical Specificity	Natrecor® no significant cross-reactivity (0 or 125 pg/mL NT-proBNP); sixteen other substances no significant cross-reactivity.	Natrecor® no significant cross-reactivity (0 or 125 pg/mL NT-proBNP); sixteen other substances no significant cross-reactivity.
Interferences	No significant interference from: Bilirubin, conj. up to 60 mg/dL; bilirubin, unconj. up to 20 mg/dL; hemoglobin up to 1000 mg/dL; triglycerides up to 3000 mg/dL; rheumatoid factors up to 500 IU/mL.	No significant interference from: Bilirubin, conj. up to 60 mg/dL; bilirubin, unconj. up to 60 mg/dL; hemoglobin up to 1000 mg/dL; triglycerides up to 3000 mg/dL; rheumatoid factors up to 500 IU/mL.
Hook Effect	No effect up to 300,000 pg/mL	No effect up to 300,000 pg/mL
Calibration Interval	30 days - same reagent lot	30 days - same reagent lot
Sample Volume	50 uL	50 uL

Study to Prove Device Meets Acceptance Criteria:

The document states: "Comparative data for human samples demonstrate good analytical and clinical agreement between the methods." This sentence refers to the study proving the new device meets the implied acceptance criteria (i.e., being substantially equivalent to the predicate).

However, the details of this study are very limited in the provided text.

Additional Information Not Available in the Text:

The provided text does not include information for the following points:

Sample size used for the test set and the data provenance: Not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not specified, and "experts" are not mentioned in the context of ground truth establishment for patient samples. Instead, the ground truth would be the measurement obtained from the predicate device.
Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable and not mentioned, as this is a medical device for quantitative determination in a lab setting, not an imaging device requiring expert consensus for interpretation.
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: Not applicable. This is a lab-based immunoassay, not an AI-assisted diagnostic tool for human review.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The device is a standalone in vitro diagnostic (immunoassay) that provides quantitative results. The performance comparison mentioned is likely between the new immunoassay and the predicate immunoassay, both operating without human interpretation in the results generation process itself.
The type of ground truth used: For the comparative data, the predicate device's measurements likely served as the reference ("ground truth") to establish analytical and clinical agreement.
The sample size for the training set: Not applicable, as this is an immunoassay, not a machine learning model.
How the ground truth for the training set was established: Not applicable.

Summary

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510(k) Summary

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

The assigned 510(k) number is:

Ko71767

AUG 2 4 2007

Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation 1.

Manufacturer:	Dade Behring Inc.P.O. Box 6101Newark, DE 19714
Contact Information:	Dade Behring Inc.P.O. Box 6101Newark, DE 19714Attn: Pamela A. JurgaTel: 302-631-8891

Date of Preparation:

June 28, 2007

2. Device Name / Classification

. Dimension® PBNP reagent cartridge/ Class II

3. Identification of the Predicate Device

Dimension® PBNP reagent cartridge/ Class II (K041417/K042347). .

FDA Guidance Document(s):

"Class II Special Control Guidance Document for B-Type Natriuretic . Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers" - 11/30/2000
"Deciding When to Submit a 510(k) for a Change to an Existing Device"-. 1/10/1997

Device Description(s): 4.

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binds to apo D-amino acid oxidase and converts it to active holo D-amino acid oxidase. Each molecule of holo D-amino acid oxidase produces multiple molecules of hydrogen peroxide (H2O2). the presence of horseradish peroxidase (HRP), converts 3,5-dichloro-2-H2O2 in a hydroxybenzenesulfonic acid (DCHBS) and 4-aminoantipyrine (4-AAP) to a colored product that absorbs at 510 nm. The color change measured is directly proportional to the concentration of NTproBNP present in the patient sample.

*Technology licensed from London Biotechnology, Ltd., London, U.K.

5. Device Intended Use:

The PBNP assay used on the Dimension® clinical chemistry system with the heterogeneous immunoassay module is an in vitro diagnostic assay for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum or plasma. 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.

Medical device to which equivalence is claimed: 6.

Substantial Equivalence:

This product is substantially equivalent to other B-type natriuretic peptide test systems, such as the Dimension® PBNP Flex® reagent cartridge immunoassay (K041417/K042347).

Comparison to Predicate Device:

The modified Dade Behring Dimension® PBNP method and the current Dade Behring Dimension® PBNP method are both in vitro diagnostic immunoassays intended for the quantitative measurement of Nterminal pro-brain natriuretic peptide. A summary of the two methods is included in the following table.

Feature	Dimension® PBNP-mono	Dimension® PBNP(K041417/K042347)
Intended Use	The PBNP assay used on theDimension® clinical chemistrysystem with the heterogeneousimmunoassay module is an in vitrodiagnostic assay for the quantitativedetermination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum orplasma. In individuals suspected ofhaving congestive heart failure(CHF), measurements of NT-proBNP are used as an aid in thediagnosis and assessment ofseverity. The test is furtherindicated for the risk stratification	The PBNP assay used on theDimension® clinical chemistrysystem with the heterogeneousimmunoassay module is an in vitrodiagnostic assay for the quantitativedetermination of N-terminal pro-brainnatriuretic peptide (NT-proBNP) inhuman plasma. In individualssuspected of having congestive heartfailure (CHF), measurements of NT-proBNP are used as an aid in thediagnosis and assessment of severity.The test is further indicated for therisk stratification of patients withacute coronary syndrome and heart
	of patients with acute coronarysyndrome and heart failure.
Assay Type(detection)	immunoassay(chemiluminescent)	immunoassay(chemiluminescent)
Reportable Range	10 - 30,000 pg/mL	10 - 30,000 pg/mL
Antibody	monoclonal (sheep) antibody	polyclonal (sheep) antibody
Cut-off	125 pg/mL for patients less than 75years and 450 pg/mL for patients 75years and older	125 pg/mL for patients less than 75years and 450 pg/mL for patients 75years and older
AnalyticalSensitivity	≤ 10 pg/mL	≤ 10 pg/mL
FunctionalSensitivity	≤ 30 pg/mL	≤ 30 pg/mL
AnalyticalSpecificity	Natrecor® shows no significantcross reactivity, 0 or 125 pg/mLNT-proBNP; sixteen othersubstances show no significantcross reactivity	Natrecor® shows no significant crossreactivity, 0 or 125 pg/mL NT-proBNP; sixteen other substancesshow no significant cross reactivity
Interferences	No significant interference from:Bilirubin, conj. up to 60 mg/dLbilirubin, unconj. up to 60 mg/dLhemoglobin up to 1000 mg/dLtriglycerides up to 3000 mg/dLrheumatoid factors up to 500 IU/mL	No significant interference from:Bilirubin, conj. up to 60 mg/dLbilirubin, unconj. up to 20 mg/dLhemoglobin up to 1000 mg/dLtriglycerides up to 3000 mg/dLrheumatoid factors up to 500 IU/mL
Hook Effect	No effect up to 300,000 pg/mL	No effect up to 300,000 pg/mL
Calibration Interval	30 days - same reagent lot	30 days - same reagent lot
Sample Volume	50 uL	50 uL

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100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

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Comments on Substantial Equivalence:

Both the modified Dade Behring Dimension® PBNP and the current Dade Behring Dimension® PBNP immunoassays are intended for the quantitative determination of NT-proBNP. Comparative data for human samples demonstrate good analytical and clinical agreement between the methods.

Conclusion:

The modified Dade Behring Dimension® PBNP method and the predicate Dade Behring Dimension® PBNP method (K041417/K042347) are substantially equivalent based on their intended use and performance characteristics as described above.

Pamela A. Jurga

Pamela A. Jurga Regulatory Affairs and Compliance Manager June 28, 2007

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wing. The eagle is facing right. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Dade Behring, Inc. c/o Ms. Pamela A. Jurga Regulatory Affairs & Compliance Manager Glasgow Business Community Bldg. 500 M.S. 514 P.O. Box 6101 Newark, DE 19714

AUG 2 4 2007

Re: K071767

Trade/Device Name: Dimension® NT-proBNP (PBNP) Flex® reagent cartridge method Regulation Number: 21 CFR§ 862.1117 Regulation Name: B-Type Natriuretic Peptide Test System. Regulatory Class: Class II Product Code: NBC Dated: June 28, 2007 Received: June 29, 2007

Dear Ms. Jurga:

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.

Jean 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

510(k) Number (if known):

Device Name:

Dimension® NT-proBNP (PBNP) Flex® reagent cartridge method

Indications For Use:

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

Over-The-Counter Use (21 CFR 801)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Page 1 of 1

Carol Benson

Division Sign-Off

Office of In Vitro Diagnostic Device

Evaluation and Safety

Ko7/767

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.”