The NTP 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® EXLTM integrated chemistry system with LOCI® Module. 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 EXL NTP 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 NTproBNP and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a particle/NT-proBNP/biotinylated 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

Here's a breakdown of the acceptance criteria and study information for the Dimension® EXL™ NTP Flex® Reagent Cartridge (RF623), based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document establishes substantial equivalence by comparing the performance characteristics of the Dimension® EXL™ NTP Flex® Reagent Cartridge (RF623) to its predicate device, the Dimension Vista® PBNP Flex® reagent cartridge (K6423A). For each characteristic, the acceptance criterion is implicitly the performance of the predicate device, which the new device matches.

Feature	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (Dimension® EXL™ NTP Flex® RF623)
Intended Use	Quantitative measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma for diagnosis and assessment of CHF severity, and risk stratification for acute coronary syndrome and heart failure.	Matches predicate's intended use (see detailed description in the document).
Device Technology	Chemiluminescent	Chemiluminescent
Measuring Range	5 - 35,000 pg/mL	5 - 35,000 pg/mL
Antibody	Monoclonal Sheep Antibody	Monoclonal Sheep Antibody
Cut-off	125 pg/mL for < 75 years old; 450 pg/mL for ≥ 75 years old	125 pg/mL for < 75 years old; 450 pg/mL for ≥ 75 years old
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) and sixteen other substances.	No significant cross-reactivity with Natrecor® (0 or 125 pg/mL NT-PBNP) and 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 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 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

Study Proving Device Meets Acceptance Criteria:

The document states: "Comparative testing performed by Siemens Healthcare Diagnostics Inc. demonstrates substantial equivalent performance." This indicates that a study was conducted to show the new device performs comparably to the predicate device across the characteristics listed above.

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

The document does not explicitly state the sample size used for the comparative testing. It also does not specify the data provenance (e.g., country of origin, retrospective or prospective nature of the sample collection).

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

This information is not provided in the document. For an in vitro diagnostic (IVD) test measuring a biomarker like NT-proBNP, the "ground truth" for the test results themselves would typically be the measurement obtained from a calibrated reference method or the predicate device, not necessarily established by human experts in the same way as, for example, image interpretation. However, the ground truth for the clinical conditions (CHF, acute coronary syndrome) mentioned in the intended use would be established by medical experts (e.g., cardiologists, emergency physicians) based on clinical evaluation, imaging, and other diagnostic tests. The document does not detail how the clinical ground truth for any patient samples used in the "comparative testing" was established, nor the qualifications of those experts.

4. Adjudication Method for the Test Set:

This information is not provided in the document. Given that this is a comparison to a predicate device for an IVD, the "adjudication method" would likely refer to how discrepancies between the new device and predicate device measurements (if any) were resolved, or how the clinical diagnosis as "ground truth" was confirmed, but this is not detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for devices involving human interpretation (e.g., imaging AI). This device is an in vitro diagnostic assay with quantitative output, so an MRMC study is not applicable. The device's "improvement" is in its performance matching the predicate, not in improving human reader performance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, the performance evaluated is inherently "standalone" in the context of an IVD. The "comparative testing" would have assessed the performance of the Dimension® EXL™ NTP Flex® Reagent Cartridge (RF623) directly against the Dimension Vista® PBNP Flex® reagent cartridge (K6423A) without human intervention in the measurement process itself, beyond operating the instruments. The output is a quantitative value from the device.

7. The Type of Ground Truth Used:

The ground truth for the device's performance is implicitly the results obtained from the legally marketed predicate device (Dimension Vista® PBNP Flex® reagent cartridge (K6423A)). The document doesn't mention the use of pathology, or direct outcomes data as the primary ground truth for establishing equivalence in analytical performance but rather the established performance of the predicate device.

8. The Sample Size for the Training Set:

The document does not specify a training set sample size. For an IVD like this, "training set" is not typically a concept that applies in the same way it does for machine learning algorithms that learn from data. The device's formulation (reagents, antibodies) and measurement principles are established through standard assay development, manufacturing, and validation processes, not through a "training set" in the common AI sense.

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

As mentioned above, the concept of a "training set" and associated "ground truth" for this type of IVD device is not applicable in the same way it is for AI/ML devices. The "ground truth" for the development and validation of the assay would be based on known concentrations of NT-proBNP standards and controls, as well as samples characterized by a reference method or the predicate device itself during its initial development. The current document focuses on demonstrating substantial equivalence to an existing device, which is a different regulatory pathway than initial device development.

Summary

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SEP 2 2 2008

510(k) Summary of Safety and Effectiveness for the

Dimension® EXL™ NTP Flex® Reagent Cartridge (RF623)

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: K082645

B. Date of Preparation: August 15, 2008

C. Proprietary and Established Names:

Dimension® EXL™ N-terminal Pro-Brain Natriuretic Peptide (NTP) Flex® Reagent Cartridge (RF623)

D. Applicant:

Siemens Healthcare Diagnostics Inc., P.O. Box 6101, Newark, DE 19714-6101

Victor M. Carrio, Senior Manager, Regulatory Affairs

Office: (302) 631-0376 Fax: (302) 631-6299

E. Regulatory Information:

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

F. Predicate Device:

The Dimension® EXLTM N-terminal Pro-Brain Natriuretic Peptide (NTP) Flex® Reagent Cartridge (RF623) is substantially equivalent to the Dimension Vista® PBNP Flex® reagent cartridge (K6423A) cleared under K080578.

G. Device Description:

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H. Intended Use:

The NTP 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® EXLTM integrated chemistry system with LOCI® Module. 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.

I. Substantial Equivalence Information:

The Dimension® EXL™ N-terminal Pro-Brain Natriuretic Peptide (NTP) Flex® Reagent Cartridge (RF623) and the Dimension Vista® PBNP Flex® reagent cartridge (K6423A), cleared under K080578, were compared. A comparison of the important similarities and differences between the device and the predicate is provided in the following table:

Feature	Dimension® EXLT™ NTP Flex®Reagent Cartridge (RF623)	Dimension Vista® PBNP Flex®reagent cartridge (K6423A)
		K080578
IntendedUse	The NTP method is an in vitro	The PBNP method is an in vitro
	diagnostic assay for the	diagnostic assay for the
	quantitative measurement of N-	quantitative measurement of N-
	terminal pro-brain natriuretic	terminal pro-brain natriuretic
	peptide (NT-proBNP) in human	peptide (NT-proBNP) in human
	serum and plasma on the	serum and plasma on the
	Dimension® EXLT™ integrated	Dimension Vista® System. In
	chemistry system with LOCI®	individuals suspected of having
	Module. In individuals suspected	congestive heart failure (CHF),
	of having congestive heart failure	measurements of NT-proBNP are
	(CHF), measurements of NT-proBNP are used as an aid in thediagnosis and assessment ofseverity. The test is furtherindicated for the risk stratificationof patients with acute coronarysyndrome and heart failure.	used as an aid in the diagnosis andassessment of severity. The test isfurther indicated for the riskstratification of patients with acutecoronary syndrome and heartfailure.
DeviceTechnology(detection)	Chemiluminescent	Chemiluminescent
MeasuringRange	5 - 35,000 pg/mL	5 - 35,000 pg/mL
Antibody	Monoclonal Sheep Antibody	Monoclonal Sheep Antibody
Cut-off	125 pg/mL for patients less than75 years old and 450 pg/mL forpatients 75 years and older.	125 pg/mL for patients less than75 years old and 450 pg/mL forpatients 75 years and older.
AnalyticalSensitivity	≤5 pg/mL	≤5 pg/mL
FunctionalSensitivity	≤30 pg/mL	≤30 pg/mL
AnalyticalSpecificity	Natrecor® shows no significantcross reactivity, 0 or 125 pg/mLNT-PBNP; sixteen othersubstances show no significantcross reactivity.	Natrecor® shows no significantcross reactivity, 0 or 125 pg/mLNT-PBNP; sixteen othersubstances show no significantcross reactivity.
Interferences	No significant interference from:Bilirubin conjugated up to 60mg/dL; Bilirubin unconjugated upto 60 mg/dL; Hemoglobin up to1000 mg/dL; Triglyceride up to3000 mg/dL	No significant interference from:Bilirubin conjugated up to 60mg/dL; Bilirubin unconjugated upto 60 mg/dL; Hemoglobin up to1000 mg/dL; Triglyceride up to3000 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

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J. Conclusion:

The Dimension® EXL™ N-terminal Pro-Brain Natriuretic Peptide (NTP) Flex® Reagent Cartridge (RF623) is substantially equivalent to the Dimension Vista® PBNP Flex® reagent cartridge (K6423A) cleared under K080578. Comparative testing performed by Siemens Healthcare Diagnostics Inc. demonstrates substantial equivalent performance.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 eagle with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics, Inc. c/o Victor Carrio Senior Manager of Regulatory Affairs P.O. Box 6101, Mail Stop 514 Newark, DE 19714-6101

Re: K082645

Trade Name: Dimension® EXL™ LOCI® N-terminal Pro-Brain Natriuretic Peptide (NTP) Flex® Reagent Cartridge (RF623) Regulation Number: 21 CFR 862.1117 Regulation Name: B-type Natriuretic Peptide Test System Regulatory Class: Class II Product Codes: NBC Dated: September 10, 2008 Received: September 11, 2008

SEP 2 2 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 I o(x) marketed predicate device results in a classification for your device and thus, permites 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 Inc Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please onte 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 the from the (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

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

Sean 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):

Device Name:

Dimension® EXL™ LOCI® N-terminal Pro-Brain Natriuretic Peptide Flex® reagent cartridge (RF623)

Indications for Use:

The NTP method is an in vitro diagnostic assay for the quantitative measurement of Nterminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma on the Dimension® EXLTM integrated chemistry system with LOCI® Module. 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.

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)

Division Sign-Off

f In Virc Diagnostic Device

K082645

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.”