DIMENSION EXL N-TERNMIAL PRO-BRAIN NATRIURETIC PEPTIDE (NTP) FLEX REAGENT CARTRIDGE, MODEL RF623

K082645 · Siemens Healthcare Diagnostics · NBC · Sep 22, 2008 · Clinical Chemistry

Device Facts

• Record ID: K082645
• Device Name: DIMENSION EXL N-TERNMIAL PRO-BRAIN NATRIURETIC PEPTIDE (NTP) FLEX REAGENT CARTRIDGE, MODEL RF623
• Applicant: Siemens Healthcare Diagnostics
• Product Code: NBC · Clinical Chemistry
• Decision Date: Sep 22, 2008
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

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 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 Story

In vitro diagnostic assay for quantitative measurement of NT-proBNP in human serum/plasma; performed on Dimension EXL integrated chemistry system with LOCI Module. Uses one-step sandwich chemiluminescent immunoassay; LOCI technology utilizes two synthetic bead reagents (Sensibeads with streptavidin/photosensitive dye; Chemibeads with antibody/chemiluminescent dye) and biotinylated monoclonal antibody. Sample incubation forms particle/NT-proBNP/biotinylated antibody sandwich; Sensibeads bind biotin to form bead-aggregated immunocomplex. Illumination at 680 nm triggers singlet oxygen release from Sensibeads, diffusing to Chemibeads to initiate chemiluminescent reaction measured at 612 nm. Signal intensity proportional to NT-proBNP concentration. Used in clinical laboratory settings by trained personnel. Results assist clinicians in diagnosing/assessing CHF severity and risk-stratifying acute coronary syndrome/heart failure patients.

Clinical Evidence

Bench testing only. Performance compared to predicate device (K080578) demonstrating substantial equivalence. Metrics include analytical sensitivity (≤5 pg/mL), functional sensitivity (≤30 pg/mL), and measuring range (5-35,000 pg/mL). Interference testing confirmed no significant impact from bilirubin, hemoglobin, or triglycerides. Hook effect observed up to 400,000 pg/mL.

Technological Characteristics

Chemiluminescent immunoassay using LOCI® technology. Reagents: synthetic beads (Sensibeads, Chemibeads) and biotinylated monoclonal sheep antibody. Detection: 680 nm excitation, 612 nm emission. Measuring range: 5-35,000 pg/mL. Sample volume: 8 µL. Calibration interval: 30 days. Platform: Dimension® EXL™ integrated chemistry system.

Indications for Use

Indicated for quantitative measurement of NT-proBNP in human serum and plasma to aid in diagnosis and severity assessment of congestive heart failure (CHF) and for risk stratification of patients with acute coronary syndrome and heart failure.

Regulatory Classification

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.

Special Controls

*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.”

Predicate Devices

• Dimension Vista® PBNP Flex® reagent cartridge (K080578)

Submission Summary (Full Text)

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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: [phone] Fax: [phone]

#### E. Regulatory Information:

- 1. Regulation section: 21 CFR § 862.1117 B-type natriuretic peptide test system
- 2. Classification: Class II
- 3. Product Code: NBC, Test, Natriuretic Peptide
- 4. 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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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.

## 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®<br>Reagent Cartridge (RF623) | Dimension Vista® PBNP Flex®<br>reagent cartridge (K6423A) |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | K080578 |
| Intended<br>Use | 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-<br>proBNP are used as an aid in the<br>diagnosis and assessment of<br>severity. The test is further<br>indicated for the risk stratification<br>of patients with acute coronary<br>syndrome and heart failure. | used as an aid in the diagnosis and<br>assessment of severity. The test is<br>further indicated for the risk<br>stratification of patients with acute<br>coronary syndrome and heart<br>failure. |
| Device<br>Technology<br>(detection) | Chemiluminescent | Chemiluminescent |
| Measuring<br>Range | 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 than<br>75 years old and 450 pg/mL for<br>patients 75 years and older. | 125 pg/mL for patients less than<br>75 years old and 450 pg/mL for<br>patients 75 years and older. |
| Analytical<br>Sensitivity | ≤5 pg/mL | ≤5 pg/mL |
| Functional<br>Sensitivity | ≤30 pg/mL | ≤30 pg/mL |
| Analytical<br>Specificity | Natrecor® shows no significant<br>cross reactivity, 0 or 125 pg/mL<br>NT-PBNP; sixteen other<br>substances show no significant<br>cross reactivity. | Natrecor® shows no significant<br>cross reactivity, 0 or 125 pg/mL<br>NT-PBNP; sixteen other<br>substances show no significant<br>cross reactivity. |
| Interferences | No significant interference from:<br>Bilirubin conjugated up to 60<br>mg/dL; Bilirubin unconjugated up<br>to 60 mg/dL; Hemoglobin up to<br>1000 mg/dL; Triglyceride up to<br>3000 mg/dL | No significant interference from:<br>Bilirubin conjugated up to 60<br>mg/dL; Bilirubin unconjugated up<br>to 60 mg/dL; Hemoglobin up to<br>1000 mg/dL; Triglyceride up to<br>3000 mg/dL |
| Hook Effect | No effect up to 400,000 pg/mL | No effect up to 400,000 pg/mL |
| Calibration<br>Interval | 30 days, same reagent lot | 30 days, same reagent lot |
| Sample<br>Volume | 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 [phone]. 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 [phone] or [phone] 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