DIMENSIONS PBNP FLEX REAGENT CARTRIDGE, MODEL RF423A

K071767 · Dade Behring, Inc. · NBC · Aug 4, 2007 · Clinical Chemistry

Device Facts

• Record ID: K071767
• Device Name: DIMENSIONS PBNP FLEX REAGENT CARTRIDGE, MODEL RF423A
• Applicant: Dade Behring, Inc.
• Product Code: NBC · Clinical Chemistry
• Decision Date: Aug 4, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

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.

Device Story

In vitro diagnostic assay; quantitative determination of NT-proBNP in human serum or plasma; used on Dimension clinical chemistry systems. Method: one-step sandwich enzyme immunoassay; sample incubated with chromium dioxide particles coated with monoclonal antibodies and ALP-labeled monoclonal antibody; magnetic separation removes unbound conjugate; amplification cascade triggered by ALP dephosphorylating FADP to FAD; FAD activates D-amino acid oxidase to produce H2O2; H2O2 reacts with DCHBS and 4-AAP to produce colored product measured at 510 nm. Output: concentration of NT-proBNP proportional to color change. Used in clinical laboratory settings by trained personnel. Results aid clinicians in diagnosing CHF, assessing severity, and risk-stratifying patients with acute coronary syndrome and heart failure.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP5-A2 (within-lab CV 4.9-5.6%). Linearity confirmed across 10-30,000 pg/mL range (r=0.9989). Analytical sensitivity ≤10 pg/mL; functional sensitivity ≤30 pg/mL. Method comparison against predicate (n=122) yielded slope 1.02, intercept -5 pg/mL, r=0.99. Concordance study (n=122) across reference and disease populations (NYHA classes I-IV) showed 98.6% overall concordance using established cut-offs (125 pg/mL for <75 years; 450 pg/mL for ≥75 years). No significant interference from common substances.

Technological Characteristics

One-step sandwich enzyme immunoassay; chromium dioxide particles; alkaline phosphatase (ALP) conjugate; synthetic flavin adenine dinucleotide phosphate (FADP) substrate; D-amino acid oxidase amplification; colorimetric detection at 510 nm. Reagents provided in flexible plastic cartridge for use on Dimension RxL Max, RxL, and Xpand systems. Monoclonal sheep antibodies. Reportable range 10-30,000 pg/mL. Traceable to Roche purified synthetic NT-proBNP.

Indications for Use

Indicated for quantitative determination of NT-proBNP in human serum or 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® PBNP reagent cartridge (K041417/K042347)

Submission Summary (Full Text)

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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.<br>P.O. Box 6101<br>Newark, DE 19714 |
|----------------------|------------------------------------------------------------------------------------------------------|
| Contact Information: | Dade Behring Inc.<br>P.O. Box 6101<br>Newark, DE 19714<br>Attn: Pamela A. Jurga<br>Tel: [phone] |

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.

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

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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<br>(K041417/K042347) |
|---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The PBNP assay used on the<br>Dimension® clinical chemistry<br>system with the heterogeneous<br>immunoassay module is an <i>in vitro</i><br>diagnostic assay for the quantitative<br>determination of N-terminal pro-<br>brain natriuretic peptide (NT-<br>proBNP) in human serum or<br>plasma. In individuals suspected of<br>having congestive heart failure<br>(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 | The PBNP assay used on the<br>Dimension® clinical chemistry<br>system with the heterogeneous<br>immunoassay module is an <i>in vitro</i><br>diagnostic assay for the quantitative<br>determination of N-terminal pro-brain<br>natriuretic peptide (NT-proBNP) in<br>human plasma. In individuals<br>suspected of having congestive heart<br>failure (CHF), measurements of NT-<br>proBNP are used as an aid in the<br>diagnosis and assessment of severity.<br>The test is further indicated for the<br>risk stratification of patients with<br>acute coronary syndrome and heart |
| | of patients with acute coronary<br>syndrome and heart failure. | |
| Assay Type<br>(detection) | immunoassay<br>(chemiluminescent) | immunoassay<br>(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 75<br>years and 450 pg/mL for patients 75<br>years and older | 125 pg/mL for patients less than 75<br>years and 450 pg/mL for patients 75<br>years and older |
| Analytical<br>Sensitivity | ≤ 10 pg/mL | ≤ 10 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-proBNP; sixteen other<br>substances show no significant<br>cross reactivity | Natrecor® shows no significant cross<br>reactivity, 0 or 125 pg/mL NT-<br>proBNP; sixteen other substances<br>show no significant cross reactivity |
| Interferences | No significant interference from:<br>Bilirubin, conj. up to 60 mg/dL<br>bilirubin, unconj. up to 60 mg/dL<br>hemoglobin up to 1000 mg/dL<br>triglycerides up to 3000 mg/dL<br>rheumatoid factors up to 500 IU/mL | No significant interference from:<br>Bilirubin, conj. up to 60 mg/dL<br>bilirubin, unconj. up to 20 mg/dL<br>hemoglobin up to 1000 mg/dL<br>triglycerides up to 3000 mg/dL<br>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 |

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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 [phone]. 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 [phone] or [phone] 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:

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.

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