DIMENSION VISTA PBNP FLEX REAGENT CARTRIDGE AND CALIBRATOR

K061795 · Dade Behring, Inc. · NBC · Sep 11, 2006 · Clinical Chemistry

Device Facts

• Record ID: K061795
• Device Name: DIMENSION VISTA PBNP FLEX REAGENT CARTRIDGE AND CALIBRATOR
• Applicant: Dade Behring, Inc.
• Product Code: NBC · Clinical Chemistry
• Decision Date: Sep 11, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

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. The NT-proBNP (PBNP) Calibrator is an in vitro diagnostic product intended to be used for calibration of N-terminal pro-brain natriuretic peptide (PBNP) method for the Dimension Vista™ System.

Device Story

Dimension Vista™ PBNP is an in vitro diagnostic immunoassay for quantitative measurement of NT-proBNP in human serum/plasma. Operates on Dimension Vista™ System using Luminescent Oxygen Channeling Immunoassay (LOCI™) technology. Input: patient serum/plasma sample. Process: sample incubated with biotinylated antibody and Chemibeads (coated with antibody specific to NT-proBNP epitope) to form sandwich; Sensibeads (streptavidin-coated with photosensitive dye) added to form bead-aggregated immunocomplex. Illumination at 680 nm generates singlet oxygen, triggering chemiluminescent reaction measured at 612 nm. Signal intensity proportional to NT-proBNP concentration. Used in clinical laboratory settings by trained personnel. Output: quantitative NT-proBNP concentration. Results assist clinicians in diagnosing/assessing CHF severity and risk-stratifying acute coronary syndrome/heart failure patients.

Clinical Evidence

No clinical data provided. Substantial equivalence is based on analytical performance characteristics, including sensitivity, specificity, interference testing, and comparative testing against the predicate device.

Technological Characteristics

One-step sandwich chemiluminescent immunoassay using LOCI™ technology. Reagents: two latex bead types (Sensibeads, Chemibeads) and biotinylated polyclonal antibody. Detection: 680 nm excitation, 612 nm emission. Sample volume: 8 µL. Calibration: 30-day interval. Calibrator: frozen liquid synthetic NT-proBNP in bovine albumin matrix.

Indications for Use

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

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

• Roche Diagnostics Elecsys® proBNP immunoassay and proBNP CalSet Calibrator (K032646/K022516)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

## ASSAY ONLY TEMPLATE

A. 510(k) Number:
k061795

B. Purpose for Submission:
New device

C. Measurand:
N-terminal pro-brain natriuretic peptide (NT-proBNP)

D. Type of Test:
Quantitative

E. Applicant:
Dade Behring, Inc.

F. Proprietary and Established Names:
Dimension® Vista™ NT-proBNP (PBNP) Flex® reagent cartridge method
Dimension® Vista™ NT-proBNP (PBNP) calibrator

G. Regulatory Information:
1. Regulation section:
21 CFR 862.1117, B-type natriuretic peptide test system
21 CFR 862.1150, Calibrator secondary
2. Classification:
Class II
3. Product code:
NBC; JIT

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4. Panel:

75 Chemistry

# H. Intended Use:

1. Intended use(s):

See Indications for use below.

2. Indication(s) 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 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 Dimension Vista NT-proBNP(PBNP) calibrator is an in vitro diagnostic product for the calibration of the N-terminal pro-brain natriuretic peptide (PBNP) method on the Dimension Vista™ System.

3. Special conditions for use statement(s):

Prescription use

4. Special instrument requirements:

Dade Behring Dimension Vista™ Integrated System

# I. Device Description:

The Flex® reagent cartridge contains reagents for 80 tests (2 x 40/catridge). Reagents contains biotinylated antibody, NT-proBNP Chemibeads, Streptavidin Sensibeads, and assay buffer in the following configuration:

| Wells | Form | Ingredient | Concentration | Quantity | Source |
| --- | --- | --- | --- | --- | --- |
| 1-2 | Liquid | Biotinylated Antibody | 9 μg/mL | 670 μL | Sheep polyclonal |
| 3-4 | Liquid | NT-proBNP Chemibeads | 150 μg/mL | 670 μL | Sheep polyclonal |
| 7-8 | Liquid | Streptavidin Sensibead | 1400 μg/mL | 565 μL | Recombinant E. coli |
| 9-12 | Liquid | Assay Buffer | na | 1300 μL | |

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The NT-proBNP (PBNP) Calibrator is a frozen liquid product containing synthetic human N-terminal pro-brain natriuretic peptide in a bovine albumin matrix with stabilizers and preservative. The kit consists of eight vials, two each of four levels (A, B, C and D), 1.0 mL per vial for levels A, C and D and 1.5 mL per vial for level B.

# J. Substantial Equivalence Information:

1. Predicate device name(s):

Roche Diagnostics Elecsys® proBNP Immunoassay

2. Predicate 510(k) number(s):

k022516

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Dimension® Vista™ NT-proBNP (PBNP) Flex® | Roche NT-proBNP |
| Assay type | Immunoassay (chemiluminescent) | Immunoassay (electrochemiluminescent) |
| Antibody | Polyclonal sheep antibody | Polyclonal sheep antibody |
| Cut-off | 125 pg/mL for patients <75 years | 125 pg/mL for patients <75 years |
| | 450 pg/mL for patients ≥75 years | 450 pg/mL for patients ≥75 years |
| Reference | Roche NT-proBNP antibody | Roche NT-proBNP antibody |
| Reportable range | 5-35,000 pg/mL | 5 - 35,000 pg/mL |
| Differences | | |
| Item | Dimension® Vista™ NT-proBNP (PBNP) Flex® | Roche NT-proBNP |
| 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 NT-proBNP are used as an aid in the diagnosis and assessment of | For the in vitro quantitative determination of NT-proBNP in human serum and plasma. The Elecsys proBNP assay is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome and congestive heart failure. |

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| Sample volume | severity. The test is further indicated for the risk stratification of patients with acute coronary syndrome and heart failure.
8 μL | 20 μL |
| --- | --- | --- |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP5-A2; CLSI EP7-A; CLSI EP9-A; and Class II Special Controls Guidance Document for B-Type Natriuretic Peptide Premarket Notifications: Final Guidance for Industry and FDA Reviewers (11/30/2000)

L. Test Principle:

The PBNP method is a one-step sandwich chemiluminescent immunoassay based on Luminescent Oxygen Channeling Immunoassay (LOCI™) technology. LOCI™ reagents include two latex bead reagents and a biotinylated polyclonal 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/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.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

CLSI EP5-A2 was used. During each day of testing, two separate runs, with two test samples, for each test material, were analyzed for 20 days. The results are presented in the table below.

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| Material | Mean pg/mL | Standard Deviation (%CV) | | | |
| --- | --- | --- | --- | --- | --- |
| | | Repeatability | | Within-Lab | |
| Serum Pool 1 | 124 | 3.04 | 2.5 | 5.49 | 4.4 |
| Serum Pool 2 | 470 | 7.55 | 1.6 | 14.14 | 3.0 |
| Serum Pool 3 | 2047 | 31.93 | 1.6 | 56.91 | 2.8 |
| Internal QC Pool 1 | 11407 | 174.72 | 1.5 | 223.60 | 2.0 |
| Internal QC Pool 2 | 26038 | 476.16 | 1.8 | 628.00 | 2.4 |
| Bio-Rad LT Level 1 | 334 | 5.68 | 1.7 | 8.84 | 2.6 |

# b. Linearity/assay reportable range:

The assay reportable range is 5-35,000 pg/mL. A patient plasma sample with a high NT-proBNP concentration was diluted across the assay range. An additional plasma sample was diluted linearly to confirm dilutional accuracy at the low end of the assay range. All samples were diluted with low level patient plasma pools.

The following table summarizes the results of these studies:

| | Sample A | Sample B |
| --- | --- | --- |
| Starting Concentration (pg/mL) | 40500 | 1147 |
| Regression Statistics | | |
| Slope | 1.007 | 1.002 |
| Intercept | -425.2 | 11.0 |
| Correlation Coefficient | 0.999 | 0.999 |
| N | 5 | 5 |
| % Recovery | | |
| Average | 98 | 102 |
| Range | 94-100 | 100-105 |

Hook effect was evaluated using samples containing NT-proBNP concentrations ranging from 0 to $400,000~\mathrm{pg / mL}$ . The samples were prepared with Roche synthetic antigen spiked into $5\%$ bovine serum base material. No hook effect was found up to $400,000~\mathrm{pg / mL}$ .

# c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The assay is referenced to Roche purified synthetic NT-proBNP (1-76). The assigned values for the Dimension Vista Calibrator are referenced to a master pool containing synthetic human N-terminal pr0-brain natriuretic peptide.

Un-open calibrators stored frozen at -20 to $-10^{\circ}\mathrm{C}$ are stable until the stated expiration date. Calibrator stability is determined using Dade Behring's shelf life stability protocol and is ongoing. Open vial stability was set at 7 days to be consistent with other Dimension Vista® system calibrators, although

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stability studies demonstrated that the calibrators were stable for longer than 7 days.

d. Detection limit:

The analytical sensitivity of the PBNP method is ≤ 5 pg/mL. Analytical sensitivity is defined as the concentration at two standard deviations (N=20) above a sample devoid of NT-proBNP, such as the PBNP Level 1 Calibrator (0 pg/mL). The analytical sensitivity was determined by assaying 20 consecutive replicates of the 0 pg/mL level calibrator. The analytical sensitivity was then calculated by determining the standard deviation (SD) of the 20 replicates, multiplying by 2 and adding it to the absolute value of the mean. The analytical sensitivity of the Dimension Vista PBNP method was 1.186. A claim of ≤ 5 pg/mL will be used to account for instrument variability.

Functional sensitivity for NT-proBNP is defined as the analyte detection concentration corresponding to a 20% CV. This was determined by performing a 20 day ANOVA experiment using samples prepared from normal human serum. Two replicates of each sample were analyzed once per day for 20 days. Total % CV was plotted vs. the target PBNP concentration. Although the functional sensitivity was determined to be 7 pg/mL, a claim of ≤ 30 pg/mL will be used to account for instrument to instrument variability.

e. Analytical specificity:

The NT-proBNP assay was evaluated for interference according to CLSI EP7-A. The following substances demonstrated no significant bias (defined as &lt; 10 %).

| Substance Tested | Substance Concentration | NT-proBNP Concentration pg/mL | Bias % |
| --- | --- | --- | --- |
| Hemoglobin | 680 mg/dL | 114 | -8.15 |
| Bilirubin | | | |
| (unconjugated) | 60 mg/dL | 114 | -5.77 % |
| Bilirubin | | | |
| (conjugated) | 60 mg/dL | 115 | -6.52 % |
| Lipemia | | | |
| Intralipid®) | 3000 mg/dL | 121 | 1.96 |

An extensive list of other compounds was evaluated for interference and was found to have no significant interference or cross reactivity. A list of these compounds is present in the product labeling. The following substances have no significant cross-reactivity (less than 1 %) at the concentrations indicated when added to samples containing 0 and approximately 125 pg/mL NT-proBNP:

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| Substance | Concentration |
| --- | --- |
| ANP28 | 3.1 μg/mL |
| NT-proANP1-30 (preproANP 26-55) | 3.5 μg/mL |
| NT-proANP31-67 (preproANP 56-92) | 1.0 ng/mL |
| NT-proANP79-98 (preproANP 104-123) | 1.0 ng/mL |
| BNP32 (Natrecor®) | 3.5 μg/mL |
| CNP32 | 2.2 μg/mL |
| DNP | 1.0 ng/mL |
| VNP | 1.0 ng/mL |
| Adrenomedullin | 1.0 ng/mL |
| Aldosterone | 1.0 ng/mL |
| Angiotensin I | 1.0 ng/mL |
| Angiotensin II | 0.6 ng/mL |
| Angiotensin III | 0.6 ng/mL |
| Endothelin | 0.6 ng/mL |
| Renin | 1.0 ng/mL |
| Urodilatin | 20 pg/mL |
| Arg-Vasopressin | 50 ng/mL |

f. Assay cut-off:

See clinical studies below. The recommended medical decision thresholds are the same as those recommended by the predicate device. They are by age group as follows:

Patients $&lt; 75$ years $125\mathrm{pg / mL}$

Patients $\geq 75$ years $450~\mathrm{pg / mL}$

2. Comparison studies:

a. Method comparison with predicate device:

A split sample comparison study was performed between the Dimension Vista NY-proBNP assay and the predicate Roche Elecsys proBNP assay with serum and heparinized plasma patient samples. CLSI EP9-A was used. Samples were obtained from patients known to have CHF $(n = 269)$ and patients with no history available $(n = 150)$ . The range of NT-proBNP values in the correlation study was 5.1 to $32,779~\mathrm{pg / mL}$ .

Regression Statistics

| Comparative Method | Slope | Intercept pg/mL | Correlation Coefficient | n |
| --- | --- | --- | --- | --- |
| Roche Elecsys® | 1.018 | 3.616 | 0.99 | 411 |

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b. Matrix comparison:

Comparison of 50 matched serum and lithium heparin plasma samples with values ranging from 33.2 pg/mL to 35,925 pg/mL on the Dimension Vista system gave a slope of 1.00, an intercept of -32.3, and a correlation coefficient of 0.999 using linear regression statistics.

Comparison of 72 matched serum and EDTA plasma samples with values ranging from 7.8 pg/mL to 29,272 pg/mL on the Dimension Vista system gave a slope of 0.99, an intercept of 2.3, and a correlation coefficient of 0.999 using linear regression statistics.

3. Clinical studies:

a. Clinical Sensitivity:

Clinical Studies: For the Reference Study Group, NT-proBNP concentrations were determined in 318 individuals without congestive heart failure (163 women and 155 men). This population included apparently healthy individuals and individuals with diabetes, hypertension, and pulmonary disease. For the Disease Study Group, NT-proBNP concentrations were determined in 269 patients diagnosed with congestive heart failure (CHF). This population included 78 women and 191 men.

The tables below show the clinical sensitivity and specificity of the Dimension Vista PBNP assay using a cutoff of 125 pg/mL for patients younger than 75 years and 450 pg/mL for patients 75 years or older.

| Males | | |
| --- | --- | --- |
| | <75 yrs | ≥75 yrs |
| Sensitivity | 94% (133/142) | 96% (47/49) |
| 95% Confidence Interval | 90 – 98 | 90 – 100 |
| Specificity | 87% (81/93) | 73% (45/62) |
| 95% Confidence Interval | 80 - 94 | 61 – 84 |
| Females | | |
| --- | --- | --- |
| | <75 yrs | ≥75 yrs |
| Sensitivity | 89% (54/61) | 88% (15/17) |
| 95% Confidence Interval | 81 – 97 | 73 – 100 |
| Specificity | 92% (95/103) | 85% (51/60) |
| 95% Confidence Interval | 87 – 97 | 76 – 94 |

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b. Clinical specificity:

See Clinical sensitivity section above.

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c. Other clinical supportive data (when a. and b. are not applicable):

# 4. Clinical cut-off:

The Receiver Operator Characteristics (ROC) Curve presents the clinical sensitivity and specificity at various cutoffs for the 269 patients diagnosed with CHF and 318 subjects without CHF. The ROC curve for the Dimension Vista PBNP assay is shown below. The area under ROC curve (AUC) for the Dimension Vista™ PBNP assay is 0.928 with a $95\%$ confidence interval of 0.907 to 0.949.


A box and whiskers plot of the clinical study population is presented below. Recommended clinical thresholds are $125~\mathrm{pg / mL}$ for patients younger than 75 years and $450~\mathrm{pg / mL}$ for patients 75 years and older.

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# 5. Expected values/Reference range:

NT-proBNP concentrations in the Reference Group are shown in the following tables. The recommended medical decision thresholds, by age group, are:

Patients $&lt; 75$ years $125\mathrm{pg / mL}$

Patients $\geq 75$ years $450~\mathrm{pg / mL}$

# Reference Study Group

NT-proBNP concentrations were determined in 318 individuals without congestive heart failure (163 women and 155 men). This population included apparently health individuals and individuals with diabetes, hypertension, and pulmonary disease. The statistics for NT-proBNP concentrations in the reference study group are shown in the following table.

Reference Study Group

All

| | <55 yrs | 55 - 64 yrs | 65 - 74 yrs | ≥ 75 yrs |
| --- | --- | --- | --- | --- |
| Mean | 45.9 | 54.6 | 175.5 | 451.3 |
| SD | 53.6 | 62.3 | 197.6 | 987.1 |
| Median | 27.2 | 28.8 | 106.2 | 173.5 |
| 95thPercentile | 131.2 | 206.6 | 880.8 | 1615.7 |
| % < 125 pg/mL | 94% | 80% | 61% | - |
| % < 450 pg/mL | - | - | - | 79% |
| N | 163 | 15 | 18 | 122 |

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Males

| | <55 yrs | 55 - 64 yrs | 65 - 74 yrs | ≥75 yrs |
| --- | --- | --- | --- | --- |
| Mean | 39.0 | 56.7 | 219.4 | 520.8 |
| SD | 57.8 | 58.2 | 242.4 | 1080.9 |
| Median | 16.6 | 25.4 | 123.6 | 173.5 |
| 95thPercentile | 168.8 | 154.7 | 880.8 | 1969.7 |
| % < 125 pg/mL | 93% | 83% | 55% | - |
| % < 450 pg/mL | - | - | - | 73% |
| N | 76 | 6 | 11 | 62 |

Females

| | <55 yrs | 55 - 64 yrs | 65 - 74 yrs | ≥75 yrs |
| --- | --- | --- | --- | --- |
| Mean | 51.9 | 53.2 | 106.6 | 379.5 |
| SD | 49.2 | 68.3 | 60.8 | 883.1 |
| Median | 39.4 | 28.8 | 87.7 | 167.3 |
| 95thPercentile | 124.0 | 206.6 | 215.2 | 1453.2 |
| % < 125 pg/mL | 95% | 78% | 71% | - |
| % < 450 pg/mL | - | - | - | 85% |
| N | 87 | 9 | 7 | 60 |

# Disease Study Group

Blood samples were obtained from 269 patients diagnosed with congestive heart failure (CHF). The population included 78 women and 191 men. The descriptive statistics and New York Heart Association (NYHA) functional classes are provided below.

CHF Population - All

| | <55 yrs | 55 - 64 yrs | 65 - 74 yrs | ≥75 yrs |
| --- | --- | --- | --- | --- |
| Mean | 6131.8 | 4455.5 | 6168.1 | 8142.7 |
| SD | 13470.3 | 9296.0 | 10950.5 | 12699.1 |
| Median | 1550.9 | 1639.5 | 2541.3 | 3780.5 |
| 95thPercentile | 28099.6 | 19481.5 | 17768.6 | 26923.1 |
| % > 125 pg/mL | 89% | 92% | 95% | - |
| % > 450 pg/mL | - | - | - | 94% |
| N | 72 | 72 | 59 | 66 |

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CHF Population - Males

| | <55 yrs | 55 – 64 yrs | 65 – 74 yrs | ≥75 yrs |
| --- | --- | --- | --- | --- |
| Mean | 7771.4 | 4954 | 6537.2 | 8827.3 |
| SD | 15797.2 | 10536.7 | 12383.9 | 12856.6 |
| Median | 2526.1 | 1699.8 | 2541.3 | 5529.2 |
| 95thPercentile | 31237.1 | 19481.5 | 17768.6 | 18634.8 |
| % > 125 pg/mL | 94% | 94% | 93% | - |
| % > 450 pg/mL | - | - | - | 96% |
| N | 48 | 51 | 43 | 49 |

CHF Population - Females

| | <55 yrs | 55 – 64 yrs | 65 – 74 yrs | ≥75 yrs |
| --- | --- | --- | --- | --- |
| Mean | 2852.6 | 3244.9 | 5176.1 | 6169.7 |
| SD | 5774.0 | 5200.7 | 5727.8 | 12397.4 |
| Median | 452.3 | 1516.9 | 2270.8 | 1125.3 |
| 95thPercentile | 15569.3 | 7903.1 | 16889.9 | 45824.4 |
| % > 125 pg/mL | 79% | 86% | 100% | - |
| % > 450 pg/mL | - | - | - | 88% |
| N | 24 | 21 | 16 | 17 |

CHF Population - All

| NYHA Functional Class | | | | | |
| --- | --- | --- | --- | --- | --- |
| | All CHF | NYHA I | NYHA II | NYHA III | NYHA IV |
| Mean | 6184.5 | 3941.9 | 3648.8 | 6643.1 | 11089.2 |
| SD | 11737.8 | 8461.3 | 4897.0 | 13567.0 | 14428.2 |
| Median | 2282.2 | 1161.0 | 1091.7 | 2541.3 | 4537.7 |
| 5thPercentile | 101.1 | 100.4 | 46.6 | 143.1 | 74.6 |
| 95thPercentile | 22331.9 | 14184.1 | 14238.5 | 17497.1 | 28099.6 |
| % > Cutoff | 92% | 93% | 90% | 94% | 88% |
| Minimum | 5.1 | 52.8 | 24.5 | 5.1 | 39.6 |
| Maximum | 91446.4 | 52327.0 | 18634.8 | 91446.4 | 78045.2 |
| N | 269 | 45 | 60 | 124 | 40 |

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CHF Population - Males

| NYHA Functional Class | | | | | |
| --- | --- | --- | --- | --- | --- |
| | All CHF | NYHA I | NYHA II | NYHA III | NYHA IV |
| Mean | 7012.1 | 4567.5 | 4402.2 | 7298.4 | 14351.2 |
| SD | 12991.9 | 9204.3 | 5167.4 | 14789.5 | 17258.9 |
| Median | 3162.6 | 1639.5 | 2230.9 | 3442.2 | 6015.9 |
| 5thPercentile | 126.1 | 136.3 | 46.5 | 126.1 | 101.1 |
| 95thPercentile | 24004.7 | 19481.5 | 14238.5 | 17497.1 | 31237.1 |
| % > Cutoff | 94% | 97% | 93% | 95% | 91% |
| Minimum | 5.1 | 72.5 | 44.7 | 5.1 | 74.6 |
| Maximum | 91446.4 | 52327.0 | 18634.8 | 91446.4 | 78045.2 |
| N | 191 | 37 | 40 | 91 | 23 |

CHF Population - Females

| NYHA Functional Class | | | | | |
| --- | --- | --- | --- | --- | --- |
| | All CHF | NYHA I | NYHA II | NYHA III | NYHA IV |
| Mean | 4157.8 | 1048.3 | 2142.1 | 4836.0 | 6676.0 |
| SD | 7561.7 | 1636.1 | 4008.9 | 9366.5 | 7864.9 |
| Median | 950.2 | 225.4 | 705.3 | 1286.7 | 3780.5 |
| 5thPercentile | 84.3 | 52.8 | 24.5 | 143.1 | 39.6 |
| 95thPercentile | 22331.9 | 4960.2 | 11020.8 | 26923.1 | 22997.0 |
| % > Cutoff | 87% | 75% | 85% | 94% | 82% |
| Minimum | 24.5 | 52.8 | 24.5 | 126.8 | 39.6 |
| Maximum | 45824.4 | 4960.2 | 15893.8 | 45824.4 | 22997.0 |
| N | 78 | 8 | 20 | 33 | 17 |

The results demonstrate a relationship between the severity of the clinical signs and symptoms of CHF and the median NT-proBNP concentration.

# N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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