← Product Code [NBC](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/NBC) · K032235

# MODIFICATION TO TRIAGE B-TYPE NATRIURETIC PEPTIDE (BNP) TEST (K032235)

_Biosite Incorporated · NBC · Jan 28, 2004 · Clinical Chemistry · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/NBC/K032235

## Device Facts

- **Applicant:** Biosite Incorporated
- **Product Code:** [NBC](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/NBC.md)
- **Decision Date:** Jan 28, 2004
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.1117
- **Device Class:** Class 2
- **Review Panel:** Clinical Chemistry

## Indications for Use

The Triage® BNP test is intended for use with the Triage® Meter for the rapid in vitro quantitative measurement of B-Type Natriuretic Peptide (BNP) in human capillary whole blood, venous whole blood or plasma specimens using EDTA as the anticoagulant. The test is used as an aid in the diagnosis and assessment of severity of congestive heart failure (also referred to as heart failure). The test is also used for the risk stratification of patients with acute coronary syndromes.

## Device Story

Triage® BNP test is a single-use fluorescence immunoassay; utilizes EDTA-anticoagulated capillary whole blood, venous whole blood, or plasma. Device contains stabilizers, murine BNP monoclonal antibodies, and fluorescently labeled BNP polyclonal antibodies. User adds 250 μL specimen to test device port; inserts into Triage® Meter. Meter automatically performs analysis; detects fluorescence intensity in measurement zone; correlates fluorescence to BNP concentration. Used in clinical settings by professionals. Output provides quantitative BNP concentration; aids diagnosis/severity assessment of congestive heart failure and risk stratification for acute coronary syndromes. Benefits include rapid, point-of-care diagnostic information for heart failure management.

## Clinical Evidence

Bench testing only. Precision evaluated via ANOVA model over 12 days; whole blood precision compared to plasma. Linearity confirmed via gravimetric dilution (recovery 92.3-105.8%). Analytical sensitivity <5 pg/mL. Specificity tested against common drugs, proteins, and peptides with no significant interference. Matrix comparison (n=67) between capillary and venous whole blood showed no significant differences.

## Technological Characteristics

In vitro diagnostic immunoassay; quantitative measurement of BNP; utilizes Triage Meter for signal detection; compatible with capillary whole blood, venous whole blood, and EDTA-anticoagulated plasma.

## Regulatory 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

- Triage® B-Type Natriuretic Peptide (BNP) test ([K021317](/device/K021317.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k032235

B. Analyte:
B-type natriuretic peptide test system (BNP)

C. Type of Test:
Quantitative

D. Applicant:
Biosite Incorporated

E. Proprietary and Established Names:
Triage® B-Type Natriuretic Peptide (BNP) Test

F. Regulatory Information:
1. Regulation section:
862.1117, B-type natriuretic peptide test system
2. Classification:
Class II
3. Product Code:
NBC
4. Panel:
75

G. Intended Use:
1. Indication(s) for use:
The Triage® BNP test is intended for use with the Triage® Meter for the rapid in vitro quantitative measurement of B-Type Natriuretic Peptide (BNP) in human capillary whole blood, venous whole blood or plasma specimens using EDTA as the anticoagulant. The test is used as an aid in the diagnosis and assessment of severity of congestive heart failure (also referred to as heart failure). The test is also used for the risk stratification of patients with acute coronary syndromes.
2. Special condition for use statement(s):
3. Special instrument Requirements:
Triage® Meter

H. Device Description:
The Triage® BNP test is a ready-to-use device. All reagents necessary to run the test are contained within the device. The reagents consist of stabilizers, murine BNP monoclonal antibodies and BNP polyclonal antibodies labeled with a fluorescent dye.

I. Substantial Equivalence Information:
1. Predicate device name(s):
Triage® B-Type Natriuretic Peptide (BNP) test

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2. Predicate K number(s):
K021317

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Triage® BNP K032235 | Triage® BNP K021317  |
|  Intended Use | Professional Use only | Professional Use only  |
|  Test principle | Same | Same  |
|  Calibration material | Same | Same  |
|  Differences  |   |   |
|  Item | Triage® BNP K032235 | Triage® BNP K021317  |
|  Indications for Use | Addition of human capillary whole blood as a sample type | Sample types are venous whole blood or plasma specimens using EDTA as the anticoagulant  |
|  Precision | Whole blood precision data included | Precision data for control material only  |
|  Labeling | Labeling has been modified into an easier to understand format |   |

J. Standard/Guidance Document Referenced (if applicable):
NCCLS EP 5-A

K. Test Principle:
The Triage® BNP test is a single use fluorescence immunoassay device designed to determine the concentration of BNP in EDTA-anticoagulated whole blood or plasma specimens. The specimen is added to the sample port of the test device with a transfer pipette that is designed to deliver the appropriate amount of sample (250 μL) to the test device. After the specimen is added, the device is inserted into the Triage® Meter. The Meter is programmed to automatically perform the BNP analysis after the sample has reacted with the reagents within the BNP device. The reaction and analysis time takes about 15 minutes. The BNP analysis is based on the amount of fluorescence the Meter detects within a measurement zone on the device. A greater amount of fluorescence detected by the Meter indicates a higher BNP concentration in the specimen.

L. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:
Previously determined for K021317. The information is included in the labeling for this submission. The average within-day and total precision were determined using the ANOVA model by testing control materials that had BNP added at concentrations near the decision points of the assay and throughout the range of the standard curve. The study was conducted over 12 days, testing

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each control 10 times per day. Each device was read on 5 Triage® Meters.

## Average Within Day Imprecision

|  Mean (pg/mL) | Standard Deviation (pg/mL) | CV  |
| --- | --- | --- |
|  71.3 | 6.3 | 8.8%  |
|  629.9 | 69.1 | 11.0%  |
|  4087.9 | 475.5 | 11.6%  |

## Average Total Imprecision

|  Mean (pg/mL) | Standard Deviation (pg/mL) | CV  |
| --- | --- | --- |
|  71.3 | 7.0 | 9.9%  |
|  629.9 | 75.5 | 12.0%  |
|  4087.9 | 500.1 | 12.2%  |

Whole blood precision was determined for this submission. EDTA-anticoagulated whole blood samples were collected on three different days, and purified BNP was spiked into the samples at two different concentrations. Each sample was measured 12 times using the Triage® BNP Test. The imprecision of each series of measurements is described below.

|  Day 1 |   |   | Day 2 |   |   | Day 3  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Mean | SD | CV | Mean | SD | CV | Mean | SD | CV  |
|  70.7 | 4.4 | 6.2% | 78.2 | 6.1 | 7.7% | 59.5 | 8.1 | 13.6%  |
|  523.1 | 61.5 | 11.8% | 516.5 | 64.6 | 12.5% | 559.0 | 39.8 | 7.1%  |

The data indicate that the test imprecision using whole blood specimens is comparable to the imprecision using EDTA-anticoagulated plasma.

## b. Linearity/assay reportable range:

Previously determined for K021317. The information is included in the labeling for this submission. Plasma specimens anticoagulated with EDTA from four apparently healthy individuals were spiked with purified BNP to final concentrations of 5000 pg/ml. Each spiked plasma specimen was diluted gravimetrically with unspiked plasma to obtain BNP values throughout the range of the Triage® BNP Test. Linear regression

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analysis of the data indicates that the assay is linear throughout the measureable range of the test. Recovery data ranged from 92.3 to  $105.8\%$ .

c. Traceability (controls, calibrators, or method):

Not stated

d. Detection limit:

Previously determined for K021317. The information is included in the labeling for this submission. The analytical sensitivity or lowest detectable concentration that is distinguishable from zero for the Triage® BNP Test was determined by testing a zero calibrator 20 times each using 3 lots of reagents and 5 meters on 5 days. The average  $95\%$  confidence limit of the analytical sensitivity of the Triage® BNP Test was less than  $5\mathrm{pg / mL}$ .

e. Analytical specificity:

Previously determined for K021317. The information is included in the labeling for this submission. Hemoglobin (up to  $10,000\mathrm{mg / dL}$ ), lipids (cholesterol up to  $1000\mathrm{mg / dL}$  and triglycerides up to  $1000\mathrm{mg / dL}$ ) or bilirubin (up to  $20\mathrm{mg / dL}$ ) added to plasma specimens containing BNP did not interfere with the recovery of BNP. The hematocrit was varied between  $27\%$  and  $51\%$  with no significant effect on the recovery of BNP.

The following drugs were evaluated for potential cross-reactivity and interference in the Triage® BNP Test. All drugs were tested at concentrations representing the blood concentrations that would result from a maximal therapeutic dose and at least twice the maximal therapeutic dose. None of the drugs interfered with the recovery of BNP. Additionally, these drugs did not produce a significant response when tested in a specimen not containing BNP. There was no significant interference with the BNP measurement, nor was there any assay cross-reactivity.

|  Abciximax | Acetaminophen | Acetylsalicylic acid  |
| --- | --- | --- |
|  Activase | Allopurinol | Amiodarone  |
|  Ampicillin | Ascorbic Acid | Amlodipine Besylate  |
|  Atenolol | Caffeine | Captopril  |
|  Cyclosporine | Chloramphenicol | Clopidogrel Bisulfate  |
|  Diclofenac | Digoxin | Diltiazem  |
|  Digitoxin | Dopamine | Enalapril Maleate  |
|  Dipyridamole | Erythromycin | Furosemide  |
|  Eptifibatide | Hydralazine | Hydrochlorothiazide  |
|  Heparin | Isosorbide dinitrate | Indomethacin  |
|  Lisinopryl | Lovastatin | Methyldopa  |
|  Mirinone lactate | Nicotine | Nicotinic Acid  |

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|  Niphedipine | Nitrofurantoin | Nitroglycerin  |
| --- | --- | --- |
|  Noraminopyrine | Oxazepam | Oxytetracycline  |
|  Phenobarbital | Phenytoin | Probenecid  |
|  Procainamide | Propanolol | Quinidine  |
|  Simvastin | Sulfamethoxazole | Theophylline  |
|  L-thyroxine | Trimethoprim | Verapamil  |
|  Warfarin |  |   |

## Proteins and Peptides

The following proteins and peptides were evaluated for potential cross-reactivity and interference in the Triage® BNP Test at the concentrations indicated below. There was no significant interference with the BNP measurement, nor was there any significant assay cross-reactivity.

## Reactivity with Related Proteins and Peptides

|   | Substance | Concentration of Substance | % Recovery  |
| --- | --- | --- | --- |
|  |   |   |   |
|  |   |   |   |
|   | Renin | 50 ng/ml | 104%  |
|   | Aldosterone | 1 ug/ml | 104%  |
|   | Angiotensin I | 600 pg/ml | 108%  |
|   | Angiotensin II | 600 pg/ml | 108%  |
|   | Endothelin I | 20 pg/ml | 101%  |
|   | Adrenomedullin (ADM) | 1000 pg/ml | 97%  |
|   | Alpha-Atrial Natriuretic polypeptide 1-28 | 1000 pg/ml | 104%  |
|   | Prepro BNP 22-46 | 1000 pg/ml | 104%  |
|   | Prepro BNP 1-21 | 1000 pg/ml | 106%  |
|   | Arg Vasopressin | 1000 pg/ml | 96%  |
|   | C-type natriuretic Peptide 53 | 1000 pg/ml | 106%  |
|   | Prepro-ANF 56-92 | 1000 pg/ml | 104%  |
|   | Prepro-ANF 104-123 | 1000 pg/ml | 97%  |
|   | Urodilatin(CCD/ANP) 95-126 | 1000 pg/ml | 100%  |
|   | Angiotensin III | 1000 pg/ml | 108%  |
|   | Prepro-ANF 26-55 | 1000 pg/ml | 107%  |

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f. Assay cut-off:

BNP results less than or equal to  $100\mathrm{pg / mL}$  are representative of normal values in patients without CHF. BNP results greater than  $100\mathrm{pg / mL}$  are considered abnormal and suggestive of patients with CHF.

# 2. Comparison studies:

a. Method comparison with predicate device:

No comparison was performed vs. the predicate device because the modification to the predicate (K021317) Triage® BNP test is the addition of capillary whole blood as a sample type. See matrix comparison below.

b. Matrix comparison:

A comparison study was performed on EDTA capillary whole blood vs. venous whole blood. Matched venous whole blood and capillary whole blood samples were used for the analysis. 67 matched capillary and venous blood samples were used for the evaluation.  $43.3\%$  of the samples were collected using a single finger stick,  $35.8\%$  of the samples were collected using two finger sticks, and  $20.9\%$  of the samples were collected using three or more finger sticks. There were no significant differences observed between measurements obtained using capillary whole blood versus venous whole blood. Regression analysis for all samples was  $\mathrm{y} = 1.001\mathrm{x}$ ,  $\mathrm{r}^2 = 0.99$ . Regression analysis for the samples collected with a single finger stick was  $\mathrm{y} = 0.994\mathrm{x}$ ,  $\mathrm{r}^2 = 0.994$ . For the samples collected with two finger sticks, regression analysis was  $\mathrm{y} = 1.100\mathrm{x}$ ,  $\mathrm{r}^2 = 0.953$ . For the samples collected with 3 or more finger sticks, the regression analysis was  $\mathrm{y} = 1.010\mathrm{x}$ ,  $\mathrm{r}^2 = 0.897$ .

# 3. Clinical studies:

a. Clinical sensitivity:

Previously determined for K021317. The following is included in the labeling for this submission.

Males

|   | Age < 45 | Age 45-54 | Age 55-64 | Age 65-74 | Age 75+  |
| --- | --- | --- | --- | --- | --- |
|  Sensitivity | 81.6% | 76.0% | 75.6% | 79.3% | 82.4%  |
|  95% Confidence Interval | 70.8-92.5% | 67.5-84.6% | 68.2-82.9% | 72.6-86% | 76.1-88.7%  |
|  Specificity | 98.9% | 99.5% | 98.3% | 98.9% | 95.8%  |
|  95% Confidence Interval | 97.4-100.4% | 98.5-100.5% | 97.7-98.9% | 98.4-99.4% | 94.7-96.9%  |

Females

|   | Age < 45 | Age 45-54 | Age 55-64 | Age 65-74 | Age 75+  |
| --- | --- | --- | --- | --- | --- |
|  Sensitivity | 82.1% | 69.0% | 82.4% | 97.9% | 91.9%  |
|  95% Confidence Interval | 68.0-96.3% | 57.1-80.9% | 71.9-92.8% | 93.7-102.0% | 85.2-98.7%  |
|  Specificity | 100.0% | 98.9% | 96.4% | 95.0% | 75.7%  |
|  95% Confidence Interval | 100.0-100.0% | 97.5-100.4% | 95.5-97.4% | 93.4-96.7% | 72.2-79.2%  |

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b. Clinical specificity:

See above

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

# 4. Clinical cut-off:

Previously determined for K021317. The information is included in the labeling for this submission. The circulating BNP concentration was determined from 1286 individuals without CHF (676 women and 610 men) using the Triage® BNP Test. This population included individuals with hypertension, diabetes, renal insufficiency, and chronic obstructive pulmonary disease. There are no statistically significant changes in BNP concentration associated with hypertension, diabetes, renal insufficiency, and chronic obstructive pulmonary disease. The decision threshold was determined by the  $95\%$  confidence limit of BNP concentration in the non-CHF population age 55 and older. The most appropriate decision threshold apparent from these distributions is  $100~\mathrm{pg / mL}$ . This value translates into a general specificity of the test of  $98\%$ , i.e. less than  $2\%$  expected false positives in individuals without CHF. Each laboratory should establish a reference range that represents the patient population that is to be evaluated.

# 5. Expected values/Reference range:

Previously determined for K021317. The information is included in the labeling for this submission. Expected values were determined from clinical studies performed for the predicate Triage® BNP test and are included in the labeling for this device.

# Descriptive Statistics - BNP Concentration (pg/ml)

Non-CHF Population

|   | All  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |  All | Age < 45 | Age 45-54 | Age 55-64 | Age 65-74 | Age 75+  |
|  Median | 12.3 | 7.7 | 11.1 | 17.9 | 19.8 | 53.9  |
|  95th Percentile | 73.5 | 39.6 | 64.5 | 76.1 | 84.7 | 179.4  |
|  Percent < 100 pg/ml | 98.0% | 99.5% | 99.2% | 97.4% | 96.9% | 84.2%  |
|  Minimum | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0  |
|  Maximum | 252.0 | 251.3 | 252.0 | 207.7 | 197.9 | 218.5  |
|  N | 1286 | 423 | 385 | 229 | 192 | 57  |
|   | Males  |   |   |   |   |   |
|   |  All | Age < 45 | Age 45-54 | Age 55-64 | Age 65-74 | Age 75+  |
|  Median | 7.1 | 5.0 | 7.2 | 9.0 | 15.7 | 39.0  |
|  95th Percentile | 56.9 | 23.8 | 39.0 | 72.4 | 62.7 | 77.9  |
|  Percent < 100 pg/ml | 98.9% | 98.9% | 99.5% | 98.3% | 98.9% | 95.8%  |
|  Minimum | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0  |
|  Maximum | 252.0 | 251.3 | 252.0 | 207.7 | 127.3 | 218.5  |
|  N | 610 | 183 | 196 | 118 | 89 | 24  |
|   | Females  |   |   |   |   |   |
|   |  All | Age < 45 | Age 45-54 | Age 55-64 | Age 65-74 | Age 75+  |
|  Median | 18.5 | 11.6 | 17.7 | 28.2 | 27.6 | 67.1  |
|  95th Percentile | 84.2 | 47.4 | 71.7 | 80.5 | 95.4 | 179.5  |
|  Percent < 100 pg/ml | 97.2% | 100.0% | 98.9% | 96.4% | 95.1% | 75.8%  |
|  Minimum | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0  |
|  Maximum | 197.9 | 92.6 | 142.8 | 143.2 | 197.9 | 194.1  |
|  N | 676 | 240 | 189 | 111 | 103 | 33  |

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## CHF Population - All

|   | All CHF* | NYHA Functional Class  |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  I | II | III | IV  |
|  Median | 359.5 | 95.4 | 221.5 | 459.1 | 1006.3  |
|  5th Percentile | 22.3 | 14.8 | 9.9 | 37.6 | 147.2  |
|  Percent > 100 pg/ml | 80.6% | 48.3% | 76.6% | 86.0% | 96.3%  |
|  Minimum | 5.0 | 5.0 | 5.0 | 5.2 | 5.0  |
|  Maximum | >5000 | 904.6 | 4435.8 | >5000 | >5000  |
|  N | 804 | 118 | 197 | 300 | 187  |

## CHF Population - Males

|   | All CHF* | NYHA Functional Class  |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  I | II | III | IV  |
|  Median | 317.8 | 87.8 | 232.6 | 458.9 | 1060.3  |
|  5th Percentile | 21.9 | 16.8 | 10.7 | 25.0 | 196.5  |
|  Percent > 100 pg/ml | 78.9% | 46.5% | 78.8% | 85.2% | 97.2%  |
|  Minimum | 5.0 | 5.0 | 5.0 | 5.2 | 5.0  |
|  Maximum | >5000 | 904.6 | 2710.6 | >5000 | >5000  |
|  N | 558 | 101 | 146 | 203 | 106  |

## CHF Population - Females

|   | All CHF | NYHA Functional Class  |   |   |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  I | II | III | IV  |
|  Median | 499.7 | 114.7 | 191.2 | 469.2 | 996.5  |
|  5th Percentile | 30.7 | 6.8 | 9.7 | 45.6 | 121.0  |
|  Percent > 100 pg/ml | 84.6% | 58.8% | 70.6% | 87.6% | 95.1%  |
|  Minimum | 5.0 | 5.0 | 5.0 | 11.7 | 15.5  |
|  Maximum | >5000 | 519.6 | 4435.8 | 4582.0 | 4706.5  |
|  N | 246 | 17 | 51 | 97 | 81  |

*2 CHF with unknown NYHA class (male)

## M. Conclusion:

Based upon a review of the information presented in this submission, I recommend that this device is substantially equivalent to devices regulated by 862.1117 B-type natriuretic peptide test system.

---

**Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/NBC/K032235](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/NBC/K032235)

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