VIDAS NT-PROBNP ASSAY, MODEL: 30 449

K073091 · bioMerieux, Inc. · NBC · Feb 29, 2008 · Clinical Chemistry

Device Facts

• Record ID: K073091
• Device Name: VIDAS NT-PROBNP ASSAY, MODEL: 30 449
• Applicant: bioMerieux, Inc.
• Product Code: NBC · Clinical Chemistry
• Decision Date: Feb 29, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1117
• Device Class: Class 2

Intended Use

VIDAS® NT-proBNP assay is an automated quantitative test for use on the VIDAS instruments for the determination of N-terminal fragment of B-type natriuretic peptide in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. The VIDAS® NT-proBNP test is used as an aid in the diagnosis of suspected congestive heart failure.

Device Story

VIDAS NT-proBNP is an automated, quantitative, sandwich enzyme-linked fluorescent immunoassay (ELFA) for use on bioMerieux VIDAS or miniVIDAS instruments. The device utilizes a disposable Solid Phase Receptacle (SPR) coated with sheep polyclonal NT-proBNP antibody. Input is human serum or lithium heparin plasma. The instrument cycles the sample and alkaline phosphatase-labeled conjugate through the SPR; unbound material is washed away. Fluorescent substrate (4-Methyl-umbelliferyl phosphate) is added; the enzyme catalyzes the production of a fluorescent product (4-methylumbelliferone). Fluorescence is measured at 450 nm; intensity is directly proportional to NT-proBNP concentration. The system provides quantitative results to clinicians to aid in the diagnosis of suspected congestive heart failure. The device is intended for prescription use in clinical laboratory settings.

Clinical Evidence

Clinical performance was evaluated across 3 sites (2 European, 1 US) using 407 samples with confirmed congestive heart failure (CHF) and 411 control samples. The overall AUC was 0.965. Sensitivity and specificity were calculated by age and gender; overall sensitivity ranged from 84.87% to 94.96% and specificity from 81.31% to 97.39% across sites. Method comparison with the predicate (n=713) showed a correlation of r=0.989, with a slope of 0.905 and intercept of -14.599.

Technological Characteristics

ELFA immunoassay; uses alkaline phosphatase-labeled sheep polyclonal NT-proBNP antibody; fluorescent substrate 4-Methyl-umbelliferyl phosphate; measurement at 450 nm. Kit includes SPRs, reagent strips, calibrators, and controls. Compatible with VIDAS/miniVIDAS instruments. Traceable to Roche purified synthetic NT-proBNP. Measurement range: 20-25,000 pg/mL. LoD: 6.7 pg/mL. LoQ: 21.9 pg/mL.

Indications for Use

Indicated for use as an aid in the diagnosis of suspected congestive heart failure in patients requiring quantitative determination of NT-proBNP in human serum or plasma.

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 Elecsys pro-BNP Immunoassay (k022516)

Submission Summary (Full Text)

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K073091

FEB 2 9 2008

# 510(k) SUMMARY

# VIDAS® NT-proBNP Assay

### A. Submitter Information

| Submitter's Name: | bioMérieux, Inc. |
|----------------------|----------------------------------------------------------------------------|
| Address: | 595 Anglum Road<br>Hazelwood, MO 63042 |
| Contact Person: | Nikita S. Mapp |
| Phone Number: | 314-731-7474 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | October 2007 (revised February 2008). |
| Device Name | VIDAS® NT-proBNP |
| Trade Name: | VIDAS® NT-proBNP |
| Common Name: | Endotoxin Assay |
| Classification Name: | 21 CFR 862.1117 Product Code NBC<br>B-type natriuretic peptide test system |

## C. Predicate Device Name

Trade Name:

B.

Elecsys proBNP Assay

#### D. Device Description

The VIDAS® NT-proBNP assay is an automated quantitative test for use on the VIDAS instruments for the determination of N terminal fragment of B-type natriuretic peptide in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. The VIDAS NT-proBNP test is used as an aid in the diagnosis of suspected congestive heart failure.

The assay principle combines a one-step immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail in the 510(k) and in the package insert.

All of the assay steps are performed automatically by the VIDAS instrument. The sample is transferred into the well containing anti-NT-proBNP antibody (conjugate) labeled with alkaline phosphatase. The sample/conjugate mixture is cycled in and out of the SPR several times. This operation enables the antigen to bind with the immunoglobulins fixed to the interior wall of

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the SPR and the conjugate to form a sandwich. Unbound compounds are eliminated during washing steps.

Two detection steps are performed successively. During each step, the substrate (4-Methylumbelliferyl phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of antigen present in the sample.

At the end of the assay, results are automatically calculated by the VIDAS instrument in relation to two calibration curves corresponding to the two detection steps stored in memory, and then printed out.

#### E. Intended Use

The VIDAS® NT-proBNP assay is an automated quantitative test for use on the VIDAS instruments for the determination of N terminal fragment of B-type natriuretic peptide in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. The VIDAS NT-proBNP test is used as an aid in the diagnosis of suspected congestive heart failure.

#### F. Technological Characteristics Summary

A general comparison of the similarities and differences of the assays is presented in the table below.

| Item | Device<br>[VIDAS NT-proBNP] | Predicate<br>[Elecsys proBNP] | |
|------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------|
| <b>General Comparison</b> | | | |
| Intended Use | Quantitative determination of N terminal<br>fragment of B-type natriuretic peptide in<br>human serum or plasma (lithium heparin).<br>The VIDAS NT-proBNP test is used as an<br>aid in the diagnosis of suspected congestive<br>heart failure. | Same as initial claim [K022516].<br>Roche obtained additional claims via<br>other 510(k)s, "risk stratification" and<br>"risk assessment " which bioMerieux is<br>not pursuing at this time. | |
| Specimen | Human serum or plasma | Same | |
| Analyte | Measures NT-proBNP | Same | |
| Antibody | Anti-NT-proBNP antibody (polyclonal<br>sheep) | Same | |
| Assay Principle | Immunoassay based on sandwich principle | Same | |
| Automated | Automated assay | Same | |
| Assay Technique | Enzyme-Linked Fluorescent Assay (ELFA) | Electrochemiluminescent assay | |
| Sample Volume | 200 μl | 20 μl | |
| Assay Time | ~20 minutes | 18 minutes | |
| Traceability/<br>Standardization | Traceable to proBNP Roche | Reference standard - purified<br>synthetic NTG-proBNP (1-76) in<br>human serum matrix | |
| Measurement range | 20-25,000 pg/mL | 5-35,000 pg/mL | |
| Test | Device<br>[VIDAS NT-proBNP] | Predicate<br>[Elecsys proBNP] | |
| Non-clinical (Analytical) Comparison | | | |
| Matrix Comparison | Serum similar to Plasma<br>For patient follow-up, assays must be performed<br>on the same type of sample tube. | Same | |
| Precision | 5 samples tested in duplicate in 40 different<br>runs (2 runs per day)<br>repeatability (intra-run): 1.5 – 2.8 %CV<br>inter-site: 3.4 – 5.1 %CV<br>inter-lot: 3.5 – 8.4 %CV | 4 samples tested in 6 times daily for<br>10 days<br>total precision: 2.2 – 3.2%CV<br>within run precision: 1.8 – 2.7%CV | |
| Detection Limits | < 20 pg/mL<br>(LoB = 3.4 pg/mL, LoD = 6.7 pg/mL, LoQ =<br>13.9 pg/mL) | 5 pg/ml | |
| Interfering Substances | No significant interference | No significant interference | |
| Bilirubin | 30 mg/dl (510 µmol/L) | 35 mg/dl | |
| Hemoglobin | 485 mg/dl (300 µmol/L) | 1.4 g/dl | |
| Triglycerides | 30 g/l | 4000 mg/dl | |
| Albumin | 100 g/L | Not tested | |
| Human IgG | 17 g/L | Not tested | |
| Human IgM | 6 g/L | Not tested | |
| Rheumatoid Factors | 1500 IU/mL | 1500 IU/mL | |
| Analytical Specificity | | | |
| Adrenomedullin | <0.1% | <0.001% | |
| Aldosterone | <0.1% | <0.001% | |
| Angiotensin I | <0.1% | <0.001% | |
| Angiotensin II | <0.1% | <0.001% | |
| Angiotensin III | <0.1% | <0.001% | |
| ANP28 | <0.1% | <0.001% | |
| Arg-Vasopressin | <0.1% | <0.001% | |
| BNP32 | <0.1% | <0.001% | |
| CNP22 | <0.1% | <0.001% | |
| Endothelin | <0.1% | <0.001% | |
| NT-proANP1-30 | <0.1% | <0.001% | |
| NT-proANP31-67 | <0.1% | <0.001% | |
| NT-proANP79-98 | <0.1% | <0.001% | |
| Renin | <0.1% | <0.001% | |
| Urodilatin | <0.1% | <0.001% | |
| Drug Interference | No interference was observed on 39<br>frequently administered drugs tested <i>in vitro</i> | No interference found on commonly<br>used pharmaceuticals | |
| Hook Effect | No hook effect found up to concentrations<br>of 500,000 pg/mL | No hook effect found up to<br>concentrations of 300,000 pg/mL | |
| Clinical Comparison | | | |
| Cut-off | 125 pg/mL for patients <75 years old<br>450 pg/mL for patients ≥ 75 years old | Same | |
| Clinical Sensitivity/Specificity Studies | | | |
| Reference Group (without CHF) | | | |
| Number of patients | 411 patients | 1411 patients | |
| Study Site(s) | US and Europe | unknown | |
| | % < cut-off (males and females) | | % < 125 pg/mL (all) |
| | <45 yrs: 92.4% | | <45 yrs: 95.7% |
| | 45-54 yrs: 90.3% | | 45-54 yrs: 93.3% |
| | 55-64 yrs: 95.4% | | 55-64 yrs: 83.3% |
| Results | 65-74 yrs: 89.5% | | 65-74 yrs: 69.8% |
| | <75 yrs: 92.2%<br>≥75+ yrs: 95.7% | | <75 yrs: 82.4% |
| | | | % < 450 pg/mL (all) |
| | | | 75+ yrs: 88.9% |
| | | Disease Group (with CHF) | |
| Number of patients | 407 patients | | 721 patients |
| Study Site(s) | US and Europe | | unknown |
| | | | % < 125 pg/mL (all)<br><45 yrs: 82.8% |
| | % ≥ cut-off (males and females)<br><45 yrs: 85.0% | | 45-54 yrs: 88.5% |
| | 45-54 yrs: 85.3% | | 55-64 yrs: 89.5% |
| | 55-64 yrs: 88.1% | | 65-74 yrs: 92.2% |
| Results | 65-74 yrs: 100.0% | | 75+ yrs: unknown |
| | <75 yrs: 92.3% | | <75 yrs: 89.3% |
| | ≥75+ yrs: 91.5% | | |
| | | | % < 450 pg/mL (all)<br>75+ yrs: 84.7% |
| | | Sensitivity and Specificity vs. gender and age | |
| | | | |
| European Site 1 | | | |
| Statistics | All patients | < 75 yrs. | ≥ 75 yrs. |
| Sensitivity (%) | 94.63 (89.64-97.29) | 100 (94.81-100) | 89.47 (80.36-94.64) |
| Specificity (%) | 97.39 (93.36-99.00) | 97.27 (92.14-99.09) | 97.67 (87.63-99.6) |
| | | | |
| | | | |
| European Site 2 | | | |
| Statistics | All patients | < 75 yrs. | ≥ 75 yrs. |
| Sensitivity (%) | 94.96 (89.84-97.57) | 94.23 (84.08-98.06) | 95.4 (88.58-98.23) |
| Specificity (%) | 96.69 (92.37-98.6) | 96.36 (90.87-98.6) | 97.56 (87.09-99.58) |
| | | | |
| US Site | | | |
| Statistics | All patients | < 75 yrs. | ≥ 75 yrs. |
| Sensitivity (%) | 84.87 (77.18-90.3) | 82.86 (72.14-90.02) | 87.76 (75.46-94.35) |
| Specificity (%) | 81.31 (72.69-87.67) | 81.82 (72.88-88.28) | 75 (40.31-93.02) |
| | | | |
| All Sites Combined | | | |
| Statistics | All patients | < 75 yrs. | ≥ 75 yrs. |
| Sensitivity (%) | 91.89 (88.76-94.21) | 92.31 (87.58-95.33) | 91.51 (86.87-94.61) |
| Specificity (%) | 92.94 (89.98-95.08) | 92.16 (88.6-94.68) | 95.65 (89.17-98.33) |
| | | | |
| | | | |
| Males: All Sites Combined | | | |
| Statistics | Males | Males < 75 yrs. | Males ≥ 75 yrs. |
| Sensitivity (%) | 92.92 (88.85-95.57) | 94.07 (88.6-97.01) | 91.43 (84.33-95.48) |
| Specificity (%) | 95.67 (92.13-97.66) | 95.31 (91.23-97.55) | 97.44 (86.49-99.56) |
| Females: All Sites Combined | | | |
| Statistics | Females | Females < 75 yrs. | Males ≥ 75 yrs. |
| Sensitivity (%) | 90.42 (84.87-94.07) | 88.33 (77.56-94.31) | 91.59 (84.61-95.57) |

G. Performance Data

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A summary of the non-clinical and clinical test results is presented in the table below.

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### H. Conclusion

## The VIDAS® NT-proBNP Assay is substantially equivalent to the Roche Elecsys proBNp Assay.

The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, rendered in a simple, black line drawing. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)", arranged in a circular fashion around the emblem.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

bioMerieux, Inc c/o Ms. Nikita Mapp Senior Regulatory Affairs Specialist 595 Anglum Road Hazelwood, MO 63042

FEB 2 9 2008

Re: k073091

Trade/Device Name: VIDAS NT-proBNP Assay Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC

Dated: February 04, 2008 Received: February 05, 2008

Dear Ms. Mapp:

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. Coopus, M.S., D.V.M.

Yean 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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# Indication for Use

510(k) Number (if known): Not yet assigned K073091

Device Name: VIDAS NT-proBNP Assay

Indication For Use: VIDAS® NT-proBNP assay is an automated quantitative test for use on the VIDAS instruments for the determination of N terminal fragment of B-type natriuretic peptide in human serum or plasma (lithium heparin) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. The VIDAS NT-proBNP test is used as an aid in the diagnosis of suspected congestive heart failure.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use __ (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Carol C. Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K093091