(120 days)
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 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 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.
Here's a breakdown of the acceptance criteria and study details for the VIDAS® NT-proBNP Assay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Device Performance
The acceptance criteria are not explicitly stated as pass/fail thresholds in the document, but rather demonstrated through comparison to the predicate device and established analytical/clinical performance figures. The reported device performance is directly from the provided text.
| Criteria Category | Specific Criterion | Predicate Device Performance [Elecsys proBNP] | VIDAS® NT-proBNP Assay Performance |
|---|---|---|---|
| Analytical Performance | |||
| Precision | Repeatability (intra-run) | 1.8 – 2.7%CV | 1.5 – 2.8 %CV |
| Inter-site precision | Not explicitly stated, total precision: 2.2 – 3.2%CV | 3.4 – 5.1 %CV | |
| Inter-lot precision | Not explicitly stated | 3.5 – 8.4 %CV | |
| Detection Limits | Lower Limit of Detection (LoD) | 5 pg/mL | < 20 pg/mL (LoD = 6.7 pg/mL) |
| Measurement Range | 5-35,000 pg/mL | 20-25,000 pg/mL | |
| Interfering Substances | Bilirubin tolerance | 35 mg/dl | 30 mg/dl (510 µmol/L) |
| Hemoglobin tolerance | 1.4 g/dl | 485 mg/dl (300 µmol/L) | |
| Triglycerides tolerance | 4000 mg/dl | 30 g/l | |
| Albumin tolerance | Not tested | 100 g/L | |
| Human IgG tolerance | Not tested | 17 g/L | |
| Human IgM tolerance | Not tested | 6 g/L | |
| Rheumatoid Factors tolerance | 1500 IU/mL | 1500 IU/mL | |
| Analytical Specificity | Adrenomedullin cross-reactivity | <0.001% | <0.1% |
| Aldosterone cross-reactivity | <0.001% | <0.1% | |
| Angiotensin I cross-reactivity | <0.001% | <0.1% | |
| Angiotensin II cross-reactivity | <0.001% | <0.1% | |
| Angiotensin III cross-reactivity | <0.001% | <0.1% | |
| ANP28 cross-reactivity | <0.001% | <0.1% | |
| Arg-Vasopressin cross-reactivity | <0.001% | <0.1% | |
| BNP32 cross-reactivity | <0.001% | <0.1% | |
| CNP22 cross-reactivity | <0.001% | <0.1% | |
| Endothelin cross-reactivity | <0.001% | <0.1% | |
| NT-proANP1-30 cross-reactivity | <0.001% | <0.1% | |
| NT-proANP31-67 cross-reactivity | <0.001% | <0.1% | |
| NT-proANP79-98 cross-reactivity | <0.001% | <0.1% | |
| Renin cross-reactivity | <0.001% | <0.1% | |
| Urodilatin cross-reactivity | <0.001% | <0.1% | |
| Drug Interference | Number of drugs tested | Not explicitly stated, "commonly used pharmaceuticals" | 39 frequently administered drugs tested in vitro (no interference observed) |
| Hook Effect | Maximum concentration without hook effect | 300,000 pg/mL | 500,000 pg/mL |
| Clinical Performance | |||
| Sensitivity (All Sites Combined, All patients) | Aid in diagnosis of suspected congestive heart failure. Performance should be comparable to predicate. | Not explicitly stated (predicate data provided for different age/gender groups with various sensitivities) | 91.89% (88.76-94.21% CI) |
| Specificity (All Sites Combined, All patients) | Aid in diagnosis of suspected congestive heart failure. Performance should be comparable to predicate. | Not explicitly stated (predicate data provided for different age/gender groups with various specificities) | 92.94% (89.98-95.08% CI) |
Acceptance Criteria: The underlying acceptance criterion for many of these performance metrics is "substantial equivalence" to the predicate device (Elecsys proBNP Assay). This means that the VIDAS® NT-proBNP Assay's performance should be similar enough to the predicate that it can be considered equally safe and effective for its intended use. For quantitative measures like precision, detection limits, and interfering substances, the performance reported for the VIDAS assay generally falls within acceptable ranges or is comparable to, or better than, the predicate. For clinical sensitivity and specificity, the provided confidence intervals are presented as the device's performance, implying they are considered acceptable given the context of aiding in diagnosis.
2. Sample Size Used for the Test Set and Data Provenance
- Reference Group (without CHF): 411 patients
- Disease Group (with CHF): 407 patients
- Total Patients in Clinical Study: 818 patients
- Data Provenance: The study was conducted at multiple sites in the US and Europe. The data is prospective in nature, as it involves the testing of the new device on patient samples collected for the purpose of evaluating its performance for aid in diagnosis.
3. Number of Experts Used to Establish the Ground Truth and Qualifications
The document does not explicitly state the number of experts used to establish the ground truth for the clinical test set, nor does it specify their qualifications (e.g., radiologist with 10 years of experience). The ground truth for Congestive Heart Failure (CHF) diagnosis would typically be established by clinical cardiologists or other medical specialists based on a comprehensive evaluation including patient history, physical examination, imaging (e.g., echocardiogram), and other laboratory tests, but these specifics are not provided in this summary.
4. Adjudication Method for the Test Set
The document does not specify any adjudication method (e.g., 2+1, 3+1, none) used for establishing the ground truth of the clinical diagnoses in the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This is a diagnostic assay (medical device) that measures a biomarker (NT-proBNP) in human serum or plasma. It is not an AI-powered diagnostic imaging tool or a system involving human readers interpreting images. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study focusing on how human readers improve with AI vs. without AI assistance is not applicable to this type of device and was not performed.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
The VIDAS® NT-proBNP Assay is an automated quantitative test. The performance data presented (analytical and clinical sensitivity/specificity) represents the standalone performance of the device without human interpretation of the assay results in a way that would alter the quantitative outcome. Clinicians use the numerical result from the assay, potentially in conjunction with cut-off values, to aid in diagnosis. So, in essence, the reported performance is the "algorithm only" performance for this type of test.
7. Type of Ground Truth Used
The ground truth used for the clinical study was the clinical diagnosis of Congestive Heart Failure (CHF), as determined by healthcare professionals, differentiating between a "Reference Group (without CHF)" and a "Disease Group (with CHF)".
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its sample size. For an IVD assay like this, development typically involves internal validation and optimization using various sets of characterized samples (some of which might be considered "training"), but the premarket notification focuses on the performance of the finalized assay on independent clinical samples.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is outlined, the method for establishing its ground truth is not provided. However, it can be inferred that any samples used during method development (analogous to a training phase) would also rely on established clinical diagnoses for CHF, similar to the clinical test set.
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FEB 2 9 2008
510(k) SUMMARY
VIDAS® NT-proBNP Assay
A. Submitter Information
| Submitter's Name: | bioMérieux, Inc. |
|---|---|
| Address: | 595 Anglum RoadHazelwood, 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 NBCB-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[VIDAS NT-proBNP] | Predicate[Elecsys proBNP] | |
|---|---|---|---|
| General Comparison | |||
| Intended Use | Quantitative determination of N terminalfragment of B-type natriuretic peptide inhuman serum or plasma (lithium heparin).The VIDAS NT-proBNP test is used as anaid in the diagnosis of suspected congestiveheart failure. | Same as initial claim [K022516].Roche obtained additional claims viaother 510(k)s, "risk stratification" and"risk assessment " which bioMerieux isnot pursuing at this time. | |
| Specimen | Human serum or plasma | Same | |
| Analyte | Measures NT-proBNP | Same | |
| Antibody | Anti-NT-proBNP antibody (polyclonalsheep) | 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/Standardization | Traceable to proBNP Roche | Reference standard - purifiedsynthetic NTG-proBNP (1-76) inhuman serum matrix | |
| Measurement range | 20-25,000 pg/mL | 5-35,000 pg/mL | |
| Test | Device[VIDAS NT-proBNP] | Predicate[Elecsys proBNP] | |
| Non-clinical (Analytical) Comparison | |||
| Matrix Comparison | Serum similar to PlasmaFor patient follow-up, assays must be performedon the same type of sample tube. | Same | |
| Precision | 5 samples tested in duplicate in 40 differentruns (2 runs per day)repeatability (intra-run): 1.5 – 2.8 %CVinter-site: 3.4 – 5.1 %CVinter-lot: 3.5 – 8.4 %CV | 4 samples tested in 6 times daily for10 daystotal precision: 2.2 – 3.2%CVwithin run precision: 1.8 – 2.7%CV | |
| Detection Limits | < 20 pg/mL(LoB = 3.4 pg/mL, LoD = 6.7 pg/mL, LoQ =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 39frequently administered drugs tested in vitro | No interference found on commonlyused pharmaceuticals | |
| Hook Effect | No hook effect found up to concentrationsof 500,000 pg/mL | No hook effect found up toconcentrations of 300,000 pg/mL | |
| Clinical Comparison | |||
| Cut-off | 125 pg/mL for patients <75 years old450 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%≥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)<45 yrs: 82.8% | |||
| % ≥ cut-off (males and females)<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)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 (240) 276-0490. 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 (800) 638-2041 or (240) 276-3150 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
§ 862.1117 B-type natriuretic peptide test system.
(a)
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.(b)
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.”