(504 days)
For in vitro diagnostic use only.
For the quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) in human serum and plasma (K2 EDTA or Lithium Heparin) using the VITROS 3600 Immunodiagnostic System to aid in the diagnosis of heart failure. The test can also be used in the assessment of heart failure severity in patients diagnosed with heart failure.
The VITROS NT-proBNP II test is performed using the VITROS VITROS NT-proBNP II Reagent Pack and the VITROS NT-proBNP II Calibrators on the VITROS Systems.
The VITROS NT-proBNP II test utilizes a one-step immunometric bridging assay design. A well is pushed from the pack and patient sample is dispensed into the antibody coated well. The assay reagent and the conjugate reagent are then dispensed into the well with the patient sample. NT-proBNP present in the sample binds with horseradish peroxidase (HRP)-labeled antibody conjugate which is captured by biotinylated anti-NT-proBNP capture antibody which is bound to Streptavidin coated microwells. The well is incubated for 8 minutes, before unbound materials are removed by washing.
The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrate (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the System. The amount of HRP conjugate bound is directly proportional to the concentration of NT-proBNP present.
The provided document describes the analytical and clinical performance of the VITROS Immunodiagnostic Products NT-proBNP II Reagent Pack, an in vitro diagnostic device used to aid in the diagnosis and assessment of heart failure.
Here's an analysis of the acceptance criteria and the study proving the device meets them:
1. Table of acceptance criteria and the reported device performance
The document does not explicitly present a "table of acceptance criteria" in terms of pre-defined thresholds for performance metrics that the device must meet for clearance. Instead, it describes the design goals and then reports the observed performance. For clarity, I will create a table summarizing the reported performance, which implicitly indicates the criteria were met or exceeded for FDA clearance.
| Test Category | Specific Test / Metric | Acceptance Criteria (Implicit/Design Goal from predicate or general IVD standards) | Reported Device Performance |
|---|---|---|---|
| Analytical Performance | |||
| Precision | Repeatability (Within-run) %CV | Typically 10% observed for most tested compounds. | Specific interferents (Cefoxitin sodium, Sodium Azide) showed >10% bias. |
| Cross-Reactivity | Various related peptides (e.g., ANP, proBNP, BNP32) | Low cross-reactivity desired. | Ranges from 0.85 or 0.90 for this type of test) |
| AUC (Age-stratified) | Ranged from 0.904 to 0.954 | ||
| AUC (Clinical Subgroups) | Ranged from 0.899 to 0.945 | ||
| Posttest Probability of HF (Positive result) | High positive predictive value/posttest probability for rule-in. | Range: 80.4% - 85.7% across age groups | |
| Posttest Probability of non-HF (Negative result) | High negative predictive value/posttest probability for rule-out. | Range: 96.5% - 98.3% across age groups | |
| Likelihood Ratio Positive (LR+) | High (e.g., > 5-10 for strong rule-in) | Range: 4.52 - 6.84 across age groups | |
| Likelihood Ratio Negative (LR-) | Low (e.g., 90%) | 91.7% (44/48) | |
| Specificity (Rule-out cutoff 125 pg/mL) | Reasonable (for rule-out, may be lower) | 67.2% (490/729) | |
| NPV (Rule-out cutoff 125 pg/mL) | High (for rule-out, e.g., >90%) | 99.2% (490/494) | |
| PPV (Rule-out cutoff 125 pg/mL) | (for rule-out, may be lower) | 15.6% (44/283) | |
| Correlation with NYHA | Statistical significance of relationship with HF severity | Statistically significant trend. | Jonckheere-Terpstra test p |
§ 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.”