(77 days)
The BD Veritor™ System for Rapid Detection of Flu A+B is a rapid chromatographic immunoassay for the direct and qualitative detection of influenza A and B viral nucleoprotein antigens from nasopharyngeal wash/aspirates of symptomatic patients. The BD Veritor System for Rapid Detection of Flu A+B is a differentiated test, such that influenza A viral antigens can be distinguished from influenza B viral antigens from a single processed sample using a single device. The test is to be used as an aid in the diagnosis of influenza A and B viral infections. A negative test is presumptive and it is recommended that these results be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Negative test results do not preclude influenza viral infection and should not be used as the sole basis for treatment or other patient management decisions. The test is not intended to detect influenza C antigens.
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in samples processed from respiratory specimens. The processed specimen is added to the test device where influenza A or influenza B viral antigens bind to antiinfluenza antibodies conjugated to detector particles on the A+B test strip. The antigenconjugate complex migrates across the test strip to the reaction area and is captured by an antibody line on the membrane. Results are interpreted by the BD Veritor™ System Reader, a portable electronic device which uses a reflectance-based measurement method to evaluate the line signal intensities on the assay test strip, and applies specific algorithms to determine the presence or absence of any target analyte(s). A liquid crystal display (LCD) on the instrument communicates the results to the operator.
- Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as a set of predefined thresholds. However, it presents the performance characteristics of the BD Veritor™ System for Rapid Detection of Flu A+B test during clinical studies. The "performance" column will reflect the PPA and NPA values achieved by the device.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Prospective Data) | Reported Device Performance (Retrospective Data) |
|---|---|---|---|
| Influenza A | (Not explicitly stated, generally high PPA/NPA expected for diagnostic devices) | PPA: 83.0% (95% C.I. 78.0%- 87.0%) | PPA: 92.1% (95% C.I. 82.7%- 96.6%) |
| NPA: 97.6% (95% C.I. 96.6%- 98.3%) | NPA: 98.9% (95% C.I. 96.2%- 99.7%) | ||
| Influenza B | (Not explicitly stated, generally high PPA/NPA expected for diagnostic devices) | PPA: 81.3% (95% C.I. 72.1%- 88.0%) | PPA: 74.0% (95% C.I. 58.9%- 85.4%) |
| NPA: 99.8% (95% C.I. 99.4%- 99.9%) | NPA: 99.0% (95% C.I. 96.6%- 99.7%) |
Note: While specific acceptance criteria are not called out, the FDA's clearance indicates that the observed performance was deemed acceptable for the intended use.
- Sample Size Used for the Test Set and Data Provenance:
- Prospective Test Set:
- Sample Size: 1471 evaluable clinical specimens (from an initial 1502 collected)
- Data Provenance: Multi-center clinical studies conducted at two U.S. trial sites and one Hong Kong trial site during the 2010-2011 respiratory season.
- Retrospective Test Set:
- Sample Size: 249 evaluable retrospective specimens (from an initial 263 collected)
- Data Provenance: Retrospective specimens, likely from banked samples, but specific origin beyond "retrospective" is not detailed.
- Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
The document does not mention the use of human experts to establish the ground truth for the clinical test sets. The ground truth was established by an "FDA-cleared influenza A and B molecular assay (PCR)."
- Adjudication Method for the Test Set:
Not applicable, as the ground truth was established by a laboratory assay (PCR) and not by expert review requiring adjudication.
- Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study was not conducted. This study focuses on the standalone performance of the BD Veritor™ System compared to PCR, not on how human readers' performance improves with or without the device.
- Standalone Performance (Algorithm Only without Human-in-the-Loop Performance):
Yes, the study primarily assessed the standalone performance of the BD Veritor™ System for Rapid Detection of Flu A+B test. The device uses an "opto-electronic reader" to interpret results and apply algorithms, reporting a positive, negative, or invalid result on an LCD screen. This means the interpretation is automated by the device, making it a standalone assessment.
- The Type of Ground Truth Used:
The ground truth used for the clinical studies (both prospective and retrospective) was an FDA-cleared Influenza A and B molecular assay (PCR).
- The Sample Size for the Training Set:
The document does not explicitly state a separate training set size for the device's algorithms. The performance data presented is for the evaluation of the final device. For in-vitro diagnostic devices like this, the "training" (development and optimization) often happens with internal validation sets and analytical studies (like LOD, specificity, cross-reactivity) rather than a distinctly separated "training set" in the machine learning sense, before being tested on independent clinical cohorts.
- How the Ground Truth for the Training Set Was Established:
As a distinct "training set" is not explicitly mentioned for algorithmic development in the provided document, the method for establishing its ground truth is also not described. However, for any internal development and validation, the ground truth would typically be established using confirmed reference methods, similar to the PCR used for the clinical evaluation. Analytical studies (LOD, specificity, cross-reactivity) involved known concentrations of viral strains and specific microorganisms, which serve as a form of ground truth for characterizing the device's analytical capabilities.
§ 866.3328 Influenza virus antigen detection test system.
(a)
Identification. An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria:
(i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method:
(A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method:
(A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies.
(3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria:
(i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains.
(ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or
(B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.
(4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.