(27 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 nasal and nasopharyngeal swabs of symptomatic patients. The BD Veritor System for Rapid Detection of Flu A+B (also referred to as the BD Veritor System and BD Veritor System 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. Outside the U.S., a negative test is presumptive and it is recommended that these results be confirmed by viral culture or a molecular assay cleared for diagnostic use in the country of use. FDA has not cleared this device for use outside of the U.S. 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 Veritor™ Flu A+B test is an immunochromatographic assay for the qualitative detection of influenza A and B viral antigens in respiratory specimens. The patient specimen is mixed in a reaction tube prefilled with RV Reagent C, gently mixed, and then added to the test device. RV Reagent C contains mucolytic agents that function to break down mucus in a patient specimen thereby exposing viral antigens and enhancing detection in the assay device. Processed specimens are expressed through a filter tip into a single sample well on the BD Veritor™ Flu A+B test device.
After addition to the test device, any influenza A or influenza B viral antigens present in the specimen bind to anti-influenza antibodies conjugated to detector particles on the Veritor™ Flu A+B test strip. The antigen-conjugate complexes migrate across the test strip to the reaction area and are captured by a line of antibody striped on the membrane. The Veritor™ Flu A+B test devices are designed with five spatially-distinct zones including positive and negative control line positions, separate test line positions for the target analytes, and a background zone. The test lines for the target analytes are labeled on the test device as 'A' for Flu A position, and 'B' for Flu B position. The onboard positive control ensures the sample has flowed correctly and is indicated on the test device as 'C'. Two of the five distinct zones on the test device are not labeled. These two zones are an onboard neqative control line and an assay background zone. The onboard negative control zone addresses non-specific signal generation. The remaining zone is used to measure the assay background.
The BD Veritor™ Flu A+B assay incorporates an active negative control feature in each test to identify and compensate for sample-related, nonspecific signal generation. The BD Veritor™ System Reader uses a proprietary algorithm that subtracts nonspecific signal at the negative control line from the signal present at both the Flu A and Flu B test lines. If the resultant test line signal is above a pre-selected assay cutoff, the specimen scores as positive. If the resultant test line signal is below the cutoff, the specimen scores as negative. Use of the active negative control feature allows the BD Veritor™ System reader to correctly interpret test results that cannot be scored visually because the human eye is unable to accurately perform the subtraction of the nonspecific signal.
This document describes an FDA 510(k) submission for the BD Veritor™ System for Rapid Detection of Flu A + B CLIA Waived Kit. This submission is for a modification to an already marketed device, primarily concerning the addition of strain reactivity data to the labeling. Therefore, the information provided below is extracted from the context of this modification rather than a de novo submission for a new device.
Here's an analysis based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state acceptance criteria in terms of specific performance metrics (e.g., sensitivity, specificity thresholds) that were set for this particular 510(k) amendment. This submission focuses on adding strain reactivity data to the device's labeling. Therefore, the "reported device performance" in this context refers to the strain reactivity data that was added. The original device would have had its own acceptance criteria and performance studies, which are not detailed in this specific document.
| Performance Characteristic | Acceptance Criteria (Explicitly stated in document) | Reported Device Performance (as updated) |
|---|---|---|
| Strain Reactivity | Not explicitly stated for this amendment | Reactivity demonstrated for (and added to labeling): |
- A/California/02/2014 (H3N2)
- B/Brisbane/33/2008 (Victoria Lineage)
- B/Guangdong-Liwan/1133/2014 (Yamagata Lineage)
- B/Hong Kong/259/2010 (Victoria Lineage)
- B/Texas/02/2013 (Victoria Lineage)
- B/Utah/09/2014 (Yamagata Lineage) |
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify the sample size used for the testing of the new strains. It only states that "strain reactivity data" was added. The provenance of this data (e.g., country of origin, retrospective/prospective) is also not detailed for these specific strain reactivity tests.
However, the general performance characteristics for influenza A and B for the original device were "established during January through March of 2011" when specific influenza viruses were in circulation. This suggests the original validation involved prospective clinical samples from the U.S., but the details like sample size for that original validation are not in this document.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not provide information on the number or qualifications of experts used to establish ground truth for the strain reactivity data specifically, or for the original clinical validation. The device is for rapid detection of viral antigens, and ground truth for such devices typically relies on more definitive laboratory tests like viral culture or molecular assays, rather than expert consensus on interpretation of the device's results.
4. Adjudication Method for the Test Set
The document does not describe any adjudication methods for the test set, as its focus is on adding strain reactivity data, not on a clinical trial with human interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done, nor is it relevant given the nature of this rapid diagnostic test described. The device is interpreted by a "BD Veritor™ System Reader" using a proprietary algorithm, not by human readers interpreting images.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this device inherently functions as a standalone (algorithm only) system in terms of result interpretation. The "BD Veritor™ System Reader" uses a "proprietary algorithm" to interpret the test strip and provide a result, subtracting non-specific signals. The human user's role is to perform sample preparation and insert the device into the reader, not to visually interpret the test lines.
7. The Type of Ground Truth Used
For the specific strain reactivity data added, the document does not explicitly state the ground truth method. However, for a device detecting influenza viral antigens, the standard ground truth for establishing performance (as referenced in the "Indications for Use" and "Intended Use" sections for negative results) would be:
- Viral Culture: Considered the traditional gold standard.
- FDA-cleared influenza A and B molecular assay: Modern standard for definitive diagnosis.
It's highly probable that these methods were used to confirm the presence and type of virus for the new strains tested for reactivity.
8. The Sample Size for the Training Set
The document does not provide information about a training set since this is a rapid diagnostic kit with a fixed detection mechanism. Machine learning models typically have training sets, but this device uses a proprietary algorithm within a reader that interprets optical signals from a lateral flow assay. The initial development of such an algorithm would involve internal validation and optimization, but the term "training set" in the context of deep learning is not applicable here.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the context of a machine learning-based algorithm is not directly applicable to this device as described. The algorithm in the BD Veritor™ System Reader optically reads the test lines and performs calculations based on pre-defined cutoffs and signal subtraction. The "ground truth" for developing this reading algorithm would be based on expertly characterized positive and negative control samples, and samples with known viral loads and types, using methods like viral culture or molecular assays to confirm their status. The document does not detail this developmental process.
§ 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.