(25 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. 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 respiratory specimens. The patient specimen is mixed in a prefilled unitized tube containing RV Reagent D and added to the test device. RV Reagent D 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 Flu A+B test device.
The specimen is mixed and added to the test device where influenza A or influenza B viral antigens bind to anti-influenza antibodies conjuqated to detector particles on the BD Flu A+B test strip. The antigen-conjugate complex migrates across the test strip to the reaction area and is captured by an antibody line on the membrane. The assay utilizes a proprietary enhanced colloidal-gold particle at the test lines as the means for identifying the presence of influenza A or B viral antigens.
The BD 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 negative control line and an assay background zone. The onboard negative control zone addresses nonspecific signal generation and is not labeled on the test device. The remaining zone is used to measure the assay background and is also not labeled.
The BD 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 which subtracts nonspecific signal at the neqative 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 is scored as positive. If the resultant test line signal is below the cutoff, the specimen is scored 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.
The provided 510(k) summary (K132692) for the BD Veritor™ System Flu A+B assay, while detailing the device and its intended use, does not contain a clinical study or performance data against specific acceptance criteria for a new device submission.
Instead, this submission is for a modification to an already marketed device (BD Veritor™ System for Rapid Detection of Flu A+B POC kit, K112277, K132239). The stated purpose of this 510(k) is to "add additional strain testing" data for H3N2v and other strains to the product insert's Analytical Strain Reactivity tables. The document explicitly states: "Risk analysis was not conducted to add this analytical sensitivity information to the product insert as no new issues of safety and effectiveness were identified for this addition to the product insert." This implies that the core performance characteristics were established in previous submissions (K112277, K132239) and are not re-evaluated here through a new clinical study with specific acceptance criteria.
Therefore, many of the requested details about acceptance criteria, study design, sample sizes, ground truth establishment, expert involvement, and comparative effectiveness studies are not present in this specific 510(k) summary.
However, based on the information provided, here's what can be gathered, along with an explanation of why other requested information is not available:
1. Table of Acceptance Criteria and Reported Device Performance
As this 510(k) is for an update to labeling with additional analytical sensitivity data for specific strains, no new clinical performance acceptance criteria are defined or reported in this document. The document focuses on "Analytical Strain Reactivity tables" for H3N2v and other strains, which are typically analytical sensitivity data, not clinical performance. Clinical performance, including sensitivity and specificity in symptomatic patients, would have been established and reviewed in the predicate device submissions (K112277, K132239).
Therefore, a table of clinical acceptance criteria and reported device performance as typically seen for a new device approval is not applicable to this specific submission. The "reported device performance" here is the addition of analytical sensitivity data to the existing product insert.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Not applicable/not provided for a new clinical study in this submission. This submission does not detail a new clinical test set. The analytical strain reactivity data would involve laboratory-prepared samples at various concentrations, not a patient-based test set.
- Data Provenance: Not specified for the analytical sensitivity data, though general performance characteristics were established during "January through March of 2011" when specific influenza viruses were predominant in the United States (according to CDC reports). This suggests retrospective or prospective clinical data from the predicate device would have originated from US patients. However, the added strain data for this 510(k) is analytical, not clinical.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. As this involves analytical sensitivity data (detection of specific viral strains in a lab setting) and not a clinical study requiring expert interpretation of diagnostic images or patient data, experts for ground truth establishment in this context are not described. The "ground truth" for analytical sensitivity is typically the known presence and concentration of the virus in the prepared samples.
4. Adjudication method for the test set
Not applicable for the analytical sensitivity data described in this submission. Adjudication methods are typically used in clinical studies where there might be discrepancies in expert readings or comparison to a gold standard, which is not the focus here.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. The BD Veritor™ System Flu A+B assay is a rapid chromatographic immunoassay that uses a proprietary algorithm for interpreting signals, but it is not an AI-assisted diagnostic tool in the typical sense of computer vision or complex decision support for human readers. It's an automated reader for an immunoassay. Therefore, an MRMC study comparing human reader performance with and without AI assistance is not relevant to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a sense. The "BD Veritor™ System Reader" uses a "proprietary algorithm which subtracts nonspecific signal... If the resultant test line signal is above a pre-selected assay cutoff, the specimen is scored as positive. If the resultant test line signal is below the cutoff, the specimen is scored as negative." This describes an automated, standalone interpretation of the test strip by the device's algorithm. The output (positive/negative) is machine-determined based on the signal readings.
7. The type of ground truth used
For the analytical sensitivity data being added to the labeling, the ground truth is the presence and concentration of specific influenza viral strains (e.g., H3N2v) in laboratory-prepared samples. This would be established by standard microbiological techniques and confirmed viral presence.
For the clinical performance data (from the predicate devices), the ground truth for Flu A+B detection would typically be viral culture or an FDA-cleared influenza A and B molecular assay, as stated in the intended use: "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."
8. The sample size for the training set
Not applicable/not provided. As this submission describes an analytical sensitivity update for an existing immunoassay interpretation algorithm, there's no mention of a "training set" in the context of machine learning. The algorithm's cutoff values would have been established during the development of the predicate device, likely using a different methodology.
9. How the ground truth for the training set was established
Not applicable/not provided, for the same reasons as point 8.
§ 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.