(19 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, aspirate and swab in transport media samples from 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 respiratory specimens. The patient specimen is mixed in a prefilled unitized tube containing RV Reagent D and 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 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 conjugated 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 non-specific 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 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 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.
This 510(k) summary describes a modification to an existing device, the BD Veritor™ System Flu A+B assay Clinical kit, primarily to update labeling with analytical sensitivity data for a new Influenza A strain (A/Anhui/1/2013 H7N9) and add strain reactivity tables. It explicitly states that no new issues of safety and effectiveness were identified for this addition and that the change did not change the intended use of the device or the fundamental scientific technology.
Therefore, the document does not contain details about a study designed to establish acceptance criteria for the original device or to demonstrate that the original device meets such criteria through clinical performance. Instead, it focuses on the analytical performance related to detecting specific influenza strains to ensure the updated labeling is accurate.
Given this, I cannot provide a table of acceptance criteria and reported device performance from this document for the overall device's clinical efficacy, nor details about a comprehensive clinical study as typically conducted for initial device clearance. The information provided heavily relates to analytical performance in detecting specific viral strains for labeling purposes, rather than a full clinical performance study for the entire device.
However, I can extract information related to the analytical performance presented for the labeling update, and other study-related details where available based on the document.
Here's the breakdown based on the provided text, focusing on what is available:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in the traditional sense for clinical performance metrics (like sensitivity/specificity targets). Instead, it discusses the establishment of analytical sensitivity (Limit of Detection - LOD) for specific influenza strains to enrich the product labeling.
| Performance Metric (Analytical) | Reported Device Performance |
|---|---|
| Analytical Sensitivity (LOD) for A/Anhui/1/2013 H7N9 | Data was added to the labeling reflecting the device's ability to detect this cultured virus. (Specific LOD values are not provided in this summary, only the fact that data was added). |
| Strain Reactivity tables | Added to labeling, indicating the device's reactivity (detection capabilities) against various influenza strains. (Specific data points are not provided in this summary, only the fact that tables were added). |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: Not explicitly stated for the analytical sensitivity (LOD) and strain reactivity testing.
- Data Provenance: The new data relates to cultured virus (A/Anhui/1/2013 H7N9) testing. The document also mentions general clinical performance characteristics for the original device were established:
- For NP washes/aspirates: January – March 2011, United States (predominant strains: A/2009 H1N1, A/H3N2, B/Victoria, B/Yamagata).
- For NP swabs in transport media: January – April 2012, United States (predominant strains: A/2009 H1N1, A/H3N2, B/Victoria, B/Yamagata).
- These dates and predominant strains suggest prospective collection of clinical samples during influenza seasons in the US for the original device's performance characterization, but detailed methodology for that original study is not provided in this 510(k) summary. The current 510(k) is about adding analytical data for a new strain.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable/Not provided for the analytical sensitivity and strain reactivity additions. This type of testing typically involves laboratory-based methods rather than expert clinical consensus for "ground truth".
4. Adjudication Method for the Test Set
Not applicable/Not provided. The analytical tests would follow standardized laboratory protocols for determining LOD and reactivity, not clinical adjudication.
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. This device is a rapid chromatographic immunoassay, not an AI-assisted diagnostic tool.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
The BD Veritor™ System Reader uses a "proprietary algorithm" to interpret test results by subtracting non-specific signal. The document states: "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 implies the "reader" (which performs the algorithm-based interpretation) operates in a standalone manner to provide results, effectively without human-in-the-loop performance for the final interpretation of the test strip signal. Specific performance metrics for this algorithm alone are not detailed in this summary, but its function is described as essential for accurate test interpretation.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc)
For the analytical sensitivity and strain reactivity data added: The ground truth would be the known presence and concentration of the cultured virus or specific viral strains, confirmed by reference laboratory methods.
For the original clinical performance of the device (referenced for historical context but not the subject of this 510(k) modification): The indication states, "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." This suggests that viral culture or FDA-cleared molecular assays likely served as the ground truth for establishing the original clinical performance characteristics.
8. The Sample Size for the Training Set
Not applicable/Not provided. This 510(k) summary is for a modification based on analytical testing, not a new device requiring a training set for model development. The original device's development (which is not detailed here) might have involved internal validation data, but that's not described as a "training set" in this context.
9. How the Ground Truth for the Training Set Was Established
Not applicable/Not provided for the reasons stated above.
Summary of Device Performance (from the document's new information context):
The core change in this 510(k) is the addition of data for Analytical Sensitivity (LOD) and Strain Reactivity tables for A/Anhui/1/2013 H7N9 to the product labeling. This indicates that the device has been analytically demonstrated to detect this specific novel avian influenza strain in a cultured setting. The document explicitly includes a disclaimer required by the FDA: "Although this test has been shown to detect the novel avian influenza A(H7N9) cultured virus, the performance characteristics of this device with clinical specimens that are positive for the novel avian influenza A(H7N9) virus have not been established." This clarifies that while analytical detection is shown, clinical performance with patient samples of H7N9 was not part of this submission.
§ 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.