(24 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 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 outside the U.S. Negative test results do not prectude influenza viral infection and should not be used as the sole basis for treatment or other 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 C 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.
The BD Veritor™ System Reader measures the amount of light reflected from various zones along the assay strip. The measurement of the assay background zone is an important factor during test interpretation as the reflectance is compared to that of the control and test zones. A background area that is white to light pink indicates the device has performed correctly. The instrument analyzes the reflectance data to provide the proper interpretation.
Here's a breakdown of the acceptance criteria and study information for the BD Veritor™ System for Rapid Detection of Flu A+B (Laboratory Kit), based on the provided document:
Acceptance Criteria and Device Performance
The acceptance criteria for this study were focused on the ability of the BD Veritor Flu A+B assay system to provide a positive instrumented read for samples of new influenza virus strains. The "reported device performance" reflects the successful detection of all tested strains.
| Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Strain Reactivity | The BD Veritor Flu A+B assay system must give a positive instrumented read with samples of subject flu viruses. | All Flu A and Flu B strains enrolled in this study were successfully detected by the respective Flu A or Flu B line of the device, with no cross-reactivity. |
| Limit of Detection (LOD) | The LOD for each strain was established, representing the lowest concentration detectable in 3/3 replicates. | Specific LOD values were determined and are provided in a table for each of the 14 tested strains (e.g., A/Fujian-Gulou/1896/2009 H1N1 at 4.5 x 10^5 CEID50/mL). |
Study Details
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 14 influenza virus strains (9 Flu A strains and 5 Flu B strains).
- Data Provenance: The viral material was obtained from the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza and the US Centers for Disease Control (CDC). Two strains were provided by the National Institute for Biological Standards and Control (UK). The study was conducted at the R/D laboratories in San Diego, CA, USA. This was a prospective study specifically designed to test the reactivity of the device against these new strains.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- Number of Experts: The document does not explicitly state the number of experts used to establish the ground truth for the test set. However, the viral material was provided by recognized expert organizations (WHO, CDC, NIBSC), implying that the characterization and titering of these virus strains were performed by qualified virologists or equivalent experts within those institutions.
- Qualifications of Experts: Not detailed for individual experts, but the providing organizations are leading authorities in influenza surveillance and characterization.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method involving multiple readers for the test set results. The BD Veritor System Reader uses a proprietary algorithm to interpret test results by subtracting non-specific signals. The "acceptance criteria was the ability of the BD Veritor test to detect these additional Flu strains," which suggests a direct measurement of instrument output against known viral presence.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not conducted. This study focused on the analytical performance (reactivity and limit of detection) of the device itself against specific viral strains, not on human reader performance with or without AI assistance. The BD Veritor System Reader automatically interprets the results, removing the subjective human-in-the-loop element for interpretation.
6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance
Yes, a standalone study was performed. The BD Veritor System Reader automatically interprets test results based on its proprietary algorithm without human interpretation of the signal. The "instrumented read" and the calculation of LODs by the device confirm its standalone performance. The document explicitly states: "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."
7. Type of Ground Truth Used
The ground truth used was the presence and quantified titer of specific influenza viral strains. These strains were obtained from reputable public health organizations (WHO, CDC, NIBSC) and their titers (e.g., CEID50/mL, EID50/mL, TCID50/mL, HA) were known and confirmed through standard virological methods (e.g., MDCK cell culture, Reed-Muench formula for TCID50 calculation).
8. Sample Size for the Training Set
The document does not specify a training set or its sample size. This particular submission is a Special 510(k) for a device modification (labeling update with new strain reactivity data) for an already cleared device (K120049, K121797, K132256, K132693, K133138). The BD Veritor™ System uses a proprietary algorithm, but the details of its original development and training data are not part of this specific submission. This study is an analytical validation testing the device's ability to detect newly identified or relevant strains.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is detailed in this document, the method for establishing its ground truth is not provided. For the current analytical validation study, the ground truth was established by acquiring known, characterized influenza viral materials with quantified titers from established public health and research institutions.
§ 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.