(34 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 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 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 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 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 document, K132693, describes the BD Veritor™ System Flu A+B Assay. However, it is a 510(k) submission for a change in labeling to reflect additional analytical strain reactivity data (specifically for H3N2v and other strains), not a primary submission for the device's original performance. As such, it references performance characteristics established in previous 510(k)s (K112277, K132259) but does not provide new clinical study data or detailed acceptance criteria for the device's performance. The main study mentioned is analytical to add strains to the product labeling.
Therefore, much of the requested information regarding a study that proves the device meets acceptance criteria (such as sample sizes, ground truth establishment for test and training sets, expert qualifications, adjudication methods, MRMC studies, or standalone performance) is not contained within this specific 510(k) submission for the labeling change. This submission focuses on demonstrating substantial equivalence despite the labeling change, arguing that the change does not alter the device's intended use or fundamental scientific technology, and thus does not require new performance studies.
However, based on the provided text, I can extract the following:
1. A table of (implied) acceptance criteria and the reported device performance:
The document doesn't explicitly state "acceptance criteria" for clinical performance in this submission. Instead, it refers to "performance characteristics established" during specific influenza seasons. The implied acceptance is that the device's performance aligns with these established characteristics, which were deemed acceptable in the predicate device’s original 510(k) clearances (K112277, K132259). This particular 510(k) focuses on analytical strain reactivity for additional strains, not clinical performance.
| Criterion Type (Implicit) | Reported Device Performance (Reference to previous studies) |
|---|---|
| Clinical Performance (Influenza A & B detection from NP washes/aspirates) | Established during Jan-March 2011, when A/2009 H1N1, A/H3N2, B/Victoria, and B/Yamagata were predominant. Specific sensitivity/specificity values are not provided in this document. |
| Clinical Performance (Influenza A & B detection from NP swabs in transport media) | Established during Jan-April 2012, when A/2009 H1N1, A/H3N2, B/Victoria, and B/Yamagata were predominant. Specific sensitivity/specificity values are not provided in this document. |
| Analytical Strain Reactivity (Influenza A H3N2v and other strains) | Data added to labeling; the submission implies that the device demonstrated reactivity to these strains, supporting the update. Specific analytical sensitivity values (e.g., limit of detection) are not provided. |
2. Sample size used for the test set and the data provenance:
- Clinical Performance Test Set Sample Size: Not provided in this document. It refers to previous studies.
- Data Provenance: The clinical performance studies were conducted during specific influenza seasons (Jan-March 2011 and Jan-April 2012) in the United States, as per CDC Morbidity and Mortality Weekly Reports referenced. This implies prospective clinical studies during those periods. This specific submission primarily discusses an analytical study to add strain data to the labeling.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not provided within this document. The ground truth method, as implied by the intended use, would typically be viral culture or an FDA-cleared molecular assay for influenza A and B.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not provided within this document.
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 is not an AI/imaging device. It's a rapid immunoassay. The device uses a proprietary algorithm to interpret results (subtracting nonspecific signal), but this is for automated reading of the immunoassay strip, not for enhancing human reader performance in an MRMC study context.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the device operates in a standalone manner in terms of result interpretation. The BD Veritor™ System Reader uses a "proprietary algorithm which subtracts nonspecific signal" and "correctly interpret test results that cannot be scored visually." This describes the device's automated interpretation without human intervention in the final result determination.
7. The type of ground truth used:
- The "Intended Use" section 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 implies that viral culture or an FDA-cleared molecular assay would be used as the ground truth for clinical performance studies.
8. The sample size for the training set:
- Not provided in this document, as it outlines a labeling modification, not the initial device development and validation.
9. How the ground truth for the training set was established:
- Not provided in this document.
§ 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.