(28 days)
The BioSign Flu A+B test is an in vitro rapid qualitative test that detects influenza type A and type B nucleoprotein antigens directly from nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens obtained from patients with signs and symptoms of respiratory infection. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. Negative test results are presumptive and it is recommended these results be confirmed by viral culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. The test is intended for professional and laboratory use. Performance characteristics for influenza were established during the 2007-2009 influenza seasons when influenza A viruses A/New Caledonia/20/99 (H1N1), A/Solomon Islands/3/2006 (H1N1), A/Brisbane/59/2007 (H1N1), A/California/07/2009 (H1N1), A/Wisconsin/67/2005 (H3N2), A/Brisbane/10/2007 (H3N2), and influenza B viruses B/Ohio/01/2005, B/Florida/4/2006, B/Brisbane/60/2008 were the predominant influenza viruses in circulation according to the Flu Activity & Surveillance report by CDC. Performance characteristics may vary against other emerging influenza viruses. If infection with a novel influenza virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL+3 facility is available to receive and culture specimens.
The modification presented in this 510(k) is the addition of influenza A/Vietnam/1194/2004 (H5N1) and influenza A/Anhui/01/2005 (H5N1) along with their respective analytical sensitivity concentrations, to the Analytical Inclusivity section of the package insert. The avian influenza A (H5N1) viruses, A/Vietnam/1194/2004 (H5N1) and A/Anhui/01/2005 (H5N1) were obtained from CDC as a non-infectious form with known titer. Analytical sensitivity is reported as the lowest dilution/concentration of the virus that the BioSign Flu A+B Test is able to detect.
The provided text describes a 510(k) summary for a modification to an existing influenza test device, the BioSign Flu A+B. The modification involves adding two specific avian influenza A (H5N1) strains and their analytical sensitivity concentrations to the package insert.
Here's an analysis based on your request:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state acceptance criteria in the typical sense of numerical thresholds (e.g., sensitivity > X%, specificity > Y%). Instead, the acceptance criteria for this specific modification are implicit: the device must be able to detect the new H5N1 strains at a certain analytical sensitivity, and this information needs to be added to the product labeling.
The reported device performance for the new H5N1 strains is their "analytical sensitivity concentrations," which are reported as "the lowest dilution/concentration of the virus that the BioSign Flu A+B Test is able to detect." However, the exact numerical concentrations for A/Vietnam/1194/2004 (H5N1) and A/Anhui/01/2005 (H5N1) are not provided in this specific 510(k) summary, only that they were determined.
Since explicit acceptance criteria are not given, and only the type of performance metric is mentioned for the modification, a direct table comparing explicit acceptance criteria to reported performance for the modification cannot be fully generated from this text. The underlying assumption is that demonstrating any detectable analytical sensitivity for the new strains is sufficient for their inclusion in the labeling, given this is primarily an information update rather than a redesign or a change to the core diagnostic performance for general influenza A/B.
2. Sample size used for the test set and the data provenance
For the specific modification concerning the H5N1 strains:
- Sample size: Not explicitly stated. The text mentions that the viruses were obtained in a non-infectious form with a known titer, and "analytical sensitivity is reported as the lowest dilution/concentration of the virus that the BioSign Flu A+B Test is able to detect." This implies a series of dilutions were tested, but the number of replicates or different samples tested at each dilution is not specified.
- Data provenance:
- Country of origin: The H5N1 viruses were obtained from the CDC (Centers for Disease Control and Prevention), which is a US-based agency. The viruses themselves are A/Vietnam/1194/2004 and A/Anhui/01/2005.
- Retrospective or prospective: This study is best described as an analytical study or in-vitro technical validation using prepared samples, rather than a clinical study with retrospective or prospective patient data. The viruses were obtained and then tested in a controlled laboratory setting.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable for this type of analytical validation study. The "ground truth" for the H5N1 strains was their known presence and concentration (titer) as determined by the CDC. This is a technical standard rather than an expert interpretation.
4. Adjudication method for the test set
Not applicable. This was an analytical sensitivity study, not a clinical study involving human interpretation or adjudication of diagnostic results. The "result" (detection or non-detection) at various dilutions would be objectively observed, not adjudicated by a panel.
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/CAD device. It is an in vitro diagnostic (IVD) rapid test for influenza. There are no human readers in the context of an MRMC study and no AI assistance involved.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. This is not an algorithm or AI device. The device itself performs the detection. The analytical sensitivity study evaluates the device's inherent ability to detect the target analytes.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the H5N1 strains was defined by the known titer/concentration of the non-infectious viral material provided by the CDC. This is essentially a "reference standard" or "analytical standard" rather than a clinical ground truth like pathology or expert consensus.
8. The sample size for the training set
Not applicable. This device is an IVD rapid test. There is no machine learning or AI model involved that would require a "training set." The device's performance is based on its biochemical reactions.
9. How the ground truth for the training set was established
Not applicable, as there is no training set for this type of device.
§ 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.