(300 days)
The BD Directigen™ EZ Flu A+B test is a rapid chromatographic immunoassay for the direct and qualitative detection of influenza A and B viral antigens from nasopharyngeal washes/aspirates and throat swabs of symptomatic patients. The BD Directigen™ EZ Flu A+B test is a differentiated test, and therefore 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. All negative test results should be confirmed by cell culture.
The BD Directigen™ EZ Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in samples processed from respiratory specimens. When specimens are processed and added to the test device, influenza A and/or B viral antigens bind to anti-influenza antibodies conjugated to visualizing particles in the corresponding A and B test strips. The antigen-conjugate complex migrates across the test strip to the reaction area and is captured by the line of antibody on the membrane. A positive result is visualized as a reddish purple line at the Test "T" position in the Flu A or Flu B read window in combination with a reddish purple line at the Control "C".
Here's an analysis of the acceptance criteria and study details for the BD Directigen™ EZ Flu A+B, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds. Instead, it demonstrates "substantial equivalence" to predicate devices and viral cell culture. The reported performance values are:
| Metric | Influenza A (compared to cell culture) | Influenza B (compared to cell culture) |
|---|---|---|
| Sensitivity | 83.2% | 75.4% |
| Specificity | 94.3% | 99.3% |
| Reproducibility | 99.6% (overall) | 99.6% (overall) |
2. Sample Size Used for the Test Set and Data Provenance
The text states: "Performance characteristics of the BD Directigen EZ Flu A+B test were determined by calculating sensitivity and specificity of the BD Directigen EZ Flu A+B test compared to culture for prospectively collected nasopharyngeal wash/aspirate and throat specimens in both an adult and pediatric population."
- Test Set Sample Size: The exact numerical sample size for the clinical study (test set) is not explicitly provided in the document.
- Data Provenance: The data was prospectively collected from a multi-center study that was "geographically diverse." The country of origin is not specified, but given the submission to the FDA, it is highly likely to be the USA. The specimens were from "symptomatic patients."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth for the clinical study was established by viral cell culture. This is a laboratory method, not reliant on human expert interpretation in the same way an imaging study would be. Therefore, the concept of "number of experts" and their "qualifications" doesn't directly apply here for establishing the primary ground truth.
4. Adjudication Method for the Test Set
As the primary ground truth was established by viral cell culture, there was no human adjudication method described for the test set interpretation itself. The BD Directigen™ EZ Flu A+B test results were compared against the cell culture results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
- No MRMC study was done. This device is a rapid diagnostic test (an immunoassay) for direct antigen detection, not an AI-powered diagnostic tool intended for interpretation by human readers. Therefore, the concept of human reader improvement with AI assistance is not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone study was done. The clinical performance reported (sensitivity and specificity) is for the BD Directigen™ EZ Flu A+B test operating as a standalone diagnostic device, comparing its results directly to cell culture. There is no human-in-the-loop element mentioned for the primary output of this device.
7. The Type of Ground Truth Used
- The primary ground truth used for the clinical performance evaluation was viral cell culture.
- The device was also compared to Direct Fluorescent Antibody (DFA) tests, the BD Directigen™ Flu A+B test, and the Remel Xpect™ FLU A/B test in a "device comparison" context, suggesting these served as secondary or comparative ground truths/references.
8. The Sample Size for the Training Set
- The document does not provide any information regarding a "training set" or its sample size. This is typical for traditional (non-AI/machine learning) diagnostic devices. The device's performance is established through analytical and clinical validation, not by training a model on a dataset.
9. How the Ground Truth for the Training Set Was Established
- As there is no mention of a training set, the method for establishing its ground truth is not applicable and not provided.
§ 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.