(90 days)
The Sofia Influenza A +B FIA employs immunofluorescence to detect influenza B viral nucleoprotein antigens in nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash in fresh or transport media specimens from symptomatic patients. This qualitative test is intended for use as an aid in the rapid differential diagnosis of acute influenza A and influenza B viral infections. The test is not intended to detect influenza C antigens. A negative test is presumptive and it is recommended these results be confirmed by virus culture or an FDA-cleared influenza A and B molecular assay. Negative results do not prectude influenza virus infections and should not be used as for treatment or other management decisions. The test is intended for professional and laboratory use.
Performance characteristics for influenza A and B were established during February through March 2011 when influenza viruses A/California 7/2009 (2009 H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008 (Victoria-Like) were the predominant influenza viruses in circulation according to the Mortality Weekly Report from the CDC entitled "Update: Influenza Activity-United States, 2010-2011 Season, and Composition of the 2011-2012 Influenza Vaccine". 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. Virus culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
The Sofia Influenza A+B FIA employs immunofluorescence technology that is used with Sofia to detect influenza virus nucleoproteins. This test allows for the differential detection of influenza A and influenza B antigens.
The Sofia Influenza A+B FIA is a lateral-flow immunoassay that uses monoclonal antibodies that are specific for influenza antigens and have no known cross-reactivity to normal flora or other known respiratory pathogens.
Nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens (both fresh and in VTM) are used for this test. The patient specimen is placed in the Reagent Tube, during which time the virus particles in the specimen are disrupted, exposing internal viral nucleoproteins. After disruption, the specimen is dispensed into the cassette sample well. From the sample well, the specimen migrates through a test strip containing various unique chemical environments. If influenza viral antigen is present, they will be trapped in a specific location.
Note: Depending upon the user's choice, the cassette is either placed inside Sofia for automatically timed development (Walk Away Mode) or placed on the counter or bench top for a manually timed development and then placed into Sofia to be scanned (Read Now Mode).
Sofia will scan the test strip and measure the fluorescent signal by processing the results using method-specific algorithms. Sofia will display the test results (Positive, or Invalid) on the screen. The results can also be automatically printed on an integrated printer if this option is selected.
The provided text describes the 510(k) summary for the Sofia® Influenza A+B FIA device. Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided information.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific performance metrics (e.g., minimum sensitivity or specificity targets). Instead, it presents performance data from a clinical study to demonstrate "substantial equivalence" to a predicate device and suitability for use with viral transport media (VTM).
Therefore, the "acceptance criteria" can be inferred to be a demonstration of substantial equivalence and acceptable performance, particularly when using VTM, compared to the predicate device which only used fresh specimens. The provided text, however, does not include a direct comparison table of the proposed device's performance against the predicate device's performance metrics for all relevant parameters (like sensitivity and specificity). It mainly focuses on the new capability (VTM use) and the overall conclusion of substantial equivalence.
Inferred "Acceptance Criteria" (Demonstrated Substantial Equivalence and Acceptable Performance with VTM)
| Feature/Metric | Proposed Device (Sofia® Influenza A+B FIA) - VTM Performance (from multi-center field clinical study) |
|---|---|
| LoD (Limit of Detection) | Determined using two (2) strains of Influenza A and two (2) strains of Influenza B viruses in negative clinical nasal matrix from virus transport mediums. (Specific values not provided in this document). |
| Clinical Performance | Demonstrated through a multi-center field clinical study using specimens in Viral Transport Media to verify performance. (Specific sensitivity/specificity values for VTM not provided in this document, but implied to be acceptable for substantial equivalence). |
| Specimen Types | Nasal swab, Nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens both direct and in VTM. |
| Clinical Performance Data | Fresh and with Viral Transport Media. |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The document does not explicitly state the numerical sample size for the multi-center field clinical study. It only mentions that a "multi-center field clinical study was performed."
- Data Provenance: The study was a "multi-center field clinical study." While the specific countries are not mentioned, it's generally understood that such studies for FDA submissions typically include data from the United States, given the context of the FDA approval. The study collected data "during February through March 2011" making it retrospective in relation to the submission date of October 13, 2015.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide details on the number or qualifications of experts used to establish the ground truth for the test set.
4. Adjudication Method for the Test Set
The document does not specify the adjudication method used for the test set.
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
An MRMC study was not done. The device, Sofia® Influenza A+B FIA, is an immunofluorescence assay read by an instrument (Sofia Analyzer), not a human visual interpretation. Therefore, the concept of human readers improving with or without AI assistance is not applicable to this device. The results are displayed by the instrument as "Positive, Negative, or Invalid."
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was done. The Sofia® Influenza A+B FIA is an automated system where the Sofia Analyzer scans the test strip and processes the results using "method-specific algorithms." The instrument then displays the results. This represents the algorithm's standalone performance.
7. The Type of Ground Truth Used
The ground truth for the clinical study is not explicitly stated in the provided text. However, for influenza diagnostic tests, the common "gold standards" or ground truths involve:
- Virus culture: This is mentioned in the "Indications for Use" as a recommended confirmation for negative test results ("confirmed by cell culture").
- FDA-cleared influenza A and B molecular assay: Also mentioned in the "Indications for Use" as a confirmation method.
Given the context, it is highly probable that a comparative method such as virus culture or an FDA-cleared molecular assay was used as the ground truth reference for the clinical performance study.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of an algorithm or AI development. The device is a lateral-flow immunoassay with an instrument reader. The "method-specific algorithms" within the Sofia Analyzer would be preset and validated, rather than "trained" on a specific dataset in the way a machine learning model is trained. Therefore, there's no explicitly stated training set for an AI/algorithm in this document.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a "training set" for an AI or algorithm in the conventional sense, the establishment of ground truth for such a set is not applicable or described in the provided information.
§ 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.