(88 days)
The Sofia Influenza A+B FIA employs immunofluorescence to detect influenza A and influenza B viral nucleoprotein antigens in nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens taken directly 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 preclude influenza virus infections and should not be used as the sole basis 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 Morbidity and 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 the Sofia Analyzer to detect influenza virus nucleoproteins.
The Sofia Influenza A+B F1A 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 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 of the Sofia Analyzer for automatically timed development (Walk Away Mode) or placed on the counter or bench top for a manually timed development and then placed into the Sofia Analyzer to be scanned (Read Now Mode).
The Sofia Analyzer will scan the test strip and measure the fluorescent signal by processing the results using method-specific algorithms. The Sofia Analyzer will display the test results (Positive, Negative, or Invalid) on the screen. The results can also be automatically printed on an integrated printer if this option is selected.
Acceptance Criteria and Device Performance Study for Sofia™ Analyzer and Influenza A+B FIA
The Sofia™ Analyzer and Influenza A+B FIA is a qualitative immunofluorescence assay intended to detect influenza A and influenza B viral nucleoprotein antigens in various respiratory specimens. The acceptance criteria and supporting study details are summarized below.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds. Instead, it demonstrates "substantial equivalence" to predicate devices through various performance studies. The clinical study results against a "gold standard" (presumably virus culture or FDA-cleared molecular assay) are as follows:
| Performance Metric | Influenza A (Nasal Swab, Nasopharyngeal Swab, Nasopharyngeal Aspirate/Wash) | Influenza B (Nasal Swab, Nasopharyngeal Swab, Nasopharyngeal Aspirate/Wash) |
|---|---|---|
| Sensitivity | Established in multi-center field clinical study | Established in multi-center field clinical study |
| Specificity | Established in multi-center field clinical study | Established in multi-center field clinical study |
| Reproducibility | Demonstrated intra- and inter-operator and lab reproducibility | Demonstrated intra- and inter-operator and lab reproducibility |
Note: The document states that a multi-center field clinical study was undertaken to "document the performance characteristics" including sensitivity and specificity, but the specific numerical values for these metrics are not provided in the summary. The "acceptance criteria" appear to be met by demonstrating performance comparable to the predicate devices and overall suitability for its intended use, as indicated by the FDA's clearance of substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The exact number of specimens collected for the "multi-center field clinical study" is not explicitly stated in the provided text.
- Data Provenance: The studies were conducted during "February through March 2011" when specific influenza strains (A/California/7/2009 (2009 H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008 (Victoria-like)) were predominant according to a CDC report. This implies the data was collected prospectively from United States (or potentially other regions following the CDC report) symptomatic patients during an influenza season.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not provide details on the number or qualifications of experts used to establish the ground truth for the test set. It refers to the ground truth as "virus culture or an FDA-cleared influenza A and B molecular assay." These methods are typically standardized laboratory procedures and do not inherently require human expert interpretation in the same way, for example, a radiological image would.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for the test set. The ground truth, being "virus culture or an FDA-cleared influenza A and B molecular assay," typically yields definitive results that do not necessitate adjudication among multiple human interpreters.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted or reported in the provided text. This study is an in-vitro diagnostic device and aims for direct detection of viral antigens, rather than an AI-assisted diagnostic aid for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.
6. Standalone Performance Study
Yes, a standalone performance study (algorithm only without human-in-the-loop performance) was performed. The "multi-center field clinical study" evaluated the Sofia™ Analyzer and Influenza A+B FIA directly against "virus culture or an FDA-cleared influenza A and B molecular assay," which represents the standalone performance of the device in detecting the target analytes. The device itself (Sofia Analyzer) reads the test strip and displays results (Positive, Negative, or Invalid) using "method-specific algorithms."
7. Type of Ground Truth Used
The type of ground truth used was expert laboratory methods, specifically "virus culture or an FDA-cleared influenza A and B molecular assay." This aligns with the gold standard for influenza diagnosis.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its sample size. This type of diagnostic device, relying on immunofluorescence and specific antibodies, does not typically undergo a machine learning training phase in the same way an AI algorithm for image analysis would. The development likely involved extensive analytical studies and optimization, but not explicit "training" on a distinct dataset as understood in AI/ML contexts.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit mention of a "training set" in the context of an AI/ML algorithm, the method for establishing its ground truth is not applicable or described in the provided text. The foundational data for developing and optimizing the assay would have come from established laboratory techniques for identifying influenza viruses.
§ 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.