(226 days)
The Sofia Influenza A+B FIA employs immunofluorescence to detect influenza B viral nucleoprotein antigens in direct nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens and nasopharyngeal swab and nasopharyngeal aspirate/wash specimens in transport media from symptomatic patients. This qualitative test is intended for use as an aid in the rapid differential diagnosis of acute influenza B viral infections. The test is not intended to detect influenza C antigens. A negative test is recommended these results be confirmed by viral 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 patient management decisions. This test is intended for professional and laboratory use.
The Sofia Influenza A+B FIA may be used with Sofia or Sofia 2.
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, samples should be collected with appropriate infection sor 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 samples.
The Sofia Influenza A+B FIA employs immunofluorescence technology that is used with Sofia and Sofia 2 to detect influenza virus nucleoproteins. This test allows for the differential detection of influenza A and influenza B antigens.
The patient sample is placed in the Reagent Tube, during which time the virus particles in the sample are disrupted, exposing internal viral nucleoproteins. After disruption, the sample is dispensed into the Test Cassette sample well. From the sample 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 Test Cassette is either placed inside of Sofia or Sofia 2 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 2 to be scanned (READ NOW Mode).
Sofia and Sofia 2 will scan the test strip and measure the fluorescent signal by processing the results using method-specific algorithms. Sofia and Sofia 2 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.
Sofia 2 is a microprocessor-controlled device about the size of a desk top telephone and weighs less than 3 pounds. Sofia 2 uses a fluorescent tag that is illuminated by an Ultraviolet (UV) light source to generate specific results.
The provided text describes the 510(k) premarket notification for the "Sofia® Influenza A+B FIA on Sofia 2" device. Here's an analysis of the acceptance criteria and the study information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state acceptance criteria in a quantitative, objective manner (e.g., "sensitivity must be >95%"). Instead, the performance studies aim to demonstrate equivalence to the predicate device (Sofia® Influenza A+B FIA on Sofia). Therefore, the "reported device performance" is framed as proving this equivalence.
| Performance Characteristic | Acceptance Criteria (Implicit: Equivalent to Predicate) | Reported Device Performance |
|---|---|---|
| Limit of Detection (LoD) | LoD on Sofia 2 equivalent to LoD on Sofia | Confirmed equivalent |
| Precision | Sofia 2 generated equivalent qualitative results to Sofia for negative and positive concentrations near positivity threshold, across multiple operators, device lots, and days. | Confirmed equivalent |
| Assay Development Time (Read Now mode) | Development time of 15-30 minutes is acceptable | Confirmed 15-30 minutes acceptable |
| Early Read (Walk Away mode) | Positive samples can be interpreted as positive as early as 3 minutes (depending on viral load) | Confirmed positive results as early as 3 minutes |
| Method Comparison | Comparable performance between Sofia 2 and Sofia using a panel of clinical samples | Demonstrated comparable performance |
| Reproducibility | Intra- and inter-operator reproducibility and intra- and inter-laboratory reproducibility, with comparable performance between Sofia 2 and Sofia. | Demonstrated successful reproducibility and comparable performance |
2. Sample Size Used for the Test Set and Data Provenance:
The document mentions a "panel of clinical samples" for the Method Comparison study but does not specify the sample size for this test set nor the specific number of samples used for other studies like LoD, Precision, Early Read, or Reproducibility.
The data provenance is described as:
- "Performance characteristics for influenza A and B were established during February through March 2011"
- Location: Implied to be United States, as it references the "Morbidity and Mortality Weekly Report from the CDC entitled 'Update: Influenza Activity—United States, 2010-2011 Season'".
- Retrospective/Prospective: The collection period (Feb-Mar 2011) and subsequent analysis suggest the data might be retrospective (collected on previously circulating strains and then tested with the devices).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
The document does not provide information on the number of experts or their qualifications for establishing ground truth for the test set.
4. Adjudication Method for the Test Set:
The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1). It states "viral culture or an FDA-cleared influenza A and B molecular assay" as confirmation methods for negative results, implying these are the primary methods for ground truth, rather than expert adjudication of the Sofia results themselves.
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:
This device is not an AI/CAD-based system designed to assist human readers. It is an in vitro diagnostic (IVD) device that provides automated results (Positive, Negative, Invalid). Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not done. The system reports a direct result, not an interpretation for human review.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the studies conducted demonstrate standalone performance of the Sofia 2 device. The device outputs "Positive, Negative, or Invalid" results based on its internal algorithms and fluorescent signal detection, without human interpretation of the signal. The "Method Comparison" study compares the device's performance against the predicate device using clinical samples, effectively evaluating its standalone accuracy.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc):
The ground truth for defining influenza positive/negative status is indicated implicitly by these statements:
- "A negative test is presumptive and it is recommended these results be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay."
- This suggests that viral culture and/or FDA-cleared molecular assays (which are highly sensitive and specific) were used as the reference standard or "ground truth" to determine the true influenza status of the clinical samples during the performance characteristic studies.
8. The Sample Size for the Training Set:
The document does not specify a sample size for a training set. This type of device (immunofluorescence detection with pre-defined algorithms) typically doesn't involve a "training set" in the machine learning sense. The algorithms are likely developed and validated on internal data during product development, but this information is not provided here. The studies described are primarily for verification and validation against the predicate and established performance characteristics.
9. How the Ground Truth for the Training Set was Established:
As mentioned above, a "training set" in the context of machine learning is not applicable here. For the development and initial validation of the device's algorithms, the ground truth would have likely been established using well-characterized samples (e.g., confirmed by viral culture or PCR) to tune the device's sensitivity thresholds for fluorescent signal detection. However, details on this process are not provided in this regulatory submission summary.
§ 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.