(526 days)
SAS™ FluAlert A & B Test is a visual and rapid assay for the presumptive in-vitro qualitative detection of influenza A and influenza B viral nucleoprotein antigens from nasal washes and nasal aspirates of symptomatic patients. Negative results should be confirmed via culture. This test is not intended for the detection of Influenza Type C viral antigen. This test is for professional use only. Negative results do not preclude infection with influenza A or B and should not be used as the sole basis for treatment or other patient management decisions. It is recommended that negative results be confirmed by cell culture.
The SAS™ FluAlert A & B Test utilizes antibodies against influenza type A and influenza type B viral nucleoproteins. After the extraction has been completed, the sample is placed into two separate sample wells. The specimen is absorbed and migrates via capillary action through membranes that contain dried gold conjugated antibody, which is specific for either influenza A or influenza B viral nucleoproteins. If these nucleoproteins are present, a "half-sandwich" immunocomplex is formed. The membrane contains immobilized antibody to influenza A or influenza B nucleoproteins, respectively, which bind the "half sandwich" complex. Thus, in the presence of influenza nucleoproteins, a "whole sandwich" immunocomplex is formed and a visible, pink-colored line develops in the specimen zone of the test device. In the absence of an influenza antigen, a "sandwich" immunocomplex is not formed and a negative result is indicated. To serve as a procedural control, a pink-colored control line will always appear in the control zone of each strip regardless of the presence or absence of influenza A or influenza B nucleoproteins.
Here's a breakdown of the acceptance criteria and study details for the SAS™ FluAlert A & B Test, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document. Instead, the study aims to demonstrate "substantial equivalence" to predicate devices (SAS™ Influenza A Test and SAS™ Influenza B Test). The performance benchmarks are effectively the agreement rates with these predicate devices for positive and negative influenza cases.
| Characteristic | Acceptance Criteria (Implied by Substantial Equivalence to Predicate Device) | Reported Device Performance (SAS™ FluAlert A & B Test) |
|---|---|---|
| Influenza A | ||
| Positive % Agreement | High agreement with individual SAS™ Influenza A Test | 97.2% (95% CI 89-100%) (Combined Fresh NW & NA) |
| Negative % Agreement | High agreement with individual SAS™ Influenza A Test | 99.7% (95% CI 98-100%) (Combined Fresh NW & NA) |
| Influenza B | ||
| Positive % Agreement | High agreement with individual SAS™ Influenza B Test | 98.7% (95% CI 92-100%) (Combined Fresh NW & NA) |
| Negative % Agreement | High agreement with individual SAS™ Influenza B Test | 99.7% (95% CI 98-100%) (Combined Fresh NW & NA) |
| Reproducibility | High agreement with expected results across sites and users | 88.8% - 100% agreement depending on panel member |
| Cross-Reactivity | No cross-reactivity with tested viral/bacterial strains | No cross-reactivity observed |
| Interference | No interference from tested viral/bacterial strains with influenza detection | No interference observed (Influenza still detected as "Pos") |
2. Sample Size Used for the Test Set and Data Provenance
- Prospective Clinical Study:
- Sample Size: 461 nasal clinical specimens (nasal washes and nasal aspirates combined).
- Data Provenance: Prospectively collected from four clinical trial sites in Texas and South Dakota, USA. An approximately equal mix of adult (>21 years) and pediatric patients (0-21 years) for nasal washes, and predominantly pediatric patients for nasal aspirates.
- Retrospective Study:
- Sample Size: 191 frozen, archived nasal wash samples.
- Data Provenance: Retrospective, from a children's hospital in Texas, USA.
In the prospective study, 13 samples yielded invalid results and were excluded from the totals.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications for establishing the ground truth for the clinical specimens. The comparison is made against the predicate devices (SAS™ Influenza A Test and SAS™ Influenza B Test) and also mentions "cell culture or DFA" for those predicate devices in the "Results Summary" chart reference, but not explicitly for the new device's test set.
4. Adjudication Method for the Test Set
The document states that the clinical specimens were tested "blindly and prospectively comparing the SAS™ Influenza A Test and The SAS™ FluAlert A&B (combined) Test performance" and similarly for Influenza B. This implies that the results of the new device were compared against the established results of the predicate devices. There is no explicit mention of an adjudication method like 2+1 or 3+1 by human readers; the comparison is device-to-device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The study compares the new device's performance directly to the predicate devices, not human readers with and without AI assistance. The "reproducibility" section involved "non-professional users," but this was to assess consistent device results, not to evaluate human reader improvement with AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, this is essentially a standalone performance study. The SAS™ FluAlert A & B Test is a rapid immunoassay (visual and rapid assay) that produces a visible, pink-colored line. Its performance is evaluated directly against predicate devices based on its ability to detect influenza viral nucleoprotein antigens. There is no "human-in-the-loop" component mentioned for interpreting the device's fundamental output beyond simply reading the presence or absence of a line.
7. The Type of Ground Truth Used
The primary ground truth for evaluating the SAS™ FluAlert A & B Test's performance in the clinical studies is the results from the substantially equivalent predicate devices (SAS™ Influenza A Test and SAS™ Influenza B Test). For these predicate devices, the document refers to a comparison to "cell culture or DFA" in an older summary, implying that those methods serve as a "gold standard" for the predicate devices, and by extension, for this new device's evaluation against the predicates.
8. The Sample Size for the Training Set
The document describes performance studies for a diagnostic device, not a machine learning algorithm that typically requires a separate training set. Therefore, there is no explicit training set or sample size for training mentioned as it's not applicable in the context of this type of diagnostic device submission.
9. How the Ground Truth for the Training Set was Established
As there is no explicit training set for a machine learning algorithm, there is no description of how ground truth for a training set was established. The studies conducted are for performance evaluation against established methods and devices.
§ 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.