(693 days)
The BioSign® Flu A+B test is an in vitro rapid qualitative test that detects influenza type A and type B antigens directly from nasal swab, nasopharyngeal swab, and nasopharyngcal aspirate/wash specimens obtained from patient with signs and symptoms of respiratory infection. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. A negative test result is presumptive and it is recommended these results be confirmed by viral culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional and laboratory use.
BioSign® Flu A+B is an immuno-chromatographic test for the rapid, qualitative detection of influenza A and B. The test device has two test lines, thereby allowing the separate identification of type A and/or type B viral antigens from the same specimen.
In the test procedure, a specimen is collected and placed into the Extraction Well of the test device containing extraction solution for one minute, during which time antigen is extracted from disrupted virus particles. The test device is then raised, tapped and laid back down onto a level surface to allow the solution in the Extraction Well to migrate through the pads containing lyophilized detector antibodies conjugated to gold dye and then through the test membrane. If influenza antigens are present in the specimen, they will react with anti-influenza antibody coupled to gold dye particles, migrate through the membrane as antigen-antibody-dye complexes, bind to the immobilized anti-influenza antibody on the membrane, and generate a colored line in the Test line position (A and/or B). The rest of the sample and unbound/bound dye complexes continue to migrate to the Control line position, where antibody to the antiinfluenza antibody is immobilized, and anti-influenza antibody-unbound/bound dye complexes form the Control line (internal procedural control).
Here's an analysis of the provided 510(k) summary, extracting the requested information:
The device under review is the BioSign® Flu A+B / Status™ Flu A & B, an immuno-chromatographic test for the rapid, qualitative detection of influenza A and B antigens.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are implicitly set by the reported performance (sensitivity and specificity) when compared against viral culture as the reference method. The document presents performance for different sample types (nasopharyngeal aspirate, nasopharyngeal swab, nasal swab).
Table of Acceptance Criteria and Reported Device Performance:
| Sample Type & Antigen | Acceptance Criteria (Implicit from Study Results) | Reported Device Performance (Sensitivity) | Reported Device Performance (Specificity) |
|---|---|---|---|
| Nasopharyngeal Aspirate | High sensitivity and specificity required for clinical utility. | ||
| Flu A (Sensitivity) | - | 95.3% (95% CI: 92.1-98.5%) | - |
| Flu A (Specificity) | - | - | 85.7% (95% CI: 83.3-88.1%) |
| Flu B (Sensitivity) | - | 91.6% (95% CI: 83.6-99.6%) | - |
| Flu B (Specificity) | - | - | 97.5% (95% CI: 96.5-98.5%) |
| Nasopharyngeal Sample | High sensitivity and specificity required for clinical utility. | ||
| Flu A (Sensitivity) | - | 89.6% (95% CI: 84.0-95.2%) | - |
| Flu A (Specificity) | - | - | 77.0% (95% CI: 74.2-79.8%) |
| Flu B (Sensitivity) | - | 86.8% (95% CI: 81.4-92.2%) | - |
| Flu B (Specificity) | - | - | 92.9% (95% CI: 91.2-94.6%) |
| Nasal Swab Sample | High sensitivity and specificity required for clinical utility. | ||
| Flu A (Sensitivity) | - | 91.7% (95% CI: 78.2-97.1%) | - |
| Flu A (Specificity) | - | - | 75.2% (95% CI: 70.2-79.6%) |
| Flu B (Sensitivity) | - | 82.4% (95% CI: 59.0-93.8%) | - |
| Flu B (Specificity) | - | - | 88.3% (95% CI: 84.4-91.3%) |
Note: The document does not explicitly state numerical "acceptance criteria" thresholds, but rather reports the observed performance and implies these values were sufficient for regulatory clearance. The wide confidence intervals in some cases suggest that the performance might vary.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Total Patients: 862
- Nasopharyngeal Aspirate: 253 cases
- Nasopharyngeal Sample: 251 cases
- Nasal Swab Sample: 358 cases
(Note: The sum of individual sample types is 862, matching the total number of patients, indicating these might be overlapping or distinct subsets of samples from the same patient pool, or simply different sample types evaluated from the overall patient population.) - Archived Samples: 80 samples for both Flu A and Flu B verification (Columbia NY Presbyterian Hospital).
- Data Provenance:
- Country of Origin: USA (samples collected at 5 sites in the USA).
- Retrospective or Prospective: Prospective clinical study, with additional testing on "Archived Samples" which would be considered retrospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not specify the number of experts used to establish the ground truth or their qualifications. The ground truth method was viral culture, and it's common for laboratory professionals to perform and interpret viral cultures, but no details on their expertise are provided.
4. Adjudication Method for the Test Set
The primary reference method for initial comparison was viral culture. For samples that produced discrepant results between the BioSign® Flu A+B test and viral culture, a third, more definitive method was used for resolution: proFLU plus by Prodesse (real-time RT-PCR, or PCR). This constitutes an adjudication method, where ambiguous cases are resolved by a higher-tier test. The document refers to the results from the PCR as "further analyzed" or used to identify cases that were "positive by both BioSign and PCR" or "negative by both BioSign and PCR".
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This study design is typically used for image-based diagnostic aids where human readers interpret results with and without AI assistance to assess the impact of AI on reader performance. The BioSign® Flu A+B is a rapid diagnostic test, not an AI-powered diagnostic imaging device.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was done for the device. The reported sensitivity and specificity values directly reflect the performance of the BioSign® Flu A+B device itself, without any human interpretation adjustments beyond standard operation and reading of a rapid diagnostic test. The entire clinical study section, including the performance tables, represents the standalone performance of the device against the ground truth.
7. Type of Ground Truth Used
The type of ground truth used was primarily viral culture, which is a laboratory-based method for identifying and growing viruses. For discrepant results, real-time RT-PCR (proFLU plus by Prodesse) was used as a confirmatory or adjudicating ground truth.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" or its sample size. This type of device (rapid diagnostic test) is typically developed and optimized during its R&D phase using various sample sets, but the clinical study described is primarily for validation/testing of the finalized device.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is described, the method for establishing ground truth for a training set (if one existed in the R&D phase) is not provided. The ground truth for the clinical test set was established by viral culture (and PCR for discrepants), as described in point 7.
§ 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.