(122 days)
Binax NOW Flu B Test is an in vitro rapid The immunochromatographic assay for the qualitative detection of influenza B nucleoprotein antigen in nasal wash and nasopharyngeal swab specimens from symptomatic patients. It is intended to aid in the rapid diagnosis of influenza B infections. Negative test results should be confirmed by cell culture.
The Binax NOW® Binax Flu B Test is an immunochromatographic membrane assay used to detect influenza B nucleoprotein antigen in nasal wash and nasopharyngeal sswab specimens. A test strip, containing goldconjugated and immobilized anti-influenza B antibodies, is mounted on the right side of a cardboard, book-shaped hinged test device. Swab specimens require a sample preparation step, in which the sample is eluted off the swab into a saline solution. The nasal wash sample does not require any preparation. The sample to be tested is added to a pad at the top of the test strip, and the test device is closed. Influenza B antigen present in the sample reacts to bind anti-influenza B conjugated antibody. The resulting antigencomplexes are captured conjugate by anti-influenza antibody, immobilized forming the Sample Line. Immobilized Control Line antibody, which appears as a blue line in an untested device, captures a visualizing conjugate, forming a pink Control Line. The sample is contained, and results are available within 15 minutes.
Here's a breakdown of the acceptance criteria and study details for the Binax NOW® FLU B Test:
Binax NOW® FLU B Test Acceptance Criteria and Study Details
1. Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied by Predicate Equivalence) | Reported Device Performance |
|---|---|---|
| Analytic Sensitivity | Detects all tested influenza B strains. | 100% positive result for 5 ATCC traceable influenza B strains across concentrations from 10^2 to 10^6 TCID50/ml, indicating detection of all tested strains. |
| Analytic Specificity (Cross-Reactivity) | No cross-reactivity with common respiratory bacteria and viruses at specified concentrations. | No cross-reactivity with 43 potential cross-reactants (bacteria tested at >1 x 10^6 organisms/ml; viruses at >1 x 10^5 TCID50/ml). |
| Clinical Sensitivity (Nasal Wash) | Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test). | 71% (95% CI: 56%-83%) |
| Clinical Specificity (Nasal Wash) | Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test). | 97% (95% CI: 93%-99%) |
| Overall Accuracy (Nasal Wash) | Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test). | 92% (95% CI: 87%-95%) |
| Clinical Sensitivity (Nasopharyngeal Swab) | Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test). | 58% (95% CI: 42%-73%) |
| Clinical Specificity (Nasopharyngeal Swab) | Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test). | 97% (95% CI: 93%-99%) |
| Overall Accuracy (Nasopharyngeal Swab) | Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test). | 90% (95% CI: 85%-94%) |
| Interfering Substances | No interference with common substances, and should properly detect spiked virus. | No cross-reactivity with 19 potentially interfering substances, and expected results generated when spiked with limit of detection (LOD) level virus. |
| Reproducibility | High percentage of correctly interpreted samples across multiple sites and operators. | 99% of 234 samples correctly interpreted in a blind study at 3 sites over 3 days. |
| Quality Control | Procedural control should indicate test failure accurately. | 97% of devices correctly interpreted (positive, negative, or invalid) by operators testing 20 kit controls on 20 devices (9 rendered inoperative). |
Note: The document primarily uses substantial equivalence to the predicate device as the overarching acceptance criterion, rather than explicit numerical thresholds. The reported performance metrics are presented to demonstrate this equivalence.
2. Sample Sizes and Data Provenance
- Clinical Study Test Set Sample Size:
- 191 nasal wash specimens
- 182 nasopharyngeal swab specimens
- Data Provenance:
- Country of Origin: Not explicitly stated, but the study was described as a "multi-site prospective study," suggesting data collected within the US, given the submission to the FDA.
- Retrospective/Prospective: Prospective clinical studies. All specimens were "freshly collected and characterized" from "patients presenting with influenza-like symptoms."
3. Number and Qualifications of Experts for Ground Truth
- The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical study.
4. Adjudication Method for the Test Set
- The document does not specify an adjudication method for the test set results beyond comparing the Binax NOW® test performance "versus viral cell culture."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a MRMC comparative effectiveness study was not done. This study focuses on the standalone performance of the diagnostic test compared to a laboratory reference method.
6. Standalone Performance Study (Algorithm Only)
- Yes, a standalone performance study was done. The entire "Performance Summary" and "Clinical Sensitivity and Specificity" sections describe the direct comparison of the Binax NOW® test results (the "algorithm only" in this context, as it's a diagnostic device) against viral cell culture (the reference method). There is no mention of a human-in-the-loop component for interpreting the Binax NOW® results in the clinical study beyond the basic reading of the test strip by clinicians/lab personnel.
7. Type of Ground Truth Used
- Viral Cell Culture: This was the primary ground truth used for assessing the clinical sensitivity and specificity of the device. The document states, "Negative test results should be confirmed by cell culture," highlighting its role as the gold standard.
8. Sample Size for the Training Set
- The document does not specify a separate "training set" in the context of machine learning, as this is a rapid immunochromatographic assay. The performance characteristics are based on the described analytical and clinical studies.
9. How Ground Truth for Training Set Was Established
- Since there isn't a "training set" in the machine learning sense for this type of device, this question is not directly applicable. The device's underlying mechanism (immunochromatographic assay) is based on known biological reactions, not a trained algorithm. The analytical and clinical studies serve to validate its performance.
§ 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.