(184 days)
The Influenza A/B Rapid Test is a qualitative immunoassay for the rapid detection of Influenza A/B viral antigens from throat swab or nasal swab specimens. This test is intended for professional in vitro diagnostic use to aid in the diagnosis of Influenza infections, and to gather epidemiological information for detection of Influenza outbreaks. When used for diagnosis, negative assay results should be confirmed by cell culture. This assay does not detect the presence of Influenza C viral antigens.
The Influenza A/B Rapid Test consists of swabs, reaction cups, test strips, and reagent solutions. The test detects the viral nucleoprotein associated with the viral nucleic acid. The nucleoprotein is released by lysing the virus envelop with the lysis/elution solution. Since the nucleoprotein is type specific only (not subtype specific), the test uses two pairs of monoclonal antibodies - one pair is specific for Influenza A, the other is specific for Influenza B. The antibody pairs are conjugated to either biotin or digoxigenin. In the presence of the viral antigen, a sandwich complex is formed, consisting of the biotin-conjugated antibody, the nucleoprotein, and the digoxigeninconjugated antibody. When the test strip is placed in the reaction cup, the complex migrates chromatographically, solubilizing colloidal gold particles incorporated in the red pad of the strip. The colloidal gold particles bind to the digoxigenin of the complex, which is then bound by the biotin to the immobilized streptavidin on the strip (positive result line). Any excess gold particles continue to migrate to the second line (control line), which then becomes visible. This indicates the correct chromatographic migration. The test reagent formulation has been modified slightly to produce improved specificity, and allow the use of nasal swab samples.
Here's an analysis of the provided 510(k) summary regarding the Roche Diagnostics Influenza A/B Rapid Test, extracting the requested information about acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state "acceptance criteria" as a set of predefined thresholds that the device must meet in a table. Instead, it presents performance data for the modified device and compares it to a predicate device. The implied acceptance is that the modified device's performance, particularly its improved specificity and expanded sample type, is deemed suitable and substantially equivalent to its predicate.
However, based on the performance data presented, we can infer the reported performance metrics:
| Performance Metric | Modified RDC Influenza A/B Rapid Test (Throat Swab) | Modified RDC Influenza A/B Rapid Test (Nasal Swab) | Predicate Device (Throat Swab) |
|---|---|---|---|
| Sensitivity | 69.7% | 77.4% | 68.4% |
| Specificity | 93.3% | 93.0% | 80.7% |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample sizes used for the performance studies of either the predicate or the modified device. It only presents the sensitivity and specificity percentages. Similarly, the data provenance (e.g., country of origin, retrospective or prospective) is not mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document states that the performance is measured "vs. Cell Culture." This indicates that cell culture was used as the gold standard (ground truth). Therefore, there were no human experts used to establish the ground truth for this diagnostic test; instead, a laboratory method was employed.
4. Adjudication Method for the Test Set
Since cell culture was the ground truth, there was no adjudication method involving human experts. The comparison was directly between the rapid test result and the cell culture result.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of Human Reader Improvement
This information is not applicable as the device is a qualitative immunoassay. It does not involve human readers interpreting images or data where their performance could be augmented by AI. The device gives a direct positive or negative result.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
This information is not applicable in the context of this device. The "algorithm" is the biochemical reaction of the immunoassay itself. The performance percentages (sensitivity and specificity) described are the standalone performance of the device, as it produces a result without human interpretation of complex outputs beyond reading a line.
7. The Type of Ground Truth Used
The type of ground truth used was cell culture. This is a laboratory-based method for detecting the presence of Influenza A/B viruses. The document explicitly states: "Performance vs. Cell Culture."
8. The Sample Size for the Training Set
The document does not mention a "training set" or its sample size. This type of immunoassay development typically involves extensive R&D and optimization (which could be considered a form of "training"), but it's not structured in the same way as machine learning algorithms where a distinct training set is published. The performance data presented are from clinical evaluation studies.
9. How the Ground Truth for the Training Set Was Established
As no training set is explicitly mentioned in the context of typical machine learning, this information is not provided. If an internal optimization process involved comparing prototype results to a gold standard, it would likely also use cell culture for establishing the ground truth.
§ 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.