(28 days)
The Clearview® Exact II Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. It is recommended that negative test results be confirmed by cell 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 Clearview Exact II Influenza A & B Test is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A and B nucleoprotein antigens in respiratory swab specimens. These antibodies and a control protein are immobilized onto a membrane support as three distinct lines and are combined with other reagents/pads to construct a Test Strip. Nasal swab samples are added to a Coated Reaction Tube to which an extraction reagent has been added. A Clearview Exact II Influenza A & B Test Strip is then placed in the Coated Reaction Tube holding the extracted liquid sample. Test results are interpreted at 10 minutes based on the presence or absence of pink-to-purcle colored Sample Lines. The yellow Control Line turns blue in a valid test.
Here's a breakdown of the acceptance criteria and study information for the Clearview® Exact II Influenza A & B Test, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the reported performance figures, as the device was deemed "substantially equivalent" which indicates these performance metrics were acceptable to the FDA. The document doesn't explicitly state pre-defined acceptance thresholds, but rather presents the results of the clinical study for evaluation.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Influenza Type A | ||
| Sensitivity | Adequate for intended use | 94% (95% CI: 83-98%) |
| Specificity | Adequate for intended use | 96% (95% CI: 93-97%) |
| Influenza Type B | ||
| Sensitivity | Adequate for intended use | 77% (95% CI: 67-85%) |
| Specificity | Adequate for intended use | 98% (95% CI: 96-99%) |
| Invalid Results Rate | Low | Less than 2% |
| Analytical Sensitivity (LOD) | Detects at specified concentrations | See detailed table below |
| Analytical Reactivity | Reacts to specified strains | See detailed table below |
| Analytical Specificity (Cross-Reactivity) | No cross-reactivity with specified microorganisms | All tested microorganisms were negative |
| Interfering Substances | No interference with specified substances | No interference found for most, whole blood interfered with positive samples |
| Reproducibility (Type A) | ||
| Moderate Positive Detection | High | 99.2% (119/120) |
| Low Positive Detection | High | 94.2% (113/120) |
| High Negative Detection | Low | 9.2% (11/120) |
| Reproducibility (Type B) | ||
| Moderate Positive Detection | High | 99.2% (116/120) |
| Low Positive Detection | High | 94.2% (113/120) |
| High Negative Detection | Low | 7.5% (9/120) |
| Negative Samples | 100% negative | 100% negative |
Analytical Sensitivity (LOD) - Reported Device Performance:
| Influenza Subtype | Concentration (TCID50/ml) | # Detected per Total Tests | % Detected |
|---|---|---|---|
| Influenza A/HongKong/8/68 | 2.37 x 10^4 | 64/66 | 97% |
| Influenza A/PuertoRico/8/34 | 3.16 x 10^5 | 37/42 | 88% |
| Influenza B/Malaysia/2506/2004 | 3.00 x 10^6 | 19/20 | 95% |
| Influenza B/Lee/40 | 4.20 x 10^5 | 19/20 | 95% |
Analytical Reactivity Testing - Reported Device Performance:
| Influenza Strain | Concentration (TCID50/ml or EIU50/ml) |
|---|---|
| Flu A/Port Chalmers/1/73 (H3N2) | 5.6 x 10^5 |
| Flu A/WS/33 (H1N1) | 5.0 x 10^4 |
| Flu A/Aichi/2/68 (H3N2) | 3.0 x 10^4 |
| Flu A/Malaya/302/54 (H1N1) | 6.0 x 10^5 |
| Flu A/New Jersey/8/76 (H1N1) | 2.8 x 10^5 |
| Flu A/Denver/1/57 (H1N1) | 8.9 x 10^3 |
| Flu A/Victoria/3/75 (H3N2) | 1.8 x 10^4 |
| Flu A/Solomon Islands/3/2006 (H1N1) | 1.5 x 10^5 |
| Flu A/Brisbane/10/07 (H3N2) | 2.5 x 10^6 EIU50/ml |
| Flu A/Puerto Rico/8/34 (H1N1) | 5.6 x 10^5 |
| Flu A/Wisconsin/67/2005 (H3N2) | 1.3 x 10^5 |
| Flu A/Hong Kong/8/68 (H3N2) | 7.9 x 10^3 |
| Flu A/California/04/2009 (H1N1) | 1.4 x 10^5 |
| Flu B/Florida/02/2006 | 1.4 x 10^4 |
| Flu B/Florida/04/2006 | 7.1 x 10^4 |
| Flu B/Florida/07/04 | 8.5 x 10^4 |
| Flu B/Malaysia/2506/04 | 1.5 x 10^6 |
| Flu B/Panama/45/90 | 1.7 x 10^4 |
| Flu B/R75 | 5.0 x 10^5 |
| Flu B/Russia/69 | 2.2 x 10^6 |
| Flu B/Taiwan/2/62 | 1.0 x 10^5 |
| Flu B/Mass/3/66 | 1.5 x 10^5 |
| Flu B/Lee/40 | 1.8 x 10^5 |
2. Sample size used for the test set and the data provenance
- Sample Size: 478 prospective clinical specimens.
- Data Provenance: Multi-center, prospective clinical study conducted at seven U.S. trial sites during the 2008-2009 respiratory season. Specimens were nasal swabs collected from symptomatic patients.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The ground truth for the clinical study was established using viral culture. This is a laboratory method and does not involve human experts in the typical "expert consensus" sense for image interpretation or diagnosis. Therefore, information about the number and qualifications of experts in this context is not applicable.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable, as the ground truth was "viral culture," which is an objective laboratory method rather than expert interpretation requiring adjudication. However, for the 19 samples where the Clearview test was negative for influenza B but viral culture was positive, an investigational RT-PCR assay was used as a follow-up ("Ten (10) of these samples were negative for influenza B by PCR"). This could be seen as a form of secondary verification for discrepant results.
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
Not applicable. This device is an immunochromatographic rapid diagnostic test for direct antigen detection, not an AI-powered diagnostic imaging or interpretation tool that assists human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the primary clinical performance study evaluated the device in a standalone manner. The results (sensitivity and specificity) represent the performance of the device itself (Clearview® Exact II Influenza A & B Test) compared to the viral culture gold standard, without human interpretation influence (other than reading the test strip, which is part of the device's intended use and not considered "human-in-the-loop AI assistance"). The reproducibility study also assessed the device's inherent performance characteristics.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the clinical study was viral culture.
8. The sample size for the training set
This information is not provided in the 510(k) summary. Given that this is an immunochromatographic assay using monoclonal antibodies, it's a traditional in vitro diagnostic, not a machine learning or AI-driven device that requires a "training set" in the computational sense. The "training" of such a device involves developing and optimizing the biochemical components and manufacturing processes, rather than training an algorithm on a dataset.
9. How the ground truth for the training set was established
Not applicable, as the device is not an AI/ML-based system requiring a training set with established ground truth in the traditional sense. The analytical studies (sensitivity, reactivity, specificity) demonstrate the performance of the developed assay against known viral strains and other microorganisms.
§ 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.