(141 days)
The Innovita Flu A/B Antigen Rapid Test is a rapid chromatographic immunoassay intended for the qualitative detection and differentiation of influenza A and B viral nucleoprotein antigens directly from nasopharyngeal swabs from patients with signs and symptoms of respiratory infection.
The test is intended for use as an aid in the differential diagnosis of acute influenza A and B viral infections. The test is not intended to detect influenza C antigens. Negative test results are presumptive and should be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Negative test results do not preclude influenza viral infection and should not be used as the sole basis for treatment or other patient management decisions.
Performance characteristics for influenza A were established during the December 2023, and July 2024 influenza season when influenza A/H1N1pdm09, influenza A/H3N2 and influenza B/Victoria viruses were the predominant influenza viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
If an infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
The Innovita Flu A/B Antigen Rapid Test is a double antibody sandwich immunoassay-based test. The test device consists of the specimen zone and the test zone. The specimen zone contains monoclonal antibody against the Flu A/Flu B antigen labeled with latex microspheres and chicken IgY antibody conjugated with latex microspheres. The test line contains the other monoclonal antibody against Flu A/Flu B antigen. The control line contains rabbit anti-chicken IgY antibody.
After the specimen is applied into the specimen well of the device, antigen in the specimen forms an immune complex with the binding reagent in the specimen zone. Then the complex migrates to the test zone. The test line in the test zone contains antibody from a specific pathogen. If the concentration of the specific antigen in the specimen is higher than LoD of Flu A or Flu B, it will be captured at Flu A or Flu B line and form a red-purple line. In contrast, if the concentration of the specific antigen is lower than LoD, it will not form a red-purple line. The test also contains an internal control system. A red-purple control line (C) should always appear after the test is completed. Absence of a red-purple control line indicates an invalid result. The product contents are listed below.
| Contents | Amount | Description |
|---|---|---|
| Test cassette | 25 | Each sealed foil pouch containing one test device and one desiccant |
| Extraction diluent | 25 | Vials with 500microliters of solution, mainly composed of Tris-HCl buffer (pH8.4), NaCl and Triton X-100. |
| Swab | 25 | Nasopharyngeal swab |
| Influenza A Positive Control | 1 | Swab is coated with non-infectious recombinant influenza A antigen |
| Influenza B Positive Control | 1 | Swab is coated with non-infectious recombinant influenza B antigen |
| Negative Control | 1 | Swab contains inactivated Staphylococcus aureus |
| Package Insert | 1 | |
| Quick Reference | 1 |
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) clearance letter:
Acceptance Criteria and Device Performance for Innovita Flu A/B Antigen Rapid Test
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state pre-defined acceptance criteria for the clinical study's Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA). However, the reported device performance is presented. For analytical performance (LoD, inclusivity, cross-reactivity, interfering substances), the acceptance criterion is generally 100% agreement or no interference/cross-reactivity as implied by the reported results.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Influenza A) | Reported Device Performance (Influenza B) |
|---|---|---|---|
| Analytical Performance | |||
| Limit of Detection (LoD) | Detect with high positivity rate (e.g., ≥95%) | 96.67% - 100% at specified LoDs | 98.33% - 100% at specified LoDs |
| Inclusivity | 100% detection at near LoD concentrations | 100% detection for all tested strains | 100% detection for all tested strains |
| Specificity / Cross-Reactivity | No false positives | 100% (no cross-reactivity for 49 tested organisms) | 100% (no cross-reactivity for 49 tested organisms) |
| Microbial Interference | No interference | 100% (no interference for 49 tested organisms) | 100% (no interference for 49 tested organisms) |
| Interfering Substances | No false positives/negatives | 100% (no interference for 30 tested substances) | 100% (no interference for 30 tested substances) |
| Biotin Interference | No interference | No interference up to 4000 ng/mL | No interference up to 4000 ng/mL |
| Precision/Reproducibility | 100% agreement between expected and read result | 100% agreement | 100% agreement |
| Clinical Performance | |||
| Positive Percent Agreement (PPA) | (Not explicitly stated, but typically a high percentage, e.g., >80%) | 85.7% (95% CI: 80.6%-89.5%) | 85.7% (95% CI: 72.2%-93.3%) |
| Negative Percent Agreement (NPA) | (Not explicitly stated, but typically a high percentage, e.g., >95%) | 99.5% (95% CI: 98.8%-99.8%) | 100% (95% CI: 99.6%-100%) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size (Clinical Study): 1101 evaluable nasopharyngeal swab specimens.
- Data Provenance:
- Country of Origin: U.S.
- Study Type: Prospective clinical study. Specimens were collected from subjects with flu-like symptoms during the 2023-2024 influenza season.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The ground truth for the clinical test set was established using an "FDA-cleared influenza A and B molecular assay" as the comparator method. The document does not specify the number of human experts involved in establishing this ground truth or their qualifications. The ground truth relies on the performance characteristics of the molecular assay itself.
4. Adjudication Method for the Test Set
The document does not describe any adjudication method (e.g., 2+1, 3+1) for the clinical test set results. The comparison appears to be a direct one-to-one comparison between the Innovita Flu A/B Antigen Rapid Test result and the result from the FDA-cleared molecular assay.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done comparing human readers with AI vs. without AI assistance. This device is a rapid diagnostic test (RDT) with visual interpretation. The precision study involved "untrained operators" to assess reproducibility, but it was not a comparative effectiveness study with or without AI assistance.
6. Standalone Performance (Algorithm Only without Human-in-the-Loop)
Yes, this study primarily assesses the standalone performance of the rapid diagnostic test device. While human operators interpret the visual results, the performance metrics (PPA, NPA) are based on the device's output compared to the ground truth, without an explicit human-in-the-loop component being evaluated for its improvement with AI, as there is no AI component mentioned for interpretation.
7. Type of Ground Truth Used
The ground truth for the clinical study was: Comparator Method (FDA-cleared influenza A and B molecular assay).
8. Sample Size for the Training Set
The document does not explicitly state a sample size for a "training set." Rapid diagnostic tests typically do not involve machine learning algorithms that require a distinct training set in the same way an AI/ML device would. The development of the assay (e.g., antibody selection, optimization) is a different process from training a machine learning model.
9. How the Ground Truth for the Training Set Was Established
Since a "training set" in the context of machine learning is not explicitly mentioned or applicable for this type of rapid diagnostic test, the method for establishing its ground truth is not applicable/not described. The analytical studies (LoD, inclusivity, specificity) use laboratory-prepared, characterized samples with known viral concentrations or presence/absence, serving as the "ground truth" for those specific analytical evaluations.
§ 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.