(155 days)
The Thermo BioStar™ FLU OIA* A/B assay is an Optical ImmunoAssay test for the qualitative, rapid detection of influenza A and B viral antigens (nucleoproteins) extracted from nasal aspirate, nasopharyngeal swab, throat swab, and sputum specimens. This test is intended for in vitro diagnostic use to aid in the differential diagnosis of influenza A and B viral infections. The FLU OIA A/B test is not intended for detection of influenza C. Negative test results should be confirmed by cell culture.
The FLU OIA A/B test involves the extraction and detection of a protein antigen unique to influenza A or B (nucleoprotein). The Optical ImmunoAssay technology enables the direct visual detection of a physical change in the optical thickness of molecular thin films. This change is a result of antigen-antibody binding on an optical surface (silicon wafer). When an extracted specimen is placed directly on the optical surface, the immobilized specific antibodies capture the antigen. After washing, the substrate is added, increasing the thickness (mass enhancement) of the molecular thin film. This change in thickness alters the reflected light path and is visually perceived as a color change. Slight changes in optical thickness produce a distinct, visible color change. A positive result appears as a purple spot on the predominant gold background. When antigen is not present in the specimen, no binding takes place. Therefore, the optical thickness remains unchanged and the surface retains the original gold color indicating a negative result.
Here's an analysis of the provided text regarding the acceptance criteria and study for the FLU OIA® A/B device, structured according to your requested information:
Acceptance Criteria and Device Performance Study for FLU OIA® A/B
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (FLU OIA® A/B) |
|---|---|---|
| Sensitivity (Influenza A) | Not explicitly stated | 82.9% (95% C.I. = 75.3-89.0) |
| Sensitivity (Influenza B) | Not explicitly stated | 63.6% (95% C.I.= 40.7-82.8%) |
| Reproducibility (Inter-Laboratory) | Not explicitly stated | 96.6% across all sites (255/264) |
| Agreement with original FLU OIA (positive specimens) | Not explicitly stated | 100% (95% Cl = 39.8 -100) |
| Overall Agreement with original FLU OIA | Not explicitly stated | 100% (95% CI = 96.8 - 100) |
Note: The document does not explicitly state pre-defined acceptance criteria values for sensitivity or agreement. The reported device performance is presented as the study outcome without direct comparison to a specified target. However, the FDA's clearance of the device implies these performance metrics were deemed acceptable.
2. Sample Size and Data Provenance for Test Set
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Sample Size:
- Clinical Sample Comparison: 184 patients enrolled in a multi-center study. Data available for analysis included 151 specimens positive by culture (129 Influenza A, 22 Influenza B).
- Comparison to original FLU OIA: 112 retrospective frozen clinical specimens.
- Reproducibility (Inter-Laboratory): Not explicitly stated as a single number for samples, but "Individual panels were prepared, each containing nine blinded specimens and two controls." This was performed on "three different occasions" by "four different laboratories."
- Reproducibility (Intra-Laboratory): Not explicitly stated as a single number, but "testing specimens at or near the cut-off in multiple replications (n=20)."
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Data Provenance:
- Clinical Sample Comparison: Multi-center study with geographically diverse clinical sites. The data is retrospective, as it's a "retrospective analysis of previously collected clinical data."
- Comparison to original FLU OIA: Retrospective frozen clinical specimens.
- Reproducibility: Not specified beyond "three POL or clinic sites, and one internal Thermo BioStar site." The specimens for reproducibility were "spiked with negative, low positive, moderate positive, and high positive specimens for each virus type."
3. Number of Experts and Qualifications for Ground Truth
- The document does not explicitly state the number or qualifications of experts used to establish the ground truth.
- The ground truth for the clinical sample comparison relied on "commercially available cell culture, with confirmation and typing by fluorescent antibody staining." This implies laboratory personnel with expertise in viral culture and fluorescent antibody staining were involved, but their specific qualifications or number are not detailed.
4. Adjudication Method for Test Set
- The document does not describe any specific adjudication method (e.g., 2+1, 3+1). The ground truth was established by "commercially available cell culture, with confirmation and typing by fluorescent antibody staining."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a MRMC comparative effectiveness study was not conducted. This device is an in-vitro diagnostic (IVD) test, not an imaging or AI-assisted diagnostic tool for human readers. Its performance is compared to a historical reference method (viral culture) or a predicate device, not in terms of human reader improvement with AI assistance.
6. Standalone Performance Study
- Yes, a standalone performance study was conducted. The performance characteristics for the FLU OIA® A/B (and the original FLU OIA) were established by comparing the device's output (positive/negative for Influenza A/B) directly against the ground truth (viral culture and fluorescent antibody staining). The reported sensitivities are standalone performance metrics.
7. Type of Ground Truth Used
- The primary ground truth used for the clinical sample comparison was viral culture, with confirmation and typing by fluorescent antibody staining.
8. Sample Size for Training Set
- The document does not mention a separate "training set" in the context of machine learning or AI. This device is an optical immunoassay, which does not typically involve training on datasets in the same way an AI algorithm would. The "Performance characteristics for the original AB FLU OIA assay were initially established in a multi-center study" but this refers to the initial validation of the technology, not a training set for a learning algorithm. Subsequent comparability studies were performed using "inactivated virus standards, live virus strains, and a panel of retrospective frozen clinical specimens."
9. How Ground Truth for Training Set Was Established
- As noted above, a "training set" in the context of an AI algorithm is not applicable here. For the "Performance characteristics for the original AB FLU OIA assay," the ground truth would have been established through methods such as viral culture, as detailed for the clinical sample comparison. The comparability studies also relied on "inactivated virus standards" and "live virus strains" where the viral status would be known.
§ 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.