(30 days)
The Alere BinaxNOW® Influenza A & B Card 2 is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal (NP) swab and nasal swab specimens. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. Negative test results are presumptive and should be confirmed by cell 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. Alere BinaxNOW® Influenza A & B Card 2 must be read by the Alere™ Reader.
Performance characteristics for influenza A were established during the 2015-2016 influenza season when influenza A/H3N2 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
If 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 Alere BinaxNOW® Influenza A & B Card 2 is an immunochromatographic membrane assay that detects influenza type A and B nucleoprotein antigens in respiratory specific antibodies and a control antibody are immobilized onto a membrane support as three distinct lines and combined with other reagents/pads to construct a test strip is mounted inside a cardboard, book-shaped hinged test card.
Swab specimens require a sample preparation step, in which the sample is eluted off the swab into Elution Solution. Sample is added to the test strip and the test card is closed. Test results are interpreted at 15 minutes based on the presence or absence of Sample Lines. Alere BinaxNOW® Influenza A & B Card 2 test results must be read by the Alere™ Reader.
The Alere™ Reader is an easy to use bench top instrument that can be used near patient and in laboratory settings which will interpret, capture and transmit test results. The Alere™ Reader is a camera based instrument that detects the presence and identity of the Alere BinaxNOW® Influenza A& B Card 2 assay, analyzes the intensity of the test and control lines and displays the results (positive or invalid) on a display screen. The screen is intended as a means of user interface informing the user how to operate the Reader and to display test results, including any errors. Data can be retrieved and downloaded by the operator at any time after testing and uploaded to the hospital LIS/LIM system, if desired. Operator ID and Subject ID can be entered manually or via the provided barcode scanner. An external printer can be attached via USB to the Alere™ Reader to print test results.
This is a 510(k) premarket notification for a software modification to the Alere™ Reader, which is used with the Alere BinaxNOW® Influenza A & B Card 2 assay. The purpose of the submission is to introduce a "Walk Away" mode to the reader's software, alongside other minor enhancements. The underlying immunochromatographic assay (Alere BinaxNOW® Influenza A & B Card 2) itself remains unchanged.
Here's an analysis of the provided text in relation to your questions:
1. Table of Acceptance Criteria and Reported Device Performance
The submission focuses on a software modification to the Alere™ Reader. It explicitly states: "There have been no changes to the Alere BinaxNOW® Influenza A & B Card 2 test." Therefore, the clinical performance (e.g., sensitivity, specificity) of the assay itself is not being re-evaluated or re-established by this specific submission, but rather the performance of the reader in interpreting those results.
The document discusses analytical performance for the reader with the new software. The acceptance criteria for the analytical studies were generally for the Alere™ Reader with the new software to maintain non-inferiority to the predicate reader (K162642) and to perform reliably in its new "Walk Away" mode.
Acceptance Criteria for Reader Performance (Implicit in comparative studies):
- Accuracy of Interpretation: The modified Reader should accurately interpret positive and negative results from the Alere BinaxNOW® Influenza A & B Card 2, consistently with the predicate device and visual interpretation.
- Timing Accuracy: The "Walk Away" mode should accurately time the 15-minute incubation period.
- Reliability: The Reader should operate reliably without significant errors or invalid results.
Reported Device Performance (from the document, primarily from the Analytical Performance section, not provided here but typically found in a full 510(k) submission):
- Analytical Sensitivity and Specificity: The document implies that the analytical performance (e.g., limit of detection, cross-reactivity) of the test card itself is unchanged, as the card hasn't been modified. The analytical performance of the reader with the new software would be demonstrated by its ability to accurately read a range of low-positive and negative samples consistently.
- Reader Equivalence: The submission aims to demonstrate that the modified Reader is substantially equivalent to the predicate (K162642) through comparative studies, which would show consistent reading of results between the two reader versions.
- "Walk Away" Mode Functionality: The new mode would have been tested to ensure it correctly times and reads the assay at the appropriate interval.
Since comprehensive performance data tables are not in the provided text, a complete table of acceptance criteria and reported numbers cannot be created. The document focuses on declaring substantial equivalence based on the software change.
2. Sample Size Used for the Test Set and Data Provenance
The provided document describes the software modification and its comparison to the predicate device. It states, "The purpose of this Special 510k submission is to bring to market a modification of the software contained on the Alere™ Reader. There have been no changes to the Alere BinaxNOW® Influenza A & B Card 2 test."
This implies that the clinical performance data (sensitivity and specificity for influenza detection) would primarily come from the predicate device's original studies (K162642) or general knowledge of the Alere BinaxNOW® Influenza A & B Card 2 assay's performance.
For the software modification itself, the typical studies would involve:
- Analytical Studies: Testing the new reader's ability to interpret positive and negative control cards, as well as cards with varying antigen concentrations (potentially low-positive). These studies would use a specific number of test cards, but this number is not provided in the excerpt.
- Comparison Studies (Reader vs. Predicate Reader): Testing both the modified reader and the predicate reader on the same set of test cards (potentially clinical samples or spiked samples) to ensure concordance. The sample size for such a comparison is not provided in the excerpt.
Data Provenance: Not explicitly stated for specific test sets related to the software modification. Clinical performance characteristics mentioned (for the assay) were established during the 2015-2016 influenza season.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
For this type of submission (software modification to an existing reader for an IVD), the "ground truth" for the reader's performance would likely be:
- Reference Method for Assay Results: For clinical performance, a "gold standard" laboratory method like cell culture or an FDA-cleared molecular assay (as mentioned in the Indications for Use) would be used to establish the true presence/absence of influenza in patient samples. This is for the assay's performance, not the reader's.
- Visual Interpretation: For evaluating the reader's accuracy, human visual interpretation by trained personnel (who are considered "experts" in reading the specific lateral flow assay) would often serve as a comparison, or the positive/negative status of contrived samples would be known from spiking.
The document does not provide specific details on the number or qualifications of experts used to establish ground truth for the reader's performance in this particular 510(k) submission.
4. Adjudication Method for the Test Set
The document does not specify any adjudication method for test sets related to the software modification. For analytical studies comparing reader performance, adjudication might involve a third reader or a consensus if discrepancies arise between the reader and a human interpreter. However, this is not explicitly stated.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
No. This device is an automated reader for a rapid influenza antigen test. It is not an AI-assisted diagnostic tool designed to improve human reader performance. The Alere™ Reader replaces human visual interpretation of the test card. Its purpose is to provide an objective, automated reading of the results from the immunochromatographic assay. Therefore, an MRMC comparative effectiveness study comparing human readers with and without AI assistance is not applicable to this device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, implicitly. The Alere™ Reader is a standalone device in the sense that it automatically interprets the test card and reports a result (positive, negative, or invalid) without human interpretation of the test lines. The human interaction is limited to inserting the card and reading the displayed result. The "algorithm" is the reader's software that analyzes the intensity of the test and control lines. The studies supporting this submission would evaluate the performance of this algorithm (software) in correctly reading the test cards.
7. The Type of Ground Truth Used
For the assay's (Alere BinaxNOW® Influenza A & B Card 2) clinical performance (established during the predicate device's evaluation), the indications for use state: "Negative test results are presumptive and should be confirmed by cell culture or an FDA-cleared influenza A and B molecular assay." This indicates that cell culture or an FDA-cleared molecular assay would be considered the ground truth for determining actual influenza infection.
For the reader's performance (the focus of this specific 510(k) for software modification), the ground truth would likely be established by:
- Known concentrations of analyte: For analytical sensitivity.
- Visual interpretation by trained personnel: For concordance studies of the reader against human interpretation of the test card.
- Results from the predicate reader: For demonstrating substantial equivalence of the modified reader.
8. The Sample Size for the Training Set
The document does not provide information about a specific training set. The Alere™ Reader's software likely uses image processing and pattern recognition algorithms that would have been developed and refined using a dataset of test cards (a "training set") to learn to identify and interpret the presence and intensity of test and control lines. However, the size or nature of such a training set is not disclosed in this regulatory summary.
9. How the Ground Truth for the Training Set Was Established
As with the training set size, the method for establishing ground truth for any training data used to develop the reader's software is not provided in this document. Typically, for such image-based interpretation systems, ground truth for training data would be established by:
- Manual annotation: Experienced individuals would visually inspect and label images of test cards (e.g., "positive for A," "negative," "invalid").
- Spiked samples with known concentrations: Cards created with precise amounts of antigen to represent known positive or negative results.
- Comparison to a gold standard: For cards from clinical samples, their true status would be confirmed by a reference method (e.g., PCR, cell culture).
§ 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.