(200 days)
Not Found
No
The description of the Alere™ Reader indicates it uses a camera to analyze the intensity of lines on the test card and display results. While this involves image processing, there is no mention of AI or ML algorithms being used for interpretation or analysis. The process described appears to be a deterministic analysis of line intensity against predefined thresholds.
No
The device is an in vitro immunochromatographic assay intended for the qualitative detection of influenza A and B nucleoprotein antigens, meaning it is a diagnostic tool, not a therapeutic device. It aids in diagnosis but does not provide therapy or treatment.
Yes
The device, the Alere BinaxNOW® Influenza A & B Card 2, is described as an "in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens" and is "intended to aid in the rapid differential diagnosis of influenza A and B viral infections." This explicitly states its purpose is for diagnosis.
No
The device description clearly outlines a physical test card (immunochromatographic assay) and a separate physical reader (camera-based instrument) that are both essential components of the system. While the reader utilizes software for interpretation, the core medical device functionality relies on both hardware and the physical assay.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device 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." This clearly indicates that the device is used outside of the body to analyze biological samples for diagnostic purposes.
- Device Description: The description details a "test strip" and a "test card" that are used to perform an assay on a "swab specimen." This further supports the in vitro nature of the device.
- Purpose: The device is intended "to aid in the rapid differential diagnosis of influenza A and B viral infections." This is a diagnostic purpose, which is a key characteristic of IVDs.
The fact that it uses a camera-based instrument (the Alere™ Reader) to interpret the results of the in vitro assay does not change its classification as an IVD. The core diagnostic test is performed on the biological sample outside the body.
N/A
Intended Use / Indications for Use
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 test results must be read by the Alere™ Reader.
Performance characteristics for influenza A were established during the 2015-2016 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.
Product codes (comma separated list FDA assigned to the subject device)
PSZ
Device Description
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. This 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. Sample is added to the top of 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 provided separately for result interpretation. The Alere™ Reader enables direct data entry of User ID, Subject ID, and retention of test results, but is interpretation only. All Alere BinaxNOW® Influenza A & B Card 2 assay steps are performed outside of the reader and the card assay is inserted at the 15 minute read time.
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 a completed Alere BinaxNOW® Influenza A & B Card 2 assay, analyzes the intensity of the sample and control line and displays the results (positive, negative or invalid) on a display screen is intended as a means of user interface informing the user how to operate the reader and to display test result, 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal (NP) swab and nasal swab specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Professional use, in a medical laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A total of 585 evaluable specimens were evaluated with Alere BinaxNOW® Influenza A & B Card 2 with results read by the Alere™ Reader. Of the 585 specimens, 565 specimens had valid test results.
Of the total specimens collected, fifty-six percent (56%) of the samples were from females and forty-four percent (44%) from males.
Performance was compared against an FDA cleared influenza real-time Polymerase Chain Reaction (RT-PCR) assay.
Specimens were collected at twelve (12) investigational sites throughout the U.S. from patients presenting with flu-like symptoms.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Study:
Sample Size: 565 evaluable specimens with valid results.
Study Type: Multi-center, prospective clinical study conducted at twelve (12) U.S. study centers during the 2015-2016 respiratory season.
Key Results:
Influenza Type A: Sensitivity: 84.3% (95% CI: 77.2%, 89.5%), Specificity: 94.7% (95% CI: 92.1%, 96.4%)
Influenza Type B: Sensitivity: 89.5% (95% CI: 78.9%, 95.1%), Specificity: 99.4% (95% CI: 98.3%, 99.8%)
Analytical Sensitivity (Limit of Detection - LoD) Study:
Evaluated different concentrations of five (5) strains of influenza A and three (3) strains of influenza B to identify the concentration that produces positive results approximately 95% of the time.
Results: Concentrations for 95% detection ranged from 1:1500 dilution (A/H7N9) to 3.16 x 10^4 TCID50/mL (A/H1N1) for Influenza A, and from 4.27 x 10^3 TCID50/mL to 1.47 x 10^6 TCID50/mL for Influenza B.
Analytical Reactivity (Inclusivity) Study:
Tested various influenza A and B strains at concentrations from 100 to 10^6 TCID50/mL. All tested strains produced positive results (3/3).
Analytical Specificity (Cross-Reactivity) Study:
58 commensal and pathogenic microorganisms (41 bacteria, 16 viruses and 1 yeast) were tested. All were negative at specified concentrations (ranging from 10^3 to 10^40 cells/mL or CFU/mL for bacteria, 10^4 to 10^8 TCID50/mL or CEID50/mL for viruses, and 10^6 cells/mL for yeast). Some cross-reactivity was observed at very high concentrations for certain bacteria, but not at diluted concentrations.
Interfering Substances Study:
Evaluated 20 substances. None were found to affect test performance at the specified concentrations.
Reproducibility Study:
Conducted by operators from three (3) sites over five (5) different days using panels of blind coded specimens (negative, low positive, moderate positive).
Results:
Influenza A: Moderate Positive: 100% agreement (90/90), Low Positive: 100% agreement (90/90), High Negative: 96.6% agreement (86/89).
Influenza B: Moderate Positive: 100% agreement (90/90), Low Positive: 100% agreement (89/89), High Negative: 97.8% agreement (88/90).
True Negative: 100% agreement (90/90).
No significant differences observed within run, between run, between sites, or between operators.
Inhibition by Other Microorganisms Study:
Evaluated test performance in the presence of non-influenza respiratory pathogens (Adenovirus Type 1, Rhinovirus Type 1A, Respiratory Syncytial Virus, Type B). No impact on test performance was observed.
Inhibition by High Levels of Influenza A and B Study:
Evaluated test performance in the presence of high levels of influenza A and B, including co-infection scenarios. No impact on test performance was observed.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Influenza Type A:
Sensitivity: 84.3% (95% CI: 77.2%, 89.5%)
Specificity: 94.7% (95% CI: 92.1%, 96.4%)
Influenza Type B:
Sensitivity: 89.5% (95% CI: 78.9%, 95.1%)
Specificity: 99.4% (95% CI: 98.3%, 99.8%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
BD Veritor System for Rapid Detection of Flu A+B, K160161.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol featuring three stylized human profiles facing to the right, stacked one behind the other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
April 10, 2017
Sara Hallowell, M.S. Regulatory Affairs Specialist Alere Scarborough, Inc. 10 Southgate Road Scarborough, Maine 04074
Re: K162642
Trade/Device Name: Alere BinaxNOW® Influenza A & B Card 2 and Alere™ Reader Regulation Number: 21 CFR 866.3328 Regulation Name: Influenza virus antigen detection test system Regulatory Class: Class II Product Code: PSZ Dated: February 7, 2017 Received: February 9, 2017
Dear Ms. Hallowell:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21
1
CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely vours.
Steven R. Gitterman -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K162642
Device Name
Alere BinaxNOW® Influenza A & B Card 2 and Alere™ Reader
Indications for Use (Describe)
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 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.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| -------------------------------------------------------------------------------------------------------- | ---------------------------------------------------------------------------- |
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510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K162642
SUBMITTER
Alere Scarborough, Inc. 10 Southgate Road Scarborough, Maine 04074 Establishment Registration Number: 1221359
PRIMARY CONTACT PERSON
Sara Hallowell (207) 730-5786 (office) (207) 730-5767 (FAX) sara.hallowell@alere.com (email)
SECONDARY CONTACT PERSON
Angela Drysdale (207) 730-5737 (office) (207) 730-5767 (FAX) angela.drysdale@alere.com (email)
DATE PREPARED
April 4, 2017
TRADE NAME Alere BinaxNOW® Influenza A & B Card 2 Alere™ Reader
COMMON NAME
BinaxNOW® Influenza A & B 2, BinaxNOW® Card 2, Alere Influenza A & B 2, BinaxNOW® Flu Card 2/ Reader, Lateral Flow Reader, Card Test Analyzer
CLASSIFICATION NAME
Influenza Virus Antigen Detection Test System (per 21 CFR 866.3328)
CLASSIFICATION
Class II
PRODUCT CODE
PSZ Devices Detecting Influenza A, B, and C Virus Antigens
PANEL
Microbiology (83)
4
PREDICATE DEVICE
BD Veritor System for Rapid Detection of Flu A+B, K160161.
DEVICE DESCRIPTION
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. This 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. Sample is added to the top of 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 provided separately for result interpretation. The Alere™ Reader enables direct data entry of User ID, Subject ID, and retention of test results, but is interpretation only. All Alere BinaxNOW® Influenza A & B Card 2 assay steps are performed outside of the reader and the card assay is inserted at the 15 minute read time.
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 a completed Alere BinaxNOW® Influenza A & B Card 2 assay, analyzes the intensity of the sample and control line and displays the results (positive, negative or invalid) on a display screen is intended as a means of user interface informing the user how to operate the reader and to display test result, 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.
INTENDED USE
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 nasopharvngeal (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 test results must be read by the Alere™ Reader.
Performance characteristics for influenza A were established during the 2015-2016 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 enidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infections 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.
TECHNICAL CHARACTERISTICS
Alere BinaxNOW® Influenza A & B Card 2 and the predicate device, BD Veritor System for Rapid Detection of Flu A+B, have the same intended use, indications for use, and utilize similar basic principles of operation. They are both chromatographic tests for the qualitative detection of influenza A and B viral antigens.
DEVICE COMPARISON
Alere BinaxNOW® Influenza A & B Card 2 was compared to the legally marketed predicate device, the BD Veritor System for Rapid Detection of Flu A+B.
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REVISED 510(K) SUMMARY
| Parameter | Alere BinaxNOW® Influenza A & B Card 2 | BD Veritor System for Rapid Detection of Flu A+B (K160161) |
|---|---|---|
| FDA Product Code | PSZ | Same |
| Assay Target | Influenza A and B nucleoprotein antigens | Same |
| Intended Use | 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 test results must be read by the Alere™ | ||
| Reader. | The BD Veritor System for Rapid Detection of Flu | |
| A+B is a rapid chromatographic immunoassay | ||
| for the direct and qualitative detection of | ||
| influenza A and B viral nucleoprotein antigens | ||
| from nasal and nasopharyngeal swabs of | ||
| symptomatic patients. The BD Veritor System for | ||
| Rapid Detection of Flu A+B (also referred to as | ||
| the BD Veritor System and BD Veritor System Flu | ||
| A+B) is a differentiated test, such that influenza | ||
| A viral antigens can be distinguished from | ||
| influenza B viral antigens from a single | ||
| processed sample using a single device. The test | ||
| is to be used as an aid in the diagnosis of | ||
| influenza A and B viral infections. A negative test | ||
| is presumptive and it is recommended that these | ||
| results be confirmed by viral culture or an FDA- | ||
| cleared influenza A and B molecular assay. | ||
| Outside the U.S., a negative test is presumptive | ||
| and it is recommended that these results be | ||
| confirmed by viral culture or a molecular assay | ||
| cleared for diagnostic use in the country of use. | ||
| FDA has not cleared this device for use outside of | ||
| the U.S. 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. The test is not intended | ||
| to detect influenza C antigens. | ||
| 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. | Performance characteristics for influenza A and | |
| B were established during January through | ||
| March of 2011 when influenza viruses A/2009 | ||
| H1N1, A/H3N2, B/Victoria lineage, and | ||
| B/Yamagata lineage were the predominant | ||
| influenza viruses in circulation according to the | ||
| Morbidity and Mortality Weekly Report from the | ||
| CDC entitled "Update: Influenza Activity — | ||
| United States, 2010-2011 Season, and | ||
| Composition of the 2011-2012 Influenza | ||
| Vaccine." Performance characteristics may vary | ||
| against other emerging influenza viruses. | ||
| 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. | If infection with a novel influenza 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 the state or local health department | ||
| for testing. Virus culture should not be attempted | ||
| in these cases unless a BSL 3+ facility is available | ||
| to receive and culture specimens. | ||
| Intended Environment | ||
| for Use | Professional use, in a medical laboratory | Professional use, in a medical laboratory or |
| point-of-care | ||
| Instrumentation | Alere™ Reader used in conjunction with device. | BD Veritor System Reader |
| Parameter | Alere BinaxNOW® Influenza A & B | |
| Card 2 | BD Veritor System for Rapid Detection of Flu | |
| A+B (K160161) | ||
| Assay Information | ||
| Sample Type | Nasopharyngeal and nasal swabs | Same |
| Technology | Immunochromatographic | Same |
| Detection Format | The camera based instrument detects the | |
| presence and identity of a completed Alere | ||
| BinaxNOW® Influenza A & B Card 2 assay, | ||
| analyzes the intensity of the sample and control | ||
| line and reports the results (positive, negative | ||
| or invalid) on a display screen. | An optoelectronic instrument that uses a | |
| reflectance-based measurement method to | ||
| evaluate the line signal intensities at each of the | ||
| spatially defined test and control line positions, | ||
| interprets the results using a scoring algorithm, | ||
| and reports a positive, negative, or invalid result | ||
| on the LCD screen based on pre-set thresholds. | ||
| Internal Control | Yes | Yes |
| Assay Result | Qualitative | Same |
| Time to Result | 15 minutes | 10 minutes |
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PERFORMANCE SUMMARY
CLINICAL STUDY
The clinical performance of Alere BinaxNOW® Influenza A & B Card 2 was established in a multi-center, prospective clinical study conducted at twelve (12) U.S. study centers during the 2015-2016 respiratory season.
A total of twelve (12) investigational sites throughout the U.S. participated in the study. To be enrolled in the study, patients had to be presenting at the participating study centers with flu-like symptoms. Either two nasal swabs were collected from one nostril from each patient with flu-like symptoms using standard collection methods and tested using the Alere BinaxNOW® Influenza A & B Card 2 assay. An FDA cleared influenza real-time Polymerase Chain Reaction (RT-PCR) assay was utilized as the comparator method for this study.
At all sites, one nasal or nasopharyngeal swab was eluted in elution and the other swab was eluted in 1mL of viral transport media (VTM). The swab elution was tested on Alere BinaxNOW® Influenza A & B Card 2, according to product instructions. All twelve (12) sites shipped the VTM sample to a central testing laboratory for RT-PCR.
A total of 585 evaluable specimens were evaluated with Alere BinaxNOW® Influenza A & B Card 2 with results read by the Alere™ Reader. Of the 585 specimens, 565 specimens had valid test results.
Of the total specimens collected, fifty-six percent (56%) of the samples were from females and forty-four percent (44%) from males. Twenty-seven percent (27%) of the population tested was ≤ 5 years of age, twenty-eight percent (28%) was 6-21 years of age, and forty-five percent (45%) was > 21 years.
Compared to the comparator method, the performance of Alere BinaxNOW® Influenza A & B Card 2 for influenza A and influenza B are provided below.
Performance of Alere BinaxNOW® Influenza A & B Card 2 Against the Comparator Method
| Influenza Type A | |||
|---|---|---|---|
| Comparator Method | |||
| Alere BinaxNOW® | |||
| Influenza A & B Card 2 | Positive | Negative | Total |
| Positive | 113 | 23 | 136 |
| Negative | 21 | 408 | 429 |
| Total | 134 | 431 | 565 |
| Sensitivity: $113/134 = 84.3%$ | |||
| (95% CI: 77.2%, 89.5%) | |||
| Specificity: $408/431 = 94.7%$ | |||
| (95% CI: 92.1%, 96.4%) |
| 429 | Negative | 6 | 505 |
|---|---|---|---|
| 565 | Total | 57 | 508 |
| Sensitivity: | |||
| Specificity: | 51/57 = 89.5% | ||
| (95% CI: 78.9%, 95.1%) |
505/508 = 99.4%
(95% CI: 98.3%, 99.8%) | |
ard 2
Positive
51
Total
54 511 ર્સ્ટર
Comparator Method
Negative
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ANALYTICAL STUDIES
ANALYTICAL SENSITIVITY
Alere BinaxMOW® Influenza A & B Card 2 limit of detection (LOD or C35), defined as the concentration of influenza virus that produces positive Alere BinaxNOW® Influenza A & B Card 2 results approximately 95% of the time, was identified by evaluating different concentrations of five (5) strains of influenza A and three (3) strains of influenza B. The concentrations identified as the LOD (or C95) levels for each strain are listed below.
Limit of Detection (LoD) Study Results
| Strain | Influenza A Subtype or
Influenza B Genetic Lineage | Concentration
TCID50/mL | % Detected |
|-----------------------------|-------------------------------------------------------|----------------------------|------------|
| A/Anhui/2013 (Inactivated)* | A/H7N9 | 1:1500 | 95% |
| A/Indiana/10/2011 | A/H3N2v | $3.67 x 10^1$ | 95% |
| A/California/7/2009 | A/2009 H1N1 (pdm) | $5.94 x 10^3$ | 95% |
| A/Perth/16/2009 | A/H3N2 | $1.68 x 10^4$ | 95% |
| A/Puerto Rico/8/34 | A/H1N1 | $3.16 x 10^4$ | 95% |
| B/Massachusetts/02/12 | B Yamagata Lineage | $1.47 x 10^6$ | 95% |
| B/Nevada/03/2011 | B Victoria Lineage | $9.72 x 10^3$ | 95% |
| B/Malaysia/2506/2004 | B Victoria Lineage | $4.27 x 10^3$ | 95% |
Note: 10µl of each virus dilution was coated onto a swab.
*The LOD is reported as a dilution factor from the inactivated stock. The concentration of the virus stock prior to inactivation was 1010.9 EID50/mL.
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ANALYTICAL REACTIVITY (INCLUSIVITY)
The following influenza A and B strains were tested (3/3) and produced positive Alere BinaxNOW® Influenza A & B Card 2 test results at concentrations ranging from 100 to 106 TCID50/mL
| Influenza Strain | Influenza A Subtype
or Influenza B
Genetic Lineage | Concentration
TCID50/mL |
|--------------------------|----------------------------------------------------------|----------------------------|
| A/Brisbane/59/2007 | A/H1N1 | 8.35 x 101 |
| A/California/4/2009 | A/H1N1 (pdm) | 3.68 x 103 |
| A/Maryland/04/2011 | A/H1N1 (pdm) | 1.07 x 102 |
| A/New Caledonia/20/1999 | A/H1N1 | 2.08 x 102 |
| A/New Jersey/8/1976 | A/H1N1 | 1.04 x 101 |
| A/New York/18/2009 | A/H1N1 (pdm) | 1.41 x 102 |
| A/Solomon Islands/3/2006 | A/H1N1 | 5.28 x 101 |
| A/WSN/33 | A/H1N1 | 5.00 x 102 |
| A/Texas/018/2014 | A/H1N1 | 7.90 x 103 |
| A/Texas/002/2014 | A/H1N1 | 1.70 x 103 |
| A/Aichi/2/68 | H3N2 | 7.90 x 103 |
| A/Brisbane/10/2007 | H3N2 | 3.68 x 100 |
| A/Hong Kong/8/68 | H3N2 | 2.41 x 101 |
| A/Port Chalmers/1/73 | H3N2 | 1.58 x 104 |
| A/Texas/50/2012 | H3N2 | 1.06 x 100 |
| A/Victoria/3/75 | H3N2 | 1.58 x 101 |
| A/Victoria/361/2011 | H3N2 | 2.11 x 100 |
| A/Wisconsin/67/2005 | H3N2 | 2.63 x 101 |
| B/Bangladesh/3333/2007 | Yamagata Lineage | 2.11 x 105 |
| B/Brisbane/60/2008 | Victoria Lineage | 3.41 x 105 |
| B/Florida/04/2006 | Yamagata Lineage | 2.97 x 105 |
| B/Lee/40 | Victoria Lineage | 6.81 x 103 |
| B/Maryland/1/59 | Yamagata Lineage | 7.90 x 103 |
| B/Montana/05/2012 | Victoria Lineage | 2.51 x 106 |
| B/Ohio/1/2005 | Victoria Lineage | 3.40 x 103 |
| B/Russia/69 | Yamagata Lineage | 5.93 x 105 |
| B/Texas/06/2011 | Yamagata Lineage | 1.47 x 106 |
| B/Victoria/304/2006 | Victoria Lineage | 1.58 x 105 |
| B/Victoria/504/2000 | Victoria Lineage | 6.81 x 104 |
| B/Wisconsin/01/2010 | Yamagata Lineage | 1.45 x 104 |
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ANALYTICAL SPECIFICITY (CROSS-REACTIVITY)
To determine the analytical specificity of Alere BinaxNOW® Influenza A & B Card 2 test, 58 commensal and pathogenic microorganisms (41 bacteria, 16 viruses and 1 yeast) that may be present in the nasal cavity or nasopharynx were tested. All of the following microorganisms were negative when tested at concentrations ranging from 103 to 1040 cells/mL or CFU/mL (bacteria), 104 to 108 TCIDso/mL or CEIDso/mL (viruses), and 10% cells/mL (yeast).
Viruses
Bacteria
Acinetobacter calcoaceticus Bacteroides fragilis Bordetella pertussis Chlamydia pneumoniae Corynebacterium diptheriae Enterococcus faecalis Escherichia coli Gardnerella vaginalis Haemophilus influenza Haemophilus parainfluenza Klebsiella pneumonia Lactobacillus casei Lactobacillus plantarum Legionella pneumophilia Listeria monocytogenes1 Moraxella/Branhamella catarrhalis Mycobacterium avium Mycobacterium intracellulare Mycobacterium tuberculosis Mycoplasma pneumonia5 Neisseria gonorrhoeae Neisseria meningitides Neisseria mucosa2 Neisseria sicca3 Neisseria subflava Peptostreptococcus anaerobius Proteus mirabilis Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens4 Staphylococcus aureus Staphylococcus epidermidis Streptococcus mutans Streptococcus pneumonia Streptococcus salivarius Streptococcus sanguinis Streptococcus Group A Streptococcus sp. Gp. B Streptococcus sp. Gp. C Streptococcus sp. Gp. F Streptococcus sp. Gp. G
Adenovirus type 1 Adenovirus type 7 Cytomegalovirus6A Human Coronavirus OC43 Human Coronavirus 229E6B Enterovirus/Coxsackievirus B4 Human Cytomegalovirus strain AD-16960 Human metapneumovirus Rhinovirus type 1A Measles virus, strain Edmonston Mumps virus, strain Enders Parainfluenza virus 1 Parainfluenza virus 2 Parainfluenza virus 3 Respiratory Syncytial virus, type B, strain 18537 Epstein Barr virus, strain P-3
Yeast Candida albicans
1Flu A positive result obtained at 7.23 x 10° cells/mL; concentration diluted to 7.23 x 10°cells/mL and generated a negative result.
2Flu A positive result obtained at 9.4 x 10 cells/mL; concentration diluted to 9.4 x 10° cells/mL and generated a negative result.
3Flu A positive result obtained at 1.0 x 1010 cells/mL; concentration diluted to 1.0 x 10° cells/mL and generated a negative result.
"Flu A positive Alere™ Reader result obtained at 6.5 x 10° cells/ml; concentration diluted to 6.5 x 10° cells/ml and generated a negative result.
5 Mycoplasma pneumonia 103 was the maximum cfu/mL that could be achieved for growth.
^ firuses were tested at concentrations lower than the recomment on received from the vendor. Viral stocks were tested at the highest achievable titer allowed by the vendor stock concentration.
-
6A Cytomegalovirus at 8.89x104 TCID50/mL
-
6B Human Coronavirus 229E at 2.81x104 TCID50/mL
-
60 Human Cytomegalovirus strain AD-169 at 8.89x104 TCIDso/mL
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INTERFERING SUBSTANCES
The following substances, naturally present in respiratory specimens or artificially introduced into the nasal cavity/ nasopharynx were evaluated with Alere BinaxNOW® Influenza A & B Card 2 at the concentrations listed below and were found not to affect test performance.
| Substance | Concentration |
|---|---|
| Mucin | 2% (w/v) |
| Whole Blood | 1% (v/v) |
| Sinus Buster Nasal Spray | 20% (v/v) |
| NeoSynephrine Cold & Sinus Extra Strength Spray | 20% (v/v) |
| Zicam Extreme Congestion Relief | 20% (v/v) |
| 4-acetamidophenol | 203 µg/mL |
| Acetylsalicylic acid (aspirin) | 652 µg/mL |
| Albuterol | 399 ng/mL |
| Chlorpheniramine | 142 ng/mL |
| Dexamethasone | 0.8 mg/mL |
| Dextromethorphan | 1 µg/mL |
| Diphenhydramine | 5 µg/mL |
| Doxylamine Succinate | 232 ng/mL |
| Ephedrine | 276 ng/mL |
| Flunisolide | 6.8 ng/mL |
| Guaiacol glycerol ether (pseudoephedrine) | 3.58 ng/mL |
| Mupirocin | 12 mg/mL |
| Oxymetazoline | 0.6 mg/mL |
| Phenylephrine | 12 mg/mL |
| Relenza | 284 ng/mL |
| Rebetol | 4.4 µg/mL |
| Rimantadine | 0.28 ng/mL |
| Tamiflu | 1.102 µg/mL |
| Tobramycin | 2.4 mg/mL |
| Triamcinolone | 40 µg/mL |
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REPRODUCIBILITY
A reproducibility study of Alere BinaxNOW® Influenza A & B Card 2 was conducted by operators from three (3) sites using panels of blind coded specimens containing negative (below the limit of detection). Jow positive (at the limit of detection), and moderate positive (above the limit of detection) influenza A and B viral samples. Participants tested the sample panels over five (5) different days.
The percent agreement with expected results, across the influenza A moderate positive, low positive, and high negative samples were 100% (90/90), 100% (90/90) and 96.6% (86/89), respectively. The percent with expected result for the influenza B moderate positive, and high negative samples were 100% (90/90), 100% (89/89) and 97.8% (88/90), respectively. All of the true negative samples (90) generated negative test results.
There were no significant differences observed within run (replicates tested by one operator), between run (five different days), between sites (three sites), or between operators (six operators).
| | Sample Type | Site 1 | Site 2 | Site 3 | Overall
% Agreement
with Expected
Results |
|-------------|-------------------|------------------|------------------|------------------|----------------------------------------------------|
| Influenza A | Moderate Positive | 100%
(30/30) | 100%
(30/30) | 100%
(30/30) | 100%
(90/90) |
| | Low Positive | 100%
(30/30) | 100%
(30/30) | 100%
(30/30) | 100%
(90/90) |
| | High Negative | 100%
(29/29)1 | 93.3%
(28/30) | 96.7%
(29/30) | 96.6%
(86/89) |
| Influenza B | Moderate Positive | 100%
(30/30) | 100%
(30/30) | 100%
(30/30) | 100%
(90/90) |
| | Low Positive | 100%
(30/30) | 100%
(30/30) | 100%
(29/29)2 | 100%
(89/89) |
| | High Negative | 100%
(30/30) | 93.3%
(28/30) | 100%
(30/30) | 97.8%
(88/90) |
| | True Negative | 100%
(30/30) | 100%
(30/30) | 100%
(30/30) | 100%
(90/90) |
Site-To-Site Qualitative Results - Percent Agreement with Expected Results
10ne sample generated an invalid result and was not re-tested.
20ne sample generated a positive Flu A and Flu B result, was considered invalid and was not re-tested.
INHIBITION BY OTHER MICROORGANISMS
Alere BinaxNOW® Influenza A & B Card 2 test performance in the presence of non-influenza respiratory pathogens was evaluated. Vendor provided stocks of influenza A and B strains were diluted in UTM to approximately 2 times the limit of detection. Contrived influenza A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. The following non-influenza viruses were tested (3/3) at the concentration provided in the table below and were found not to affect test performance.
| Virus Panel | Concentration
(TCID50/mL) |
|---------------------------------------------------|------------------------------|
| Adenovirus Type 1 | 1.58 x 107 |
| Rhinovirus Type 1A | 1.58 x 108 |
| Respiratory Syncytial Virus, Type B, Strain 18537 | 8.89 x 105 |
INHIBITION BY HIGH LEVELS OF INFLUENZA A AND B
Alere BinaxNOW® Influenza A & B Card 2 test performance in the presence of high levels of influenza A and B was evaluated. Vendor provided stocks of influenza A and B strains were diluted in UTM to approximately 2 times the limit of detection. Contrived influenza A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. To create the co-infection swabs, diluted influenza A (at a concentration approximately 20 times the LoD) was added to
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the near LoD Flu B swab. Likewise, diluted influenza B (at a concentration approximately 20 times the LoD) was added to the near LoD Flu A swab. No impact on test performance was observed.
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