Alere BinaxNOW Influenza A & B Card 2, Alere Reader

K181853 · Alere Scarborough, Inc. · PSZ · Aug 8, 2018 · Microbiology

Device Facts

• Record ID: K181853
• Device Name: Alere BinaxNOW Influenza A & B Card 2, Alere Reader
• Applicant: Alere Scarborough, Inc.
• Product Code: PSZ · Microbiology
• Decision Date: Aug 8, 2018
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3328
• Device Class: Class 2

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 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.

Device Story

Device is an in vitro immunochromatographic assay for influenza A and B detection. Input: nasopharyngeal or nasal swab samples placed on test card. Operation: Alere Reader (camera-based) captures images of test card; analyzes intensity of sample and control lines. Modification: software update adds 'Robust Quant Algorithm' to mitigate false positives from non-specific binding (dark spots). If specific signal-to-noise conditions are met, system triggers parallel quantification; both original and new algorithms must validate result. Output: qualitative result (positive, negative, or invalid) displayed on screen. Used in clinical settings; operated by healthcare personnel. Benefits: improved specificity by reducing false positive Influenza A results.

Clinical Evidence

Regression testing performed on saved image files from the 2015-2016 clinical study (n=original study size). Reprocessing with new firmware identified two previously false positive Influenza A samples that correctly changed to negative, resulting in improved specificity. No changes to Influenza B results. Analytical study data reprocessing (n > 2000 tests) confirmed intended functionality by converting known false positives to negative results without creating new false results.

Technological Characteristics

Immunochromatographic membrane assay; lateral flow test strip in hinged cardboard card. Reader is a camera-based benchtop instrument. Connectivity via USB for printer and LIS/LIM data transmission. Software-based image analysis for line intensity detection.

Indications for Use

Indicated for qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal and nasal swab specimens to aid in rapid differential diagnosis of influenza A and B viral infections.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Alere BinaxNOW® Influenza A & B Card 2 and Alere™ Reader (K173502)

Submission Summary (Full Text)

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SPECIAL 510(k): Device Modification Decision Summary

To: Alere Scarborough, Inc.
RE: K181853

This 510(k) submission contains information/data on modifications made to the SUBMITTER'S own Class II, Class III or Class I devices requiring 510(k). The following items are present and acceptable (delete/add items as necessary):

1. The name and 510(k) number of the SUBMITTER'S previously cleared device:

Alere BinaxNOW Influenza A & B Card 2

510(k) number: K173502

2. Submitter's statement that the INDICATION/INTENDED USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling, and, if available, advertisements or promotional materials (labeling changes are permitted as long as they do not affect the intended use).

3. Description of the device MODIFICATION(S):

A software modification has been added to mitigate a low frequency failure mode associated with detectable but not visible dark spots within the Influenza A test line due to non-specific binding. The modification checks for a unique signal-to-noise ratio and implements an additional, parallel quantification algorithm if the specific conditions are detected. Both the original quantification algorithm and the triggered new algorithm must meet certain criteria in this situation to provide a valid result. Failure of the new algorithm to meet the necessary analysis conditions (when triggered) results in an invalid result. The purpose and effect of the change is to reduce the number of false positive Influenza A results. The Alere BinaxNOW Influenza A & B Card 2 assay package insert and Quick Reference Instructions (QRI) have not changed. The instrument user manual has been updated to include the software changes.

4. The FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed.

5. Comparison Information

A. Similarities

| | Predicate Device | Modified Device |
| --- | --- | --- |
| Features | Alere BinaxNOW Influenza A & B Card 2 (K173502) | Alere BinaxNOW Influenza A & B Card 2 (K181853) |
| 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 | Same |

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| | 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. | |
| --- | --- | --- |
| Sample Type | Nasopharyngeal and nasal swabs | Same |
| Assay Target | Nucleoprotein Antigen of Influenza A and B | Same |
| Instrumentation | Alere Reader | Same |
| Detection Format | The camera-based Reader detects the presence and identity of the 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. | Same |
| Internally Controlled? | Yes | Same |
| Assay Result | Qualitative | Same |
| Time to Result | 15 minutes | Same |

B. Differences

The Alere Reader user manual has been updated to identify minor changes to the software.

6. Design Control Activities Summary:

A risk assessment and hazard analysis of the device modification was conducted and documented according to applicable ISO standards as well as an internal Alere Scarborough Inc. Risk Management Process. The modification made to the software does not affect the assay procedure, and this change

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was not expected to impact the performance of the test or its safety and effectiveness. To confirm assay performance was not negatively impacted, Alere Scarborough performed the following validation studies:

A. Design Specification Validation Testing
B. Analytical Study Data Reprocessing
C. Regression Testing of Clinical Study Data

## Design Specification Validation Testing

Software design specifications were tested internally to verify the functionality of the requested changes prior to verification studies. Pass/Fail criteria were set for each design input and the results were summarized in the submission. There was one design specification that failed the criteria and cited as an unresolved anomaly. The unresolved anomaly does not affect the performance of the device. All other design specifications passed validation testing.

## Analytical Study Data Reprocessing

Saved image files from various analytical studies performed in support of 510(k) clearance and annual reactivity testing were reprocessed by the firmware that includes the new Robust Quant Algorithm. Eight different analytical study data sets comprised of over 2000 individual tests were reprocessed and compared to the results from the original studies. All documented changes to the original results following reprocessing supported the intended functionality of the new algorithm by changing known false positive results into negative results. There were no documented instances of the software modification creating new false results in these studies.

## Regression Testing of Clinical Study Data

Saved image files from the 2015-2016 Influenza season clinical study performed in support of 510(k) clearance were reprocessed by the firmware that utilized the new Robust Quant Algorithm. Results of the reprocessing were compared to the results from the original study. Two previously false positive samples changed from Influenza A positive to Influenza A negative resulting in a slightly improved specificity for the test running the new firmware. No other changes to Influenza A results were identified and no changes to Influenza B results were observed after applying the new algorithm. The results of the clinical study data regression testing do not raise any concerns regarding effects of the new firmware on the performance of the device.

## 7. Truthful and Accurate Statement, a 510(k) Summary or Statement and the Indications for Use Enclosure.

The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the submitter's description of the particular modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The submitter has provided the design control information as specified in The New 510(k) Paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared device.