ALERE INFLUENZA A & B TEST

K133637 · Alere Scarborough, Inc D/B/A Binax, Inc. · PSZ · Dec 18, 2013 · Microbiology

Device Facts

• Record ID: K133637
• Device Name: ALERE INFLUENZA A & B TEST
• Applicant: Alere Scarborough, Inc D/B/A Binax, Inc.
• Product Code: PSZ · Microbiology
• Decision Date: Dec 18, 2013
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3328
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

The Alere™ Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. 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.

Device Story

Lateral flow immunochromatographic assay; detects influenza A and B nucleoprotein antigens in respiratory specimens (NP swab, nasal swab, nasal wash/aspirate). Device uses solid-phase immobilized nucleoprotein-specific antibodies to capture viral antigens. Operator performs test; visual interpretation of results. Modification adds analytical reactivity data for H7N9 (A/Anhui/1/2013) to package insert. Device aids rapid differential diagnosis; negative results require confirmation by cell culture or molecular assay. Does not differentiate influenza A subtypes.

Clinical Evidence

Prospective multi-center study (2008-2009 season) with 470 nasal swab specimens from symptomatic patients of all ages. Compared to viral culture. Influenza A: 93.8% sensitivity (95% CI: 83.2-97.9%), 95.8% specificity (95% CI: 93.5-97.3%). Influenza B: 77% sensitivity (95% CI: 67.4-85.0%), 98.0% specificity (95% CI: 96.1-99.0%). Invalid rate 1.9%. Analytical studies included LOD determination, cross-reactivity with 54 microorganisms, and interference testing.

Technological Characteristics

Lateral flow immunochromatographic membrane assay. Components: monoclonal antibodies and control protein immobilized on membrane support, extraction reagent, Coated Reaction Tube. Form factor: test strip. Qualitative visual readout. No electronic components or software.

Indications for Use

Indicated for symptomatic patients of all ages for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens to aid in rapid differential diagnosis.

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™ Influenza A & B Test (K103610)

Submission Summary (Full Text)

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SPECIAL 510(k): Device Modification

OIR Review Memorandum (Decision Making Document is Attached)

To: Alere Scarborough Inc.

RE: K133637

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:

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

Alere™ Influenza A & B Test

510(k) number: K103610

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):

The modification presented in this special 510(k) consisted of expanded reactivity table to include reactivity information for the H7N9 influenza A virus. The firm tested the ability of the Alere Influenza A & B Test to detect H7N9 influenza A virus. The virus used (A/Anhui/1/2013) was obtained from the Centers for Disease Control and Prevention as non-infectious beta-propiolactone inactivated virus. A reactivity study was performed with the A/Anhui/1/2013 influenza strain at three dilutions run in triplicate. Each result was interpreted by two operators for a total of six determinations per dilution. The lowest level that generated positive results in all six determinations was identified as the reactivity concentration.

The reactivity concentration was determined to be $8.70 \times 10^{6} \mathrm{EID}_{50} / \mathrm{ml}$. The Alere Influenza A & B Test package insert has been updated to include the additional analytical reactivity information.

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

5. Comparison Information

Similarities

| | Predicate Device | Modified Device |
| --- | --- | --- |
| | Alere Influenza A & B Test (K103610) | Alere Influenza A & B Test (K133637) |
| Intended Use | The Alere Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal (NP) swab, nasal swab, and nasal wash/aspirate specimens. It is intended to | The Alere Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal (NP) swab, nasal swab, and nasal wash/aspirate specimens. It |
| | is intended to | is intended to |
| behavior | is a non-infectious or non-infectious | is a non-infectious or non-infectious |

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| | aid in the rapid differential diagnosis of influenza A and B viral infections. Negative test results should be confirmed by cell culture. | 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. |
| --- | --- | --- |
| Organism Detected | Influenza A virus and Influenza B virus | Same |
| Specimen Types | Nasal swabs | Same |
| Device Technology | Lateral flow immunochromatography | Same |
| Detection Mechanism | Solid phase immobilized nucleoprotein specific antibodies | Same |

## Differences

The package insert has been updated to include detection of the A/Anhui/1/2013 H7N9 virus in the analytical reactivity information section:

A/Anhui/1/2013 - A - H7N9 - 8.7x10⁶ EID₅₀/mL

Although this test has been shown to detect H7N9 virus cultured from positive human respiratory specimens, the performance characteristics of this device with clinical specimens that are positive for H7N9 influenza viruses have not been established. The Alere Influenza A & B Test can distinguish between influenza A and B viruses, but it cannot differentiate influenza A subtypes.

## 6. Design Control Activities Summary:

Analytical Reactivity Testing was conducted as described on Page 57 of the submission, "Analytical Reactivity".

A "Declaration of Conformity" statement was submitted for the manufacturing facility and validation activities and signed by the Senior Vice President of Clinical and Regulatory Affairs. The statements indicate that:

1. The manufacturing facility is in conformance with design control procedure requirements as specified in 21 CFR 820.30 and the records are available for review.
2. The validation activities, as required by the risk analysis, for the modification were performed by the designated individuals and the results demonstrated that the predetermined acceptance criteria were met.

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In conclusion, based on the results of the analytical reactivity testing the modified labeling is truthful and accurate. The changes do not affect the performance of the test and it is therefore substantially equivalent to the current cleared test.

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.