BD VERITOR SYSTEM FOR THE RAPID DETECTION OF FLU A+B

K132256 · Becton, Dickinson and Company · PSZ · Aug 7, 2013 · Microbiology

Device Facts

• Record ID: K132256
• Device Name: BD VERITOR SYSTEM FOR THE RAPID DETECTION OF FLU A+B
• Applicant: Becton, Dickinson and Company
• Product Code: PSZ · Microbiology
• Decision Date: Aug 7, 2013
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.3328
• Device Class: Class 2

Indications for Use

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 nasopharyngeal wash, aspirate and swab in transport media samples from symptomatic patients. The BD Veritor System for Rapid Detection of 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. 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 and B nasopharyngeal (NP) washes/aspirates 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. Performance characteristics for influenza A and B NP swabs in transport media were established during January through April of 2012 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, 2011-2012 Season, and Composition of the 2012-2013 Influenza Vaccine.” Performance characteristics may vary against other emerging influenza viruses. 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.

Device Story

Rapid chromatographic immunoassay for qualitative detection of influenza A and B viral nucleoprotein antigens. Input: nasopharyngeal wash, aspirate, or swab in transport media. Process: specimen mixed with mucolytic reagent; applied to test device; antigens bind to colloidal-gold conjugated antibodies; complex migrates to reaction area. Reader device uses proprietary algorithm to subtract nonspecific signal from negative control line; compares resultant signal to pre-selected cutoff. Output: positive/negative result for Flu A and Flu B. Used in clinical settings; aids diagnosis; negative results require confirmation by culture or molecular assay.

Clinical Evidence

No new clinical data presented. The submission relies on previously established performance characteristics for NP washes/aspirates (2011) and NP swabs (2012) during predominant influenza circulation periods.

Technological Characteristics

Immunochromatographic assay. Opto-electronic reader for automated interpretation of test/control line intensity. Qualitative output. Total assay time approximately 10 minutes. Includes procedural and internal controls.

Indications for Use

Indicated for symptomatic patients requiring rapid qualitative detection of influenza A and B viral nucleoprotein antigens from nasopharyngeal wash, aspirate, or swab in transport media. Not intended for influenza C detection.

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

• BD Veritor™ System for Rapid Detection of Flu A+B POC (120049 and k121797)

Submission Summary (Full Text)

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SPECIAL 510(k)

Device Modification Decision Summary

To: BD Diagnostics RE: K132256

This 510(k) submission contains information/data on modifications made to the SUBMITTER'S own Class II device requiring 510(k). The following items are present and acceptable

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

Trade Name: BD Veritor™ System Flu A+B assay Clinical kit

510(k) number: K120049, K121797

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.

3. A description of the device MODIFICATION(S). The modification presented in this 510(k) is the inclusion of the H7N9 influenza A virus strain below, to the analytical sensitivity information. The submitter tested the ability of the BD Veritor System Flu A+B test to detect the H7N9 influenza A virus. The virus used (A/Anhui/1/2013) was inactivated viral material in clarified allontoic fluid from chicken eggs obtained from the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza, US Centers for Disease Control and Prevention. Analytical sensitivity testing was done at 10 fold dilutions from the stock received from CDC and was tested in triplicate using the BD Veritor System Flu A+B test to establish the approximate level for the LOD:

- 7.94 x 10⁸ CEID₅₀/mL
- 7.94 x 10⁷ CEID₅₀/mL
- 7.94 x 10⁶ CEID₅₀/mL
- 3.97 x 10⁶ CEID₅₀/mL
- 1.99 x 10⁶ CEID₅₀/mL
- 7.94 x 10⁵ CEID₅₀/mL
- 7.94 x 10⁴ CEID₅₀/mL

(CEID₅₀/mL = 50% Chicken Egg Infectious Dose)

A final dilution was prepared and tested in replicates of 60:

- 5.42 x 10⁶ CEID₅₀/mL

The limit of detection of the BD Veritor System Flu A+B test with A/Anhui/1/2013 H7N9 was 5.42 x 10⁶ CEID₅₀/mL with a positivity of 98.3% (59/60).

The BD Veritor System Flu A+B Clinical kit package insert has been updated to include the additional analytical sensitivity information.

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

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5. Comparison Information (similarities and differences) to applicant's legally marketed predicate device including, labeling, intended use, and physical characteristics:

Similarities

| Device Characteristics | Predicate Device: BD Veritor System Flu A+B assay (K120049, K121797) | New Device: BD Veritor System Flu A+B assay Clinical kit (K132256) |
| --- | --- | --- |
| Intended Use | 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 nasopharyngeal wash, aspirate and swab in transport media samples from symptomatic patients. The BD Veritor System for Rapid Detection of 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. 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 and B nasopharyngeal (NP) washes/aspirates 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 | 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 nasopharyngeal wash, aspirate and swab in transport media samples from symptomatic patients. The BD Veritor System for Rapid Detection of 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. 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 and B nasopharyngeal (NP) washes/aspirates 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 |

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| | influenza viruses.
Performance characteristics for influenza A and B NP swabs in transport media were established during January through April of 2012 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, 2011-2012 Season, and Composition of the 2012-2013 Influenza Vaccine.” Performance characteristics may vary against other emerging influenza viruses.
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. | influenza viruses.
Performance characteristics for influenza A and B NP swabs in transport media were established during January through April of 2012 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, 2011-2012 Season, and Composition of the 2012-2013 Influenza Vaccine.” Performance characteristics may vary against other emerging influenza viruses.
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. |
| --- | --- | --- |
| Specimen Types | Liquid nasopharyngeal wash, aspirate and swab in transport media | Liquid nasopharyngeal wash, aspirate and swab in transport media |
| Assay Technology | Immunochromotographic | Immunochromotographic |
| Detection Format | An opto-electronic reader determines the line intensity at each of the spatially-defined test and control line positions, interprets the results using the scoring algorithm, and reports a positive, negative, or invalid result on the LCD screen based on pre-set thresholds. | An opto-electronic reader determines the line intensity at each of the spatially-defined test and control line positions, interprets the results using the scoring algorithm, and reports a positive, negative, or invalid result on the LCD screen based on pre-set thresholds. |
| Qualitative | Yes | Yes |
| Total Assay Time | Approximately 10 minutes | Approximately 10 minutes |
| Control format | • Kit Flu A+/B- dry swab procedural control
• Kit Flu B+/A- dry swab procedural control
• Internal positive control | • Kit Flu A+/B- dry swab procedural control
• Kit Flu B+/A- dry swab procedural control
• Internal positive control |

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| | • Internal negative control | • Internal negative control |
| --- | --- | --- |
| Detection of Flu A and B viruses | Differentiated influenza A and influenza B | Differentiated influenza A and influenza B |

## Differences

The package insert has been updated to include detection of the following H7N9 virus in the analytical sensitivity information section and strain reactivity tables:

A/Anhui/1/2013 H7N9

Disclaimer: "Although this test has been shown to detect the novel avian influenza A(H7N9) cultured virus, the performance characteristics of this device with clinical specimens that are positive for the novel avian influenza A(H7N9) virus have not been established. The BD Veritor System Flu A+B test can distinguish between influenza A and B viruses, but it cannot differentiate influenza A subtypes."

## 6. Design Control Activities Summary:

Analytical Sensitivity Testing was conducted as described in section 7, "Summary of Studies".

### Declaration of Conformity to Design Control

A "Declaration of Conformity" statement was submitted for the manufacturing facility and validation activities and signed by the Director, Regulatory Affairs and Quality Systems. The statements indicate that;

1. The verification activities, as required by the risk analysis, for the modification were performed by the designated individual(s) and the results demonstrated that the predetermined acceptance criteria were met.
2. The manufacturing facility, BD Rapid Diagnostics Co Ltd, is in conformance with the design control requirements as specified in 21 CFR 820. 30 and the records are available for review.

In conclusion, based on both the results of the analytical sensitivity testing and the risk management report, 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. A Truthful and Accurate Statement, a 510(k) Summary, 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 and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. On this basis, I recommend the device be determined substantially equivalent to the previously cleared device.