BD VERITOR(TM) SYSTEM FOR RAPID DETECTION OF FLU A+B
Device Facts
| Record ID | K112277 |
|---|---|
| Device Name | BD VERITOR(TM) SYSTEM FOR RAPID DETECTION OF FLU A+B |
| Applicant | Becton, Dickinson and Company |
| Product Code | PSZ · Microbiology |
| Decision Date | Oct 28, 2011 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3328 |
| Device Class | Class 2 |
| Attributes | Pediatric |
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 and nasal swabs of 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 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 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
The BD Veritor System is a point-of-care diagnostic tool for influenza A and B. It utilizes a chromatographic immunoassay where processed respiratory samples are applied to a test strip; influenza antigens bind to antibody-conjugated detector particles; the complex migrates to a reaction area for capture by an antibody line. A portable electronic reader performs reflectance-based measurement of line signal intensities on the strip. The reader applies algorithms to evaluate these intensities against pre-set thresholds to determine the presence or absence of analytes. Results are displayed on an LCD screen for the operator. This system aids clinicians in rapid diagnosis, allowing for immediate patient management decisions, though negative results are presumptive and require molecular or culture confirmation.
Clinical Evidence
Multi-center POC study (5 U.S. sites, 8 Japan sites) with 736 prospective nasopharyngeal and nasal swab specimens. Compared against FDA-cleared molecular PCR assays. U.S. PPA: 78.7% (Flu A), 74.3% (Flu B); NPA: 97.8% (Flu A), 99.5% (Flu B). Japan PPA: 94.4% (Flu A), 91.4% (Flu B); NPA: 96.7% (Flu A), 94.7% (Flu B). Reproducibility evaluated at 3 POC sites using 30 simulated samples.
Technological Characteristics
Immunochromatographic assay; portable electronic reader; reflectance-based measurement; LCD output. Uses internal positive/negative controls and external dry swab procedural controls.
Indications for Use
Indicated for symptomatic patients requiring rapid, qualitative, differentiated detection of influenza A and B viral nucleoprotein antigens from nasopharyngeal and nasal swabs. Not for detection of influenza C.
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
- Quidel QuickVue Influenza A+B (k053146)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
A. 510(k) Number:
k112277
B. Purpose for Submission:
New Device
C. Measurand:
Influenza A and B nucleoprotein antigens in nasopharyngeal and nasal swabs
D. Type of Test:
Qualitative immunochromatogenic assay
E. Applicant:
Becton Dickenson and Company
F. Proprietary and Established Names:
BD Veritor System for Rapid Detection of Flu A+B
G. Regulatory Information:
1. Regulation section:
21 CFR § 866.3330, Influenza Serological Reagents
2. Classification:
Class I
3. Product code:
GNX, Antigens, including CF controls, Influenza A, B, and C
4. Panel:
Microbiology (83)
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H. Intended Use:
1. Intended use(s):
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 and nasal swabs of 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 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 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.
2. Indication(s) for use:
Same as Intended Use
3. Special conditions for use statement(s):
The device is for prescription use only
4. Special instrument requirements:
Requires the use of the BD Veritor System Reader
I. Device Description:
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral nucleoprotein antigens in samples processed from respiratory specimens (nasal and nasopharyngeal swabs). The processed specimen is added to the test device where influenza
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A or influenza B viral antigens bind to anti-influenza antibodies conjugated to detector particles on the A+B test strip. The antigen-conjugate complex migrates across the test strip to the reaction area and is captured by an antibody line on the membrane. Results are interpreted by the BD Veritor™ System Reader, a portable electronic device which uses a reflectance-based measurement method to evaluate the line signal intensities on the assay test strip, and applies specific algorithms to determine the presence or absence of any target analyte(s). A liquid crystal display (LCD) on the instrument communicates the results to the operator.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Quidel QuickVue Influenza A+B
2. Predicate 510(k) number(s):
k053146
3. Comparison with predicate:
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| Product Feature | BD Veritor™ System for Flu A+B (k112277) | Quidel QuickVue Influenza A+B (k053146) |
| --- | --- | --- |
| 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 and nasal swabs of 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 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 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. | The QuickVue® Influenza A+B test allows for the rapid, qualitative detection of influenza type A and type B antigens directly from nasal swab, nasopharyngeal swab, nasal aspirate, and nasal wash specimens. The test is intended for use as an aid in the rapid differential diagnosis of acute influenza type A and type B viral infections. The test is not intended to detect influenza C antigens. Negative results should be confirmed by cell culture; they do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional and laboratory use. |
| Specimen Types | Nasopharyngeal and nasal swabs | Nasal swab, nasopharyngeal swab, nasal wash/aspirate |
| Assay Technology | Immunochromatographic | Immunochromatographic |
| 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 | Visual determination of presence or absence of pink-to-red Test Line and the appearance of a blue Procedural Control Line on the test strip indicate the presence of influenza A and/or B antigen. |
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| Product Feature | BD Veritor™ System for Flu A+B (k112277) | Quidel QuickVue Influenza A+B (k053146) |
| --- | --- | --- |
| | result on the LCD screen based on pre-set thresholds. | |
| Qualitative | Yes | Yes |
| Total Assay Time | Approximately 10 minutes | Less than 15 minutes |
| Control format | • Kit Flu A+/B- dry swab procedural control
• Kit Flu B+/A- dry swab procedural control
• Internal positive control
• Internal negative control | • Kit Flu A+ control swab
• Kit Flu B+ control swab
• Kit Negative control swab
• Internal control lines |
| Detection of Flu A and B viruses | Differentiated influenza A and influenza B | Differentiated influenza A and influenza B |
# K. Standard/Guidance Document Referenced (if applicable):
Not Applicable
# L. Test Principle:
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens (nucleoproteins) in upper respiratory swab specimens. The patient specimen is mixed in a prefilled unitized tube containing RV Reagent D and added to the test device. RV Reagent D contains mucolytic agents that function to break down mucus in a patient specimen thereby exposing viral antigens and enhancing detection in the assay device. Processed specimens are expressed through a filter tip into a single sample well on the BD Flu A+B test device.
The specimen is mixed and added to the test device where influenza A or influenza B viral antigens bind to anti-influenza antibodies conjugated to detector particles on the $\mathrm{A + B}$ test strip. The antigen-conjugate complex migrates across the test strip to the reaction area and is captured by an antibody line on the membrane. The assay utilizes a proprietary enhanced colloidal-gold particle at the test lines as the means for identifying the presence of influenza A or B viral antigens and requires the use of the BD Flu $\mathrm{A + B}$ Veritor System Reader.
The BD Flu A+B test devices are designed with five spatially-distinct zones including positive and negative control line positions, separate test line positions for the target analytes, and a background zone. The test lines for the target analytes are labeled on the test device as 'A' for flu A position, and 'B' for flu B position. The onboard positive control ensures the sample has flowed correctly and is indicated on the test device as 'C'. Two of the five distinct zones on the test device are not labeled. These two zones are an onboard negative control line and an assay background zone. The onboard negative control zone addresses non-specific signal generation and is not labeled on the test device. The remaining zone is used to measure the assay background and is also not labeled.
The BD Flu A+B assay incorporates an active negative control feature in each test to identify and compensate for sample-related, nonspecific signal generation. The BD Veritor™ System
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Reader uses a proprietary algorithm which subtracts nonspecific signal at the negative control line from the signal present at both the Flu A and Flu B test lines. If the resultant test line signal is above a pre-selected assay cutoff, the specimen is scored as positive. If the resultant test line signal is below the cutoff, the specimen is scored as negative. Use of the active negative control feature allows the BD Veritor™ System reader to correctly interpret test results that cannot be scored visually because the human eye is unable to accurately perform the subtraction of the nonspecific signal. The BD Veritor™ System Reader measures the amount of light reflected from various zones along the assay strip. The measurement of the assay background zone is an important factor during test interpretation as the reflectance is compared to that of the control and test zones. A background area that is white to light pink indicates the device has performed correctly. The instrument analyzes the reflectance data to provide the proper interpretation.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
The reproducibility of the BD Veritor™ System for Rapid Detection of Flu A+B assay was evaluated at three non-laboratory intended use Point of Care (POC) sites. The reproducibility panels consisted of varying levels of positivity and were masked and randomized prior to shipment to the sites. The swab samples for the study were prepared in the same way as the control swabs. Briefly, swabs were dipped into solutions containing various dilutions of virus to achieve the indicated test level and allowed to dry completely before being pouched with desiccant. Sample panels consisted of test levels with viral concentrations at a low positive level (positive ~ 95%, at or near LoD), moderate positive level (positive 100%), high negative level (positive 5%) and true negatives. Each site had two operators who tested each panel for five consecutive days with the device. Each panel was processed and tested in a single device according to the draft package insert. Each operator was assigned a specific reader for use throughout the duration of the reproducibility evaluation. No readers were replaced during the evaluation of reproducibility. The table below highlights the results of the multisite reproducibility study with the calculated percentage and the 95% confidence interval in parentheses below each result.
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| Summary of Reproducibility Flu A | | | | |
| --- | --- | --- | --- | --- |
| Sample | Site 1 | Site 2 | Site 3 | Total |
| High negative H1N1 A | 0% (0/30) (0%, 11.3%) | 10% (3/30) (3.5%, 25.6%) | 26.7% (8/30) (14.2%, 44.4%) | 12.2% (11/90) (7%, 20.6%) |
| Low positive H1N1 A | 86.7% (26/30) (70.3%, 94.7%) | 96.7% (29/30) (83.3%, 99.4%) | 100% (30/30) (88.6%, 100%) | 94.4% (85/90) (87.6%, 97.6%) |
| Moderate positive H1N1 A | 100% (30/30) (88.6%, 100%) | 100% (30/30) (88.6%, 100%) | 100% (30/30) (88.6%, 100%) | 100% (90/90) (95.9%, 100%) |
| High negative H3N2 A | 0% (0/30) (0%, 11.3%) | 10% (3/30) (3.5%, 25.6%) | 16.7% (5/30) (7.3%, 33.6%) | 8.9% (8/90) (4.6%, 16.6%) |
| Low positive H3N2 A | 100% (30/30) (88.6%, 100%) | 93.3% (28/30) (78.7%, 98.2%) | 96.7% (29/30) (83.3%, 99.4%) | 96.7% (87/90) (90.7%, 98.9%) |
| Moderate positive H3N2 A | 100% (30/30) (88.6%, 100%) | 100% (30/30) (88.6%, 100%) | 100% (30/30) (88.6%, 100%) | 100% (90/90) (95.9%, 100%) |
| Negatives | 0% (0/119) (0%, 3.1%) | 0.8% (1/119) (0.1%, 4.6%) | 0% (0/119) (0%, 3.1%) | 0.3% (1/357) (0%, 1.6%) |
| Summary of Reproducibility Flu B | | | | |
| Sample | Site 1 | Site 2 | Site 3 | Total |
| High negative B | 0% (0/30) (0%, 11.3%) | 3.3% (1/30) (0.6%, 16.7%) | 26.7% (8/30) (14.2%, 44.4%) | 10% (9/90) (5.4%, 17.9%) |
| Low positive B | 73.3% (22/30) (55.6%, 85.8%) | 90% (27/30) (74.4%, 96.5%) | 90% (27/30) (74.4%, 96.5%) | 84.4% (76/90) (75.6%, 90.5%) |
| Moderate positive B | 100% (29/29) (88.3%, 100%) | 96.6% (28/29) (82.8%, 99.4%) | 100% (29/29) (88.3%, 100%) | 98.9% (86/87) (93.8%, 99.8%) |
| Negatives | 0% (0/210) (0%, 1.8%) | 1.0% (2/210) (0.3%, 3.4%) | 0% (0/210) (0%, 1.8%) | 0.3% (2/630) (0.1%, 1.2%) |
An evaluation of precision over a period of 12 days with two different operators in order to evaluate the precision of the BD Flu A+B test was conducted. Each day each operator tested a group of 20 swabs samples, prepared in the same manner as previously stated, that were blinded and randomized and ranged from negative to 5% positive, 95% positive and 100% positive. These dilutions were determined based on the criteria that one sample be targeted around a high negative; that is, a sample that would be negative approximately 95% of the time. The second sample was targeted to a low positive sample: that is, a sample that would be positive approximately 95% of the time. The final dilution was targeted to a moderate positive; that is, a sample that would be positive approximately 100% of the time.
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| | Operator 1 | | | | Operator 2 | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample-Target Concentration | Positive /total tested swabs | % Positivity | 95% CI Lower bound | 95% CI Upper bound | Positive /total tested swabs | % Positivity | 95% CI Lower bound | 95% CI Upper bound |
| Neg-A | 0/24 | 0.0% | 0.0% | 14.2% | 0/24 | 0.0% | 0.0% | 14.2% |
| Neg-B | 0/24 | 0.0% | 0.0% | 14.2% | 0/24 | 0.0% | 0.0% | 14.2% |
| H1N1-5% | 2/24 | 8.3% | 1.0% | 27.0% | 3/24 | 12.5% | 2.7% | 32.4% |
| H3N2-5% | 2/24 | 8.3% | 1.0% | 27.0% | 1/24 | 4.2% | 0.1% | 21.1% |
| Flu B-5% | 1/24 | 4.2% | 0.1% | 21.1% | 2/24 | 8.3% | 1.0% | 27.0% |
| H1N1-95% | 23/24 | 95.8% | 78.9% | 99.9% | 23/24 | 95.8% | 78.9% | 99.9% |
| H3N2-95% | 23/24 | 95.8% | 78.9% | 99.9% | 24/24 | 100% | 85.8% | 100.0% |
| Flu B-95% | 24/24 | 100% | 85.8% | 100 % | 23/24 | 95.8% | 78.9% | 99.9% |
| H1N1-100% | 24/24 | 100% | 85.8% | 100% | 24/24 | 100% | 85.8% | 100 % |
| H3N2-100% | 24/24 | 100% | 85.8% | 100% | 24/24 | 100% | 85.8% | 100% |
| Flu B-100% | 24/24 | 100% | 85.8% | 100% | 24/24 | 100% | 85.8% | 100% |
b. Linearity/assay reportable range:
Not Applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Not Applicable
d. Detection limit:
All strains used to establish the analytical limit of detection were re-grown and re-titered. Serial 10-fold dilutions were made to determine the lowest detectable analyte level. Further characterization was carried out using a narrower range of dilutions. The LoD was then determined as the concentration producing a $95\%$ positivity rate. This concentration was tested using 60 replicates to define the LoD. The data representing the LOD are shaded and the $\mathrm{TCID}_{50} / \mathrm{mL}$ is highlighted in bold.
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| Strain | Dilution | Positivity (pos/total test) | LOD Concentration TCID_{50}/mL |
| --- | --- | --- | --- |
| A/California/7/2009 H1N1 (Pandemic) | 1:18000 | 100% (20/20) | 5.6E+03 |
| | 1:20000 | 95% (57/60) | 5.00E+03 |
| | 1:22000 | 85% (17/20) | 4.5E+03 |
| | 1:25000 | 60% (6/10) | 4.0E+03 |
| A/Brisbane/59/2007 H1N1 (Seasonal) | 1:8000 | 100% (20/20) | 7.3E+02 |
| | 1:16000 | 100% (20/20) | 3.7E+02 |
| | 1:17600 | 98.3% (59/60) | 3.3E+02 |
| | 1:17800 | 95% (57/60) | 3.30E+02 |
| | 1:18500 | 90% (18/20) | 3.2E+02 |
| A/Victoria/3/75 H3N2 | 1:12000 | 100% (20/20) | 3.43E+03 |
| | 1:13200 | 98.3% (59/60) | 3.11E+03 |
| | 1:13600 | 100% (60/60) | 3.02E+03 |
| | 1:14000 | 91.7% (55/60) | 2.94E+03 |
| | 1:16000 | 85% (17/20) | 2.57E+03 |
| A/Brisbane/10/2007 H3N2 | 1:8000 | 100% (20/20) | 9.54E+02 |
| | 1:10000 | 98.3% (59/60) | 7.63E+02 |
| | 1:10500 | 95% (57/60) | 7.27E+02 |
| | 1:12000 | 95% (19/20) | 6.36E+02 |
| | 1:15000 | 50% (10/20) | 5.09E+02 |
| B/Brisbane/60/2008 Victoria Lineage | 1:7500 | 100% (20/20) | 8.4E+03 |
| | 1:8500 | 96.7% (58/60) | 7.42E+03 |
| | 1:10000 | 65% (13/20) | 6.3E+03 |
| | 1:11000 | 15% (3/20) | 5.7E+03 |
| B/Florida/4/2006 Yamagata Lineage | 1:10000 | 100% (20/20) | 2.1E+03 |
| | 1:14500 | 100% (20/20) | 1.5E+03 |
| | 1:16000 | 98.3% (59/60) | 1.3E+03 |
| | 1:16500 | 96.7% (58/60) | 1.30E+03 |
| | 1:19000 | 65% (13/20) | 1.1E+03 |
| B/Lee/40 | 1:1000 | 100% (20/20) | 4.44E+04 |
| | 1:1200 | 93.3% (56/60) | 3.70E+04 |
| | 1:1250 | 75% (15/20) | 3.55E+04 |
| | 1:1300 | 80% (16/20) | 3.42E+04 |
e. Analytical specificity:
An analytical study to evaluate 51 microorganisms (36 bacteria, one yeast, and 14 viruses) for potential false positive reactions (cross-reactivity) with the BD Flu A+B test was done. Each of the bacteria (36) and yeast (1) were cultured on appropriate plated media. Bacteria and yeast were tested at a target concentration of approximately $10^{7}$ CFU/mL, with the exception of *Staphylococcus aureus*, which was tested at a final concentration of $10^{6}$ CFU/mL. The organisms were diluted if necessary with saline (10- to 100-fold) from stock in order to achieve the target
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concentration.
The 14 viruses were evaluated at concentrations of $10^{3}$ to $10^{10}\mathrm{TCID}_{50} / \mathrm{mL}$ and all viruses were tested at the stock concentration with the exception of Respiratory Syncytial Virus, which was diluted 10-fold from stock in saline.
All bacteria, yeast and viral frozen stock cultures were thawed and brought to room temperature prior to preparing target concentrations for testing. Three hundred microliters of each organism suspension were added to the unitized tube of RV Reagent C and the attached filter tip was snapped in place. The sample was mixed and three drops of the suspension were added to the test well of a BD Flu A+B device. After 10 minutes at room temperature, the device was inserted into the BD Veritor™ System Reader for interpretation. All determinations were performed in triplicate with no cross reactivity observed for any of the tested organisms.
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| Microorganism Name | Concentration Tested | Cross Reactivity with Flu A | Cross Reactivity with Flu B |
| --- | --- | --- | --- |
| Bacteriodes fragilis | 6.5 x 107CFU/mL | No | No |
| Bordetella pertussis | 5.0 x 107CFU/mL | No | No |
| Candida albicans | 3.5 x 107CFU/mL | No | No |
| Chlamydia pneumoniae | 2.8X106TCID50/mL | No | No |
| Corynebacterium diphtherium | 1.5 x 107CFU/mL | No | No |
| Escherichia coli | 1.5 x 107CFU/mL | No | No |
| Fusobacterium nucleatum | 1.2 x 107CFU/mL | No | No |
| Haemophilus influenzae | 1.5 x 107CFU/mL | No | No |
| Haemophilus parainfluenzae | 1.0 x 107CFU/mL | No | No |
| Kingella kingae | 5.0 x 107CFU/mL | No | No |
| Klebsiella pneumoniae | 1.5 x 107CFU/mL | No | No |
| Lactobacillus sp. | 1.5 x 107CFU/mL | No | No |
| Legionella sp. | 1.5 x 107CFU/mL | No | No |
| Moraxella catarrhalis | 5.0 x 107CFU/mL | No | No |
| Mycobacterium tuberculosis | 5.0 x 108CFU/mL | No | No |
| Mycoplasma pneumoniae | 5.0 x 107CFU/mL | No | No |
| Neisseria gonorrhoeae | 1.0 x 107CFU/mL | No | No |
| Neisseria meningitidis | 2.5 x 107CFU/mL | No | No |
| Neisseria mucosa | 2.0 x 107CFU/mL | No | No |
| Neisseria sp.(Neisseria perflaus) | 1.5 x 107CFU/mL | No | No |
| Neisseria subflava | 5.0 x 107CFU/mL | No | No |
| Peptostreptococcus anaerobius | 8.0 x 107CFU/mL | No | No |
| Porphyromonas asaccharolyticus | 5.0 x 107CFU/mL | No | No |
| Prevotella oralis | 5.0 x 107CFU/mL | No | No |
| Propionibacterium acnes | 2.0 x 107CFU/mL | No | No |
| Proteus mirabilis | 4.0 x 107CFU/mL | No | No |
| Pseudomonas aeruginosa | 5.0 x 107CFU/mL | No | No |
| Serratia marcescens | 4.0 x 107CFU/mL | No | No |
| Staphylococcus aureus | 5.0 x 106CFU/mL | No | No |
| Staphylococcus epidermidis | 3.0 x 107CFU/mL | No | No |
| Streptococcus mutans | 3.0 x 107CFU/mL | No | No |
| Streptococcus pneumoniae | 1.5 x 107CFU/mL | No | No |
| Streptococcus pyogenes | 2.0 x 107CFU/mL | No | No |
| Streptococcus sp. Group C | 4.0 x 107CFU/mL | No | No |
| Streptococcus sp. Group G | 2.5 x 107CFU/mL | No | No |
| Streptococcus salivarius | 2.3 x 107CFU/mL | No | No |
| Veillonella parvula | 1.5 x 107CFU/mL | No | No |
# f. Inclusivity:
An analytical study to evaluate a panel of 52 influenza viral strains including 20 Influenza A strains and 32 Influenza B strains was conducted. These strains were selected to evaluate the reactivity and specificity of the BD Flu $\mathrm{A + B}$ . Influenza A and Influenza B viral stock strains were thawed to room temperature and diluted 100-fold
{11}
with saline (with the exception of A/Moscow/10, which was diluted 10-fold). Three hundred microliters of each diluted viral suspension were added to the unitized tube containing RV Reagent C and the attached filter tip was snapped in place. The sample was mixed and three drops of the extracted sample were added to the test well of a BD Flu A+B device. After 10 minutes at room temperature the device was inserted into the BD Veritor™ System Reader for interpretation. All determinations were performed in triplicate. Triplicate test results were concordant for all strains evaluated. All Influenza A viruses and all Influenza B viruses were correctly detected by the test and no cross-reactivity was observed.
| Influenza Viral Strain | Concentration Tested | Flu A Test Result | Flu B Test Result |
| --- | --- | --- | --- |
| A2/Aichi2/68 H3N2 | 1.58 x 10^{6}CEID_{50}/mL | Positive | Negative |
| A/Brisbane/10/2007 H3N2 | 5.88 x 10^{4} TCID_{50}/mL | Positive | Negative |
| A/Brisbane/59/2007 H1N1 | 7.63 x 10^{4} TCID_{50}/mL | Positive | Negative |
| A/California/7/2009 H1N1 (2009 H1N1) | 1.0 x 10^{6} TCID_{50}/mL | Positive | Negative |
| A1/Denver/1/57 H1N1 | 8.89 x 10^{6}CEID_{50}/mL | Positive | Negative |
| A/FM/1/47 H1N1 | 1.58 x 10^{7}CEID_{50}/mL | Positive | Negative |
| A/Hong Kong/8/68 H3N2 | 8.89 x 10^{6}CEID_{50}/mL | Positive | Negative |
| A/New Caledonia/20/1999 | 1.0 x 10^{4} TCID_{50}/mL | Positive | Negative |
| A/New Jersey/8/76 H1N1 | 1.58 x 10^{5}CEID_{50}/mL | Positive | Negative |
| A/NWS/33 H1N1 | 1.58 x 10^{5}CEID_{50}/mL | Positive | Negative |
| A/Perth/16/2009 H3N2 | 1.0 x 10^{7} TCID_{50}/mL | Positive | Negative |
| A/Port Chalmers/1/73 H3N2 | 1.58 x 10^{6}CEID_{50}/mL | Positive | Negative |
| A/PR/8/34 H1N1 | 6.31 x 10^{3} TCID_{50}/mL | Positive | Negative |
| A/Wisconsin/67/2005 H3N2 | 1.0 x 10^{7} TCID_{50}/mL | Positive | Negative |
| A/Victoria/3/75 H3N2 | 8.89 x 10^{5}CEID_{50}/mL | Positive | Negative |
| A/Weiss/43 H1N1 | 2.81 x 10^{9}CEID_{50}/mL | Positive | Negative |
| A/Mal/302/54 H1N1 | 8.89 x 10^{7}CEID_{50}/mL | Positive | Negative |
| A/WS/33 H1N1 | 1.58 x 10^{4}CEID_{50}/mL | Positive | Negative |
| A/Moscow/10/99 H3N2 | 4.64 x 10^{7} TCID_{50}/mL | Positive | Negative |
| A/Solomon Island/03/2006 H1N1 | 1.0 x 10^{6} TCID_{50}/mL | Positive | Negative |
Positive = presence of influenza A or B antigen
Negative = absence of influenza A or B antigen
{12}
| Influenza Viral Strain | Concentration Tested | Flu B Result | Flu A Result |
| --- | --- | --- | --- |
| B/Brazil/178/96 | 4.64 x 105TCID50/mL | Positive | Negative |
| B/Brisbane/60/2008 | 6.31 x 105TCID50/mL | Positive | Negative |
| B/Brisbane/72/97 | 1.0 x 106TCID50/mL | Positive | Negative |
| B/Canada/548/99 | HA titer > 1.28 | Positive | Negative |
| B/Egypt/00393/99 | HA titer > 1.28 | Positive | Negative |
| B/Florida/2/2006 | 2.15 x 105TCID50/mL | Positive | Negative |
| B/Florida/4/2006 | 2.15 x 105TCID50/mL | Positive | Negative |
| B/Fujian/93/97 | 1.58 x 107TCID50/mL | Positive | Negative |
| B/Fukushima/220/99 | 3.73 x 104TCID50/mL | Positive | Negative |
| B/GuangXi/547/98 | 4.64 x 106TCID50/mL | Positive | Negative |
| B/Hawaii/01/97 | HA titer > 1.28 | Positive | Negative |
| B/Hong Kong/5/72 | 8.89 x 104CEID50/mL | Positive | Negative |
| B/Hong Kong/219/98 | HA titer 0.08 | Positive | Negative |
| B/Johannesburg/5/99 | 1.58 x 106TCID50/mL | Positive | Negative |
| B/Lee/40 | 8.89 x 104CEID50/mL | Positive | Negative |
| B/Lisbon/03/96 | HA titer > 0.08 | Positive | Negative |
| B/Malaysia/2506/2004 | 1.0 x 106TCID50/mL | Positive | Negative |
| B/Maryland/1/59 | 2.81 x 103CEID50/mL | Positive | Negative |
| B/Ohio/1/05 | 2.68 x 106TCID50/mL | Positive | Negative |
| B/Ohio/11/96 | HA titer > 0.16 | Positive | Negative |
| B/Puerto Mont/10427/98 | HA titer 0.08 | Positive | Negative |
| B/Russia/69 | 3.9 x 103TCID50/mL | Positive | Negative |
| B/Shangdong/7/97 | 6.31 x 107TCID50/mL | Positive | Negative |
| B/Shanghai/04/97 | 1.58 x 107TCID50/mL | Positive | Negative |
| B/Shenzhen/135/97 | 6.31 x 106TCID50/mL | Positive | Negative |
| B/Sichuan/116/96 | HA titer 0.64 | Positive | Negative |
| B/Taiwan/2/62 | 2.81 x 103CEID50/mL | Positive | Negative |
| B/Victoria/504/00 | 4.64 x 106TCID50/mL | Positive | Negative |
| B/Yamanashi/166/98 | 1.95 x 105TCID50/mL | Positive | Negative |
| B/Yamanashi/16/88 | 1.95 x 105TCID50/mL | Positive | Negative |
| B/Jiangsu/10/2003 | 4.64 x 105TCID50/mL | Positive | Negative |
| B/Mass/3/66 | 1.58 x 106CEID50/mL | Positive | Negative |
Positive = presence of influenza A or B antigen
Negative = absence of influenza A or B antigen
{13}
In addition, analytical inclusivity was also tested at dilutions much closer to the analytical limit of detection on a subset of Influenza A and Influenza B strains. The table below summarizes the detection of three replicates at the indicated test level.
| Type | Influenza Viral Strain | Stock Concentration (CEID50/mL) | Concentration Tested | Result |
| --- | --- | --- | --- | --- |
| A | A2/Aichi2/68 H3N2 | 1.58 X 108 CEID50/mL | 7.91 x 103 CEID50/mL | Detected |
| A | A/Brisbane/10/2007 H3N2 | 7.63 X 106 TCID50/mL | 9.54 x 102 TCID50/mL | Detected |
| A | A/Brisbane/59/2007 H1N1 | 5.88 X 106 TCID50/mL | 5.88 x 102 TCID50/mL | Detected |
| A | A/California/7/2009 H1N1 (2009 H1N1) | 1.0 X 108 TCID50/mL | 5.0 x 103 TCID50/mL | Detected |
| A | A1/Denver/1/57 H1N1 | 8.89 X 108 CEID50/mL | 4.45 x 104 CEID50/mL | Detected |
| A | A/FM/1/47 H1N1 | 1.0 X 109 CEID50/mL | 7.91 x 104 CEID50/mL | Detected |
| A | A/Hong Kong/8/68 H3N2 | 8.89 X 108 CEID50/mL | 8.89 x 104 CEID50/mL | Detected |
| A | A/New Caledonia/20/1999 H1N1 | 1.0 X 106 TCID50/mL | 5.0 x 103 TCID50/mL | Detected |
| A | A/New Jersey/8/76 H1N1 | 1.58 X 107 CEID50/mL | 1.58 x 103 CEID50/mL | Detected |
| A | A/NWS/33 H1N1 | 1.58 X 107 CEID50/mL | 1.58 x 104 CEID50/mL | Detected |
| A | A/Perth/16/2009 H3N2 | 1.0 X 109 TCID50/mL | 1.0 x 106 TCID50/mL | Detected |
| A | A/Port Chalmers/1/73 H3N2 | 1.58 X 108 CEID50/mL | 3.95 x 104 CEID50/mL | Detected |
| A | A/PR/8/34 H1N1 | 6.31 x 105 TCID50/mL | 6.31 x 102 TCID50/mL | Detected |
| A | A/Wisconsin/67/2005 H3N2 | 1.0 X 109 TCID50/mL | 2.5 x 105 TCID50/mL | Detected |
| A | A/Victoria/3/75 H3N2 | 1.58 X 107 CEID50/mL | 8.89 x 101 CEID50/mL | Detected |
| B | B/Brisbane/60/2008 | 6.31 X 107 TCID50/mL | 6.31 x 103 TCID50/mL | Detected |
| B | B/Florida/4/2006 | 2.15 X 107 TCID50/mL | 2.15 x 103 TCID50/mL | Detected |
| B | B/Hong Kong/5/72 | 1.58 X 107 CEID50/mL | 1.11 x 104 CEID50/mL | Detected |
| B | B/Lee/40 | 1.58 X 107 CEID50/mL | 8.89 x 103 CEID50/mL | Detected |
| B | B/Malaysia/2506/2004 | 1.0 X 108 TCID50/mL | 5.0 x 104 TCID50/mL | Detected |
| B | B/Maryland/1/59 | 2.81 X 105 CEID50/mL | 3.51 x 102 CEID50/mL | Detected |
| B | B/Taiwan/2/62 | 2.81 X 105 CEID50/mL | 2.81 x 102 CEID50/mL | Detected |
# g. Interfering substances:
An analytical study to evaluate a total of 43 substances including whole blood, prescription medications and over-the-counter (OTC) medications commonly taken to relieve flu symptoms was carried out. These substances were tested for potential interference with the BD Flu A+B test. To screen for potential interference, Influenza A (flu A/PR/8/34) and Influenza B (flu B/Lee/40) positive samples were prepared to yield a final concentration corresponding to a moderate positive (~5 times LoD). Test interference may be seen in the form of a false positive result with Influenza A or Influenza B negative samples or a false negative result with an Influenza A or Influenza B positive sample. Of the 43 substances tested in this study, none exhibited interference with the BD Veritor™ System for Rapid Detection of Flu A+B test.
The FluMist® is made from attenuated live Flu virus and although the concentration tested was non-interfering, it is possible when tested with higher concentrations that an Influenza A and/or Influenza B false positive may occur. Therefore, the following statement is included in the Warnings and Precautions section of the product package insert: "FluMist® is made from attenuated live Flu virus and although the concentration tested (1%) was non-interfering, it is possible when tested with higher concentrations that an influenza A and/or influenza B false positive may occur."
{14}
| Substance | Concentration Tested | Interference with Flu A Result | Interference with Flu B Result |
| --- | --- | --- | --- |
| Whole Blood | 2% | No | No |
| 4-Acetamidophenol | 10 mg/mL | No | No |
| Acetylsalicylic acid | 20 mg/mL | No | No |
| Albuterol | 0.083 mg/mL | No | No |
| Amantadine | 500 ng/mL | No | No |
| Ayr Saline Nasal Gel | 10 mg/mL | No | No |
| Beclomethasone | 500 ng/mL | No | No |
| Budesonide | 500 ng/mL | No | No |
| Chlorpheniramine maleate | 5 mg/mL | No | No |
| Dextromethoraphan | 10 mg/mL | No | No |
| Diphenhydramine HCl | 5 mg/mL | No | No |
| Dexamethasone | 10 mg/mL | No | No |
| Fexofenadine | 500 ng/mL | No | No |
| FluMist® | 1% | No | No |
| Flunisolide | 500 ng/mL | No | No |
| Fluticasone | 500 ng/mL | No | No |
| Guaiacol Glyceryl Ether | 20 mg/mL | No | No |
| Ibuprofen | 10 mg/mL | No | No |
| Loratidine | 100 ng/mL | No | No |
| Menthol Throat Lozenges | 10 mg/mL | No | No |
| Mometasone | 500 ng/mL | No | No |
| Mupirocin | 500 ng/mL | No | No |
| Oxymetazoline | 0.05 mg/mL | No | No |
| Osteltamivir | 500 ng/mL | No | No |
| Phenylephrine | 1 mg/mL | No | No |
| Pseudoephedrine HCl | 20 mg/mL | No | No |
| Purified Mucin Protein | 1 mg/mL | No | No |
| Ribavirin | 500 ng/mL | No | No |
| Rimantadine | 500 ng/mL | No | No |
| Tobramycin | 500 ng/mL | No | No |
| Triamcinolone | 500 ng/mL | No | No |
| Zanamivir | 1 mg/mL | No | No |
| Antiseptic Mouthwash (CVS) | 5% | No | No |
| Cool Mint Listerine Antiseptic | 5% | No | No |
| Scope Outlast Mouthwash | 5% | No | No |
| Ibuprofen Concentrated Drops | 25% | No | No |
| Pedia Care Drops for infants | 25% | No | No |
| Triaminic infants drops | 25% | No | No |
| Infants Advil concentrated Drops | 25% | No | No |
| Nasal Spray | 10% | No | No |
| Nasal Spray | 10% | No | No |
| Nasal Spray | 10% | No | No |
| Homeopathic Allergy Medicine | 10 mg/mL | No | No |
{15}
2. Comparison studies:
a. Method comparison with predicate device:
Not Applicable
b. Matrix comparison:
Not Applicable
3. Clinical studies:
Performance characteristics were established for the BD Veritor™ System for Rapid Detection of Flu A+B Point of Care (POC) kit as compared to an FDA-cleared Influenza A and B molecular assay reference method using clinical specimens from symptomatic pediatric and adult patients. A multi-center study was conducted at five POC centers located in geographically diverse areas within the United States and at seven different POC centers in Japan during the 2010-2011 respiratory season. During this time in the U.S. the following viruses were predominately circulating, A/California/7/2009-like (H1N1), A/Perth 16-2009-like (H3N2), B/Victoria lineage B/Brisbane/60/2008-like and B/Yamagata16/88.
16
{16}
Nasopharyngeal swab or nasal swab specimens were collected from 537 U.S. patients and 238 Japan patients enrolled at point of care settings (physician offices and clinics). The patient population includes both genders, and ranges across the pediatric, adult and geriatric populations:
| Demographics – U.S | | |
| --- | --- | --- |
| | | N (%) |
| Gender | F | 290 (54.0%) |
| | M | 247 (46.0%) |
| Age Group | <=5 | 109 (20.3%) |
| | 6 - 21 | 219 (40.8%) |
| | 22 - 59 | 191 (35.6%) |
| | 60+ | 18 (3.3%) |
| Demographics – Japan | | |
| --- | --- | --- |
| | | N (%) |
| Gender | F | 103 (43.3%) |
| | M | 135 (56.7%) |
| Age Group | <=5 | 65 (27.3%) |
| | 6 - 21 | 139 (58.4%) |
| | 22 - 59 | 31 (13.0%) |
| | 60+ | 3 (1.3%) |
For testing specimens with the BD Veritor Flu A+B test, sites were instructed to follow the procedures outlined in the draft package insert. Briefly, the swab was inserted into the prefilled unitized tube containing RV Reagent D, swirled inside the well three times. The swab was removed while squeezing the sides of the tube to expel excess liquid and the attached filter tip was snapped in place. Three drops of the mixture were added to the sample well of the BD Flu A+B device. After 10 minutes at room temperature the device was inserted into the BD Veritor™ System Reader for interpretation. Visual interpretation of results was not permitted from the device.
The reference method was performed following the package insert of an FDA-cleared molecular Influenza A and B assay. Briefly, nucleic acids were extracted from specimens using the indicated extraction system according to the package insert. An internal control (IC) was added to each specimen prior to extraction in order to monitor for inhibitors of PCR present in the extracted samples. Amplification was carried out for 50 cycles using the indicated instrument according to the assay procedure described in the package insert. Interpretation of PCR results for all specimens and controls was determined using the device software and according to the protocol outlined in the
17
{17}
package insert.
The clinical specimen types used in the evaluation of clinical performance were nasopharyngeal (NP) and nasal swabs. Test results were analyzed based on positive and negative Influenza A or B results with the BD Flu A+B assay. The data were tabulated using reference method (an FDA-cleared Influenza A and B molecular assay) results to categorize the BD Flu A+B test results into the following categories:
- True Positive: Any BD Flu A+B test result which exhibits a positive result and has a paired reference method positive result shall be deemed a true positive.
- False Positive: Any BD Flu A+B test result which exhibits a positive result but the paired reference method is negative shall be deemed a false positive.
- True Negative: Any BD Flu A+B test result which exhibits a negative result for which reference method is negative shall be deemed a true negative.
- False Negative: Any BD Flu A+B test result that exhibits a negative result but for which the reference method is positive shall be deemed false negative.
| NP Swab Specimens and Nasal Swabs Combined – All U.S. Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| All Swabs | P | 122 | 8 | 130 | | All Swabs | P | 75 | 2 | 77 |
| | N | 33* | 352 | 385 | | | N | 26* | 412 | 438 |
| | | 155 | 360 | 515 | | | | 101 | 414 | 515 |
| Reference Method: PCR PPA: 78.7% (95% C.I. 71.6%-84.4%) NPA: 97.8% (95% C.I. 95.7%-98.9%) | | | | | | Reference Method: PCR PPA: 74.3% (95% C.I. 65.0%-81.8%) NPA: 99.5% (95% C.I. 98.3%-99.9%) | | | | |
* 33 PCR positive, BD Veritor negative Influenza A specimens, eight were positive in the BD Veritor assay using a second swab specimen (reference method specimen) collected from the same patient.
* 26 PCR positive BD Veritor negative Influenza B specimens, six were positive in the BD Veritor assay using a second swab specimen (reference method specimen) collected from the same patient.
| NP Swab Specimens – All U.S. Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| NPS | P | 53 | 5 | 58 | | NPS | P | 22 | 1 | 23 |
| | N | 18 | 135 | 153 | | | N | 8 | 180 | 188 |
{18}
19
| NP Swab Specimens – All U.S. Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| | | 71 | 140 | 211 | | | | 30 | 181 | 211 |
| Reference Method: PCR
PPA: 74.6% (95% C.I. 63.4%-83.3%)
NPA: 96.4% (95% C.I. 91.9%-98.5%) | | | | | | Reference Method: PCR
PPA: 73.3% (55.6%-85.8%)
NPA: 99.4% (96.9%-99.9%) | | | | |
| Nasal Swab Specimens – All U.S. Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| NS | P | 69 | 3 | 72 | | NS | P | 53 | 1 | 54 |
| | N | 15 | 217 | 232 | | | N | 18 | 232 | 250 |
| | | 84 | 220 | 304 | | | | 71 | 233 | 304 |
| Reference Method: PCR
PPA: 82.1% (95% C.I. 72.6%-88.9%)
NPA: 98.6% (95% C.I. 96.1%-99.5%) | | | | | | Reference Method: PCR
PPA: 74.6% (95% C.I. 63.4%-83.3%)
NPA: 99.6% (95% C.I. 97.6%-99.9%) | | | | |
| NP Swab and Nasal Swab Combined – All Japan Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| All Swabs | P | 67 | 5 | 72 | | All Swabs | P | 64 | 8 | 72 |
| | N | 4 | 145 | 149 | | | N | 6 | 143 | 149 |
| | | 71 | 150 | 221 | | | | 70 | 151 | 221 |
| Reference Method: PCR
PPA: 94.4% (95% C.I. 86.4%-97.8%)
NPA: 96.7% (95% C.I. 92.4%-98.6%) | | | | | | Reference Method: PCR
PPA: 91.4% (95% C.I. 82.5%-96.0%)
NPA: 94.7% (95% C.I. 89.9%-97.3%) | | | | |
{19}
20
| NP Swab Specimens – All Japan Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| NPS | P | 30 | 1 | 31 | | NPS | P | 38 | 2 | 40 |
| | N | 2 | 83 | 85 | | | N | 1 | 75 | 76 |
| | | 32 | 84 | 116 | | | | 39 | 77 | 116 |
| Reference Method: PCR
PPA: 93.8% (95% C.I. 79.9%-98.3%)
NPA: 98.8% (95% C.I. 93.6%-99.8%) | | | | | | Reference Method: PCR
PPA: 97.4% (95% C.I.86.8%-99.5%)
NPA: 97.4% (95% C.I. 91%-99.3%) | | | | |
| Nasal Swab Specimens – All Japan Sites | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Reference PCR | | | | | | Reference PCR | | |
| Specimen Type | POC: BD Flu A | P | N | | | Specimen Type | POC: BD Flu B | P | N | |
| NS | P | 37 | 4 | 41 | | NS | P | 26 | 6 | 32 |
| | N | 2 | 62 | 64 | | | N | 5 | 68 | 73 |
| | | 39 | 66 | 105 | | | | 31 | 74 | 105 |
| Reference Method: PCR
PPA: 94.9% (95% C.I. 83.1%-98.6%)
NPA: 93.9% (95% C.I. 85.4%-97.6%) | | | | | | Reference Method: PCR
PPA: 83.9% (95% C.I.67.4%-92.9%)
NPA: 91.9% (95% C.I. 83.4%-96.2%) | | | | |
{20}
Results were also stratified by patient demographics for the U.S. sites. The PPA and the NPA for each age group of patients in the U.S. can be found in the following tables.
Performance by Age Group for Influenza A (U.S.)
| | PPA | NPA |
| --- | --- | --- |
| <= 5 years | 82.6% (19/23)
(95% CI = 62.9% - 93%) | 100% (82/82)
(95% CI = 95.5% - 100%) |
| 6 to 21 years | 82.8% (48/58)
(95% CI = 71.1% - 90.4%) | 98.0% (148/151)
(95% CI = 94.3% - 99.3%) |
| 22 to 59 years | 76.5% (52/68)
(95% CI = 65.1% - 85.0%) | 95.7% (110/115)
(95% CI = 90.2% - 98.1%) |
| 60 Years and up | 50.0% (3/6)
(95% CI = 18.8% - 81.2%) | 100% (12/12)
(95% CI = 75.8% - 100%) |
| All Ages | 78.7% (122/155)
(95% CI = 71.6% - 84.4%) | 97.8% (352/360)
(95% CI = 95.7% - 98.9%) |
Performance by Age Group for Influenza B (U.S.)
| | PPA | NPA |
| --- | --- | --- |
| <= 5 years | 81.8% (18/22)
(95% CI = 61.5% - 92.7%) | 100% (83/83)
(95% CI = 95.6% - 100%) |
| 6 to 21 years | 70.8% (46/65)
(95% CI = 58.8% - 80.4%) | 99.3% (143/144)
(95% CI = 96.2% - 99.9%) |
| 22 to 59 years | 90.9% (10/11)
(95% CI = 62.3% - 98.4%) | 99.4% (171/172)
(95% CI = 96.8% - 99.9%) |
| 60 Years and up | 33.3% (1/3)
(95% CI = 6.1% - 71.2%) | 100% (15/15)
(95% CI = 79.6% - 100%) |
| All Ages | 74.3% (75/101)
(95% CI = 65.0% - 81.8%) | 99.5% (412/414)
(95% CI = 98.3% - 99.9%) |
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Results were also stratified by patient demographics for the Japan sites. The PPA and the NPA for each age group of patients in Japan can be found in the following tables:
Performance by Age Group for Influenza A (Japan)
| | PPA | NPA |
| --- | --- | --- |
| <= 5 years | 95.5% (21/22)
(95% CI = 78.2% - 99.2%) | 97.4% (38/39)
(95% CI = 86.8% - 99.5%) |
| 6 to 21 years | 92.1% (35/38)
(95% CI = 79.2% - 97.3%) | 95.7% (90/94)
(95% CI = 89.6% - 98.3%) |
| 22 to 59 years | 100% (9/9)
(95% CI = 70.1% - 100.%) | 100% (16/16)
(95% CI = 80.6% - 100%) |
| 60 Years and up | 100% (2/2)
(95% CI = 34.2% - 100%) | 100% (1/1)
(95% CI = 20.7% - 100%) |
| All Ages | 94.4% (67/71)
(95% CI = 86.4% - 97.8%) | 96.7% (145/150)
(95% CI = 92.4% - 98.6%) |
Performance by Age Group for Influenza B (Japan)
| | PPA | NPA |
| --- | --- | --- |
| <= 5 years | 100% (6/6)
(95% CI = 61.0% - 100%) | 96.4% (53/55)
(95% CI = 87.7% - 99.0%) |
| 6 to 21 years | 89.5% (51/57)
(95% CI = 78.9% - 95.1%) | 93.3% (70/75)
(95% CI = 85.3% - 97.1%) |
| 22 to 59 years | 100% (7/7)
(95% CI = 64.6% - 100%) | 94.4% (17/18)
(95% CI = 74.2% - 99.0%) |
| 60 Years and up | N/A (0/0) | 100% (3/3)
(95% CI = 43.9% - 100%) |
| All Ages | 91.4% (64/70)
(95% CI = 82.5% - 96.0%) | 94.7% (143/151)
(95% CI = 89.9% - 97.3%) |
Invalid rates for the BD Flu A+B POC assay while running patient specimens were calculated. Invalid rates were calculated from the specimen data as the number of invalid results divided by the total number of compliant results. The following tables report the invalid rates for the U.S. investigational sites followed by the invalid rates for the Japan investigational sites. Invalid rates for the BD Veritor System for Rapid Detection of Flu A+B POC assay for the U.S. and Japan sites combined were calculated as 1.4% (11/762, 0.8% - 2.6%).
| Invalid Rates – U.S sites | | |
| --- | --- | --- |
| Investigational Sites | Invalid Rate | CI of Invalid Rate |
| P1 | 4.8% (1/21) | (0.8% - 22.7%) |
| P2 | 0.0% (0/4) | (0.0% - 49.0%) |
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| Invalid Rates – U.S sites | | |
| --- | --- | --- |
| Investigational Sites | Invalid Rate | CI of Invalid Rate |
| P3 | 0.0% (0/43) | (0.0% - 8.2%) |
| P4 | 0.5% (2/420) | (0.1% - 1.7%) |
| P5 | 0.0% (0/36) | (0.0% - 9.6%) |
| Overall study | 0.6% (3/524) | (0.2% - 1.7%) |
| Invalid Rates – Japan sites | | |
| --- | --- | --- |
| Investigational Sites | Invalid Rate | CI of Invalid Rate |
| FB2 | 0.0% (0/2) | (0.0% - 65.8%) |
| FB3 | 18.2% (2/11) | (5.1% - 47.7%) |
| KS1 | 1.6% (1/64) | (0.3% - 8.3%) |
| KS2 | 16.7% (5/30) | (7.3% - 33.6%) |
| KS3 | 0.0% (0/50) | (0.0% - 7.1%) |
| KS4 | 0.0% (0/32) | (0.0% - 10.7%) |
| KS5 | 0.0% (0/49) | (0.0% - 7.3%) |
| Overall study | 3.4% (8/238) | (1.7% - 6.5%) |
During the clinical studies, Quality Control (QC) testing was performed for the BD Flu A+B test. QC testing for the BD Flu A+B assay was performed each day of testing and consisted of a verification cartridge for the instrument, an A+/B- control and an A-/B+ control for the assay. The table below provides the overall QC data.
| Overall QC Report | | | | | | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Site | QC APOS | | | | | | QC BPOS | | | | | | VERIFY | | | | | |
| | Pass | | Fail | | Invalid | | Pass | | Fail | | Invalid | | Pass | | Fail | | Invalid | |
| | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % |
| | | | | | | | | | | | | | | | | | | |
| P1 | 32 | 97 | 0 | 0.0 | 1 | 3.0 | 32 | 94.1 | 0 | 0.0 | 2 | 5.9 | 32 | 100 | 0 | 0.0 | 0 | 0.0 |
| P2 | 18 | 100 | 0 | 0.0 | 0 | 0.0 | 18 | 94.7 | 1 | 5.3 | 0 | 0.0 | 18 | 100 | 0 | 0.0 | 0 | 0.0 |
| P3 | 45 | 100 | 0 | 0.0 | 0 | 0.0 | 45 | 100.0 | 0 | 0.0 | 0 | 0.0 | 45 | 100 | 0 | 0.0 | 0 | 0.0 |
| P4 | 113 | 100 | 0 | 0.0 | 0 | 0.0 | 114 | 100.0 | 0 | 0.0 | 0 | 0.0 | 110 | 100 | 0 | 0.0 | 0 | 0.0 |
| P5 | 25 | 100 | 0 | 0.0 | 0 | 0.0 | 24 | 96.0 | 0 | 0.0 | 1 | 4.0 | 26 | 100 | 0 | 0.0 | 0 | 0.0 |
| Total | 233 | 99.6 | 0 | 0.0 | 1 | 0.4 | 233 | 98.3 | 1 | 0.4 | 3 | 1.3 | 231 | 100 | 0 | 0.0 | 0 | 0.0 |
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4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
The prevalence from the five participating U.S. sites is summarized below based on the PCR reference method for NP and nasal swabs at the POC sites. Across the U.S. POC sites, Influenza A prevalence averaged 29.9% (range 19.0% to 30.6%) while Influenza B prevalence averaged 19.7% (range 14.3% to 25.0%).
| Prevalence Rates Based on PCR Reference Method | | | | |
| --- | --- | --- | --- | --- |
| | Influenza A | | Influenza B | |
| Site | Prevalence | #Positives/Total | Prevalence | #Positives/Total |
| P1 | 19.0% | 4/21 | 14.3% | 3/21 |
| P2 | 25.0% | 1/4 | 25.0% | 1/4 |
| P3 | 28.9% | 11/38 | 18.4% | 7/38 |
| P4 | 30.5% | 128/419 | 19.6% | 82/419 |
| P5 | 30.6% | 11/36 | 25.0% | 9/36 |
| Overall | 29.9% | 155/518 | 19.7% | 102/518 |
N. Instrument Name:
BD Veritor System Reader
O. System Descriptions:
1. Modes of Operation:
The Veritor Reader is a small, battery powered, bench top instrument that is used to read the Veritor lateral flow test cassette. After the extracted patient sample has been added to the test cassette, the test is developed at room temperature for 10 minutes. The cassette is then placed into the reader where it is scanned. The cassette is divided into distinct zones where the analyzer reads the negative background, positive control, and the Influenza A and B specific zones. The reader applies an algorithm to determine the background of the test as well as the specific signal from the A or B test zones. The reader has a finite number of reads and will prompt the end-user as the total reads approaches the lifetime of the unit.
2. Software:
FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:
Yes ☐ X ☐ or No ☐
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3. Specimen Identification:
Not Applicable
4. Specimen Sampling and Handling:
Not Applicable
5. Calibration:
The Veritor Reader is not configurable by the end user and is designed to have a finite lifetime based on number of tests performed or shelf life from date of manufacture. Device calibration is not required, however, a verification device is provided with the reader to QC the device function.
6. Quality Control:
Each BD Flu A+B test strip is designed with spatially-distinct zones containing a positive and negative internal controls. The positive control zone ensures that the sample has flowed correctly, and the negative control zone serves to monitor non-specific signal generation. The BD Veritor™ System Reader determines the line intensity at each of the spatially-defined control zones and utilizes specific algorithms to determine the presence or absence of any target analyte. The BD Veritor™ System Reader must be used to read the BD Flu A+B test devices, as these devices cannot be interpreted visually by the user.
In addition to the two internal controls, each BD Flu A+B kit contains the following external controls:
1. Control A+/B- is a dry swab control that is tested in the same manner as patient specimens and may be used as an external control. A positive flu A test result and a negative flu B test result on the reader LCD display confirm that the operator performed the test correctly.
2. Control B+/A- is a dry swab control that is tested in the same manner as patient specimens and may be used as an external control. A positive flu B test result and a negative flu A test result on the reader LCD display confirm that the operator performed the test correctly.
The BD Flu A+B device is to be read only by the instrument and cannot be read manually. At a minimum, the external dry swab controls should be run as a quality control procedure for each new lot and new shipment received. Controls should be tested in accordance with local, state and/or federal regulations or accreditation requirements and the standard Quality Control procedures. A BD Veritor System Verification Cartridge is also included with the reader. This allows the user to perform a functional test on the reader. Upon completion the reader will display QC Pass or QC Fail. If the reader has passed QC with the Verification Cartridge, it may be used to test specimens;
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QC failure requires contacting technical assistance. If desired, appropriate reagent performance and proper testing technique may also be determined by using specimens qualified as positive or negative for the influenza A or B virus. The user is instructed not to use the BD Flu A+B test if control A+/B- and control B+/A- do not yield appropriate results.
P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:
Not Applicable
Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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