(24 days)
Not Found
No
The device description mentions a "proprietary algorithm" used by the reader to interpret results by subtracting a nonspecific signal. While this involves computation, the description does not indicate the use of AI or ML techniques like training on data or learning from patterns. The algorithm appears to be a fixed, rule-based calculation.
No
This device is a diagnostic tool used to detect influenza A and B viral antigens, aiding in the diagnosis of infection, rather than directly providing therapy.
Yes
The device is described as an "aid in the diagnosis of influenza A and B viral infections," which clearly indicates its diagnostic purpose.
No
The device description clearly outlines a physical test device (chromatographic assay, test strip, sample well) and a reader (BD Veritor™ System Reader) that measures light reflectance. While software is involved in interpreting the results, it is integral to a hardware system.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is 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." This describes a test performed on a biological sample taken from the human body to provide information about a person's health status (diagnosis of influenza A and B viral infections).
- Device Description: The description details a "chromatographic assay to qualitatively detect influenza A and B viral antigens in respiratory specimens." This is a laboratory-based test method used to analyze biological samples.
- Sample Type: The device uses "nasopharyngeal wash, aspirate and swab in transport media samples," which are biological specimens.
- Purpose: The test is used "as an aid in the diagnosis of influenza A and B viral infections." Diagnosis is a key function of IVDs.
The definition of an In Vitro Diagnostic (IVD) device is a medical device that is used to perform tests on samples such as blood, urine, tissues, and other body fluids to detect diseases, conditions, or infections. The BD Veritor™ System for Rapid Detection of Flu A+B fits this definition perfectly.
N/A
Intended Use / 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 a single processed sample using a single device. The test is to be used as an aid in the diagnosis of influenza A and B viral infections. A negative test is presumptive and it is recommended that these results be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Outside the U.S. a negative test is presumptive and it is recommended that these results be confirmed by viral culture or a molecular assay cleared for diagnostic use in the country of use. FDA has not cleared this device outside the U.S. Negative test results do not prectude influenza viral infection and should not be used as the sole basis for treatment or other management decisions. The test is not intended to detect influenza C antigens.
Product codes (comma separated list FDA assigned to the subject device)
GNX
Device Description
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in respiratory specimens. The patient specimen is mixed in a prefilled unitized tube containing RV Reagent C and added to the test device. RV Reagent C 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 BD Flu 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. 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 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal wash, aspirate and swab in transport media samples
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory Kit
clinicians
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Study acceptance criteria were that the Veritor Flu A+B assay system needed to give a positive instrumented read with samples of subject flu viruses in order to support this claim in a revised Package Insert. Subject Flu strains were chosen based on strains forecasted for the 2015/2016 Flu season, additional influenza strains available from CDC and WHO and also in response to customer requests. The testing protocol was the same as has been used in previous submissions to FDA regarding strain reactivity and is detailed in BD protocol Document SDSP15001. This study was conducted under the direction of Richard Anderson Ph.D. at the R/D laboratories in San Diego, CA. Viral material in allantoic fluid from chicken eggs was used in this study.
Twelve virus strains were provided by the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza and the US Centres for Disease Control. The two strains provided by National Institute for Biological Standards and Control (UK) used in this testing, A/Switzerland//9715293/2013 and B/Phuket/3073/2013, were received as lyophilized preparations and were subsequently reconstituted, amplified in culture and titred following procedures outlined in the WHO Manual on Animal Influenza Diagnosis and Surveillance (2002) before supplying this material for reactivity testing in the Veritor system.
Materials and procedures for this step are as follows: MDCK cells: TPCK-trypsin (2 mg/ml): Complete MEM medium for MDCK cells: Penicillin (10.000 U/ml) + Streptomycin (10,000 ug/ml) Fetal Bovine Serum DMSO.
- Prepare TPCK-trypsin stocks:
a. Dissolve 20 mg TPCK-trypsin in 10 mL dH2O. Filter through 0.2 uL membrane. Store in aliquots at -20°C - Prepare Complete MEM medium (CMM):
a. 500 mL MEM + 5.5 mL Penicillin (10.000 U/mL)/ Streptomycin (10,000 ua/mL) - Prepare cell growth medium (CGM) from CMM above: 500mL CMM + 50mL FBS
- Prepare compete virus growth medium (VGM) : 0.5 mL of TPCK-trypsin to CMM.
- Freeze Medium: Add 5% DMSO to cell growth medium, freeze overnight at minus 80°C in liquid Nitrogen.
MDCK cells are routinely maintained in T-75 flasks in Cell Growth Media (CGM) supplemented with 10 % (v/v) FBS and Penicillin/Streptomycin. One day before virus infection, MDCK cells were seeded into T-25 and T-75 flasks at 50-60% confluency resulting in 90-100% confluency at the time of infection. Reconstituted virus was incubated with CGM and VGM at 37°C, in a 5% CO2 incubator for 1 hour. The flasks containing MDCK cells were washed with VGM and 1 ml of the incubated virus was added to a T-25 flask and the remaining to a T-75 flask, and then incubated at 37°C, 5% CO2 incubator for 2 hours. These flasks were washed twice with VGM, and then 3 mL of VGM was added to the T-25 flask, 10 mL of VGM was added to the T-75 flask. The infected cells were incubated at 37°C, in a 5% CO2 incubator for 2-5 days. The flasks were examined under a microscope for signs of infection. When more than 80% cells were infected, the supernatants were aliquoted into 1 mL tubes and kept in liquid nitrogen. These preparations were assigned a lot number based on date.
Viral titer was measured using a 96 well plate with MDCK host cells inoculated with 10 fold serial dilutions of virus. After 3-4 days at 37°C in a CO2 incubator, the titration plate was examined for Viral Cytopathic effects and TCID50 is calculated by the Reed-Muench formula.
10 fold dilutions from the stock received were tested in triplicate using the BD Veritor System Flu A+B test to establish the approximate level for the LQD.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Strain Reactivity Testing
Sample Size:
9 Flu A strains: A/Fujian-Gulou/1896/2009 H1N1, A/Washington/24/2012 H1N1, A/Switzerland//9715293/2013 H3N2, A/Texas/50/2012 H3N2, A/Anhui/01/05 H5N1, A/Vietnam/1203/04 H5N1, A/Pheasant/New Jersey/1355/1998 H5N2, A/Mallard/Netherlands/12/2000 H7N7, A/Chicken/Hong Kong/G9/1997 H9N2,
5 Flu B strains: B/Massachusetts/2/2012 (Yamagata Lineage), B/Montana/5/2012, B/Phuket/3073/2013, B/Texas/06/2011 (Yamagata Lineage), B/Wisconsin/01/2010 (Yamagata Lineage).
Key Results: The data indicate that all Flu A strains enrolled in this study can be detected by the Flu A line of the Veritor System Flu A+B device and none cross react with the Flu B line. All five Flu B strains enrolled in this study can be detected by the Flu B line of the Veritor System Flu A+B device and none cross react with the Flu A line.
Lowest Concentration (LOD) of influenza A and influenza B viruses detected:
A/Fujian-Gulou/1896/2009 H1N1: 4.5 x 10^5 CEID50/mL
A/Washington/24/2012 H1N1: 3.16 x 10^4 EID50/mL
A/Switzerland//9715293/2013 H3N2: 3.25 x 10^2 TCID50/mL
A/Texas/50/2012 H3N2: 1.75 x 10^3 TCID50/mL
A/Anhui/01/05 H5N1: 0.512 HA
A/Vietnam/1203/04 H5N1: 0.512 HA
A/Pheasant/New Jersey/1355/1998 H5N2: 0.256 HA
A/Mallard/Netherlands/12/2000 H7N7: 0.256 HA
A/Chicken/Hong Kong/G9/1997 H9N2: 1.024 HA
B/Massachusetts/2/2012 (Yamagata Lineage): 1.25 x 10^6 CEID50/mL
B/Montana/5/2012: 3.14 x 10^5 EID50/mL
B/Phuket/3073/2013: 6.08 x 10^3 TCID50/mL
B/Texas/06/2011 (Yamagata Lineage): 6.2 x 10^5 CEID50/mL
B/Wisconsin/01/2010 (Yamagata Lineage): 7.0 x 10^2 CEID50/mL
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K120049, K121797, K132256, K132693, K133138
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3328 Influenza virus antigen detection test system.
(a)
Identification. An influenza virus antigen detection test system is a device intended for the qualitative detection of influenza viral antigens directly from clinical specimens in patients with signs and symptoms of respiratory infection. The test aids in the diagnosis of influenza infection and provides epidemiological information on influenza. Due to the propensity of the virus to mutate, new strains emerge over time which may potentially affect the performance of these devices. Because influenza is highly contagious and may lead to an acute respiratory tract infection causing severe illness and even death, the accuracy of these devices has serious public health implications.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device's sensitivity and specificity performance characteristics or positive percent agreement and negative percent agreement, for each specimen type claimed in the intended use of the device, must meet one of the following two minimum clinical performance criteria:
(i) For devices evaluated as compared to an FDA-cleared nucleic acid based-test or other currently appropriate and FDA accepted comparator method other than correctly performed viral culture method:
(A) The positive percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The negative percent agreement estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(ii) For devices evaluated as compared to correctly performed viral culture method as the comparator method:
(A) The sensitivity estimate for the device when testing for influenza A must be at the point estimate of at least 90 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 80 percent. The sensitivity estimate for the device when testing for influenza B must be at the point estimate of at least 80 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 70 percent.
(B) The specificity estimate for the device when testing for influenza A and influenza B must be at the point estimate of at least 95 percent with a lower bound of the 95 percent confidence interval that is greater than or equal to 90 percent.
(2) When performing testing to demonstrate the device meets the requirements in paragraph (b)(1) of this section, a currently appropriate and FDA accepted comparator method must be used to establish assay performance in clinical studies.
(3) Annual analytical reactivity testing of the device must be performed with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria:
(i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA-designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains.
(ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or
(B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.
(4) If one of the actions listed at section 564(b)(1)(A)-(D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's § 809.10(b) of this chapter compliant labeling that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public Web site where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's Web site that discusses the device, must provide a prominently placed hyperlink to the Web page containing this information and must allow unrestricted viewing access.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles three human profiles facing right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 8, 2015
Becton Dickinson and Company Gregory Payne, RAC Director of Regulatory Affairs 10865 Road to the Cure, Suite 200 San Diego CA 92121
Re: K151301
Trade/Device Name: BD Veritor™ System for Rapid Detection of Flu A+B (Laboratory Kit)
Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: I Product Code: GNX Dated: May 14, 2015 Received: May 15, 2015
Dear Mr. Payne:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Tamara V. Feldblyum -S for
Sally Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K151301
Device Name
BD Veritor™ System for Rapid Detection of Flu A+B (Laboratory Kit)
Indications for Use (Describe)
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 a single processed sample using a single device. The test is to be used as an aid in the diagnosis of influenza A and B viral infections. A negative test is presumptive and it is recommended that these results be confirmed by viral culture or an FDA-cleared influenza A and B molecular assay. Outside the U.S. a negative test is presumptive and it is recommended that these results be confirmed by viral culture or a molecular assay cleared for diagnostic use in the country of use. FDA has not cleared this device outside the U.S. Negative test results do not prectude influenza viral infection and should not be used as the sole basis for treatment or other 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 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/Y amagata lineage were the predominant influenza viruses in circulation according to the 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.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(K) SUMMARY
| SUBMITTED BY: | BECTON, DICKINSON AND COMPANY
10865 Road to the Cure, Suite 200
San Diego, CA 92121
Tel: (858) 795 7890
Fax: (858) 795 7885 |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|
| CONTACT NAME: | Gregory P. Payne, RAC, Director Regulatory Aff |
| DATE PREPARED: | June 2, 2015, 2015 |
| DEVICE TRADE NAME: | BD Veritor™ System Flu A+B assay |
| DEVICE COMMON NAME: | Influenza virus serological reagents |
| DEVICE CLASSIFICATION: | 21 CFR 866.3330 |
| PREDICATE DEVICES : | BD Veritor™ System for Rapid Detection of Flu
Laboratory Kit
(K120049,K121797,K132256,K132693,K133138) |
INTENDED USE :
Laboratory Kit
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. Outside the U.S. a negative test is presumptive and it is recommended that these results be confirmed by viral culture or a molecular assay cleared for diagnostic use in the country of use. FDA has not cleared this device outside the U.S. Negative test results do not preclude influenza viral infection and should not be used as the sole basis for treatment or other patient management decisions. The test is not intended to
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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 emerqing 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/Yamaqata 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 DESCRIPTION :
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in respiratory specimens. The patient specimen is mixed in a prefilled unitized tube containing RV Reagent C and added to the test device. RV Reagent C 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 BD Flu 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. 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.
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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 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
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Confidential
| Positive Ctrl
Flu B test line
Flu A test line
Negative Ctrl
Background | C
L4
L3
L2 |
| ------------------------------------------------------------------------------------ | --------------------- |
|---|
visually because the human eye is unable to accurately perform the subtraction of the nonspecific signal.
DEVICE COMPARISON:
The modified device differs from the currently marketed BD Veritor™ System Flu A+ B in the following way:
The labeling has been changed to reflect the addition of strain reactivity data for the following strains:
| A/Fujian-Gulou/1896/2009 | H1N1 | B/Massachusetts/2/2012 (Yamagata Lineage) |
|---|---|---|
| A/Washington/24/2012 | H1N1 | B/Montana/5/2012 |
| A/Switzerland//9715293/2013 | H3N2 | B/Phuket/3073/2013 |
| A/Texas/50/2012 | H3N2 | B/Texas/06/2011 (Yamagata Lineage) |
| A/Anhui/01/05 | H5N1 | B/Wisconsin/01/2010 (Yamagata Lineage) |
| A/Vietnam/1203/04 | H5N1 | |
| A/Pheasant/New Jersey/1355/1998 | H5N2 | |
| A/Mallard/Netherlands/12/2000 | H7N7 | |
| A/Chicken/Hong Kong/G9/1997 | H9N2 |
SUBSTANTIAL EQUIVALENCE:
The modified device BD Veritor™ System Flu A+ B is substantially equivalent to the current legally marketed device, BD Veritor™ System Flu A+B assay. Additions made to the labeling to add additional strain testing did not change the intended use of the device or the fundamental scientific technology.
A Risk Analysis was conducted and is detailed in the Design Control Summary Section. No new issues of safety and effectiveness were identified during this process.
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Additions are as follows:
| Change | Potential Impact of Change |
|---|---|
| Addition of data for Strain reactivity of: | Additional information provided to users regarding strain reactivity. |
| A/Fujian-Gulou/1896/2009 H1N1 | Additional information provided to users regarding strain reactivity. |
| A/Washington/24/2012 H1N1 | Additional information provided to users regarding strain reactivity. |
| A/Switzerland//9715293/2013 H3N2 | Additional information provided to users regarding strain reactivity. |
| A/Texas/50/2012 H3N2 | Additional information provided to users regarding strain reactivity. |
| A/Anhui/01/05 H5N1 | Additional information provided to users regarding strain reactivity. |
| A/Vietnam/1203/04 H5N1 | Additional information provided to users regarding strain reactivity. |
| A/Pheasant/New Jersey/1355/1998 H5N2 | Additional information provided to users regarding strain reactivity. |
| A/Mallard/Netherlands/12/2000 H7N7 | Additional information provided to users regarding strain reactivity. |
| A/Chicken/Hong Kong/G9/1997/H9N2 | Additional information provided to users regarding strain reactivity. |
| B/Massachusetts/2/2012 (Yamagata Lineage) | Additional information provided to users regarding strain reactivity. |
| B/Montana/5/2012 | Additional information provided to users regarding strain reactivity. |
| B/Phuket/3073/2013 | Additional information provided to users regarding strain reactivity. |
| B/Texas/06/2011 (Yamagata Lineage) | Additional information provided to users regarding strain reactivity. |
| B/Wisconsin/01/2010 (Yamagata Lineage) | Additional information provided to users regarding strain reactivity. |
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1. SUBMISSION STRATEGY
This premarket notification is submitted in accordance with the requirements of 21 CFR 807.81 as a Special 510(k): Device Modification for a device that has been cleared under the 510(k) process but has been modified using the design control requirements of the Quality Systems Requlations (QSR). Modifications made to the BD Veritor™ System Flu A+ B product insert did not change the intended use of the device or the fundamental scientific technology thereby meeting the requirements for submission of a Special 510(k).
This device submission is a modification of the currently marketed BD Veritor™ System Flu A+ B assay product insert to update the strain reactivity section of the product insert to include information on 14 new influenza strains.
2. DEVICE INFORMATION (CURRENT AND MODIFIED)
| Device Trade Name | BD Veritor™ System Flu A+ B assay |
|---|---|
| Common/Classification Name | Influenza virus serological reagents |
| Device Classification | 21 CFR 866.3330 Class I |
| Product Code | GNX |
| Device Panel | Microbiology |
| Premarket Notification | K120049, K121797, K132256, K132693, |
| K133138 | |
| MODIFIED DEVICE | |
| Device Trade Name | BD Veritor™ System Flu A+ B assay |
| Common/Classification Name | Influenza virus serological reagents |
| Device Classification | 21 CFR 866.3330 Class I |
| Product Code | GNX |
| Device Panel | Microbiology |
LEGALLY MARKETED DEVICE (CURRENT)
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3. DEVICE DESCRIPTION
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in samples processed from respiratory specimens. The processed specimen is added to the test device where influenza 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.
4. PRINCIPLE OF PROCEDURE
The BD Flu A+B test is a chromatographic assay to qualitatively detect influenza A and B viral antigens in respiratory specimens. The patient specimen is mixed in a prefilled unitized tube containing RV Reagent C and added to the test device. RV Reagent C 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 BD Flu 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.
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.
Positive Ctrl C Flu B test line L4 Flu A test line L3 Negative Ctrl L2 Background
Image /page/9/Figure/9 description: The image shows a white rectangular object with rounded corners at the top. Inside the rectangle, there are five horizontal black lines evenly spaced apart. The lines appear to be solid and of uniform thickness. The object is oriented vertically.
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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 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.
5. DEVICE COMPARISON
The BD Veritor™ System Flu A+ B assay is substantially equivalent to the current legally marketed device, BD Veritor™ System Flu A+ B assay. Modifications made to the BD Veritor™ System Flu A+ B assay product insert did not change the intended use of the device or the fundamental scientific technology.
The BD Veritor™ System Flu A+ B assay product insert differs from the current legally marketed BD Veritor™ System Flu A+ B assay product insert in the following way:
The product inserts includes an update to include information on Strain Reactivity to 14 additional strains of flu virus.
6. DESIGN CONTROL SUMMARY
Our Risk Assessment process is based on a BD Product Risk Management procedure which meets the requirement for risk management as set forth in ISO 14971:2007 and EN ISO 14971:2012. Using this procedure, the following are estimated:
- the Hazard,
- the Adverse Effect (Harm to Patient),
- . the Potential Causes of the Hazard,
- The probability of Severity and ■
- The probability of Occurrence are estimated.
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Based on a resulting calculated Risk Index, Risk Control Measures are identified, required verification and validation activities are determined, and verification of the effectiveness of risk control measures is determined.
The tables below are taken from the procedure and provide guidelines to determine the probability of severity and occurrence. Additionally, a risk chart is provided below which depicts the areas of risk.
| Indicator | Category | Definition |
|---|---|---|
| S-1 | Negligible | No adverse health consequences; may result in annoyance to user or to |
| patient. Could include cosmetic defect and/or need to replace defective product | ||
| prior to initial use. | ||
| S-2 | Limited | Injury, without a significant discomfort or any degree of disability. Symptoms are |
| transient easily tolerated with no interference with subject's daily activities. Illness | ||
| or injuries are transient, self-limited and require no medical intervention or require | ||
| medical intervention that is limited in scope (i.e., non-significant risk). | ||
| Device Examples: product failure requiring: reinsertion of a peripheral IV catheter, | ||
| repeat skin injection (without impact to dose), peripheral venous blood sampling, or | ||
| one which results in clean (unused on patient, not contaminated) needle stick | ||
| and/or blade injury, or which results in a mild, non-painful electrical shock, first | ||
| degree (superficial) burns, or mild retinal laser light exposures. | ||
| IVD Examples: | ||
| Patient: erroneous patient results (e.g. false positive results, false negative results, | ||
| incorrect patient ID with results), delayed treatment for IVD medical devices which | ||
| are not the sole determinant and are classified in lower risk classes. Although the | ||
| erroneous patient results might not be corrected by other means, the impact to the | ||
| patient is negligible to none. | ||
| Third party (e.g. user, service engineer, etc.): non painful electrical shock, first | ||
| degree (superficial) burns, mild retinal laser light exposure. | ||
| S-3 | Moderate | Injury which may include significant discomfort, minor non-permanent injury and/or |
| temporary disability. Symptoms are temporary and /or reversible. These injuries | ||
| usually require medical intervention to treat the injury. This category includes, but is | ||
| not limited to: | ||
| Injuries which require the need for minor, local surgery or the need to repeat | ||
| a semi-invasive low-risk procedure due to product failure. | ||
| The misdiagnosis or wrong treatment of a non-serious illness due to | ||
| erroneous results | ||
| Device Examples: product failures resulting in fractured needle requiring local | ||
| exploratory surgery to remove part, requiring reinsertion of a central venous | ||
| catheter, peripherally inserted central catheter, or invasive diagnostic procedure | ||
| such as a spinal tap, or which results in a contaminated sharps injury without | ||
| seroconversion or transmission of blood borne disease, or which results in painful | ||
| electrical shock, second degree (partial thickness) burns or moderate retinal laser | ||
| light exposure. | ||
| IVD Examples: | ||
| Patient: erroneous patient results (e.g. false positive results, false negative results, | ||
| incorrect patient ID with results), delayed treatment for IVD medical devices which | ||
| are not the sole determinant but which are classified in higher risk classes. | ||
| Third party (e.g. user, service engineer, etc.): painful electrical shock, second | ||
| degree burns, moderate retinal laser light exposure, contaminated sharps injury | ||
| without seroconversion or transmission of blood borne disease. | ||
| S-4 | Severe | Injury which results in severe symptoms, significant injury, potential long-term risk to |
| health, or permanent impairment as a direct result of product failure, or due to a | ||
| delay in treatment as a result of product failure. The injury/symptoms may be | ||
| irreversible despite medical intervention, but are not immediately life threatening. This category includes, but is not limited to: | ||
| ☐ Injuries which require major or invasive (i.e., moderate to high-risk) surgery or other intervention for treatment, exposure of patient to a high level of cumulative risk due to multiple medical interventions, or injuries which require patient hospitalization or which extend length of patient hospitalization for treatment. | ||
| ☐ The transmission or causation of a potentially chronically debilitating or life threatening disease as a result of the product malfunction | ||
| ☐ The misdiagnosis or wrong treatment of a serious illness due to erroneous results | ||
| Device Examples: product failures that require such procedures as exploratory | ||
| laparotomy or other invasive diagnostic procedure with significant risk, removal and | ||
| reinsertion of a fully inserted pulmonary arterial catheter, or retrieval of catheter fragment from the heart. Also included are product failures which result in loss of sight, amputation or loss of use of a limb, pneumonia, bacteremia, seroconversion for blood borne disease such as HIV/AIDS or Hepatitis C, electrical exposure above the "let go" threshold but which does not result in cardiac or respiratory compromise, widespread partial thickness or limited full-thickness (third degree) burns or severe moderate retinal laser light exposure. | ||
| IVD Examples: | ||
| Patient : erroneous patient results (e.g. false positive results, false negative results, | ||
| incorrect patient ID with results), delayed treatment for IVD medical devices which are the sole determinant and/or are in the highest risk class | ||
| Third party (e.g. user, service engineer, etc.): electrical exposure above the "let go" | ||
| threshold but which does not result in cardiac or respiratory compromise, third degree burns, severe retinal laser light exposure, contaminated sharps injury with seroconversion for blood borne disease such as HIV/AIDS or Hepatitis C. | ||
| S-5 | Catastrophic | Fatal or immediately life threatening. Fatal means death has already occurred. Life threatening means that death could occur in the near term despite treatment or that the patient was or would be at immediate risk of death if medical intervention had not occurred |
| Device Examples: anaphylactic reaction, severe hemorrhage, cardiac tamponade, | ||
| cardiac arrest, septic shock, electrocution with cardiac or respiratory compromise, | ||
| extensive third-degree burns. | ||
| IVD Examples: | ||
| Patient: erroneous patient results (e.g. false positive results, false negative results, | ||
| incorrect patient ID with results) for IVD medical devices with a large public health risk (e.g. contamination of the blood supply). | ||
| Third party (e.g. user, service engineer, etc.): electrocution with cardiac or respiratory compromise, extensive third-degree burns. |
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13
| Probability
| Indicator | Category | Probability of Harm (Definition) |
|---|---|---|
| P1 | Improbable | Extremely unlikely in the life of the system at any |
| given site | ||
| P2 | Remote | Likely to occur once in the life of the system at any |
| given site | ||
| P3 | Occasional | Likely to occur once every year for each system at |
| any given site | ||
| P4 | Reasonably | |
| Probable | Likely to occur a few times per year for each system | |
| at any given site | ||
| P5 | Frequent | Likely to occur many times per year for each system |
| at any given site |
| Severity | ||||||
|---|---|---|---|---|---|---|
| S1 | S2 | S3 | S4 | S5 | ||
| Occurrence | P5 | GR | RE | RE | RE | RE |
| P4 | GR | YE | RE | RE | RE | |
| P3 | GR | GR | YE | RE | RE | |
| P2 | GR | GR | GR | YE | RE | |
| P1 | GR | GR | GR | YE | YE |
Three-Region Risk Chart
Risk regions include:
Insignificant (GR) - individual risks in the green region are deemed negligible in comparison with other risks and in relation to the benefit of using the product. Even if the risk falls into this region, the risk must be reduced as far as possible. For risks falling into this region , the medical benefit are considered to outweigh the individual residual risk since the combination of the occurrence and severity is considered low. These risks do not require individual risk benefit analysis. Because risk of harm in this region are deemed negligible, risk control measures implemented in this region, will not require documented verification of risk control measure effectiveness.
Investigate (YE) – individual risks in the yellow region are not negligible in comparison with other risks, therefore further risk reduction must be investigated. This category requires evaluation for risk reduction and once all possible risk control measures have been implemented, the residual risk is not reduced to insignificant (GR) is not possible, the individual item in this region require a documented risk/benefit analysis to document acceptance of the residual risk (See Attachment 3 for a Risk Benefit Analysis model.
Unacceptable/Intolerable (RE) - individual risks in the red region are unacceptable. This region requires the implementation of risk control measures to reduce the risk. In general, BDDS products should not have items with residual risks falling into this region. However, in an exceptional and rare circumstance, these items may be
14
documented in the risk/benefit analysis with approval by Medical Affairs at a director level or higher.
The risk assessment identified the need to confirm the Veritor system's reactivity to new strains forecast for 2015/2016 Influenza Season, as well as other strains not previously tested available through CDC and WHO.
RESULTS OF THE ANALYSIS:
The results of the analysis indicated an initial possible combination of severity and occurrence that fell into S-3/P-3 category. To implement the indicated investigation, Protocol SDSP15001 was developed and approved based on previously accepted FDA submissions regarding strain reactivity. The design of the study is below and is replicated from a previous Special 510(k) submission. Acceptability criteria was the ability of the BD Veritor test to detect these additional Flu strains. Veritor was successful in detecting all strains tested. The data to be included in the insert are the actual values obtained during this testing. The results of the strain testing reduced the probability of occurrence from P-3 to P-1 and reduced the risk to the "negligible" category.
| Hazard | False Negative | Testing | |
|---|---|---|---|
| Adverse | |||
| Effect (Harm) | Effect on patient is that they | ||
| could be inappropriately treated | |||
| leading to flu progression | Obtain and test additional flu strains | ||
| Probability of | |||
| Severity | S-3 | Risk Control | |
| Measure | |||
| Potential | |||
| Causes of the | |||
| Hazard | Assay does not detect the | ||
| predicted strains for 2015/2016 | |||
| Flu Season or other available | |||
| new and circulating strains | Labeling | ||
| Probability of | |||
| Occurrence | P-3 | Update PI with new reactivity after | |
| FDA special 510(k) clearance | |||
| Existing Risk | |||
| Control | |||
| Measure | Current strain reactivity has | ||
| been determined and is | |||
| provided in the Product Insert | Risk Control | ||
| Measure | |||
| Effectiveness | |||
| Reference | SDSP15001 | ||
| Risk Index | YE | Probability of | |
| Severity | S-3 | ||
| Responsibility | |||
| for Risk | |||
| Control | |||
| Measure | R&D | Probability of | |
| Occurrence | P-1 | ||
| Risk Index | GR |
Finally, after review and clearance of this submission by FDA, a change control will be initiated to document this activity in the design history file and to route the new PI for approval.
Modifications to the product insert will be implemented in accordance to BD Change Control Procedure RDQP0401.
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SUMMARY OF STUDIES 7.
Study acceptance criteria were that the Veritor Flu A+B assay system needed to give a positive instrumented read with samples of subject flu viruses in order to support this claim in a revised Package Insert. Subject Flu strains were chosen based on strains forecasted for the 2015/2016 Flu season, additional influenza strains available from CDC and WHO and also in response to customer requests. The testing protocol was the same as has been used in previous submissions to FDA regarding strain reactivity and is detailed in BD protocol Document SDSP15001. This study was conducted under the direction of Richard Anderson Ph.D. at the R/D laboratories in San Diego, CA. Viral material in allantoic fluid from chicken eggs was used in this study.
Viruses tested
Twelve virus strains were provided by the WHO Collaborating Centre for Surveillance, Epidemiology and Control of Influenza and the US Centres for Disease Control. The two strains provided by National Institute for Biological Standards and Control (UK) used in this testing, A/Switzerland//9715293/2013 and B/Phuket/3073/2013, were received as lyophilized preparations and were subsequently reconstituted, amplified in culture and titred following procedures outlined in the WHO Manual on Animal Influenza Diagnosis and Surveillance (2002) before supplying this material for reactivity testing in the Veritor system.
Materials and procedures for this step are as follows:
MDCK cells: TPCK-trypsin (2 mg/ml): Complete MEM medium for MDCK cells: Penicillin (10.000 U/ml) + Streptomycin (10,000 μα/ml) Fetal Bovine Serum DMSO
ATCC, Cat# CCL-34 Sigma, Cat #T1426-50MG ATCC, Cat # 30-2003 Invitrogen, Cat # 15140-122 Sigma Cat. # 30-2020 Sigma Cat #D2438
-
- Prepare TPCK-trypsin stocks:
- a. Dissolve 20 mg TPCK-trypsin in 10 mL dH2O. Filter through 0.2 uL membrane. Store in aliquots at -20°C
-
- Prepare Complete MEM medium (CMM):
- a. 500 mL MEM + 5.5 mL Penicillin (10.000 U/mL)/ Streptomycin (10,000 ua/mL)
-
- Prepare cell growth medium (CGM) from CMM above: 500mL CMM + 50mL FBS
-
- Prepare compete virus growth medium (VGM) : 0.5 mL of TPCK-trypsin to CMM.
-
- Freeze Medium: Add 5% DMSO to cell growth medium, freeze overnight at minus 80°C in liquid Nitrogen.
MDCK cells are routinely maintained in T-75 flasks in Cell Growth Media (CGM) supplemented with 10 % (v/v) FBS and Penicillin/Streptomycin. One day before virus infection, MDCK cells were seeded into T-25 and T-75 flasks at 50-60%
16
Confidential
confluency resulting in 90-100% confluency at the time of infection. Reconstituted virus was incubated with CGM and VGM at 37°C, in a 5% CO2 incubator for 1 hour. The flasks containing MDCK cells were washed with VGM and 1 ml of the incubated virus was added to a T-25 flask and the remaining to a T-75 flask, and then incubated at 37°C, 5% CO2 incubator for 2 hours. These flasks were washed twice with VGM, and then 3 mL of VGM was added to the T-25 flask, 10 mL of VGM was added to the T-75 flask. The infected cells were incubated at 37°C, in a 5% CO2 incubator for 2-5 days. The flasks were examined under a microscope for signs of infection. When more than 80% cells were infected, the supernatants were aliquoted into 1 mL tubes and kept in liquid nitrogen. These preparations were assigned a lot number based on date.
Viral titer was measured using a 96 well plate with MDCK host cells inoculated with 10 fold serial dilutions of virus. After 3-4 days at 37°C in a CO2 incubator, the titration plate was examined for Viral Cytopathic effects and TCID50 is calculated by the Reed-Muench formula
| No. | Sample Description | Lot No. | Titer of stock |
|---|---|---|---|
| 1 | A/Fujian-Gulou/1896/2009 H1N1 | 59433572 | $1.8 x 10^9$ CEID50/mL |
| 2 | A/Washington/24/2012 H1N1 | 7/12/2013 | $3.16 x 10^8$ EID50/mL |
| 3 | A/Switzerland//9715293/2013 H3N2 | 02262015 | $1.3 x 10^6$ TCID50/mL |
| 4 | A/Texas/50/2012 H3N2 | 61757568 | $3.5 x 10^6$ TCID50/mL |
| 5 | A/Anhui/01/05 H5N1 | 62539790 | 512 HA |
| 6 | A/Vietnam/1203/04 H5N1 | 59613801 | 512 HA |
| 7 | A/Pheasant/New Jersey/1355/1998 H5N2 | 61647886 | 256 HA |
| 8 | A/Mallard/Netherlands/12/2000 H7N7 | 61572488 | 512 HA |
| 9 | A/Chicken/Hong Kong/G9/1997 H9N2 | 60429654 | 1024 HA |
| 10 | B/Massachusetts/2/2012 | ||
| (Yamagata Lineage) | 61649126 | $1.0 x 10^{10}$ CEID50/mL | |
| 11 | B/Montana/5/2012 | 7/12/2013 | $2.51 x 10^8$ EID50/mL |
| 12 | B/Phuket/3073/2013 | 04102015 | 2.43x $10^7$ TCID50/mL |
| 13 | B/Texas/06/2011 (Yamagata Lineage) | 61070013 | $6.2 x 10^8$ CEID50/mL |
| 14 | B/Wisconsin/01/2010 (Yamagata Lineage) | 61176817 | $2.8 x 10^6$ CEID50/mL |
10 fold dilutions from the stock received were tested in triplicate using the BD Veritor System Flu A+B test to establish the approximate level for the LQD.
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BD Veritor System Flu A+B test materials
Veritor System Flu A+B devices: two lots expiration date 2017/07/24 expiration date 2015/10/13 Reagent C. lot# 11071104, #13092703 Unitized tube, lot# IM046-0000 Test Standard diluent lot #90-185 Veritor System Readers SN #1212145789CN2
Conclusions
Nine Flu A strains and Five Flu B strains were enrolled in this study. The data indicate that all Flu A strains enrolled in this study can be detected by the Flu A line of the Veritor System Flu A+B device and none cross react with the Flu B line. All five Flu B strains enrolled in this study can be detected by the Flu B line of the Veritor System Flu A+B device and none cross react with the Flu A line. The lowest concentration (LOD) of influenza A and influenza B viruses that can be detected by Veritor System Flu A+B device are listed here:
| No. | Strain | Final Dilution
Factor | Estimated LOD 1 |
|-----|----------------------------------------------|--------------------------|---------------------------------|
| 1 | A/Fujian-Gulou/1896/2009 H1N1 | 4000 | $4.5 \times 10^5$
CEID50/mL |
| 2 | A/Washington/24/2012 H1N1 | 10000 | $3.16 \times 10^4$
EID50/mL |
| 3 | A/Switzerland//9715293/2013 H3N2 | 4000 | $3.25 \times 10^2$
TCID50/mL |
| 4 | A/Texas/50/2012 H3N2 | 2000 | $1.75 \times 10^3$
TCID50/mL |
| 5 | A/Anhui/01/05 H5N1 | 2000 | 0.512 HA |
| 6 | A/Vietnam/1203/04 H5N1 | 2000 | 0.512 HA |
| 7 | A/Pheasant/New Jersey/1355/1998 H5N2 | 1000 | 0.256 HA |
| 8 | A/Mallard/Netherlands/12/2000 H7N7 | 2000 | 0.256 HA |
| 9 | A/Chicken/Hong Kong/G9/1997 H9N2 | 1000 | 1.024 HA |
| 10 | B/Massachusetts/2/2012
(Yamagata Lineage) | 8000 | $1.25 \times 10^6$
CEID50/mL |
| 11 | B/Montana/5/2012 | 800 | $3.14 \times 10^5$
EID50/mL |
| 12 | B/Phuket/3073/2013 | 4000 | $6.08 \times 10^3$
TCID50/mL |
| 13 | B/Texas/06/2011
(Yamagata Lineage) | 1000 | $6.2 \times 10^5$
CEID50/mL |
| 14 | B/Wisconsin/01/2010
(Yamagata Lineage) | 4000 | $7.0 \times 10^2$
CEID50/mL |
1 Estimated LOD is the lowest concentration of influenza A and B virus strains that can be detected by the BD Veritor System Flu A + B Assay in 3/3 replicates.
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The strain reactivity data provided above and proposed for inclusion into the PI demonstrates that the acceptance criteria were met by all strains tested.
DECLARATION OF CONFORMITY 8.
The manufacturing facility is in conformance with design control procedure requirements as specified in 21 CFR 820.30. This statement can be found in Appendix 1.
9 . CONCLUSION FROM THE TESTING
The studies conducted on the BD Veritor™ System Flu A+B assay demonstrated that labeling changes can be made to the product insert to reflect the analytical sensitivity and reactivity data generated. This will be used to update the strain reactivity section of the product insert to include information on the aforementioned strains.
10. LABELING
Copies of the revised product inserts for the BD Veritor System Flu A+B assay are provided in Attachment 3. The labeling for this device has been modified from the current labeling to update the strain reactivity section of the product insert. The changes can be found in Appendix 3 page 10.
The intended use of this modified device as described in the labeling has not changed as a result of this modification.
All performance characteristics as well as other sections of the Package Insert from the current BD Veritor System Flu A+B assay have remained the same in the revised Package Insert.