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 nasal and nasopharyngeal swabs of symptomatic patients. The BD Veritor System for Rapid Detection of Flu A+B (also referred to as the BD Veritor System and BD Veritor System 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 for use outside of 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 detect influenza C antigens.

Device Description

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 antigens from nasopharyngeal and nasal swabs of symptomatic patients. The test is to be used as an aid in the diagnosis of influenza A and B viral infections. It 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 test device. Negative test results do not preclude influenza viral infection and should not be used as the sole basis for treatment or other management decisions. All negative test results should be confirmed by another methodology, such as a nucleic acid based method. All BD Veritor System Flu A+B test devices are interpreted by a BD Veritor System Instrument, either a BD Veritor Reader or BD Veritor Plus Analyzer.

The BD Veritor Flu A+B test is an immuno-chromatographic assay for detection of influenza A and B viral antigens in samples processed from respiratory specimens. The viral antigens detected by the BD Flu A+B test are nucleoprotein, not hemagglutinin (HA) or neuraminidase (NA) proteins. Flu viruses are prone to minor point mutations (i.e., antigenic drift) in either one or both of the surface proteins (i.e., HA or NA). The BD Flu A+B test is not affected by antigenic drift or shift because it detects the highly conserved nucleoprotein of the influenza viruses 12. To perform the test, the patient specimen swab is treated in a supplied reaction tube prefilled with a lysing agent that serves to expose the target viral antigens, and then expressed through a filter tip into the sample well on a BD Veritor Flu A+B test device. Any influenza A or influenza B viral antigens present in the specimen bind to anti-influenza antibodies conjugated to colloidal gold micro-particles on the Veritor Flu A+B test strip. The antigen-coniugate complex then migrates across the test strip to the capture zone and reacts with either Anti-Flu A or Anti-Flu B antibodies that are immobilized on the two test lines on the membrane.

The BD Flu A+B test device shown in Figure 1 is 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 active negative control feature in each test identifies and compensates for specimen-related, nonspecific signal generation. The remaining zone is used to measure the assay background.

The Veritor System is made up of assay kits with analyte specific reagents and an optoelectronic interpretation instrument.

The BD Veritor System instruments use a reflectance-based measurement method and apply assay specific algorithms to determine the presence or absence of the target analyte. In the case of the Flu A + B test. the BD Veritor System instruments subtract nonspecific signal at the negative control line from the signal present at both the Flu A and Flu B test lines. If the resultant line signal is above a pre-selected assay cutoff, the specimen scores as positive. If the resultant line signal is below the cutoff, the specimen scores as negative. Use of the active negative control feature allows the BD Veritor System instruments 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 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. Sample preparation is the same for use with both instruments, and both can utilize the same kit components. Neither instrument requires calibration.

The Veritor Reader and the Veritor Plus Analyzer use the functional components and decision algorithm in the firmware. The BD Veritor Plus Analyzer has the flexibility of an optional bar code scanning module and cellular connectivity designed to facilitate record keeping as well as the addition of a "Walk Away" work flow mode. Depending on the configuration chosen by the operator, the Veritor Plus Analyzer communicates status and results to the operator via a liquid crystal display (LCD) on the instrument, a connected printer, or through a secure connection to the facility's information system.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the BD Veritor System for Rapid Detection of Flu A + B CLIA Waived Kit, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" numerical targets. Instead, it presents performance data compared to a reference method (PCR) which implies these are the achieved performance metrics considered acceptable for substantial equivalence. The key performance indicators are Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) for influenza A and B.

Performance Metric	Acceptance Criteria (Implied)	Reported Performance (All Swabs - All Sites)
Influenza A
PPA	Not explicitly stated	83.6% (95% CI: 76.1%, 89.1%)
NPA	Not explicitly stated	97.5% (95% CI: 95.7%, 98.5%)
Influenza B
PPA	Not explicitly stated	81.3% (95% CI: 71.1%, 88.5%)
NPA	Not explicitly stated	98.2% (95% CI: 95.7%, 99.3%)

2. Sample Size and Data Provenance for the Test Set

The reported performance data in the table (PPA and NPA) are derived from a test set with the following characteristics:

Sample Size for Influenza A: 736 total samples (226 PCR positive, 510 PCR negative).
Sample Size for Influenza B: 736 total samples (171 PCR positive, 565 PCR negative).
Data Provenance: The document states the performance characteristics were established "during January through March of 2011" and summarizes data "across all age groups, clinical testing sites and sample types." This indicates a prospective clinical study involving collection of symptomatic patient samples. The country of origin is not explicitly stated for the "All Sites" data, but given it's an FDA submission, it's highly likely to include data from the United States. It is a prospective study during the influenza season.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of human experts to establish ground truth for the primary clinical performance data. The reference method for ground truth was a Molecular Assay (PCR).

4. Adjudication Method for the Test Set

Not applicable, as the ground truth was established by a molecular assay (PCR), not expert consensus.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

The document does not describe an MRMC comparative effectiveness study involving human readers with and without AI assistance. The device is a rapid chromatographic immunoassay interpreted by an instrument (BD Veritor Reader or Veritor Plus Analyzer), not an AI-assisted diagnostic for human readers.

The device itself is an automated system for interpreting rapid tests, not a tool to assist human readers in interpreting complex images or data.

6. Standalone (Algorithm Only) Performance

Yes, the study focuses on the standalone performance of the BD Veritor System (the rapid immunoassay device interpreted by the Veritor Reader or Veritor Plus Analyzer). The reported PPA and NPA values represent the performance of the device itself against a reference standard (PCR) without human interpretation.

The "Principle of the Test" section explains: "All BD Veritor System Flu A+B test devices are interpreted by a BD Veritor System Instrument, either a BD Veritor Reader or BD Veritor Plus Analyzer." The instrument's algorithms make the determination.

7. Type of Ground Truth Used

The ground truth used for the clinical performance evaluation was PCR (Polymerase Chain Reaction), which is a molecular assay for detecting influenza A and B. It is referred to as "Reference PCR" in the performance tables.

8. Sample Size for the Training Set

The document does not provide specific details on the sample size used for the training set of the device's inherent algorithms or cutoff thresholds. It mentions that "performance characteristics for influenza A and B were established during January through March of 2011," implying a dataset used for development and validation. For the comparison between Veritor Reader and Veritor Plus Analyzer, the following samples were assessed:

102 Flu A-/B- samples
52 Flu A+ samples
52 Flu B+ samples

These samples were used to confirm equivalency between the interpreting instruments, not necessarily as a "training set" for the assay itself.

9. How the Ground Truth for the Training Set Was Established

The document does not explicitly describe how the ground truth for any "training set" was established. However, given the context, it's highly probable that if a training set was used for algorithm development, the ground truth would also have been established by a highly sensitive and specific reference method like PCR or viral culture, similar to how the ground truth for the test set was established.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath in a smaller font.

March 20, 2018

Becton, Dickinson and Company Mary Ann Fiechtner Regulatory Affairs Specialist 10865 Road to the Cure Suite 200 San Diego, California 92121

Re: K180438

Trade/Device Name: BD Veritor System for Rapid Detection of Flu A + B CLIA Waived Kit Regulation Number: 21 CFR 866.3328 Regulation Name: Influenza virus antigen detection test systems Regulatory Class: Class II Product Code: PSZ Dated: February 15, 2018 Received: February 20, 2018

Dear Mary Ann Fiechtner:

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{1}------------------------------------------------

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.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Tamara V. Feldblyum -S for

Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Indications for Use

510(k) Number (if known)

K 180438

Device Name

BD Veritor System for Rapid Detection of Flu A + B - CLIA waived kit

Indications for Use (Describe)

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 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.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda. hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

5. 510(K) SUMMARY

DATE PREPARED:	March 16, 2018
SUBMITTED BY:	BECTON, DICKINSON AND COMPANY10865 Road to the Cure, Suite 200San Diego, CA 92121Tel: (858) 795-7857Fax: (858) 812-8505
CONTACT NAME:	Mary Ann Fiechtner, RACRegulatory Affairs Specialist
DEVICE TRADE NAME:	BD Veritor™ System for Rapid Detection of Flu A + BCLIA-Waived Kit
DEVICE COMMON NAME:	Influenza Virus Antigen Detection Test System
DEVICE CLASSIFICATION:	21 CFR 866.3328
CLASSIFICATION:	CLASS 2
PANEL:	Microbiology
PREDICATE DEVICES :	BD Veritor™ System for Rapid Detection of Flu A+BCLIA waived kit (K112277, K132259, K132692,K151291, K160161)

INTENDED USE :

The BD Veritor System for Rapid Detection of Flu A+B CLIA waived assay is a rapid chromatographic immunoassay for the direct and qualitative detection of influenza A and B viral nucleoprotein antigens from nasal and nasopharyngeal swabs of symptomatic patients.

The BD Veritor System for Rapid Detection of Flu A+B (also referred to as the BD Veritor System and BD Veritor System 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 for use outside of 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 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

{4}------------------------------------------------

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.

DEVICE DESCRIPTION :

A. Summary

B. Principle of the Test

1 Shu, L.L., Bean, W.J., and Webster, R.G. 1993. Analysis of the evolution and variation of the human influenza A virus nucleoprotein gene from 1933 to 1990. J. Virol. 67:2723-2729.

2 Kendal, A.P., and Dowdle, W.R. 1986. Influenza Virus p. 515. Manual of Clinical Laboratory Immunology, 30 edition, In Lenette et. Al. (ed.). American Society for Microbiology, Washington, D.C.

{5}------------------------------------------------

	Positive CtrlFlu B test lineFlu A test lineNegative CtrlBackground	CL4L3L2
--	------------------------------------------------------------------------------------	---------------------	--

Fiqure 1. BD Veritor Flu A + B Assay Device

C. System Components

The Veritor System is made up of assay kits with analyte specific reagents and an optoelectronic interpretation instrument.

D. Flu A + B CLIA waived assay kit contents

The components included in the BD Veritor System for Rapid Detection of Flu A+B CLIA waived test kit (BD product #256045) are detailed in Table 1.

Table 1: Contents of the Veritor System for Rapid Detection of Flu A + B CLIA waived


Veritor™ SystemFlu A+B TestDevices	30 Test Devices	Foil pouched device containing one reactive strip.Each strip has two test lines of antibodies specific toeither influenza A or influenza B viral antigen, andpositive and negative control lines.
RV Reagent D	30 tubes with400 µL reagent	Detergent with less than 0.1% sodium azide(preservative)
Flexible minitipflocked swab	30 each	Swab for nasopharyngeal or nasal collection
Control A+/B-	1 each	Flu A positive and flu B negative control swab,influenza A antigen (inactive recombinantnucleoprotein) with less than 0.1% sodium azide
Control B+/A-	1 each	Flu B positive and flu A negative control swab,influenza B antigen (inactive recombinantnucleoprotein) with less than 0.1% sodium azide

E. Veritor™ System Interpretation Instruments

{6}------------------------------------------------

nonspecific signal at the negative control line from the signal present at both the Flu A and Flu B test lines. If the resultant line signal is above a pre-selected assay cutoff, the specimen scores as positive. If the resultant line signal is below the cutoff, the specimen scores as negative. Use of the active negative control feature allows the BD Veritor System instruments 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 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. Sample preparation is the same for use with both instruments, and both can utilize the same kit components. Neither instrument requires calibration.

The following components are included with the BD Veritor" "Instruments (purchased separately from Veritor Assays).

Table 2. Veritor System Instrument components
BD VeritorTM Reader
BD VeritorTM SystemReader	1 each	Portable, rechargeable instrument for interpretation ofBD VeritorTM System test devices
AA Alkaline Batteries	2 each	Reader arrives ready to use with batteries installed.
Instructions for Use	1 each	Printed instructions for use
BD VeritorTMVerification Cartridge	1 each	Used to verify the proper functionality of the Reader.
BD VeritorTM Plus Analyzer
BD VeritorTM PlusSystem Analyzer	1 each	Portable, rechargeable instrument for interpretation ofBD VeritorTM System test devices
Instructions for Use	1 each	Printed instructions for use
USB Port Unlock Label	1 each	Adhesive label used to unlock the USB port
Compact AC powerAdapter with blades forUSA, Japan, UK andEU	1 each	Used to charge the internal rechargeable battery powersource.
BD VeritorTMVerification Cartridge	1 each	Used to verify the proper functionality of the Analyzer.

Table 2: Veritor System Instrument components

{7}------------------------------------------------

BD Veritor™ Plus System InfoScan Module

Barcode scanning module	1 each	Allows users to capture and record or display user ID, patient ID and/or kit lot ID numbers with an associated assay result
Quick Installation guide	1 each	Pictogram illustrating simple, slide in installation
USB Cable (USB-A to micro-B)	1 each	Allows download of assay results to a connected PC from the secure internal drive.
BD Veritor™ Plus System InfoSync Module
Cellular enabled barcode scanning module	1 each	Allows users to capture and record user ID, patient ID and/or kit lot ID numbers, and transmit them to a cloud connected LIS system with associated assay results.
Quick Installation guide	1 each	Pictogram illustrating simple, slide in installation

Table 3: Optional Veritor System accessory module compnents

DEVICE COMPARISON:

The device labeling has been changed to reflect the addition of a new data table and explanation in the Clinical Performance section. This appears as Table 1 in the Package Insert as shown below.

Table 1: Summary of Performance Data of the BD Veritor System for Rapid Detection of Flu A + B Compared to PCR for All Swabs - All Sites.

Note: The data in this table summarizes the performance of the Veritor Flu A + B assay test system across all age groups, clinical testing sites and sample types. The 95% Confidence intervals are calculated using an analysis that accounts for sources of heterogeneity.

	Reference PCR					Reference PCR
POC: BD FluA	P	N	Total	POC: BD FluB	P	N	Total
P	189	13	202	P	139	10	149
N	37	497	534	N	32	555	587
Total	226	510	736	Total	171	565	736
Reference Method: PCR				Reference Method: PCR
PPA: 83.6% (76.1%, 89.1%)				PPA: 81.3% (71.1%, 88.5%)
NPA: 97.5% (95.7%, 98.5%)				NPA: 98.2% (95.7%, 99.3%)
Wald 95% Confidence intervals corrected for over-dispersion, where needed, due
to potential variability between sites.

{8}------------------------------------------------

Product Feature	Veritor System Reader	Veritor Plus Analyzer
GENERAL:
Appearance anddimensions	Image: Veritor System Reader with dimensions ~77mm, ~60mm, ~120mm	Image: Veritor Plus Analyzer with dimensions ~90mm, ~67mm, ~140mm
Intended use	For use with BD VeritorSystem test devices	Same
Firmwarefunctionalverification	Verification cartridge suppliedwith each Reader	Same
Assay typedetermination	Internal camera readsbarcode on test device	Same
Assay test devicecompatibility	Original	Same
Lifetime	3000 tests24 months from first use34 months from date ofmanufacture	3500 tests24 months from first use34 months from date of manufacture
Assay workflowoptions	Original or "Analyze Now":Assay device is prepared withprocessed patient sample,user manually times theassay development andinserts assay device whendevelopment time iscomplete.	Analyze Now: unchanged Walk-Away: Assay device isprepared with processed patientsample, inserted into the Analyzerimmediately. Assay developmentis automatically timed by theinstrument and result is displayedwhen development time iscomplete.
Qualitative orQuantitative Result	Qualitative	Qualitative, unchanged
Optional modularbarcode scanner	Not Present	Captures and records Operator ID,Specimen ID, and/or test device lotinformation. Can be used to configuredisplay languages.
Cellular modemavailable withInfoSync module	Not Present	Using HTTPS secure link, endpointauthentication, receipt confirmation.Automated connection to LIS/EMR.
Removablemodule or coverplate	Not Present	Analyzers have either a cover plate orare equipped with optional scanningmodule.
Printer	Not printer compatible	Compatible with external dedicated printer via USB.
ELECTRICAL:
Batteries	User replaceable alkaline AA batteries	Li-ion rechargeable battery
AC power adapter	N/A	To charge the Li-ion battery and/or operate the analyzer from facility power.
Graphical display	40 mm x 19 mm	56 mm x 33 mm
Flash Memory	4 MB	8 MB
FIRMWARE:
Assay positivity algorithm	Original	Same
Assay cutoff thresholds	Original	Same
Test menu	Original	Same
Cybersecurity controls	Not Present	To meet requirements for data privacy and anti-hacking protection.
USB OTG port	Not Present	To connect to printer or to a computer to display or print results. Input firmware or menu updates from flash drive.
Display languages	English or Japanese only	Six user selectable languages; English, French, Italian, German, Spanish, Swedish. (optional scanning module required for language configuration). Japanese model sold separately

Table 5: Comparison of Veritor System Reader and Veritor Plus Analyzer

{9}------------------------------------------------

{10}------------------------------------------------

SUBSTANTIAL EQUIVALENCE:

The modified BD Veritor™ System Flu A+ B CLIA waived kit is substantially equivalent to the current legally marketed, BD Veritor™ System Flu A+B CLIA waived kit. Additions made to the labeling to add the performance data table and to allow interpretation with the Veritor Plus Analyzer have changed neither the intended use of the device nor the fundamental scientific technology.

RISK ASSESSMENT SUMMARY:

The BD Diagnostic Systems Risk Assessment process is based on the BD 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.
I the Adverse Effect (Harm to Patient),
. the Potential Causes of the Hazard,
The probability of Hazard Severity and
. The probability of Occurrence

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.

RESULTS OF THE RISK ANALYSIS:

1. Addition of the inclusion of the additional performance table in the Clinical Performance section of the BD Veritor™ System Flu A+ B CLIA-Waived assay product insert does not create any new product risks, or issues of safety and effectiveness.
  Additions to labeling are as follows:

Change	Potential Impact of Change
Addition of performance data re-analyses	Additional information provided to users regarding performance of the device.

1. The risk assessment identified the need to confirm the Veritor Plus System's ability to produce assay results equivalent to those obtained with the Veritor Reader in either Analyze Now or Walk Away work flow mode. The identified studies were performed according to appropriate design control procedures to assess the addition of the Veritor Plus Analyzer in either mode as an interpretation instrument for the Veritor System Flu A + B CLIA-Waived assay product. The results of testing did not identify new issues of safety and effectiveness.
1. The risk assessment identified the need to confirm that the addition of the bar code scanning functions of InfoScan and InfoSync modules, and any associated screen displays, alerts and error messages had no effect on safety or effectiveness when

{11}------------------------------------------------

the Veritor Plus Analyzer was used with the Veritor CLIA-waived Flu A + B Assay. Software verification activities were performed and all testing criteria were met to confirm that changes and addtions made to firmware to add new functionality had no impact on the abiltiy of the instrument to give a correct assay result.

1. Cybersecurity risks and vulnerabilities associated with the use of the InfoSync module were assessed and BD procedures and controls were verified as acceptable to protect user and patient data.
1. The risk assessment also identified the need to confirm that the Veritor Plus Analyzer was simple and easy to use in the CLIA waived environment.

SUMMARY OF PERFORMANCE STUDIES:

At the BD Diagnostics Systems research and development center in San Diego, CA, staff performed studies on both analytical and clinical samples to confirm that the performance of the Veritor Plus Analyzer is equivalent to the Veritor Reader when used in both Read Now and Walk-Away modes.

These studies included:

· Reproducibility studies
- o Samples with true zero values (no analyte)
- o High negative and low positive samples (near cut-off samples)

The data collected using analytical samples demonstrated that the percentage positivity for Veritor Readers and Veritor Plus Analyzers are equivalent.

The R&D staff also performed assessments of the following clinical samples:

102 Flu A-/B- samples ●
52 Flu A+ samples .
52 Flu B+ samples ●

The data collected with clinical samples also indicate that assay results obtained using Veritor Readers and Veritor Plus Analyzers are either identical or statistically equivalent. Results included less than 2% either False Positive or False Negative results.

Regulation Number and Section

§ 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.