The Sofia Influenza A+B FIA employs immunofluorescence to detect influenza A and influenza B viral nucleoprotein antigens in nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens taken directly from symptomatic patients. This qualitative test is intended for use as an aid in the rapid differential diagnosis of acute influenza A and influenza B viral infections. The test is not intended to detect influenza C antigens. A negative test is presumptive and it is recommended these results be confirmed by virus culture or FDA-cleared influenza A and B molecular assay. Negative results do not preclude influenza virus infections and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional and laboratory use.

Performance characteristics for influenza A and B were established during February through March 2011 when influenza viruses A/California/7/2009 (2009 H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008 (Victoria-Like) were the predominant influenza viruses in circulation according to the Morbidity and Mortality Weekly Report from the CDC entitled "Update: Influenza Activity--United States, 2010-2011 Season, and Composition of the 2011-2012 Influenza Vaccine". Performance characteristics may vary against other emerging influenza viruses.

If infection with a novel influenza virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to 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 Sofia Influenza A+B FIA employs immunofluorescence technology that is used with the Sofia Analyzer to detect influenza virus nucleoproteins.

The Sofia Influenza A+B FIA is a lateral-flow immunoassay that uses monoclonal antibodies that are specific for influenza antigens and have no known cross-reactivity to normal flora or other known respiratory pathogens.

Nasal swab, nasopharyngeal swab, and nasopharyngeal aspirate/wash specimens are used for this test. The patient specimen is placed in the Reagent Tube, during which time the virus particles in the specimen are disrupted, exposing internal viral nucleoproteins. After disruption, the specimen is dispensed into the cassette sample well. From the sample well, the specimen migrates through a test strip containing various unique chemical environments. If influenza viral antigen is present, they will be trapped in a specific location.

Note: Depending upon the user's choice, the cassette is either placed inside of the Sofia Analyzer for automatically timed development (Walk Away Mode) or placed on the counter or bench top for a manually timed development and then placed into the Sofia Analyzer to be scanned (Read Now Mode).
The Sofia Analyzer will scan the test strip and measure the fluorescent signal by processing the results using method-specific algorithms. The Sofia Analyzer will display the test results (Positive, Negative, or Invalid) on the screen. The results can also be automatically printed on an integrated printer if this option is selected.

AI/ML Overview

Here's an analysis of the provided text regarding the Sofia® Influenza A+B FIA device:

1. Table of Acceptance Criteria and Reported Device Performance

Criterion	Acceptance Criteria (Implied)	Reported Device Performance
Detection of Influenza A H7N9	The device should be able to detect the novel influenza A H7N9 virus.	The Sofia Influenza A+B FIA detects H7N9.
Limit of Detection (LoD) for H7N9	Not explicitly stated, but the study aims to establish the LoD. Compliance with a specific threshold would be the implied criterion for acceptable sensitivity.	The minimum detectable level for H7N9 is 3.95 x 10^0 Egg Infective Dose (EID)30/mL.
Substantial Equivalence	The device must be demonstrated as substantially equivalent to the predicate device.	"The Sofia Influenza A+B FIA is substantially equivalent with the current Sofia Influenza A+B FIA." (This statement implicitly confirms the device meets the criteria for substantial equivalence, which is a regulatory standard rather than a performance metric itself).
Intended Use	The device must meet the performance characteristics for its stated intended use (rapid differential diagnosis of acute influenza A and B viral infections).	Performance characteristics for influenza A and B were established during February-March 2011 against specific influenza strains (A/California/7/2009 (2009 H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008 (Victoria-Like)). No specific metrics (e.g., sensitivity, specificity) for these strains are provided in this summary.
Cross-Reactivity	No known cross-reactivity to normal flora or other known respiratory pathogens.	"The Sofia Influenza A+B FIA is a lateral-flow immunoassay that uses monoclonal antibodies that are specific for influenza antigens and have no known cross-reactivity to normal flora or other known respiratory pathogens." This summarizes the design principle rather than providing direct study results for this submission.

2. Sample Size for Test Set and Data Provenance

The provided text describes one analytical study (for H7N9 detection) and refers to previously established performance characteristics for common influenza strains.

H7N9 Study (Analytical): The sample size for this specific study is not explicitly stated. The study focuses on establishing the Limit of Detection (LoD).
Previous Performance Characteristics (Clinical): The text mentions that performance characteristics for influenza A and B were established during February through March 2011 when specific influenza viruses were prevalent.
- Data Provenance: The general context indicates this data would be from the United States, as it references the CDC's Morbidity and Mortality Weekly Report regarding influenza activity in the US.
- Retrospective or Prospective: The phrasing "performance characteristics were established during February through March 2011" suggests prospective data collection during a specific influenza season. However, no details on how many patient samples were tested are provided in this summary.

3. Number of Experts Used to Establish Ground Truth for Test Set and Qualifications

The provided summary does not explicitly state the number of experts used or their qualifications for establishing ground truth for the test set that determined the original performance characteristics.

For the H7N9 analytical study, the nature of establishing "minimum detectable level" implies laboratory testing rather than expert-based ground truth on clinical samples.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method for establishing the ground truth for the clinical test sets (both for the previously established performance and the H7N9 study).

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

No mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study or human reader improvement with/without AI assistance. This device is an immunoassay and an analyzer, not an AI-powered diagnostic imaging tool. Therefore, an MRMC study as typically understood in AI/imaging would not be applicable.

6. Standalone (Algorithm Only) Performance

Yes, the device's performance, as described by the "minimum detectable level" for H7N9 and the "performance characteristics" established for other influenza strains, represents its standalone performance. The Sofia Analyzer processes the results using "method-specific algorithms" and displays "Positive, Negative, or Invalid" results. There is no human-in-the-loop component for interpreting the test outcome itself; the human operates the device and reads its output.

7. Type of Ground Truth Used

H7N9 Analytical Study: The ground truth for the H7N9 study is based on a known concentration of H7N9 virus (Egg Infective Dose (EID)30/mL), which is a common method for establishing the Limit of Detection for in vitro diagnostic tests.
Previous Performance Characteristics (Clinical): The intended use statement mentions that for negative results, it is "recommended these results be confirmed by virus culture or FDA-cleared influenza A and B molecular assay." This implies that the ground truth for the clinical performance characteristics (established in 2011) was likely based on confirmation by these more definitive laboratory methods.

8. Sample Size for the Training Set

The document does not provide any information about a "training set" or its sample size. This is an in vitro diagnostic device based on immunofluorescence with specific reagent antibodies and an analyzer using "method-specific algorithms." The development process for such a device would involve extensive analytical validation (e.g., sensitivity, specificity, cross-reactivity) rather than a "training set" in the context of machine learning.

9. How Ground Truth for Training Set Was Established

As no training set is mentioned in the context of machine learning, this question is not applicable based on the provided text. The "method-specific algorithms" in the Sofia Analyzer would have been developed and validated through internal R&D and analytical studies, not typically through a machine learning training process with a dedicated training set and labeled ground truth in the same way an AI imaging algorithm would be.

Summary

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K131606

510(k) SUMMARY

JUL 0 5 2013

Submitted By:	Quidel Corporation10165 McKellar CourtSan Diego, California 92121Telephone: 858-552-7908Fax: 858-646-8045
Submission Contact:	John D. Tamerius, Ph.D.
Date Prepared:	May 30, 2013
Device Trade Name:	Sofia® Influenza A+B FIA
Common Name:	Influenza A+B immunological test
Predicate Devices:	Sofia Influenza A+B FIA
Device Classification/Name:	21 CFR 866.3330 / Influenza virus serologicalreagents
Intended Use:	These tests are used to aid in the diagnosis ofinfluenza and provide epidemiological information oninfluenza (21 CFR 866.3330). The Food and DrugAdministration has classified serological test systemsfor the detection of influenza virus as Class I.The Sofia Influenza A+B FIA employsimmunofluorescence to detect influenza A andinfluenza B viral nucleoprotein antigens in nasal swab,nasopharyngeal swab, and nasopharyngealaspirate/wash specimens taken directly fromsymptomatic patients. This qualitative test is intendedfor use as an aid in the rapid differential diagnosis ofacute influenza A and influenza B viral infections. Thetest is not intended to detect influenza C antigens. Anegative test is presumptive and it is recommendedthese results be confirmed by virus culture or FDA-cleared influenza A and B molecular assay. Negativeresults do not preclude influenza virus infections andshould not be used as the sole basis for treatment orother management decisions. The test is intended forprofessional and laboratory use.Performance characteristics for influenza A and Bwere established during February through March2011 when influenza viruses A/California/7/2009(2009 H1N1), A/Perth/16/2009 (H3N2), andB/Brisbane/60/2008 (Victoria-Like) were the

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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.

lf 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 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.

Physiologic Basis of the Test:

Influenza viruses are causative agents of highly contagious, acute, viral infections of the respiratory tract.

Influenza viruses are immunologically diverse, singlestranded RNA viruses. There are three types of influenza viruses: A. B. and C. Type A viruses are the most prevalent and are associated with most serious epidemics. Type B viruses produce a disease that is generally milder than that caused by type A. Type C viruses have never been associated with a large epidemic of human disease. Both Type A and B viruses can circulate simultaneously, but usually one type is dominant during a given season.

Every year in the United States, on average 5% to 20% of the population contract influenza; more than 200,000 people are hospitalized from influenza complications; and, about 36,000 people die from influenza-related causes. Some people, such as older people, voung children, and people with certain health conditions, are at high risk for serious influenza complications.

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Device Description:

The Sofia Influenza A+B FIA employs immunofluorescence technology that is used with the Sofia Analyzer to detect influenza virus nucleoproteins.

Note: Depending upon the user's choice, the cassette is either placed inside of the Sofia Analyzer for automatically timed development (Walk Away Mode) or placed on the counter or bench top for a manually timed development and then placed into the Sofia Analyzer to be scanned (Read Now Mode).
The Sofia Analyzer will scan the test strip and measure the fluorescent signal by processing the results using method-specific algorithms. The Sofia Analyzer will display the test results (Positive, Neqative, or Invalid) on the screen. The results can also be automatically printed on an integrated printer if this option is selected.

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Device Comparison:

ltem	Proposed Device	Proposed Device
Features	Sofia Influenza A+B FIA	Sofia Influenza A+B FIA
Intended Use	The Sofia Influenza A+B FIAemploys immunofluorescence todetect influenza A and influenza Bviral nucleoprotein antigens in nasalswab, nasopharyngeal swab, andnasopharyngeal aspirate/washspecimens taken directly fromsymptomatic patients. Thisqualitative test is intended for use asan aid in the rapid differentialdiagnosis of acute influenza A andinfluenza B viral infections. The testis not intended to detect influenza Cantigens. A negative test ispresumptive and it is recommendedthese results be confirmed by virusculture or FDA-cleared influenza Aand B molecular assay. Negativeresults do not preclude influenzavirus infections and should not beused as the sole basis for treatmentor other management decisions. Thetest is intended for professional andlaboratory use.Performance characteristics forinfluenza A and B were establishedduring February through March2011 when influenza virusesA/California/7/2009 (2009 H1N1),A/Perth/16/2009 (H3N2), andB/Brisbane/60/2008 (Victoria-Like)were the predominant influenzaviruses in circulation according tothe Morbidity and Mortality WeeklyReport from the CDC entitled"Update: Influenza Activity -- UnitedStates, 2010-2011 Season, andComposition of the 2011-2012Influenza Vaccine". Performancecharacteristics may vary againstother emerging influenza viruses.If infection with a novel influenzavirus is suspected based on currentclinical and epidemiologicalscreening criteria recommended bypublic health authorities, specimensshould be collected with appropriateinfection control precautions fornovel virulent influenza viruses andsent to state or local healthdepartment for testing. Virus cultureshould not be attempted in these	The Sofia Influenza A+B FIAemploys immunofluorescence todetect influenza A and influenza Bviral nucleoprotein antigens in nasalswab, nasopharyngeal swab, andnasopharyngeal aspirate/washspecimens taken directly fromsymptomatic patients. Thisqualitative test is intended for use asan aid in the rapid differentialdiagnosis of acute influenza A andinfluenza B viral infections. The testis not intended to detect influenza Cantigens. A negative test ispresumptive and it is recommendedthese results be confirmed by virusculture or FDA-cleared influenza Aand B molecular assay. Negativeresults do not preclude influenzavirus infections and should not beused as the sole basis for treatmentor other management decisions. Thetest is intended for professional andlaboratory use.Performance characteristics forinfluenza A and B were establishedduring February through March2011 when influenza virusesA/California/7/2009 (2009 H1N1),A/Perth/16/2009 (H3N2), andB/Brisbane/60/2008 (Victoria-Like)were the predominant influenzaviruses in circulation according tothe Morbidity and Mortality WeeklyReport from the CDC entitled"Update: Influenza Activity -- UnitedStates, 2010-2011 Season, andComposition of the 2011-2012Influenza Vaccine". Performancecharacteristics may vary aqainstother emerging influenza viruses.If infection with a novel influenzavirus is suspected based on currentclinical and epidemiologicalscreening criteria recommended bypublic health authorities, specimensshould be collected with appropriateinfection control precautions fornovel virulent influenza viruses andsent to state or local healthdepartment for testing. Virus cultureshould not be attempted in these
	cases unless a BSL 3+ facility isavailable to receive and culture	cases unless a BSL 3+ facility isavailable to receive and culture
	specimens.	specimens.
Item	Proposed Device	Proposed Device
Features	Sofia Influenza A+B FIA	Sofia Influenza A+B FIA
Read Results	Read results on instrumentscreen or print with optionalprinter	Read results on instrumentscreen or print with optionalprinter
Instrument	Sofia Analyzer	Sofia Analyzer
Calibrator	Yes - Calibration Cassette and QCCard provided	Yes - Calibration Cassette and QCCard provided
SpecimenTypes	nasal swab, nasopharyngeal swab,and nasopharyngeal aspirate/wash	nasal swab, nasopharyngeal swab,and nasopharyngeal aspirate/wash
Read ResultTime	15 Minutes	15 Minutes
ExternalControls	Test kit contains Positive andNegative Control swabs	Test kit contains Positive andNegative Control swabs

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Summary of Performance Data:

An analytical study was performed to assess the ability of the Sofia Influenza A+B FIA to detect the Influenza A virus H7N9 (A/Anhui/1/2013) and establish the Limit of Detection.

Conclusion:

The results of this study show that Sofia Influenza A+B FIA detects H7N9 with a minimum detectable level of 3.95 x 10° Egg Infective Dose (EID)30/mL. The Sofia Influenza A+B FIA is substantially equivalent with the current Sofia Influenza A+B FIA.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

JOHN D TAMERIUS SENIOR VICE PRESIDENT OF CLINICAL AND REGULATORY AFFAIRS QUIDEL CORPORATION 10165 MCKELLAR COURT SAN DIEGO CA 92121

July 5,2013

Re: K131606

Trade/Device Name: Sofia® Influenza A+B FIA Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza virus serological reagents Regulatory Class: I Product Code: GNX Dated: May 30, 2013 Received: June 05, 2013

Dear Dr. Tamerius:

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 rou may, aroney interest 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 (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.

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Page 2-Dr. Tamerius

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fdag.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 Small Manufacturers, International and Consumer Assistance 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,

Sally A. Hojvat -S

Sally A. Hojvat Ph.D. M.Sc Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Intended Use

510(k) Number (if known): K131606

Device Name: Sofia® Influenza A+B FIA

Intended Use: The Sofia Influenza A+B FJA employs immunofluorescence to detect influenza B viral nucleoprotein antigens in nasal swab, and nasopharyngeal aspiratelwash specimens taken directly from symptomatic patients. This qualitative test is intended for use as an aid in the rapid differential diagnosis of acute influenza A and influenza B viral infections. The test is not intended to detect influenza C antigens. A negalive test is presumptive and it is recommended these results be confirmed by virus culture or an FDA-cleared influenza A and B molecular assay. Negative results do not preclude influenza virus infections and should not be used as the sole basis for treatment or other management decisions. The test is intended for professional and laboratory use.

Performance characteristics for influenza A and B were established during February through March 2011 when influenza viruses A/California/7/2009 (2009 H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008 (Victoria-Like) were the oredominant influenza viruses in circulation according to the Morbidity and Mortality Weekly Report from the CDC entiled "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.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH; Office of In Vitro Diagnostics and Radiological Health (OlR)

Tamara V. Feldblyum -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

510(k) K131606

Regulation Number and Section

§ 866.3330 Influenza virus serological reagents.

(a)
Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.