The CareStart™ Flu A&B Plus is an in vitro rapid immunochromatographic assay for the qualitative detection of influenza virus type A and B nucleoprotein antigens directly from nasopharyngeal swab specimens of symptomatic patients.

The test is intended for use as an aid in the rapid differential diagnosis of acute influenza type A and B viral infections. This test is intended to distinguish between influenza type A and/or B virus in a single test. This test is not intended to detect influenza type C viral antigens. Negative test results are presumptive and should be confirmed by viral 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 basis for treatment or other patient management decisions.

Performance characteristics for influenza A and B were established during the 2018-2019 influenza season when influenza A/H3N2, A/H1N1pdm09, and B/Victoria were the predominant influenza viruses in circulation. When other influenza viruses are emerging, performance characteristics may vary.

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. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to received and culture specimens.

Device Description

The CareStart™ Flu A&B Plus test is an immunochromatographic assay for detection of extracted influenza type A and B virus nucleoprotein antigens in nasopharyngeal specimens.

Nasopharyngeal swabs require a sample preparation step in which the sample is eluted and washed off into the extraction buffer solution. Extracted swab sample is added to the sample well of the test device to initiate the test. When the swab sample migrates in the test strip, influenza A or B viral antigens bind to anti-influenza antibodies conjugated to indicator particles in the test strip forming an immune complex. The immune complex is then captured by each test line and control line on the membrane as it migrates through the strip.

Test results are interpreted at 10 minutes. The presence of two colored lines, a purplecolored line in the control region "C" and a red-colored line in the influenza A test region "A", indicates influenza A positive. The presence of two colored lines, a purplecolored line in the control region "C" and a blue-colored line in the influenza B test region "B", indicates influenza B positive. The presence of three colored lines, a purple-colored line in the control region "C", a red-colored line in the influenza A test region "A", and a blue-colored line in the influenza B test region "B indicates, influenza A and B dual positive result. The absence of a line on both influenza A and B test regions with a purple-colored line in the control region "C" indicates negative. No appearance of purple-colored line in the control region "C" indicates invalid test.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device Name: CareStart™ Flu A&B Plus (Influenza Virus Antigen Detection Test System)

General Acceptance Criteria (Implied by FDA 510(k) Clearance):
The primary acceptance criterion for a 510(k) submission is that the device is substantially equivalent to a legally marketed predicate device. This is demonstrated by showing that the new device has the same intended use and technological characteristics, and that its performance is at least as safe and effective as the predicate device. Specific performance criteria are established through analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values (e.g., "PPA must be >X%"). Instead, the performance estimates are presented, and the implication is that these results demonstrate substantial equivalence to the predicate device. For the purpose of this analysis, I will treat the reported performance as the "met criteria" that led to substantial equivalence.

Performance Metric	Acceptance Criteria (Implied/Demonstrated)	Reported Device Performance
Clinical Performance (Influenza A)	Sufficiently high PPA and NPA compared to molecular assay	PPA: 79.9% (95% CI: 75.7% – 83.7%) NPA: 98.4% (95% CI: 97.0% – 99.2%)
Clinical Performance (Influenza B)	Sufficiently high PPA and NPA compared to molecular assay	PPA: 88.2% (95% CI: 65.7% – 96.7%) (Prospective) PPA: 96.6% (95% CI: 91.5% – 98.7%) (Retrospective) NPA: 100.0% (95% CI: 99.6% – 100.0%) (Prospective) NPA: 97.8% (95% CI: 88.4% – 99.6%) (Retrospective)
Analytical Sensitivity (LoD)	Detection of virus strains at specified concentrations	All tested strains detected at concentrations ranging from $2.0 \times 10^{5.2}$ to $1.6 \times 10^{6.4}$ for Influenza A and $2.0 \times 10^{5.5}$ to $1.6 \times 10^{6.4}$ for Influenza B, with 95-100% reactivity.
Reactivity (Inclusivity)	Detection of various influenza A and B strains	All 15 Influenza A and 10 Influenza B strains detected in 3/3 replicates at specified concentrations.
Analytical Specificity (Cross-Reactivity/Interference)	No false positives (cross-reactivity); no interference with positive samples	No false positives with 31 bacteria and 15 non-influenza viruses. No interference with influenza A/B positive samples. Biotin concentrations >500 ng/ml can cause false negative influenza A results (caveat).
Reproducibility	High agreement across sites, operators, and days	100.0% overall agreement for all sample categories across 3 sites, 3 operators, and 5 days.
Lot-to-Lot Precision	Consistent results across different reagent lots	100.0% agreement across 3 reagent lots for all sample categories.

2. Sample Size Used for the Test Set and Data Provenance

Clinical Test Set:
- Prospective Clinical Study: 944 evaluable nasopharyngeal swab specimens.
  - Provenance: Collected from symptomatic patients during the 2018-2019 influenza season at 10 Point-of-Care investigational sites throughout the U.S. (prospective, U.S. origin).
- Retrospective Study (supplemental for Influenza B): 162 swab samples prepared from archived respiratory specimens.
  - Provenance: Archived respiratory specimens from patients with influenza-like symptoms, confirmed positive or negative by an FDA-cleared molecular assay. Samples were distributed among four investigational sites (retrospective, likely U.S. origin, as it supplemental for the U.S. prospective study).
Analytical Sensitivity (LoD): 20 replicates per virus strain (8 strains tested).
Analytical Sensitivity (Reactivity/Inclusivity): 3 replicates per virus strain (25 strains tested).
Analytical Specificity (Cross-Reactivity/Interference): 3 replicates per organism/virus, both with and without influenza viruses (31 bacteria, 15 non-influenza viruses, 30 interfering substances).
Reproducibility Study: 7 sample categories tested in a blinded manner by 3 operators at 3 sites on 5 non-consecutive days (7 samples * 3 operators * 3 sites * 5 days = 315 tests, per virus type if applicable). Counted as 135/135 for each category overall.
Lot-to-Lot Precision: 7 sample categories tested across 3 reagent lots (counted as 27/27 for each category overall).

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

The document does not specify the number or qualifications of experts for establishing ground truth.

Clinical Study Ground Truth: The ground truth for the clinical studies (prospective and retrospective) was established using an FDA-cleared influenza A and B molecular assay (comparator method). For discrepant results in the prospective study, an alternative FDA-cleared molecular assay was used for investigation. These are laboratory-based, highly sensitive and specific molecular tests for influenza, which are considered a gold standard for pathogen detection.
Analytical Studies Ground Truth: For analytical studies (LoD, Reactivity, Cross-Reactivity, Interference, Reproducibility, Lot-to-Lot Precision), the ground truth was inherent to the carefully prepared samples (e.g., known virus concentrations, known interfering substances).

4. Adjudication Method for the Test Set

Clinical Studies: For the prospective clinical study, discrepancies between the CareStart™ Flu A&B Plus results and the initial molecular comparator assay results were investigated using an alternative FDA-cleared molecular influenza A/B assay. The results of this secondary testing were captured in footnotes but not included in the primary calculations of the performance estimates. This suggests a form of 2+1 adjudication not directly applied to the final performance metrics but used for understanding discrepancies.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is an in vitro rapid immunochromatographic assay (a rapid diagnostic test kit) and does not involve AI assistance or human readers interpreting AI outputs. The results are interpreted visually by a human or using a simple instrument (like the predicate, though the proposed device is visually interpreted). Therefore, an MRMC study related to AI assistance for human readers was not performed.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, in essence, the "device performance" in the clinical and analytical studies represents the standalone performance of the assay. The CareStart™ Flu A&B Plus itself is a rapid test that produces visual results. The clinical studies compare the device's output (positive/negative for Flu A/B) directly against a molecular truth, effectively testing its "standalone" diagnostic capabilities without a human interpretation model beyond reading a test line. The detection format is "Visual determination of presence or absence of colored line indicators" for the proposed device, indicating it functions as a standalone diagnostic tool without requiring an additional human interpretation step or an algorithm to read the result in a complex way.

7. The type of ground truth used

Molecular Assay: The primary ground truth for clinical performance evaluation (prospective and retrospective studies) was an FDA-cleared influenza A and B molecular assay. An alternative FDA-cleared molecular assay was used to investigate discrepant results.
Known Concentrations/Absence of Analytes: For analytical studies (LoD, Reactivity, Cross-Reactivity, Interference, Reproducibility, Lot-to-Lot Precision), the ground truth was based on samples with known concentrations of specific virus strains or known absence of target analytes/presence of interfering substances.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI. As a rapid diagnostic test, the device's development typically involves iterative design and testing using various lab-prepared and clinical samples, which implicitly serve as a development/training phase. However, there isn't a formally described training set as one might see for an AI algorithm. The performance evaluation presented focuses on the validation of the device.

9. How the ground truth for the training set was established

As there is no explicitly defined "training set" in the provided document, the method for establishing its ground truth is not described. The analytical and clinical studies described serve as validation of the final device. The ground truth for those validation studies was established through FDA-cleared molecular assays or by controlled preparation of samples with known viral content.

Summary

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February 18, 2020

Access Bio, Inc. Jongrak Kim Department General Manager, Regulatory Affairs 65 Clyde Road, Suite A. Somerset, New Jersey 08873

Re: K191514

Trade/Device Name: CareStart Flu A&B Plus Regulation Number: 21 CFR 866.3328 Regulation Name: Influenza Virus Antigen Detection Test System Regulatory Class: Class II Product Code: PSZ Dated: Nov 20, 2019 Received: Nov 21, 2019

Dear Jongrak Kim:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Steven Gitterman, M.D., Ph.D. Deputy Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K191514

Device Name CareStart™ Flu A&B Plus

Indications for Use (Describe)

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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Image /page/3/Picture/0 description: The image shows the logo for Access Bio, Inc. The logo includes a blue square with a flower design and a green stem. The text "Access Bio, Inc." is written in bold, black letters, and the address "65 Clyde Rd, Suite A, Somerset, NJ 08873" is written below the company name.

Section 5. 510(k) Summary of Safety and Effectiveness

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR 807.92.

The assigned 510(k) number is: K191514

5.1. Submitter

Company Name: Access Bio Incorporate -
Address: 65 Clyde Road, Suite A, Somerset, NJ 08873 -
Phone Number: -1-732-873-4040
Fax Number: 1-732-873-4043 -
FDA Registration Number: -3003966368

5.2. Contact Person

-Jongrak Kim / Manager, Regulatory Affairs Division
Sang Joon Han / Manager, Research and Development Division -

5.3. Device Information

-Trade Name: CareStart™ Flu A&B Plus -Common Name: Influenza virus antigen detection test system
-Device Class: Class II under 21 CFR 866.3328
Devices Detecting Influenza A and B Virus -Classification Name: Antigens
Product Code: -PSZ

5.4. Predicate Device

BD Veritor™ System for Rapid Detection of Flu A -Device Name: + B CLIA waived Kit -510(k) Number: K180438 - Manufacturer: Becton, Dickinson and Company

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Image /page/4/Picture/1 description: The image shows the logo of Access Bio, Inc. The logo includes a blue square with a flower design inside. The text "Access Bio, Inc." is written in bold, black letters. Below the company name is the address, which is "65 Clyde Rd, Suite A, Somerset".

5.5. Device Description

The CareStart™ Flu A&B Plus test is an immunochromatographic assay for detection of extracted influenza type A and B virus nucleoprotein antigens in nasopharyngeal specimens.

Intended Use / Indications for Use 5.6.

The test is intended for use as an aid in the rapid differential diagnosis of acute

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ss Bio. Inc.

65 Clyde Rd. Suite A. Somerset, NJ 08873 II Tel: (732)-873-4040 II Fax: (732)-873-4043 II info@accessbio.net

influenza type A and B viral infections. This test is intended to distinguish between influenza type A and/or B virus in a single test. This test is not intended to detect influenza type C viral antigens. Negative test results are presumptive and should be confirmed by viral 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 basis for treatment or other patient management decisions.

Contents Name	Quantity(in a kit)	Description
Test device	20 each	Foil pouched test device containing one teststrip which is encased on plastic devicecassette.
Extraction vial / cap	20 vials andcaps	The extraction vial contains 400 µL extractionbuffer solution.
Nasopharyngeal swab	20 each	Swab for nasopharyngeal specimencollection.
Influenza A positivecontrol swab	1 each	Influenza A positive and influenza B negativeexternal control swab.Inactivated influenza A antigen is dried on thetip of the swab.
Influenza B positivecontrol swab	1 each	Influenza A negative and influenza B positiveexternal control swab.Inactivated influenza B antigen is dried onthe tip of the swab.

5.7. Product Contents

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Influenza Negativecontrol swab	1 each	Influenza A negative and influenza Bnegative external control swab.Inactivated Group A, Streptococcus is driedon the tip of the swab.
Package insert	1 each	Instructions for use
Quick ReferenceInstructions (QRI)	1 each	Quick reference instructions
The following materials are needed but not provided:
• Pair of gloves	• Timer / Pen	• Biohazard or sharps container

5.8. Comparison of Technological Characteristics with the Predicate Device

Contents	Predicate Device	Proposed Device
	BD VeritorTM Systemfor Rapid Detection of Flu A+B	CareStartTM Flu A&B Plus
510(k) Number	K180438	K191514
RegulationNumber	21 CFR 866.3328	Same
RegulationName	Influenza virus antigen detectiontest system	Same
RegulatoryClass	Class II	Same
Product Code	PSZ	Same
Assay Target	Influenza A and B nucleoproteinantigens	Same
	Predicate Device	Proposed Device
Contents	BD VeritorTM Systemfor Rapid Detection of Flu A+B	CareStartTM Flu A&B Plus
Intended Use	The BD VeritorTM 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 VeritorTM System for Rapid Detection of Flu A+B (also referred to as the BD VeritorTM System and BD VeritorTM 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 lineage	The CareStartTM Flu A&B Plus is anin vitro rapidimmunochromatographic assay forthe qualitative detection of influenzavirus type A and B nucleoproteinantigens directly fromnasopharyngeal swab specimens ofsymptomatic patients.The test is intended for use as anaid in the rapid differential diagnosisof acute influenza type A and B viralinfections. This test is intended todistinguish between influenza typeA and/or B virus in a single test.This test is not intended to detectinfluenza type C viral antigens.Negative test results arepresumptive and should beconfirmed by viral culture or anFDA-cleared influenza A and Bmolecular assay. Negative resultsdo not preclude influenza virusinfections and should not be usedas the basis for treatment or otherpatient management decisions.Performance characteristics forinfluenza A and B were establishedduring the 2018-2019 influenzaseason when influenza A/H3N2,A/H1N1pdm09, and B/Victoria werethe predominant influenza viruses incirculation. When other influenzaviruses are emerging, performancecharacteristics may vary.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 for
	Predicate Device	Proposed Device
Contents	BD VeritorTM Systemfor Rapid Detection of Flu A+Band B/Yamagata lineage were thepredominant influenza viruses incirculation according to theMorbidity 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 the state or local healthdepartment for testing. Virus cultureshould not be attempted in thesecases unless a BSL 3+ facility isavailable to receive and culturespecimens.	CareStartTM Flu A&B Plusnovel virulent influenza viruses andsent to the state or local healthdepartment for testing. Viral cultureshould not be attempted in thesecases unless a BSL 3+ facility isavailable to received and culturespecimens.
Specimens Type	Nasopharyngeal andnasal swabs	Nasopharyngeal swabs
Assay Result	Qualitative	Same
Technology	Immunochromatographic assay	Same
Instrumentation	BD VeritorTM System Reader	None
	Predicate Device	Proposed Device
Contents	BD Veritor™ Systemfor Rapid Detection of Flu A+B	CareStart™ Flu A&B Plus
DetectionFormat	An optoelectronic instrumentevaluates the line signal intensitiesat each of the spatially defined testand control line positions, interpretsthe results using a scoringalgorithm, and reports a positive,negative, or invalid result on theLCD screen based on pre-setthresholds.	Visual determination of presence orabsence of colored line indicatorsfor the test line and control line onthe test strip indicate the presenceof influenza A and/or B antigen.
Time to Result	10 minutes	Same
Intendedenvironment foruse	Prescription use and CLIA waived	Prescription use
StorageCondition	2-30 °C	1-30 °C
Controls	Kit Flu A+/B- dry swab proceduralcontrolKit Flu B+/A- dry swab proceduralcontrolInternal positive controlInternal negative control	Influenza A positive control swabInfluenza B positive control swabInfluenza negative control swabInternal positive control

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Access Bio, Inc.

65 Clyde Rd. Somerset, NJ 08873 II Tel: (732)-873-4040 II Fax: (732)-873-4043 II info@accessbio.net

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Summary of Performance 5.9.

To verify and validate the device performance and characteristics, the following studies were conducted.

5.9.1. Analytical Sensitivity: Limit of Detection (LoD)

To determine the Limit of Detection (LoD) of CareStart™ Flu A&B Plus, four influenza A virus with two common currently or recently circulating influenza A subtypes (i.e.,

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Access Bio, Inc.

H3N2, H1N1 pdm09) and four influenza B virus with two genetic lineages (i.e., Victoria lineage and Yamagata lineage) were tested in this study.

In this study, each influenza virus strain of the panel was serially diluted to the concentration at which at least one negative result was obtained from replicate testing. The estimated LoD for each virus strain was confirmed by testing twenty replicates. The results presented in the table below.

Influenza Virus			% Reactive (No. of positive / Total No. of Replicates)
Type/Subtype	Strain	LoD (EID50/ml)
A (H3N2)	A/Perth/16/2009	$3.2 x 10^{4.9}$	100% (20/20)
A (H3N2)	A/Singapore/INFIMH-16-0019/2016	$2.0 x 10^{5.2}$	100% (20/20)
A (H1N1) pdm09	A/California/07/2009	$3.2 x 10^{4.9}$	100% (20/20)
A (H1N1) pdm09	A/Michigan/45/2015	$3.2 x 10^{4.2}$	100% (20/20)
B (Victoria lineage)	B/Brisbane/60/2008	$2.0 x 10^{5.5}$	95% (19/20)
B (Victoria lineage)	B/Colorado/06/2017	$1.6 x 10^{6.4}$	100% (20/20)
B (Yamagata lineage)	B/Wisconsin/01/2010	$4.0 x 10^{4.9}$	100% (20/20)
B (Yamagata lineage)	B/Phuket/3073/2013	$1.6 x 10^{5.5}$	100% (20/20)

EID50= 50% Egg Infectious Dose

5.9.2. Analytical Sensitivity: Reactivity (Inclusivity)

To determine the detectability of CareStart™ Flu A&B Plus, fifteen strains of influenza A virus representing each of three common currently or recently circulating influenza A subtypes (i.e., H3N2, H3N2v, and H1N1 pdm09) and ten strains of influenza B virus representing each of two influenza B genetic lineages (i.e., Yamagata lineage and Victoria lineage) were tested in this study.

In this study, each influenza virus strain of the panel was serially diluted to the concentration at which at least one negative result was obtained from replicate testing. All viruses were detected in all three replicates at the concentrations shown below.

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Influenza Virus		Lowest Concentrationdetected byCareStart™ Flu A&BPlus	Test Results(# of positives /# of replicates)
Subtype	Virus Strain Name		Flu AResult	Flu BResult
	A/Alaska/232/2015	2.6 x 106 CEID50/ml	3/3	0/3
	A/California/02/2014	5.8 x 102 TCID50/ml	3/3	0/3
A (H3N2)	A/Hong Kong/4801/2014	9.6 x 105 CEID50/ml	3/3	0/3
	A/Michigan/15/2014	9.3 x 104 FFU/ml	3/3	0/3
	A/Texas/71/2017	9.3 x 104 FFU/ml	3/3	0/3
	A/Indiana/08/2011	8.1 x 102 TCID50/ml	3/3	0/3
A (H3N2)v	A/Minnesota/11/2010	2.2 x 104 CEID50/ml	3/3	0/3
	A/Bangladesh/3002/2015	1.3 x 105 CEID50/ml	3/3	0/3
	A/Dominican Republic/7293/2013	5.0 x 103 TCID50/ml	3/3	0/3
	A/Iowa/53/2015	2.9 x 106 CEID50/ml	3/3	0/3
A (H1N1)pdm09	A/Massachusetts/15/2013	1.6 x 106 CEID50/ml	3/3	0/3
	A/Michigan/272/2017	9.6 x 103 TCID50/ml	3/3	0/3
	A/New Hampshire/02/2010	1.8 x 106 CEID50/ml	3/3	0/3
	A/South Carolina/2/2010	2.5 x 105 CEID50/ml	3/3	0/3
	A/St. Petersburg/61/2015	9.3 x 105 CEID50/ml	3/3	0/3
	B/New Jersey/1/2012	8.8 x 104 TCID50/ml	0/3	3/3
	B/Colorado/6/2017	1.6 x 106 CEID50/ml	0/3	3/3
B (Victorialineage)	B/Florida/78/2015	1.7 x 106 CEID50/ml	0/3	3/3
	B/Hong Kong/286/2017	2.7 x 103 TCID50/ml	0/3	3/3
	B/Maryland/15/2016	1.3 x 103 TCID50/ml	0/3	3/3
	B/Guangdong-Liwan/1133/2014	1.8 x 106 CEID50/ml	0/3	3/3
B(Yamagatalineage)	B/Massachusetts/2/2012	1.0 x 107 CEID50/ml	0/3	3/3
	B/Phuket/3073/2013	1.1 x 106 CEID50/ml	0/3	3/3
	B/Texas/06/2011	6.2 x 106 CEID50/ml	0/3	3/3
	B/Utah/09/2014	6.3 x 104 CEID50/ml	0/3	3/3

CEID50= 50% Chicken Embryo Infectious Dose TCID50= 50% Tissue Culture Infectious Dose FFU= Focus Forming Assay Unit

Analytical Specificity: Cross-Reactivity (Exclusivity) and Microbial 5.9.3. Interference

The potential cross-reactivity (exclusivity) of a panel of common organisms was evaluated with influenza negative samples using the CareStart™ Flu A&B Plus.

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65 Clyde Rd. Suite A. Somerset, NJ 08873 II Tel: (732)-873-4040 II Fax: (732)-873-4043 II info@accessbio.net

Potential microbial interference was evaluated with samples containing influenza A or influenza B at approximately 2x LoD. A total of 31 bacteria were tested at a target concentration of approximately 107 cfu/ml with the exception of Mycoplasma pneumoniae, which was tested at a final concentration of 1.5 x 103 cfu/ml. The 15 non-influenza viruses were tested at concentrations between 105.86 and 104-2 TCIDsolml. All influenza negative samples gave negative results at the concentrations of the potentially cross-reactive common organisms tested showing no crossreactivity with CareStart™ Flu A&B Plus assay. All samples with influenza A or influenza B tested positive showing no microbial interference at the concentrations of the potentially interfering common organisms tested.

Bacteria	ATCC#	StockConcentration (cfu/ml)	TestingConcentration (cfu/ml)	Results oftriplicatewithoutinfluenzavirus (# ofpositives / #ofreplicates)	Results oftriplicate inpresence ofinfluenza Avirus(# ofpositives / #ofreplicates)	Results oftriplicate inpresence ofinfluenza Bvirus(# ofpositives / #ofreplicates)
Acinetobactercalcoaceticus	17902	109	107	0/3	3/3	3/3
Bordetella pertussis	9340	109	107	0/3	3/3	3/3
Candida albicans	11006	109	107	0/3	3/3	3/3
Chlamydophilapneumoniae	53592	109	107	0/3	3/3	3/3
Corynebacteriumdiphtheriae	296	109	107	0/3	3/3	3/3
Enterococcus faecalis	4079	109	107	0/3	3/3	3/3
Escherichia coli	26	109	107	0/3	3/3	3/3
Gardnerella vaginalis	14018	109	107	0/3	3/3	3/3
Haemophilusinfluenzae	49144	109	107	0/3	3/3	3/3
Klebsiellapneumoniae	33495	109	107	0/3	3/3	3/3
Lactobacillus casei	393	109	107	0/3	3/3	3/3
Legionellapneumophila	33152	109	107	0/3	3/3	3/3

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Listeriamonocytogenes	7302	109	107	0/3	3/3	3/3
Moraxella catarrhalis	25238	109	107	0/3	3/3	3/3
Mycobacteriumtuberculosis	NR-122	109	107	0/3	3/3	3/3
Mycoplasmapneumoniae	29342	1.5 x 105	1.5 x 103	0/3	3/3	3/3
Neisseriagonorrhoeae	19424	109	107	0/3	3/3	3/3
Neisseria meningitidis	13077	109	107	0/3	3/3	3/3
Neisseria sicca	9913	109	107	0/3	3/3	3/3
Proteus vulgaris	33420	109	107	0/3	3/3	3/3
Pseudomonasaeruginosa	9721	109	107	0/3	3/3	3/3
Staphylococcusaureus	12600	109	107	0/3	3/3	3/3
Staphylococcusepidermidis	14990	109	107	0/3	3/3	3/3
Serratia marcescens	13880	109	107	0/3	3/3	3/3
Streptococcusmutans	25175	109	107	0/3	3/3	3/3
Streptococcuspneumoniae	49136	109	107	0/3	3/3	3/3
Streptococcuspyogenes	19615	109	107	0/3	3/3	3/3
Streptococcus sp.Group B	12386	109	107	0/3	3/3	3/3
Streptococcus sp.Group C	12388	109	107	0/3	3/3	3/3
Streptococcus sp.Group F	700231	109	107	0/3	3/3	3/3
Streptococcussanguinis	10556	109	107	0/3	3/3	3/3

cfu/ml: colony-forming units per milliliter

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65 Clyde Rd. Suite A. Somerset, NJ 08873 II Tel: (732)-873-4040 II Fax: (732)-873-4043 II info@accessbio.net

Viruses	ATCC#	StockConcentration(TCID50/ml)	TestingConcentration(TCID50/ml)	Results oftriplicatewithoutinfluenzavirus (# ofpositives / #ofreplicates)	Results oftriplicate inpresence ofinfluenza Avirus(# ofpositives / #ofreplicates)	Results oftriplicate inpresence ofinfluenza Bvirus(# ofpositives / #ofreplicates)
Adenovirus 1	VR-1	107.20	105.20	0/3	3/3	3/3
Adenovirus 7	VR-7	106.45	105.45	0/3	3/3	3/3
Coronavirus (OC43)	VR-1558	105.45	105.45	0/3	3/3	3/3
Coronavirus (229E)	VR-740	104.45	104.45	0/3	3/3	3/3
Cytomegalovirus	VR-538	105.95	104.95	0/3	3/3	3/3
HumanCoxsackievirus B4	VR-184	107.45	105.45	0/3	3/3	3/3
Humanmetapneumovirus	NR-22227	2.8 x 106	2.8 x 105	0/3	3/3	3/3
Measles	VR-24	104.20	104.20	0/3	3/3	3/3
Mumps (Enders)	VR-106	105.20	105.20	0/3	3/3	3/3
Parainfluenza virustype 1	VR-94	107.86	105.86	0/3	3/3	3/3
Parainfluenza virustype 2	VR-92	107.20	105.20	0/3	3/3	3/3
Parainfluenza virustype 3	VR-93	107.20	105.20	0/3	3/3	3/3
Respiratory SyncytialVirus Type B	VR-1400	106.20	105.20	0/3	3/3	3/3
Rhinovirus 1A	VR-1559	107.20	105.20	0/3	3/3	3/3
Rubella	VR-315	106.20	105.20	0/3	3/3	3/3

TCID50= 50% Tissue Culture Infectious Dose

5.9.4. Analytical Specificity: Interfering Substances Effect

To assess the potential interference effects, the CareStart™ Flu A&B Plus was evaluated with thirty substances naturally or artificially present in the respiratory specimen or nasal cavity/nasopharynx.

The positive samples were prepared using the influenza A and B virus strains diluted to

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a concentration approximately two times the respective LoD levels. Each influenza strain combined with each interfering substance was evaluated separately. Negative samples were prepared by adding each interfering substance to the Universal Transport Medium (UTM). Each positive and negative sample, combined with each interfering substance, was tested in triplicate. None of the thirty potential interfering substances tested produced false positive or false negative test results using CareStart™ Flu A&B Plus with influenza positive and negative samples at the concentrations specified below.

InterferingSubstances	Concentration Tested	Test Results (# of positives / # of replicates)
		A/Perth/16/2009	A/Michigann/45/2015	B/Colorado/06/2017	B/Phuket/3073/2013	NegativeSamples
Acetaminophen	10 mg/ml	3/3	3/3	3/3	3/3	0/3
Acetyl salicylicacid	15 mg/ml	3/3	3/3	3/3	3/3	0/3
Beclomethasone	0.5 mg/ml	3/3	3/3	3/3	3/3	0/3
Benzocaine	5 mg/ml	3/3	3/3	3/3	3/3	0/3
Budesonide	2 mg/ml	3/3	3/3	3/3	3/3	0/3
Chlorpheniraminemaleate	5 mg/ml	3/3	3/3	3/3	3/3	0/3
Dexamethasone	1 mg/ml	3/3	3/3	3/3	3/3	0/3
DextromethorphanHBr	2 mg/ml	3/3	3/3	3/3	3/3	0/3
DiphenhydramineHCl	5 mg/ml	3/3	3/3	3/3	3/3	0/3
Ephedrine HCl	10 mg/ml	3/3	3/3	3/3	3/3	0/3
Flunisolide	5 mg/ml	3/3	3/3	3/3	3/3	0/3
Fluticasone	1 mg/ml	3/3	3/3	3/3	3/3	0/3
Guaiacol GlycerylEther	20 mg/ml	3/3	3/3	3/3	3/3	0/3
HistamineDihydrochloride	10 mg/ml	3/3	3/3	3/3	3/3	0/3

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Interfering	Concentra	Test Results (# of positives / # of replicates)
Substances	tion Tested	A/Perth/16/2009	A/Michigann/45/2015	B/Colorado/06/2017	B/Phuket/3073/2013	NegativeSamples
Menthol	10 mg/ml	3/3	3/3	3/3	3/3	0/3
Mometasone	1 mg/ml	3/3	3/3	3/3	3/3	0/3
Mucin	2%	3/3	3/3	3/3	3/3	0/3
Mupirocin	1 mg/ml	3/3	3/3	3/3	3/3	0/3
OTC Throat drop(Halls)	15%	3/3	3/3	3/3	3/3	0/3
OTC Throat drop(Ricola)	15%	3/3	3/3	3/3	3/3	0/3
OTC Nasal spray(Afrin)	15%	3/3	3/3	3/3	3/3	0/3
OTC Nasal spray(Vicks Sinex)	15%	3/3	3/3	3/3	3/3	0/3
OTC Nasal spray(Zicam)	15%	3/3	3/3	3/3	3/3	0/3
OxymetazolineHCl	10 mg/ml	3/3	3/3	3/3	3/3	0/3
Phenylephrine HCl	5 mg/ml	3/3	3/3	3/3	3/3	0/3
Phenylpropanolamine	5 mg/ml	3/3	3/3	3/3	3/3	0/3
Tobramycin	1 mg/ml	3/3	3/3	3/3	3/3	0/3
Triamcinolone	1 mg/ml	3/3	3/3	3/3	3/3	0/3
Whole Blood	2%	3/3	3/3	3/3	3/3	0/3
Zanamivir	1 mg/ml	3/3	3/3	3/3	3/3	0/3

The interfering effects of biotin concentrations ranging between 125 ng/mL and 2 µg/mL were tested in a separate study. Biotin concentrations up to 500 ng/ml did not lead to false results. Biotin concentrations >500 ng/ml can cause false negative influenza A results with the CareStart™ Flu A&B Plus.

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Access Bio. Inc.

65 Clyde Rd. Suite A. Somerset, NJ 08873 II Tel: (732)-873-4040 II Fax: (732)-873-4043 II info@accessbio.net

5.9.5. Expected Values

The prevalence of influenza varies from year to year, with outbreaks occurring during the fall and winter months. The influenza positivity rate is dependent upon many factors, including specimen collection, test method, and geographic location. Prevalence varies throughout the flu season and from location to location. The CareStart™ Flu A&B Plus prospective clinical study was conducted during the 2018-2019 influenza season. The following tables show the number of influenza A and influenza B positive cases and its percentage in four subject age categories, as observed during the clinical study.

	Positivity Rates for Influenza A with the CareStartTM Flu A&B Plusduring the Clinical Study
Age Group	Number ofNasopharyngealSwabSpecimens	Number ofInfluenza APositives	Influenza APositivityRate
≤5 Years of Age	174	61	35.1%
6-21 Years of Age	333	143	42.9%
22-59 Years of Age	394	101	25.6%
≥60 Years of Age	43	11	25.6%
Total	944	316	33.5%

	Positivity Rates for Influenza B with the CareStartTM Flu A&B Plus during the Clinical Study
Age Group	Number of Nasopharyngeal Swab Specimens	Number of Influenza B Positives	Influenza B Positivity Rate
≤5 Years of Age	174	2	1.1%
6-21 Years of Age	333	7	2.1%
22-59 Years of Age	394	5	1.3%
≥60 Years of Age	43	1	2.3%
Total	944	15	1.6%

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5.9.6. Prospective Clinical Study

The clinical performance characteristics of CareStart™ Flu A&B Plus were evaluated in a multi-site prospective study during the 2018-2019 influenza season in the U.S. against an FDA-cleared influenza A and B molecular assay. A total of 10 Point-of-Care investigational sites throughout the U.S. participated in the study. To be enrolled in the study, patients had to be presenting at the participating study centers with flu-like symptoms and meet inclusion/exclusion criteria.

Two nasopharyngeal swabs were collected from one nostril from each subject using standard collection methods. At all sites, the first collected nasopharyngeal swab was eluted in 3 ml of viral transport media and transported to the central laboratory for testing using the FDA-cleared molecular assay as a comparator method. The second collected nasopharyngeal swab was tested directly on CareStart™ Flu A&B Plus according to product instructions.

A total of 955 subjects were enrolled in this study. Of those, 11 specimens are unevaluable (i.e., four samples failed to meet inclusion criteria, two samples were not collected due to subject refusal after enrollment, one sample was transported to the central laboratory in damaged and leaking state, and four samples transported to the central laboratory were mislabeled). A total of 944 nasopharyngeal swab specimens were considered evaluable. The performance of the CareStart™ Flu A&B Plus for influenza A and influenza B as compared to the comparator method is presented in the tables below.

All discrepant results were investigated by testing using an alternative FDA-cleared molecular assay at the same central laboratory. The results of this testing are captured in the footnotes but were not included in the calculations of the performance estimates shown below.

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CareStart™ Flu A&B Plus Influenza A Performance against the Comparator Method

CareStartTM Flu A&B Plus –Influenza A	Molecular Comparator
	Positive	Negative	Total
Positive	307	9a	316
Negative	77b	551	628
Total	384	560	944
Positive Percent Agreement (PPA)	79.9% (95% CI: 75.7% – 83.7%)
Negative Percent Agreement (NPA)	98.4% (95% CI: 97.0% – 99.2%)

a Influenza A was detected in 2/9 false positive specimens using an alternative FDA-cleared molecular influenza A/B assay

b Influenza A was not detected in 15/77 false negative specimens using an alternative FDA-cleared molecular influenza A/B assay

CareStart™ Flu A&B Plus Influenza B Performance against the Comparator Method

CareStart™ Flu A&B Plus -	Molecular Comparator
Influenza B	Positive	Negative	Total
Positive	15	0	15
Negative	2a	927	929
Total	17	927	944
Positive Percent Agreement (PPA)	88.2% (95% CI: 65.7% – 96.7%)
Negative Percent Agreement (NPA)	100.0% (95% CI: 99.6% – 100.0%)

a Influenza B was detected in 2/2 false negative specimens using an alternative FDA-cleared molecular influenza A/B assay

CareStart™ Flu A&B Plus Influenza A and B Performance against the Comparator Method (Percent Agreement) by Age Group

		Prospective Study during the 2018-2019 influenza season
		Influenza A	Influenza B
≤5 Years of Age	PPA	83.3% (55/66)95% CI: 72.6% – 90.4%	100% (2/2)95% CI: 34.2% – 100%
	NPA	94.4% (102/108)95% CI: 88.4% – 97.4%	100% (172/172)95% CI: 97.8% – 100%
6-21 Years of Age	PPA	82.5% (141/171)95% CI: 76.1% - 87.4%	87.5% (7/8)95% CI: 52.9% – 97.8%
	NPA	98.8% (160/162)95% CI: 95.6% – 99.7%	100% (325/325)95% CI: 98.8% – 100%
22-59 Years of Age	PPA	74.1% (100/135)95% CI: 66.1% - 80.7%	83.3% (5/6)95% CI: 43.7% - 97.0%

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	NPA
	NPA	99.6% (258/259)95% CI: 97.8% – 99.9%	100% (388/388)95% CI: 99.0% – 100%
≥60 Years of Age	PPA	91.7% (11/12)95% CI: 64.6% – 98.5%	100% (1/1)95% CI: 20.7% – 100%
	NPA	100% (31/31)95% CI: 89.0% – 100%	100% (42/42)95% CI: 91.6% – 100%

5.9.7. Retrospective Study

Due to extremely low prevalence of influenza B observed during the 2018-2019 influenza season in the U.S., the prospective clinical study performance data were supplemented with data from a retrospective study testing 162 swab samples prepared from archived respiratory specimens that were obtained from patients with influenzalike symptoms and were confirmed positive or negative by an FDA-cleared molecular assay for influenza A and influenza B. These swab samples (112 samples positive for influenza B and 50 neqative samples) were distributed (blinded and randomized) among four of the investigational sites and the testing was incorporated into the daily workflow at each site during the prospective clinical study period.

All of the 162 swab specimens enrolled in the retrospective study were considered evaluable to supplement the prospective clinical performance data for influenza B. The performance of the CareStart™ Flu A&B Plus for influenza B with archived samples as compared to the FDA-cleared molecular method is presented in the table below.

CareStart™ Flu A&B Plus Influenza B (swab specimens prepared from frozen archived respiratory specimens) Performance against the Comparator Method

CareStart™ Flu A&B Plus – Influenza B(swab specimens prepared from frozen archivedrespiratory specimens)	Molecular Comparator
	Positive	Negative	Total
Positive	113	1	114
Negative	4	44	48
Total	117	45	162
Positive Percent Agreement (PPA)	96.6% (95% CI: 91.5% – 98.7%)
Negative Percent Agreement (NPA)	97.8% (95% CI: 88.4% – 99.6%)

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Reproducibility Study 5.9.8. -

The reproducibility study was performed to evaluate the reproducibility of the CareStart™ Flu A&B Plus with contrived swab samples at three Point-of-Care sites in the U.S. The test sample panels consisted of seven samples at various virus concentrations including near the respective LoD (i.e., true negative, high negative influenza A, low positive influenza A, moderate positive influenza A, high negative influenza B, low positive influenza B, and moderate positive influenza B). The sample panel was tested in a blinded manner by three operators at each of three test sites on five non-consecutive days. Agreement of obtained results with expected results was 100% across all sites, operators, and days.

	Site 1		Site 2		Site 3		Overall % Agreement and 95% CI
Sample Category	%	Count	%	Count	%	Count
True Negativea (no virus)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)
High Negative Aa (0.1x LoD)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)
Low Positive A (1x LoD)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)
Moderate Positive A (3x LoD)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)
High Negative Ba (0.1x LoD)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)
Low Positive B (1x LoD)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)
Moderate Positive B (3x LoD)	100.0%	45/45	100.0%	45/45	100.0%	45/45	100.0% (135/135) (97.2% - 100.0%)

Reproducibility by Study Site

a The expected results for true negative and high negative samples are negative results.

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5.9.9. Lot-to-Lot Precision

Three different lots of the CareStart™ Flu A&B Plus were evaluated for precision. Agreement of observed results with expected results was 100%. No variability was observed between reagent lots.

Sample Category	Reagent Lot 1		Reagent Lot 2		Reagent Lot 3		Overall % Agreement and 95% CI
	%	Count	%	Count	%	Count
True Negativea(no virus)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)
High Negative Aa(0.1x LoD)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)
Low Positive A(1x LoD)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)
Moderate Positive A(3x LoD)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)
High Negative Ba(0.1x LoD)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)
Low Positive B(1x LoD)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)
Moderate Positive B(3x LoD)	100%	9/9	100%	9/9	100%	9/9	100% (27/27)(87.5% - 100%)

a The expected results for true negative and high negative samples are negative results.

5.10. Conclusion

Based on the data submitted in this traditional 510(k) submission, the CareStart™ Flu A&B Plus has been shown to be substantially equivalent in terms of intended use, technological characteristics, and assay performance to the predicate device.

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.