Binax NOW Flu B Test is an in vitro rapid The immunochromatographic assay for the qualitative detection of influenza B nucleoprotein antigen in nasal wash and nasopharyngeal swab specimens from symptomatic patients. It is intended to aid in the rapid diagnosis of influenza B infections. Negative test results should be confirmed by cell culture.

Device Description

The Binax NOW® Binax Flu B Test is an immunochromatographic membrane assay used to detect influenza B nucleoprotein antigen in nasal wash and nasopharyngeal sswab specimens. A test strip, containing goldconjugated and immobilized anti-influenza B antibodies, is mounted on the right side of a cardboard, book-shaped hinged test device. Swab specimens require a sample preparation step, in which the sample is eluted off the swab into a saline solution. The nasal wash sample does not require any preparation. The sample to be tested is added to a pad at the top of the test strip, and the test device is closed. Influenza B antigen present in the sample reacts to bind anti-influenza B conjugated antibody. The resulting antigencomplexes are captured conjugate by anti-influenza antibody, immobilized forming the Sample Line. Immobilized Control Line antibody, which appears as a blue line in an untested device, captures a visualizing conjugate, forming a pink Control Line. The sample is contained, and results are available within 15 minutes.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Binax NOW® FLU B Test:

Binax NOW® FLU B Test Acceptance Criteria and Study Details

1. Acceptance Criteria and Reported Device Performance

Parameter	Acceptance Criteria (Implied by Predicate Equivalence)	Reported Device Performance
Analytic Sensitivity	Detects all tested influenza B strains.	100% positive result for 5 ATCC traceable influenza B strains across concentrations from 10^2 to 10^6 TCID50/ml, indicating detection of all tested strains.
Analytic Specificity (Cross-Reactivity)	No cross-reactivity with common respiratory bacteria and viruses at specified concentrations.	No cross-reactivity with 43 potential cross-reactants (bacteria tested at >1 x 10^6 organisms/ml; viruses at >1 x 10^5 TCID50/ml).
Clinical Sensitivity (Nasal Wash)	Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test).	71% (95% CI: 56%-83%)
Clinical Specificity (Nasal Wash)	Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test).	97% (95% CI: 93%-99%)
Overall Accuracy (Nasal Wash)	Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test).	92% (95% CI: 87%-95%)
Clinical Sensitivity (Nasopharyngeal Swab)	Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test).	58% (95% CI: 42%-73%)
Clinical Specificity (Nasopharyngeal Swab)	Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test).	97% (95% CI: 93%-99%)
Overall Accuracy (Nasopharyngeal Swab)	Substantially equivalent to predicate device (Quidel QuickVue® Influenza Test).	90% (95% CI: 85%-94%)
Interfering Substances	No interference with common substances, and should properly detect spiked virus.	No cross-reactivity with 19 potentially interfering substances, and expected results generated when spiked with limit of detection (LOD) level virus.
Reproducibility	High percentage of correctly interpreted samples across multiple sites and operators.	99% of 234 samples correctly interpreted in a blind study at 3 sites over 3 days.
Quality Control	Procedural control should indicate test failure accurately.	97% of devices correctly interpreted (positive, negative, or invalid) by operators testing 20 kit controls on 20 devices (9 rendered inoperative).

Note: The document primarily uses substantial equivalence to the predicate device as the overarching acceptance criterion, rather than explicit numerical thresholds. The reported performance metrics are presented to demonstrate this equivalence.

2. Sample Sizes and Data Provenance

Clinical Study Test Set Sample Size:
- 191 nasal wash specimens
- 182 nasopharyngeal swab specimens
Data Provenance:
- Country of Origin: Not explicitly stated, but the study was described as a "multi-site prospective study," suggesting data collected within the US, given the submission to the FDA.
- Retrospective/Prospective: Prospective clinical studies. All specimens were "freshly collected and characterized" from "patients presenting with influenza-like symptoms."

3. Number and Qualifications of Experts for Ground Truth

The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical study.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method for the test set results beyond comparing the Binax NOW® test performance "versus viral cell culture."

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

No, a MRMC comparative effectiveness study was not done. This study focuses on the standalone performance of the diagnostic test compared to a laboratory reference method.

6. Standalone Performance Study (Algorithm Only)

Yes, a standalone performance study was done. The entire "Performance Summary" and "Clinical Sensitivity and Specificity" sections describe the direct comparison of the Binax NOW® test results (the "algorithm only" in this context, as it's a diagnostic device) against viral cell culture (the reference method). There is no mention of a human-in-the-loop component for interpreting the Binax NOW® results in the clinical study beyond the basic reading of the test strip by clinicians/lab personnel.

7. Type of Ground Truth Used

Viral Cell Culture: This was the primary ground truth used for assessing the clinical sensitivity and specificity of the device. The document states, "Negative test results should be confirmed by cell culture," highlighting its role as the gold standard.

8. Sample Size for the Training Set

The document does not specify a separate "training set" in the context of machine learning, as this is a rapid immunochromatographic assay. The performance characteristics are based on the described analytical and clinical studies.

9. How Ground Truth for Training Set Was Established

Since there isn't a "training set" in the machine learning sense for this type of device, this question is not directly applicable. The device's underlying mechanism (immunochromatographic assay) is based on known biological reactions, not a trained algorithm. The analytical and clinical studies serve to validate its performance.

Summary

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SEP 1 9 2002 KC021646

510 (k) SUMMARY OF SAFETY AND EFFECTIVENESS Binax NOW® FLU B Test

This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Submitter: Binax, Inc. 217 Read Street Portland, Maine 04103

Attention: Anne Jepson (207) 772-3988 (Office) (207) 871-5751 (FAX) ajepson@binax.com (email)

Binax NOW® Flu B Test Trade Name:

Flu B ICT, NOW Flu B Test, NOW Influenza B, Common Name : Influenza B ICT

Classification Name: Antigens, CF (including CE Control), Influenza virus A, в, С (per 21 CFR 866.3330)
Quidel QuickVue® Influenza Test, 510 (k) Predicate Device: number K991633
NOW® NOW® Binax Flu B Test is Device Description: The an immunochromatographic membrane assay used to detect influenza B nucleoprotein antigen in nasal wash and nasopharyngeal sswab specimens. A test strip, containing goldconjugated and immobilized anti-influenza B antibodies, is mounted on the right side of a cardboard, book-shaped hinged test device. Swab specimens require a sample preparation step, in which the sample is eluted off the swab into a saline solution. The nasal wash sample does not require any preparation. The sample to be tested is added to a pad at the top of the test strip, and the test device is closed. Influenza B antigen present in the sample reacts to bind anti-influenza B conjugated antibody. The resulting antigencomplexes are captured conjugate by anti-influenza antibody, immobilized മ്മ forming the Sample Line. Immobilized

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Binax NOW® FLU B Test

Control Line antibody, which appears as a blue line in an untested device, captures a visualizing conjugate, forming a pink Control Line. The sample is contained, and results are available within 15 minutes.

The Binax NOW® Flu B Test is an in vitro Intended Use: rapid immunochromatographic assay for the qualitative detection of influenza B nucleoprotein antigen in nasal wash and nasopharyngeal swab specimens from symptomatic patients. It is intended to aid in the rapid diagnosis of influenza B infections. Neqative test results should be confirmed by cell culture.

Technological Characteristics:

Both the Binax NOW® Flu B Test and the Quidel QuickVue® Influenza Test are simple rapid immunochromatographic tests with a visual result interpretation. Both employ antibodies conjugated to visualizing particles and an antibody striped membrane to capture and visualize influenza B antigen. The Quidel QuickVue® Test also detects influenza A antigen.

The Binax NOW® Flu B Test is substantially Performance Summary: equivalent to the predicate device, the Quidel QuickVue® Influenza Test (K991633), for the detection of influenza B antigen. The performance of the Binax NOW® Flu B Test was verified using freshly collected and characterized nasal wash and nasopharyngeal specimens. Refer to attached swab PERFORMANCE CHARACTERISTICS.

Signed Date

Karen Hickey Vice President, Regulatory Affairs

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PERFORMANCE CHARACTERISTICS BINAX NOW® FLU B TEST

Analytic Sensitivity:

Although the specific influenza B strains causing infection in humans can vary year to year, all contain the conserved nucleoprotein targeted by the Binax NOW® test.' Five (5) ATCC traceable influenza B strains were assayed in the Binax NOW test at concentrations ranging from 102 to 10° TCID30/ml. One hundred percent (100%) were positive, indicating that the Binax NOW test detects all influenza B strains.

Analytic Specificity (Cross-Reactivity):

To demonstrate the immunologic specificity of the Binax NOW® test, 43 potential cross-reactants were tested in the Binax NOW® test. The cross-reactant panel included bacteria and viruses that may be present in respiratory specimens. Bacteria tested at concentrations greater than 1 x 10° organisms/ml and viruses tested at concentrations greater than 1 x 105 TCID56/ml did not cross-react in the Binax NOW® Test.

Clinical Sensitivity and Specificity:

The Binax NOW® Flu B Test was evaluated in prospective clinical studies.

In a multi-site prospective study, 191 nasal wash specimens and 182 nasopharyngeal swab specimens collected from patients presenting with influenza-like symptoms were tested in the NOW® test and in culture. Now test performance versus viral cell culture, calculated using standard methods, was as follows:

Nasal wash specimens:	71% sensitivity	97% specificity	92% overall accuracy
Nasopharyngeal swab specimens:	58% sensitivity	97% specificity	90% overall accuracy

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PERFORMANCE CHARACTERISTICS BINAX NOW® FLU B TEST

Ninety-five percent (95%) confidence intervals are listed below.

Nasal Wash Specimens:

		Viral Culture
NOW®	+29	ਪ
Result	12	146
SensitivitySpecificityAccuracy	71%97%92%	156%83% !193899%)-187%95%)-

Nasopharyngeal Swab Specimens:

	Viral Culture
	+	-
NOW®Result	21	4
	15	142
Sensitivity	$ = 58%$	(42% - 73%)
Specificity	$ = 97%$	(93% - 99%)
Accuracy	$ = 90%$	(85% - 94%)

Interfering Substances:

The Binax NOW® test was found not to cross-react with 19 substances that may be artificially introduced into the nasal cavity or nasopharynx or that are naturally present in respiratory specimens. These 19 potentially interfering substances were diluted to appropriate concentrations in a saline/BSA solution and tested in the Binax NOW® Test. A portion of each of these solutions was also spiked with the limit of detection (LOD) level of a viable influenza B strain (See LOD Testing, Section 9) before testing in the Binax NOW Test. All negative (no virus) and positive (spiked with LOD virus) samples generated expected results in the Binax NOW® Test.

Reproducibility:

A blind study of the Binax NOW® test was conducted at 3 separate sites using a panel of coded specimens containing negative, low positive, and moderate positive controls. Participants performed

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PERFORMANCE CHARACTERISTICS BINAX NOW® FLU B TEST

testing on 3 different days. Ninety-nine percent (99%) of the 234 samples tested were correctly interpreted.

Quality Control:

The ability of the Binax NOW® Test procedural control to indicate test failure was evaluated when 3 operators each ran 20 kit controls in a panel of 20 devices, 9 of which had been rendered inoperative. The number of defective devices and the defect itself were not apparent to the operator. Ninety-seven percent (97%) of the devices were correctly interpreted as positive, negative, or invalid.

Preliminary Stability:

Preliminary stability studies of the Binax NOW® Flu B Test and kit controls are ongoing. Test results are consistent with other Binax 510 (k) cleared ICT products. A minimum shelf life of one year is anticipated.

References:

Dowdle, W.R. Kendal, A.P., and Noble, G.R. 1980. Influenza Virus, p 1 836-884. Manual of Clinical Microbiology, 35ª edition, In Lennette, et. Al (ed.). American Society for Microbiology, Washington, D.C.

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Image /page/5/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. In the center of the seal is an abstract image of three human profiles facing to the right. The profiles are stylized and appear to be connected, possibly representing the interconnectedness of health and human services.

Food and Drug Administration 2098 Gaither Road Rockville · MD 20850

SEP 1 9 2002

Ms. Anne Jepson Manager, Technical Support and Services Binax, Inc. 217 Read Street Portland, ME 04103

Re: K021646

Trade/Device Name: Binax Now® Flu B Test Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: Class I Product Code: GNX Dated: July 31, 2002 Received: August 1, 2002

Dear Ms. Jepson:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 mav 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); 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 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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APPENDIX B

INDICATIONS FOR USE FORM

510 (k) Number (if known):

K021646

Device Name:

Binax NOW® Flu B Test

Indications For Use:

Woody Dubris

k) Numbe

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.