FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The BinaxNOW® Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasopharyngeal (NP) swab, nasal swab, and nasal wash/aspirate specimens. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. Negative test results should be confirmed by cell culture.

Device Description

The BinaxNOW* Influenza A & B Test is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A & B nucleoprotein antigens in nasopharyngeal (NP) swab, nasal swab, and nasal wash/aspirate specimens. These antibodies and a control antibody are immobilized onto a membrane support as three distinct lines and combined with other reagents/pads to construct a test strip. This test strip is mounted inside a cardboard, book-shaped hinged test device. Swab specimens require a sample preparation step, in which the sample is eluted off the swab into elution solution or transport media. Nasal wash/aspirate samples require no preparation. Sample is added to the top of the test strip and the test device is closed. Test results are interpreted at 15 minutes based on the presence or absence of pink-to-purple colored Sample Lines. The blue Control Line turns pink in a valid assay.

AI/ML Overview

Here's an analysis of the BinaxNOW® Influenza A & B Test, detailing its acceptance criteria and the supporting studies:

Acceptance Criteria and Device Performance for BinaxNOW® Influenza A & B Test

The provided document describes a 510(k) submission to expand the claims of the BinaxNOW® Influenza A & B Test. While explicit "acceptance criteria" in a numerical target format are not directly stated, the document presents detailed performance data from clinical and analytical studies. The implied acceptance criteria are that the device demonstrates adequate sensitivity and specificity for the detection of influenza A and B antigens in various sample types, comparable to the reference standard (cell culture/DFA). The analytical studies further establish the device's limit of detection, reactivity to various strains, and cross-reactivity.

1. Table of Acceptance Criteria (Implied) and Reported Device Performance

Given the nature of the submission (expansion of claims for an existing device), the "acceptance criteria" are implicitly set by regulatory expectations for diagnostics and comparison to the predicate device and reference methods. The reported performance is directly from the clinical studies presented.

Clinical Performance vs. Cell Culture/DFA (Prospective Study)

Sample Type	Analyte	Implied Acceptance Criterion (e.g., ≥X%)	Reported % Sensitivity (95% CI)	Reported % Specificity (95% CI)
NP Swab	Flu A	Good Sensitivity/Specificity	77% (65-86%)	99% (97-100%)
Nasal Swab	Flu A	Good Sensitivity/Specificity	83% (74-90%)	96% (93-98%)
Overall (Flu A)	Flu A	Good Sensitivity/Specificity	81% (74-86%)	97% (96-98%)
NP Swab	Flu B	Good Sensitivity/Specificity	50% (9-91%)	100% (99-100%)
Nasal Swab	Flu B	Good Sensitivity/Specificity	69% (39-90%)	100% (98-100%)
Overall (Flu B)	Flu B	Good Sensitivity/Specificity	65% (39-85%)	100% (99-100%)

Clinical Performance vs. Cell Culture/DFA (Retrospective Study)

Sample Type	Analyte	Implied Acceptance Criterion (e.g., ≥X%)	Reported % Sensitivity (95% CI)	Reported % Specificity (95% CI)
NP Swab	Flu A	Good Sensitivity/Specificity	70% (50-86%)	90% (81-95%)
Wash/Aspirate	Flu A	Good Sensitivity/Specificity	89% (78-96%)	95% (89-98%)
Overall (Flu A)	Flu A	Good Sensitivity/Specificity	83% (73-90%)	93% (88-96%)
NP Swab	Flu B	Good Sensitivity/Specificity	N/A (0/0)	98% (93-100%)
Wash/Aspirate	Flu B	Good Sensitivity/Specificity	53% (27-78%)	94% (89-97%)
Overall (Flu B)	Flu B	Good Sensitivity/Specificity	53% (27-78%)	96% (92-98%)

Analytical Sensitivity (Limit of Detection - LOD)

Analyte	Implied Acceptance Criterion (e.g., LOD at 95% detection)	Reported LOD	Reported % Detected at LOD
Flu A/Beijing	Identify concentration for 95% detection	$1.03 \times 10^2$ ng/ml	96% (23/24)
Flu B/Harbin	Identify concentration for 95% detection	$6.05 \times 10^1$ ng/ml	96% (23/24)

Reactivity Testing

Analyte	Implied Acceptance Criterion	Reported Performance
Various Flu A strains	Detect at specified concentrations	Positive at $10^2-10^6$ CEID50/ml or $10^2-10^5$ TCID50/ml or $10^4-10^5$ EID50/ml
Various Flu B strains	Detect at specified concentrations	Positive at $10^2-10^6$ CEID50/ml
Swine-lineage Flu A (H1N1)	Detect at specified concentrations	Positive at $5.63 \times 10^4$ TCID50/ml or $1.0 \times 10^5$ TCID50/ml

Analytical Specificity (Cross Reactivity)

Interfering Agents	Implied Acceptance Criterion	Reported Performance
36 commensal & pathogenic microorganisms	No cross-reactivity	All identified microorganisms were negative at concentrations $10^5-10^6$ TCID/ml (viruses), $10^7-10^8$ organisms/ml (bacteria), $10^8$ organisms/ml (yeast).

Interfering Substances

Interfering Substances	Implied Acceptance Criterion	Reported Performance
Various OTC drugs, blood	No interference with test interpretation	No interference found for listed substances at specified concentrations. Whole blood (1%) interfered with Flu A LOD positive samples, but not negative results.

Transport Media

Transport Media	Implied Acceptance Criterion	Reported Performance
Various media	No impact on test performance	Media alone tested negative; media inoculated with LOD Flu A & B tested positive on appropriate test line. Sucrose-Phosphate Buffer may not be suitable.

Reproducibility

Performance Aspect	Implied Acceptance Criterion (e.g., High agreement)	Reported Performance
Overall agreement with expected results	High agreement	97% (242/250) agreement
Differences (within run, between run, between sites)	No significant differences	No significant differences observed

Study Details:

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

Clinical Studies (Prospective):
- Sample Size: 846 prospective specimens.
- Data Provenance: Not explicitly stated, but the mention of "patients presenting with influenza-like symptoms" and demographic breakdown (male/female, pediatric/adult) suggests a general clinical population. No specific country is mentioned, implying it could be multi-site within the US or a general US population. The study is prospective.
Clinical Studies (Retrospective):
- Sample Size: 293 retrospective frozen clinical samples.
- Data Provenance: Clinical samples collected from symptomatic patients at multiple physician offices, clinics, and hospitals located in the Southern, Northeastern, and Midwestern regions of the United States, and from one hospital in Sweden. The study is retrospective.
Analytical Sensitivity:
- Sample Size: 24 determinations per concentration level (12 operators x 2 devices).
- Data Provenance: Not specified, likely internal lab studies.

3. Number of Experts and Qualifications for Ground Truth (Clinical Studies):

The ground truth for the clinical studies was established by Cell Culture / DFA (Direct Fluorescent Antibody assay). This is a laboratory-based method.
Number of Experts: The document does not specify the number of human experts involved in interpreting the cell culture or DFA results, nor their specific qualifications. It is assumed that trained laboratory personnel performed these reference tests.

4. Adjudication Method for the Test Set:

The document implies that the BinaxNOW® test results were directly compared to the Cell Culture/DFA results. There is no mention of a separate adjudication method (e.g., 2+1, 3+1 consensus) for the test set itself, as the Cell Culture/DFA is treated as the definitive ground truth.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done comparing human reader performance with and without AI assistance. The device is a rapid diagnostic kit, not an AI-powered image analysis system interpreted by human readers. The clinical studies evaluate the device's performance against a reference standard. The "operators" mentioned in the analytical sensitivity section are performing the device test, not interpreting complex medical images.

6. Standalone Performance:

Yes, standalone performance was done. The entire clinical and analytical performance sections evaluate the device (algorithm/test kit) in a standalone manner against a reference standard (Cell Culture/DFA) or known concentrations/strains. There is no human-in-the-loop component being evaluated in the reported performance. The "interpretation" of the BinaxNOW test results is based on visible lines, which is a direct reading of the device's output.

7. Type of Ground Truth Used:

Clinical Studies: The type of ground truth used was Cell Culture / DFA. This is a laboratory-based diagnostic method considered a gold standard for influenza detection at the time of the study.
Analytical Studies: The ground truth for analytical sensitivity, reactivity, and specificity used known concentrations of inactivated viruses, specific influenza strains, or panels of other microorganisms at known concentrations.

8. Sample Size for the Training Set:

The document describes a 510(k) for an existing device (BinaxNOW® Influenza A & B Test; K062109). This type of submission typically focuses on validation and verification of the device's performance, not on the explicit "training" of an algorithm in the machine learning sense.
Therefore, there is no identifiable "training set" sample size in the context of an algorithm or AI. The immunoassay technology relies on pre-designed antibodies, not a trained computational model.

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

As there is no explicit "training set" in the context of an AI/algorithm, this question is not applicable to this device submission. The immunoassay is developed and validated through laboratory methods (antibody selection, antigen-antibody binding studies) rather than machine learning training.

Summary

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.