(110 days)
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 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 culture.
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 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.
Here's a breakdown of the acceptance criteria and study details based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity and specificity. Instead, it demonstrates performance by comparing the new BinaxNOW® Influenza A & B Test to existing predicate devices (Binax NOW® Flu A Test and Binax NOW® Flu B Test) and viral culture. The key indication of "acceptance" is the determination of "substantial equivalence" to the predicate devices by the FDA.
Based on the performance data presented, here's a summary:
| Performance Metric | Target/Comparison for "Acceptance" | Reported Device Performance (BinaxNOW® Influenza A & B Test) |
|---|---|---|
| Clinical Performance | Equivalent to individual NOW® Flu A and Flu B Tests | Vs. NOW® Flu A Test (for Influenza A):- Sensitivity: 100%- Specificity: 96%Vs. NOW® Flu B Test (for Influenza B):- Sensitivity: 93%- Specificity: 97% |
| Compared to viral culture (historical data from original A & B tests) | Historical Data (from original A & B tests vs. viral culture, 2002 study):- Flu A Sensitivity (nasal wash): 82%- Flu A Sensitivity (NP swab): 78%- Flu B Sensitivity (nasal wash): 71%- Flu B Sensitivity (NP swab): 58%- Specificity (washes and swabs): 92% to 97% | |
| Analytical Sensitivity | Equivalent to individual NOW® Flu A and Flu B Tests | LOD for Flu A/Beijing: 1.03 x 10^2 ng/mlLOD for Flu B/Harbin: 6.05 x 10^1 ng/ml"Cutoff" sample detection rates comparable to predicate devices (50% for Flu A, 46% vs. 10% for Flu B) |
| Reactivity | Positive detection for common influenza A and B strains | Positive detection for 7 live influenza A strains and 5 live influenza B strains at various concentrations. |
| Analytical Specificity / Cross-Reactivity | No cross-reactivity with common respiratory microorganisms | No cross-reactivity with 27 bacteria, 8 viruses, and 1 yeast. |
| Interfering Substances | No interference with test interpretation | No interference with listed substances at specified concentrations (except 1% whole blood interfering with Flu A LOD negative samples). |
| Transport Media | No impact on test performance | Media alone tested negative; media inoculated with LOD levels tested positive. |
| Reproducibility | High agreement between runs, operators, and sites | 97% agreement with expected test results across multiple runs, operators, and 3 sites. |
2. Sample Sizes Used for the Test Set and Data Provenance
-
Clinical Sample Comparison (BinaxNOW® A & B vs. individual NOW® A & B tests):
- Influenza A comparison: 306 retrospective frozen clinical samples.
- Influenza B comparison: 303 retrospective frozen clinical samples.
- Data Provenance: Retrospective frozen clinical samples collected from symptomatic patients at multiple physician offices, clinics, and hospitals in the Southern, Northeastern, and Midwestern regions of the United States, and one hospital in Sweden.
-
Original Multi-site Prospective Clinical Study (comparing individual NOW® Flu A & B Tests to viral culture, 2002):
- 191 nasal wash specimens
- 182 nasopharyngeal (NP) swab specimens
- Data Provenance: Multi-center prospective study during the 2002 flu season at physician offices and clinics located in the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical comparison directly assessing the BinaxNOW® Influenza A & B Test.
-
For the comparison against the predicate devices: The predicate devices (individual NOW® Flu A and NOW® Flu B Tests) were used as the reference standard (ground truth). The ground truth for these predicate devices themselves would have been established historically (likely via viral culture).
-
For the historical 2002 multi-site prospective clinical study: The ground truth was viral culture, which is considered an objective laboratory method, not reliant on expert interpretation of the rapid test results.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for the clinical test sets in terms of resolving discrepancies between readers or between the device and ground truth. The comparisons are presented as direct measures against a reference standard (predicate devices or viral culture).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
- No, an MRMC comparative effectiveness study was not done as described in the context of assistance from AI.
- This device is a rapid diagnostic test (immunochromatographic assay), not an AI-powered diagnostic imaging or interpretation system. The "readers" for the analytical sensitivity experiment were "operators" interpreting the device results, not expert diagnosticians being assisted by AI.
6. If a Standalone (i.e. Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, standalone performance was assessed in the context of a rapid diagnostic test. The results (sensitivity, specificity) presented for the BinaxNOW® Influenza A & B Test were generated by having operators read the test strip, not by integrating it with human interpretive assistance beyond the basic instruction of how to read the pink-to-purple lines.
- The "Analytical Sensitivity Comparison" section involved 12 different operators interpreting devices for LOD and cutoff levels. This is a form of standalone performance evaluation for the test itself.
7. The Type of Ground Truth Used
- Clinical Sample Comparison (BinaxNOW® A & B vs. individual NOW® A & B tests): The ground truth was the result from the predicate devices (Binax NOW® Flu A Test and Binax NOW® Flu B Test). This implies that the predicate devices were considered the accepted standard for influenza detection in these samples.
- Original Multi-site Prospective Clinical Study (of individual NOW® Flu A & B Tests): The ground truth was viral culture. Viral culture is generally considered a gold standard for influenza diagnosis.
8. The Sample Size for the Training Set
The document does not specify a training set in the context of machine learning or algorithm development. This device is an immunochromatographic assay, which is a chemical and biological test, not typically "trained" in the way an AI algorithm is. The "development" of the test would involve optimization of its biological components and chemical reactions.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a training set for an algorithm, this question is not applicable. The development of the immunochromatographic assay relies on chemical and biological principles and optimization, not on a "training set" with established ground truth in the AI sense.
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AUG 1 0 2004
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in This Summary of or or or or or or of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________
SUBMITTER
Binax, Inc. 217 Read Street Portland, Maine 04103 (207) 772-3988 (Office) (207) 871-5751 (FAX)
CONTACT PERSON
Pamela S. Angell pangell@binax.com (email)
DATE PREPARED
April 21, 2004
TRADE NAME BinaxNOW® Influenza A & B Test
COMMON NAME
NOW® Flu A/B Test, NOW® Influenza A/B, NOW® Influenza A & B, Binax NOW® Influenza A & B, Binax NOW® Influenza A/B
CLASSIFICATION NAME
Antigen, CF (including CF Controls), Influenza Virus A, B, C (per 21 CFR 866.3330)
PREDICATE DEVICES
Binax NOW® Flu A Test, K021649 Binax NOW® Flu B Test; K021646 FLU OIA A/B Test Kit; K023556
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 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 oreparation. 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.
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INTENDED USE
The BinaxNOW® Influenza A & B Test is an in vitro immunochromatographic assay for The BinaxNOVP "Influenza A and B nucleoprotein antigens in nasopharyngeal
the qualitative detection of influenza A and B nucleoprotein antigens in nasophary the qualitative delection of influenza A and B hasto provid in the rapid differential Swab and flashfaspirate opedination will infections. Negative test results should be confirmed by culture.
TECHNOLOGICAL CHARACTERISTICS
The BinaxNOW® Influenza A & B Test and the two predicate Binax NOW® Flu Tests rne DinaxNOW - Innlaoize Annochromatographic technology while the Thermo Biostar tuse identival librar low minner. All tests are rapid immunoassays that employ specific test is an option infridhodoud). All this phase to capture and visualize influenza nucleoprotein antigens.
PERFORMANCE SUMMARY
Analytical and Clinical Comparison to Predicates
Allarytoar and Olinkour Companies of the individual NOW® Flu A and NOW® Flu B Tests vs. rne oiltion performance were originally established in a multi-center prospective conventional ouring the 2002 flu season at physician offices and clinics located in stady of national auring and States. The analytical sensitivity and specificity of the BinaxNOW® Influenza A & B Test are equivalent to that of the individual NOW® Flu the Binaxive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . clinical specimens and inactivated viral standards.
Clinical Sample Comparison:
A total of 191 nasal wash and 182 nasopharyngeal (NP) swab specimens were evaluated as part of a 2002 multi-site prospective clinical study comparing the original Binax NOW® Flu A and Flu B Tests to viral culture. In this study, sensitivity to influenza A was 82% (95% Cl of 69-90%) for nasal washes and 78% (95% Cl of 62-88%) for NP swabs. Sensitivity to influenza B was 71% (95% CI of 56-83%) for nasal washes and 58% for NP swabs (95% CI of 42-73%). Specificity for washes and swabs ranged from 92% to 97% with 95% CI of 86% to 99%.
Performance of the BinaxNOW® Influenza A & B Test was compared to the current NOW® Flu A Test on 306 retrospective frozen clinical samples and to the NOW® Flu B Test on 303 retrospective frozen clinical samples. All clinical samples were 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. Fifty-three percent (53%) of the population tested was male, 47% female, 64% pediatric (< 18 years) and 36% adult (≥ 18 years). Nasal wash/aspirate specimens comprised approximately 57% of the samples tested, while NP swabs represented 42%. No differences in test performance were observed based on patient age and gender or based on sample type tested.
The BinaxNOW® Influenza A & B Test was 100% sensitive and 96% specific for detection of influenza A vs. the NOW® Flu A Test and 93% sensitive and 97% specific for detection of influenza B vs. the NOW® Flu B Test. Test performance by
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virus type (A vs. B), by sample type (NP swab vs. wash/aspirate), and overall, including 95% confidence intervals, is detailed in the following tables.
| Sample | +/+ | +/- | % Sens | 95% CI | -/- | +/- | % Spec | 95% CI |
|---|---|---|---|---|---|---|---|---|
| NP Swab | 30 | 0 | 100% | 89-100% | 96 | 1 | 99% | 94-100% |
| Wash/Aspirate | 47 | 0 | 100% | 93-100% | 123 | 9 | 93% | 88-96% |
| Overall | 77 | 0 | 100% | 95-100% | 219 | 10 | 96% | 88-96% |
| BinaxNOW® Influenza A & B Test vs. NOW® Flu B Test for Detection of Influenza B | |
|---|---|
| and the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the consistence of the con |
| FLU B SENSITIVITY | ||||
|---|---|---|---|---|
| Sample | +/+ | -/+ | % Sens | 95% CI |
| NP Swab | 2 | 0 | 100% | 29-99% |
| Wash/Aspirate | 12 | 1 | 92% | 66-98% |
| Overall | 14 | 1 | 93% | 70-98% |
| FLU B SPECIFICITY | |||||
|---|---|---|---|---|---|
| +/- | % Spec | 95% C | |||
| 126 | යිති බවට ගිහිටි මිතිවර්තිය හිටි බවට පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි පිහිටි මිතිබු මිත්රියා හිටි පිහිටි මිතිබු මිත්රියා හිත්යයි. | 96-100% | |||
| 152 | ರಾ | 94% | 90-97% | ||
| 278 | 10 | 97% | 94-98% |
Analytical Sensitivity Comparison:
The BinaxNOW® test limit of detection (LOD), defined as the concentration of influenza virus that produces positive BinaxNOW® test results approximately 95% of the time, was identified by evaluating different concentrations of inactivated Flu A/Beijing and inactivated Flu B/Harbin in the BinaxNOW® test.
Twelve (12) different operators each interpreted 2 devices run at each concentration for a total of 24 determinations per level. The following results identify a concentration of 1.03 x 102 ng/ml as the LOD for Flu A/Beijing and 6.05 x 10' na/mi for Flu B/Harbin.
| Influenza A/Beijing | Influenza B/Harbin | ||||
|---|---|---|---|---|---|
| Concentration (ng/ml) | # Detected | % Detected | Concentration (ng/ml) | # Detected | % Detected |
| $1.03 \times 10^2$ (LOD) | 23/24 | 96 | $6.05 \times 10^1$ (LOD) | 23/24 | 96 |
| $5.60 \times 10^1$ (Cutoff) | * | 50 | $2.42 \times 10^1$ (Cutoff) | 11/24 | 46 |
| $3.27 \times 10^1$ (High Neg) | 4/24 | 17 | $1.51 \times 10^1$ (High Neg) | 6/24 | 25 |
| True Negative | 0/24 | 0 | True Negative | 0/24 | 0 |
*Linear regression was used to calculate a line equation, which was then used to project the cutoff concentration of Flu A/Beijing.
To demonstrate comparable analytical sensitivity of the BinaxNOW® Influenza A & B Test and the individual NOW® Flu A and Flu B Tests, the Flu A and B cutoff levels identified above were evaluated in the NOW® Flu A and Flu B Tests.
The A/Beijing cutoff sample detected 50% of the time in the BinaxNOW® Influenza A & B Test was also detected 50% (12/24) of the time in the NOW® Flu A Test when tested by six (6) operators interpreting a total of 24 devices. Likewise, the B/Harbin cutoff sample detected 46% of the time in the BinaxNOW® Influenza A & B Test was detected 10% (4/40) of the time in the NOW® Flu B Test when tested by ten (10) operators interpreting 40 devices.
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These data demonstrate that the analytical sensitivity of the BinaxNOW® Influenza These data demonorate than that of the individual NOW® Flu A and B Tests.
Reactivity Testing
The seven (7) live influenza A strains and five (5) live influenza B strains listed below The seven (7) Inve mindenza A Strains and The (6) The Tat concentrations ranging from lested positive in the BinaxNOW - militenza strains causing infection in humans 10 -10 GEIDsomm. All contain the conserved nucleoproteins targeted by the BinaxNOW® test.1
| Influenza Strain | ATCC # |
|---|---|
| Flu A/WS/33 | VR-825 |
| Flu A/NWS/33 | VR-219 |
| Flu A/Hong Kong/8/68 | VR-544 |
| Flu A/Aichi/2/68 | VR-547 |
| Flu A/New Jersey/8/76 | VR-897 |
| Flu A/Mal/302/54 | VR-98 |
| Flu A/Port Chalmers/1/73 | VR-810 |
| Flu B/Lee/40 | VR-101 |
| Flu B/Brigit | VR-786 |
| Flu B/Russia/69 | VR-790 |
| Flu B/Hong Kong/5/72 | VR-791 |
| Flu B/R75 | VR-789 |
Analytic Specificity (Cross-Reactivity)
Allariti Specificity (Sross Reasting)
To determine the analytical specificity of the BinaxNOW® Influenza A & B Test, 36 commensal and pathogenic microorganisms (27 bacteria, 8 viruses and 1 yeast) that may be present in the nasal cavity or nasopharynx were tested. All of the following may be probons were negative when tested at concentrations ranging from 104 to 108 TCIDsoml (viruses), 10 to 10° organisms/ml (bacteria) and 10° organisms/ml (yeast).
| Bacteria | Viruses | Yeast |
|---|---|---|
| Acinetobacter | Adenovirus | Candida albicans |
| Bordetella pertussis | Coronavirus | |
| Enterococcus faecalis | Coxsackie B4 | |
| Escherichia coli | Cytomegalovirus (CMV) | |
| Gardnerella vaginalis | Parainfluenza 1 | |
| Haemophilus influenzae | Parainfluenza 2 | |
| Klebsiella pneumoniae | Parainfluenza 3 | |
| Lactobacillus casei | Respiratory Syncytial Virus (RSV) | |
| Legionella pneumophila | ||
| Listeria monocytogenes | ||
| Moraxella catarrhalis | ||
| Neisseria gonorhoeae | ||
| Neisseria meningitidis | ||
| Neisseria sicca | ||
| Neisseria subflava | ||
| Proteus vulgaris | ||
| Pseudomonas aeruginosa | ||
| Serratia marcescens | ||
| Staphylococcus aureus | ||
| Staphylococcus aureus | ||
| (Cowan protein A producing strain) | ||
| Staphylococcus epidermidis | ||
| Streptococcus, Group A | ||
| Streptococcus, Group B | ||
| Streptococcus, Group C | ||
| Streptococcus, Group F | ||
| Streptococcus mutans | ||
| Streptococcus pneumoniae |
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Interfering Substances
Interientig oubstances, naturally present in respiratory specimens or that may be The lollowing oubotarioo, haturaly cavity or nasopharynx, were evaluated in the armicially influenza A & B Test at the concentrations listed and were found not to Diffect test performance. Whole blood (1%) did not interfere with the interpretation of anest test performance. but did interfere with the interpretation of Flu A LOD negative samples. Therefore, visibly bloody samples may not be appropriate for use in this test.
| Substance | Concentration |
|---|---|
| 1 OTC mouthwash | 20% |
| 3 OTC nasal sprays | 15% |
| 3 OTC throat drops | 15% |
| 2 OTC throat sprays | 20% |
| 4-acetamidophenol | 10 mg/ml |
| Acetylsalicylic acid | 15 mg/ml |
| Albuterol | 20 mg/ml |
| Chlorpheniramine | 5 mg/ml |
| Dextromethorphan | 10 mg/ml |
| Diphenhydramine | 5 mg/ml |
| Guaiacol glycerol ether | 20 mg/ml |
| Oxymetazoline | 0.05% |
| Phenylephrine | 50 mg/ml |
| Phenylpropanolamine | 20 mg/ml |
| Rebetol | 500 ng/ml |
| Relenza | 20 mg/ml |
| Rimantadine | 500 ng/ml |
| Synagis | 0.1 mg/ml |
| Tamiflu | 50 mg/ml |
Transport Media
The following transport media were tested in the BinaxNOW® Influenza A & B Test as negative samples (no virus present) and after inoculation with the LOD levels of Inflyenza A & B. Media did not impact BinaxNOW® test performance, with the media alone testing negative in the NOW® test and media inoculated with LOD Influenza A & B testing positive on the appropriate test line in BinaxNOW® test.
Amies Media Hank's Balanced Salt Solution M4 Media M4-RT Media M5 Media Stuart's Media Saline
Reproducibility
A blind study of the BinaxNOW® Influenza A & B Test was conducted at 3 separate sites using panels of blind coded specimens containing negative, low positive, and moderate positive samples. Participants tested each sample multiple times on 3 different days. There was 97% (242/250) agreement with expected test results, with no significant differences within run (replicates tested by one operator), between run (3 different days) or between sites (3 sites).
Signed Karen Hickey Date
Date April 21, 2004
Karen Hickey VP Regulatory & Clinical Affairs
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- Dowdle, W.R., Kendal, A.P., and Noble, G.R. 1980. Influenza Virus, p 836-884. Manual of Clinical Microbiology, 3rd
edition, In Lennette, et. Al (ed.). American So
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
AUG 1 0 2004
Ms. Pamela Angell Regulatory Manager Binax, Inc 217 Read Street Portland, ME 04103
K041049 Re:
Trade/Device Name: BinaxNOW Influenza A & B Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: Class I Product Code: GNX Dated: April 21, 2004 Received: April 22, 2004
Dear Ms. Angell:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your bection 510(x) premained is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the caciosate) to regally manation program and of the Medical Device American Comments, or to commerce prof to May 20, 1970, the encentialic and the Federal Food, Drug, devices mat have been reciasmed in acce aapsoval of a premarket approval application (PMA). and Cosmetic Acr (110) market the device, subject to the general controls provisions of the Act. The Y bu may, merciole, market the act include requirements for annual registration, listing of general controls provisions of the free 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 If your device is classified (500 a0070) and existing major regulations affecting your device can
may be subject to such additional controls. Existing major regulation withi may be subject to such additional ocharely into and to 895. In addition, FDA be found in Thic 21, Oods of Peach one one ming your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that FDA s issualled of a backannal requirements of the Act
that FDA has made a determination that your device complies with other requirements of the Act that FDA has made a decertifications administered by other Federal agencies. You must or any rederal statutes and regulations and limited to: registration and listing (21 comply with an the Ace 3 requirements, more of 809); and good manufacturing practice CFR Fart 807), labeling (21 CF ruality systems (QS) regulation (21 CFR Part 820).
{7}------------------------------------------------
Page 2
This letter will allow you to begin marketing your device as described in your Section 510(k) I his letter will anow you to ocgin manoming your antial equivalence of your device to a legally premarket notification. The PDF maing of Gassification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, II you desite specific mornation assectiving of your device, please contact the Office of of questions on the promotion and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Tou may obtain other general information on your responsibilities under the Act from the I bu may obtain other geleral marketing 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,
Salartys
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K041049
Device Name: BinaxNow® Influenza A&B Test
Indications for Use:
The BinaxNOW® Influenza A & B Test is an in vitro immunochromatographic assay for The DillaXNO w - Influenza A co B A and B nucleoprotein antigens in nasopharyngeal (NP) swab and nasal wash/aspirate specimens. It is intended to aid in the rapid (Nr) >Wav and nasar wasn't wasn't level infections. Negative test results should be confirmed by culture.
X Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off
ාස්ථි Device Evaluation and Safety
Page 1 of 1
*10(k) Ko4104 9
§ 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.