(20 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, 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.
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.
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.
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510(k) SUMMARY
AUG 12 2009
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K092223
The purpose of this 510(k) submission is to expand the Analytical Reactivity claims of the currently 510(k) cleared BinaxNOW® Influenza A & B Test (510(k) K062109).
SUBMITTER
Binax. Inc. 10 Southgate Road Scarborough, Maine 04074 (207) 730-5737 (Office) (207) 730-5717 (FAX)
CONTACT PERSON
Angela Drysdale Angela.drysdale@invmed.com (email)
DATE PREPARED August 10, 2009
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 DEVICE Binax NOW® Influenza A & B Test; K062109
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.
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INTENDED USE
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 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 culture.
TECHNOLOGICAL CHARACTERISTICS
The Expanded Claim BinaxNOW® Influenza A & B Test is exactly the same as the currently 510(k) cleared BinaxNOW® Influenza A & B Test. Both tests use identical lateral flow immunochromatographic technology. Both tests are rapid immunoassays that employ specific antibodies immobilized onto a solid phase to capture and visualize influenza nucleoprotein antigens.
PERFORMANCE SUMMARY
CLINICAL STUDIES
BinaxNOW Influenza A & B Test Performance vs. Cell Culture / DFA - Prospective Study
A total of 846 prospective specimens collected from children (less than 18 years of age) and adults (18 years or older) were evaluated in the BinaxNOW* Influenza A & B Test and compared to culture/DFA. Evaluated specimens include nasopharyngeal swabs and nasal swabs collected from patients presenting with influenza-like symptoms. Forty-four percent (44%) of the population tested was male, 56% female, 54% pediatric (< 18 years), and 46% adult (> 18 years). No differences in test performance were observed based on patient age or gender. A/H3 and A/H1 were the predominant influenza subtypes observed during this time.
BinaxNOW" A & B Test performance by sample type versus cell culture / DFA, including 95% confidence intervals, is listed below.
| Sample | +/+ | -/+ | % Sens | 95% CI | -/ | +/- | % Spec | 95% CI |
|---|---|---|---|---|---|---|---|---|
| NP Swab | 53 | 16 | 77% | 65-86% | 278 | 3 | 99% | 97-100% |
| Nasal Swab | 85 | 17 | 83% | 74-90% | 378 | 16 | 96% | 93-98% |
| Overall | 138 | 33 | 81% | 74-86% | 656 | 19 | 97% | 96-98% |
BinaxNOW* Influenza A & B Test Performance vs. Cell Culture/DFA for Detection of Flu A
BinaxNOW* Influenza A & B Test Performance vs. Cell Culture/DFA for Detection of Flu B
| Sample | +/+ | -/+ | % Sens | 95% CI | -/- | +/- | % Spec | 95% CI |
|---|---|---|---|---|---|---|---|---|
| NP Swab | 2 | 2 | 50% | 9-91% | 346 | 0 | 100% | 99-100% |
| Nasal Swab | 9 | 4 | 69% | 39-90% | 481 | 2 | 100% | 98-100% |
| Overall | 11 | 6 | 65% | 39-85% | 827 | 2 | 100% | 99-100% |
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BinaxNOW Influenza A & B Test Performance vs. Cell Culture / DFA - Retrospective Study
A total of 293 retrospective frozen clinical samples were evaluated in the BinaxNOW™ Influenza A & B Test and compared to culture/DFA. 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, 62% pediatric (<18 years) and 38% adult (≥ 18 years). Nasal wash/aspirate specimens comprised approximately 61% of the samples tested, while NP swabs represented 39%. No differences in test performance were observed based on patient age and gender or based on sample type tested.
BinaxNOW" A & B Test performance by sample type versus cell culture / DFA, including 95% confidence intervals, is listed below.
| Sample | +/+ | -/+ | % Sens | 95% CI | -/- | +/- | % Spec | 95% CI |
|---|---|---|---|---|---|---|---|---|
| NP Swab | 19 | 8 | 70% | 50-86% | 77 | 9 | 90% | 81-95% |
| Wash/Aspirate | 51 | 6 | 89% | 78-96% | 117 | 6 | 95% | 89-98% |
| Overall | 70 | 14 | 83% | 73-90% | 194 | 15 | 93% | 88-96% |
BinaxNOW" Influenza A & B Test Performance vs. Cell Culture/DFA for Detection of Flu A
BinaxNOW" Influenza A & B Test Performance vs. Cell Culture/DFA for Detection of Flu B
| Sample | Test Sensitivity | Test Specificity | ||||||
|---|---|---|---|---|---|---|---|---|
| +/+ | -/+ | % Sens | 95% CI | -/+ | +/+ | % Spec | 95% CI | |
| NP Swab | 0 | 0 | N/A | N/A | 111 | 2 | 98% | 93-100% |
| Wash/Aspirate | 8 | 7 | 53% | 27-78% | 155 | 10 | 94% | 89-97% |
| Overall | 8 | 7 | 53% | 27-78% | 266 | 12 | 96% | 92-98% |
ANALYTICAL STUDIES
ANALYTICAL SENSITIVITY
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 xg/ml as the LOD for Flu A/Beijing and 6.05 x 101 ng/ml for Flu B/Harbin.
| Influenza A/Beijing | ||
|---|---|---|
| Concentration (ng/ml) | # Detected | % Detected |
| $1.03 \times 10^2$ (LOD) | 23/24 | 96 |
| $5.60 \times 10^1$ (Cutoff) | * | 50 |
| $3.27 \times 10^1$ (High Neg) | 4/24 | 17 |
| True Negative | 0/24 | 0 |
| Influenza B/Harbin | ||
|---|---|---|
| Concentration (ng/ml) | # Detected | % Detected |
| 6.05 x 10¹ (LOD) | 23/24 | 96 |
| 2.42 x 10¹ (Cutoff) | 11/24 | 46 |
| 1.51 x 10¹ (High Neg) | 6/24 | 25 |
| True Negative | 0/24 | 0 |
0/ 24 *Limear regression was used to calculate a line equation, which was then used to project the cutoff concentration of Flu A/Beijing.
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REACTIVITY TESTING
The influenza A and B strains listed tested positive in the BinaxNOW" Influenza A & B Test at concentrations specified. Although the specific influenza strains causing infection in humans can vary year to year, all contain the conserved nucleoproteins targeted by the BinaxNOW" test. ' Performance characteristics of the BinaxNOW" Influenza A & B Test for detecting influenza A virus from human specimens was established when H1 and H3 subtypes were prevalent. Performance characteristics of the test when other influenza A virus subtypes are emerging as human pathogens have not been established.
| Influenza Strain | ATCC # | Concentration |
|---|---|---|
| Flu A/WS/33 (H1N1) | VR-825 | 102-106 CEID50/ml |
| Flu A/NWS/33 (H1N1) | VR-219 | 102-106 CEID50/ml |
| Flu A/Hong Kong/8/68 (H3N2) | VR-544 | 102-106 CEID50/ml |
| Flu A/Aichi/2/68 (H3N2) | VR-547 | 102-106 CEID50/ml |
| Flu A/New Jersey/8/76 (Hsw1N1) | VR-897 | 102-106 CEID50/ml |
| Flu A/Mal/302/54 (H1N1) | VR-98 | 102-106 CEID50/ml |
| Flu A/Port Chalmers/1/73 (H3N2) | VR-810 | 102-105 CEID50/ml |
| Flu A/Hong Kong/156/97 (H5N1) | - | 1.3 x 102 TCID50/ml |
| Flu A/Vietnam/1194/04 (H5N1) | - | 1.0 x 104 TCID50/ml |
| Flu A/California/04/2009 (H1N1) swl (swine lineage) | - | 5.63 x 104 TCID50/ml |
| Flu A/ Auckland / 1 / 2009 A (H1N1) swl | - | 1.0 x 105 TCID50/ml |
| Flu A/ Auckland / 3 / 2009 A (H1N1) swl | - | 1.0 x 105 TCID50/ml |
| Flu A/Chicken/NY/117228-7/01 (H5N2) | - | 1.0 x 104 EID50/ml |
| Flu A/Turkey/VA/SEP-66/02 (H7N2) | - | 1.0 x 105 EID50/ml |
| Flu B/Lee/40 | VR-101 | 102-106 CEID50/ml |
| Flu B/Brigit | VR-786 | 102-106 CEID50/ml |
| Flu B/Russia/69 | VR-790 | 102-106 CEID50/ml |
| Flu B/Hong Kong/5/72 | VR-791 | 102-106 CEID50/ml |
| Flu B/R75 | VR-789 | 102-106 CEID50/ml |
Although this test has been shown to detect the Flu A/California/04/2009 (H1N1) virus cultured from a positive human specimen, the performance characteristics of this device with human specimens infected with the 2009 H1N1 influenza virus have not been established. The BinaxNOW® test can distinguish between influenza A and B viruses, but it does not differentiate seasonal influenza A virus from the novel influenza A (i.e. 2009 H1N1) and it's ability to detect human infection with the 2009 HTN1 influenza virus in clinical specimens is unknown.
ANALYTICAL SPECIFICITY (CROSS REACTIVITY)
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 microorganisms were negative when tested at concentrations ranging from 10+ to 10* TCID .. /ml (viruses), 10' to 10* organisms/ml (bacteria) and 10* organisms/ml (yeast).
Bacteria Acinetobacter Bordetella pertussis Enterococcus faecalis Escherichia coli Gardnerella vaginalis Haemophilus influenzae Klebsiella pneumoniae Lactobacillus casei Legionella pneumophila Listeria monocytogenes
BinaxNOW® Influenza A & B Test Special 510(k) Notification
Viruses Adenovirus Coronavirus Coxsackie B4 Cytomegalovirus (CMV) Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Respiratory Syncytial Virus (RSV)
Yeast
Candida albicans
Revision 08/10/09
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Moraxella catarrhalis Neisseria gonorrhoeae 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
INTERFERING SUBSTANCES
The following substances, naturally present in respiratory speciment or that may be artificially introduced into the nasal cavity or nasopharynx, were evaluated in the BinaxNOW" Influenza A & B Test at the concentrations listed and were found not to affect test performance. Whole blood (1%) did not interfere with the interpretation of negative BinaxNOW® test results, but did interfere with the interpretation of Flu A LOD positive 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 Influenza 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 Brain Heart Infusion Broth Dulbecco Medium Hank's Balanced Salt Solution
BinaxNOW® Influenza A & B Test Special 510(k) Notification
Revision 08/10/09
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M4 Media M4-RT Media M5 Media Phosphate Buffer Solution Saline Stuart's Media Tryptose Phosphate Broth UTM-RT Media Veal Infusion Broth
It has been determined that Sucrose-Phosphate Buffer may not be suitable for use with this test.
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 Angela Drysdale Date 8/10/09
Sr. Manager, Clinical Affairs
- 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 Society for Microbiology, Washington, D.C.
BinaxNOW® Influenza A & B Test Special 510(k) Notification
Revision 08/10/09
- 6 -
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Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. The text is in all capital letters and is positioned around the upper half of the circle.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
AUG 12 2009
BINAX, INC. Angela Drysdale 10 Southgate Road Scarborough, ME 04074
Re: K092223
Trade/Device Name: BinaxNOW Influenza A & B Test Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: Class I Product Code: GNX Dated: July 20, 2009 Received: July 23, 2009
Dear Ms. Drysdale:
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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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
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Page 2 - Ms. Drysdale
or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
toly alting
Sally A. Hoivat, 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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STATEMENT OF INDICATIONS FOR USE
510(k) Number (if known): K092223
Device Name: BinaxNOW® Influenza A & B Test
Indications For Use:
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.
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 IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Mhdd W.L. for UXS
Division Sign-Off
Division Sign-On
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K092223
Page 1 of 1
§ 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.