(279 days)
The Clearview Exact II Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. It is recommended that negative test results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.
The Clearview® Exact II Influenza A & B Test is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A and B nucleoprotein antigens in respiratory swab specimens. These antibodies and a control protein are immobilized onto a membrane support as three distinct lines and are combined with other reagents/pads to construct a Test Strip. Nasal swab samples are added to a Coated Reaction Tube to which an extraction reagent has been added. A Clearview Exact II Influenza A & B Test Strip is then placed in the Coated Reaction Tube holding the extracted liquid sample. Test results are interpreted at 10 minutes based on the presence of pink-to-purple colored Sample Lines. The yellow Control Line tums blue in a valid test.
Here's a breakdown of the acceptance criteria and the study details for the Clearview® Exact II Influenza A & B Test, 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 numerical terms (e.g., "Sensitivity must be > 90%"). Instead, it presents the device's performance against a gold standard (viral culture) as the evidence for substantial equivalence. The predicate device's performance often serves as an implicit benchmark for acceptance.
However, we can infer what constitutes acceptable performance from the presented results, as there's no indication that the results were unacceptable.
| Criterion (Inferred from Performance Data) | Acceptance Criteria (Implicit/Benchmark) | Reported Device Performance |
|---|---|---|
| Influenza Type A Detection | ||
| Sensitivity (vs. Viral Culture) | Likely comparable to predicate device | 94% (95% CI: 83-98%) |
| Specificity (vs. Viral Culture) | Likely comparable to predicate device | 94% (95% CI: 91-96%) |
| Positive Predictive Value (PPV) | Likely comparable to predicate device | 63% (95% CI: 52-74%) |
| Negative Predictive Value (NPV) | Likely comparable to predicate device | 99% (95% CI: 98-100%) |
| Influenza Type B Detection | ||
| Sensitivity (vs. Viral Culture) | Likely comparable to predicate device | 78% (95% CI: 68-86%) |
| Specificity (vs. Viral Culture) | Likely comparable to predicate device | 97% (95% CI: 95-98%) |
| Positive Predictive Value (PPV) | Likely comparable to predicate device | 84% (95% CI = 74-90%) |
| Negative Predictive Value (NPV) | Likely comparable to predicate device | 95% (95% CI = 93-97%) |
| Analytical Sensitivity (LOD 95%) | Likely comparable to predicate device | |
| A/HongKong/8/68 | Not explicitly stated | $2.37 \times 10^4$ TCID50/ml (97% detected) |
| A/PuertoRico/8/34 | Not explicitly stated | $3.16 \times 10^5$ TCID50/ml (88% detected) |
| B/Malaysia/2506/2004 | Not explicitly stated | $3.00 \times 10^6$ TCID50/ml (95% detected) |
| B/Lee/40 | Not explicitly stated | $4.20 \times 10^5$ TCID50/ml (95% detected) |
| Reproducibility | Likely high detection rates for positive samples, very low for negative | |
| Influenza A Moderate Positive | Not explicitly stated | 99.2% |
| Influenza A Low Positive | Not explicitly stated | 94.2% |
| Influenza A High Negative | Not explicitly stated | 9.2% |
| Influenza B Moderate Positive | Not explicitly stated | 99.2% |
| Influenza B Low Positive | Not explicitly stated | 96.7% |
| Influenza B High Negative | Not explicitly stated | 7.5% |
| Negative Samples (Overall) | Not explicitly stated | 100% (118/118) negative results |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 486 prospective specimens
- Data Provenance:
- Country of Origin: U.S. (multi-center, seven trial sites)
- Retrospective or Prospective: Prospective study, conducted during the 2008-2009 respiratory season. Specimens were collected from symptomatic patients.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number or specific qualifications of experts involved in establishing the ground truth. It relies on viral culture as the ground truth. Viral culture is a laboratory method, not typically performed by "experts" in the sense of clinicians or radiologists, but by trained laboratory personnel.
4. Adjudication Method for the Test Set
The document does not mention an explicit adjudication method (e.g., 2+1, 3+1). The primary comparison is the Clearview® Exact II test result directly against the viral culture result. For discrepant results with Influenza B (19 samples positive by culture, negative by Clearview), an investigational RT-PCR assay was used as a secondary check, showing 10 of these were negative by PCR. This suggests a form of post-hoc investigation for specific discrepancies, rather than a pre-defined adjudication process, but not a consensus reading among multiple human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a standalone performance evaluation of a rapid diagnostic test against a gold standard (viral culture), not a study involving human readers or AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance study was done for the device. The Clearview® Exact II Influenza A & B Test is itself a rapid immunoassay, a "device-only" test. The "performance vs. viral culture" is the standalone performance of the diagnostic test without human interpretation of complex images or data beyond reading simple color lines.
7. The Type of Ground Truth Used
The ground truth used for the clinical study was Viral Culture. For the 19 discrepant Influenza B samples, an investigational RT-PCR assay was also used as a secondary reference.
8. The Sample Size for the Training Set
The document does not mention a separate "training set" for the clinical performance evaluation. The clinical study described is a prospective validation set. For a device like this, the "training" (development and optimization) would typically involve internal efforts during the assay development process, using laboratory-prepared samples or retrospective samples, but a dedicated "training set" for clinical evaluation is not described for this type of diagnostic device.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" for clinical performance is described, the method for establishing its ground truth is not provided. For analytical studies (e.g., analytical sensitivity, reactivity), the ground truth is typically precisely quantified viral cultures or preparations.
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MAY 1 0 2010
510(k) SUMMARY
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: _ K092349
To establish substantial equivalence to the predicate, the Clearview® Exact II Influenza A & B Test was compared to the BinaxNOW® Influenza A & B Test (510(k) # K062109).
SUBMITTER
Binax, Inc., d/b/a Invemess Medical 10 Southgate Road Scarborough, Maine 04074 (207) 730-5739 (Office) (207) 730-5717 (FAX) Establishment Registration Number: 1221359
CONTACT PERSON Anne Jepson anne.jepson@invmed.com (email)
ALTERNATE CONTACT PERSON Angela Drysdale angela.drysdale@invmed.com (email)
DATE PREPARED
May 7, 2010
TRADE NAME
Clearview® Exact II Influenza A & B Test
COMMON NAME Not applicable
CLASSIFICATION NAME Antigen, Cf (including Cf Control), Influenza Virus A, B, C (per 21 CFR 866.3330)
PREDICATE DEVICE BinaxNOW® Influenza A & B Test, K062109
DEVICE DESCRIPTION
The Clearview® Exact II Influenza A & B Test is an immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect influenza type A and B nucleoprotein antigens in respiratory swab specimens. These antibodies and a control protein are immobilized onto a membrane support as three distinct lines and are combined with other reagents/pads to construct a Test Strip.
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Nasal swab samples are added to a Coated Reaction Tube to which an extraction reagent has been added. A Clearview Exact II Influenza A & B Test Strip is then placed in the Coated Reaction Tube holding the extracted liquid sample. Test results are interpreted at 10 minutes based on the presence of pink-to-purple colored Sample Lines. The yellow Control Line tums blue in a valid test.
INTENDED USE
The Clearview Exact II Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. It is recommended that negative test results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.
TECHNOLOGICAL CHARACTERISTICS
The Clearview® Exact II Influenza A & B Test and the predicate, the BinaxNOW® Influenza A & B Test, both use lateral flow immunochromatographic technology. Both tests are rapid immunoassays that employ specific antibodies immobilized onto solid phases to capture and visualize influenza nucleoprotein antigens.
PERFORMANCE SUMMARY
CLINICAL STUDY
Clearview Exact II Influenza A & B Test Performance vs. Viral Culture -Prospective Study
The clinical performance of the Clearview® Exact II Influenza A & B Test was established in a multi-center, prospective, clinical study conducted at seven U.S. trial sites during the 2008-2009 respiratory season.
A total of 486 prospective specimens, collected from children (less than 18 years of age) and adults (18 years or older), were evaluated in the Clearview® Exact II Influenza A & B Test and compared to viral culture. Evaluated specimens were nasal swabs collected from patients presenting with influenza-like symptoms. Forty-four percent (44%) of the population tested was < 5 years of age, 31% was 5 - < 18 years of age, and 25% was > 18 years. A/H3 and A/H1 were the predominant influenza A subtypes observed during this time.
Clearview® Exact II Influenza A & B Test performance versus viral culture, including 95% confidence intervals, is detailed below.
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Clearview Exact II Influenza A & B Test Performance vs. Culture
| Influenza Type A | |||
|---|---|---|---|
| Culture + | Culture - | ||
| Clearview + | 45 | 26 | 71 |
| Clearview - | 3 | 412 | 415 |
| 48 | 438 | 486 |
| Influenza Type B | |||
|---|---|---|---|
| Culture + | Culture - | ||
| Clearview + | 68 | 13 | 81 |
| Clearview - | 19* | 386 | 405 |
| 87 | 399 | 486 |
Sensitivity: 45/48 = 94% (95% CI: 83-98%) Specificity: 412/438 = 94% (95% Cl: 91-96%) PPV: 45/71 = 63% (95% Cl: 52-74%) NPV: 412/415 = 99% (95% CI: 98-100%)
Sensitivity: 68/87 = 78% (95% CI: 68-86%) Specificity: 386/399 = 97% (95% CI: 95-98%) PPV: 68/81 = 84% (95% Cl = 74-90%) NPV: 386/405 = 95% (95% CI = 93-97%)
- The nineteen samples that tested positive on culture for influenza B, but were negative on the Clearview Exact II Test, were also tested on an investigational RT-PCR assay. Ten (10) of these samples were negative for influenza B by PCR.
ANALYTICAL STUDIES
ANALYTICAL SENSITIVITY
The Clearview® Exact II Test limit of detection (LOD or Cos), defined as the concentration of influenza virus that produces positive Clearview® Exact II Test results approximately 95% of the time, was identified by evaluating different concentrations of 2 subtypes of live influenza A and 2 strains of live influenza B in the Clearview® Exact II Test. Multiple operators tested each concentration of the four influenza strains multiple times. The concentrations identified as the LOD (Cgs) levels for each strain tested are listed below.
| Influenza Strain | Concentration(TCID50/ml) | # Detected perTotal Tests | % Detected |
|---|---|---|---|
| Influenza A/HongKong/8/68 | $2.37 x 10^4$ | 64/66 | 97% |
| Influenza A/PuertoRico/8/34 | $3.16 x 10^5$ | 37/42 | 88% |
| Influenza B/Malaysia/2506/2004 | $3.00 x 10^6$ | 19/20 | 95% |
| Influenza B/Lee/40 | $4.20 x 10^5$ | 19/20 | 95% |
ANALYTICAL REACTIVITY TESTING
The influenza A and B strains listed tested positive in the Clearview® Exact II Influenza A & B Test at the concentrations specified. Although the specific influenza strains causing infection in humans can vary year to year, all contain the conserved nucleoproteins targeted by the Clearview® Exact II test. 1 Performance characteristics of the Clearview® Exact II 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 emerqing as human pathogens have not been established.
Influenza Strain
Flu A/Port Chalmers/1/73 (H3N2) Flu A/WS/33 (H1N1) Flu A/Aichi/2/68 (H3N2) Flu A/Malaya/302/54 (H1N1) Flu A/New Jersey/8/76 (H1N1) Flu A/Denver/1/57 (H1N1)
Concentration
- 5.6 x 105 TCID50/ml 5.0 x 104 TCID50/ml 3.0 x 104 TCID50/ml 6.0 x 103 TCID50/ml 2.8 x 105 TCID50/ml 8.9 x 103 TCID50/ml
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1 8 x 104 TCID50/ml Flu A/Victoria/3/75 (H3N2) 1.5 x 105 TCID50/ml Flu A/Solomon İslands/3/2006 (H1N1) 2.5 x 106 EiU50/ml Flu A/Brisbane/10/07 (H3N2) 5.6 x 105 TCID50/ml Flu A/PuertoRico/8/34 (H1N1) 1.3 x 105 TCID50/ml Flu A/Wisconsin/67/2005 (H3N2) Flu A/Hong Kong/8/68 (H3N2) 7.9 x 103 TCID50/ml 1.4 x 105 TCID50/ml Flu A/California/04/2009 (H1N1) 1.4 x 104 TCID50/ml Flu B/Florida/02/2006 7.1 x 104 TCID50/ml Flu B/Florida/04/2006 8.5 x 104 TCID50/ml Flu B/Florida/07/04 1.5 x 106 TCID50/ml Flu B/Malavsia/2506/04 1.7 x 104 TCID50/ml Flu B/Panama/45/90 5.0 x 105 TCID50/ml Flu B/R75 2.2 x 10° TCID50/ml Flu B/Russia/69 1.0 x 105 TCIDso/ml
1.5 x 105 TCIDso/ml Flu B/Taiwan/2/62 Flu B/Mass/3/66 1.8 x 10° TCID50/ml Flu B/Lee/40
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 Clearview Exact II Influenza A & B test can distinguish between influenza A and B viruses, but it does not differentiate seasonal influenza A virus from the novel influenza A (2009 H1N1) virus, and the test's ability to detect human infection with the novel influenza A 2009 H1N1 virus in clinical specimens is unknown.
ANALYTICAL SPECIFICITY (CROSS-REACTIVITY)
To determine the analytical specificity of the Clearview® Exact II Influenza A & B Test, 54 commensal and pathogenic microorganisms (38 bacteria, 15 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° cells/ml, CFU/ml or IFU/ml (bacteria), 105 to 10° TCIDso/ml or CEIDso/ml (viruses), and 109 cells/ml (veast).
Bacteria
Acinetobacter calcoaceticus Bacteroides fragilis Bordetella pertussis Chlamydia pneumoniae Corynebacterium diphtheria Enterococcus faecalis Escherichia coli Gardnerella vaginalis Haemophilus influenzae Klebsiella pneumoniae Lactobacillus casei Lactobacillus plantarum Legionella pneumophila Listeria monocytogenes Moraxella catarrhalis Mycobacterium avium
Yeast Viruses Adenovirus type 1 Adenovirus type 7 Coronavirus OC43 Coronavirus 229E Coxsackievirus B4 Cytomegalovirus (CMV) (Herpes V) Epstein Barr Virus Human metapneumovirus Measles (Edmonston) Mumps (Enders) Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Respiratory Syncytial Virus type B Rhinovirus type 1A
Candida albicans
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Mycobacterium intracellulare Mycobacterium tuberculosis Mycoplasma pneumoniae Neisseria gonorrhoeae Neissena 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, Group G Streptococcus mutans Streptococcus pneumoniae Streptococcus salivaris Streptococcus sanguis
INTERFERING SUBSTANCES
The following substances, naturally present in respiratory specimens or that may be artificially introduced into the nasal cavity or nasopharynx, were evaluated in the Clearview Exact II Influenza A & B Test at the concentrations listed below and were found not to affect test performance. Whole blood (1%) did not interfere with the interpretation of negative Clearview Exact II Test results, but did interfere with the interpretation of influenza A LOD (Cgs) positive samples. Therefore, visibly bloody samples may not be appropriate for use in this test.
| Substance | Concentration |
|---|---|
| 3 OTC nasal sprays | 10% |
| 3 OTC mouthwashes | 10% |
| 3 OTC throat drops | 10% |
| 4-acetamidophenol | 10 mg/ml |
| Acetylsalicylic acid | 20 mg/ml |
| Albuterol | 20 mg/ml |
| Chlorpheniramine | 5 mg/ml |
| Dexamethasone | 5 mg/ml |
| Dextromethorphan | 10 mg/ml |
| Diphenhydramine | 5 mg/ml |
| Doxylamine succinate | 1 mg/ml |
| Flunisolide | 3 mg/ml |
| Guaiacol glycerol ether | 20 mg/ml |
| Mucin | 1% |
| Mupirocin | 250 µg/ml |
| Oxymetazoline | 10 mg/ml |
| Phenylephrine | 10 mg/ml |
| Phenylpropanolamine | 20 mg/ml |
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Rebetol® (Ribavirin)
Relenza® (Zanamivir) Rimantadine Tamiflu® (Oseltamivir) Tobramvcin Triamcinolone
500 ng/ml 20 mg/ml 500 ng/ml 100 mg/ml 40 mg/ml 14 mg/ml
REPRODUCIBILITY
A reproducibility study of the Clearview® Exact II Influenza A & B Test was conducted by operators from 3 sites using panels of blind coded specimens containing negative, high negative (below the limit of detection), low positive (at the limit of detection), and moderate positive (above the limit of detection) influenza A and B viral samples. Participants tested each sample multiple times on 5 different days. The detection rates for the influenza A moderate positive, low positive, and high negative samples were 99.2% (119/120), 94.2 % (113/120) and 9.2% (11/120), respectfully. The detection rates for the influenza B moderate positive, low positive, and high negative samples were 99.2% (119/120); 96.7 % (116/120); and 7:5 % (9/120); respectfully. All of the negative samples (118) generated negative test results.
Signed Angela Drysdale Date 5/7/20
Director, Clinical Affairs Binax, Inc., d/b/a Inverness Medical
1 Dowdle, W.R. Kendal, A.P., and Noble, G.R. 1980. Influenza Virus, p 836-884. Ma Clinical Microbiology, 3rd edition, In Lennette, et. Al (ed.). American Society for Microbiolo Washington, D.C.
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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes representing the three levels of government: federal, state, and local. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
Ms. Anne Jepson Manager, Clinical Affairs Binax, Inc. Inverness Medical Inc. 10 Southgate Road Scarborough, ME 04074
Y 1.0 .20
Re: K092349
Trade/Device Name: Binax Clearview® Exact II Influenza A &B Test. Regulation Number: 21 CFR 866.3300 Regulation Name: Influenza Virus Serological Reagents Regulatory Class: Class I Product Code: GNX Dated: April 30, 2010 Received: May 3, 2010
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 vour 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.
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Page 2 - Anne Jepson
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 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/ReportalProblem/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/cdrl/industry/support/index.html.
Sincerely vours.
Saly ator
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
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INDICATIONS FOR USE STATEMENT
K092349 510(k) Number (if known):
Clearview® Exact II Influenza A & B Test Device Name:
Indications For Use:
The Clearview Exact II Influenza A & B Test is an in vitro immunochromatographic assay for the qualitative detection of influenza A and B nucleoprotein antigens in nasal swab specimens collected from symptomatic patients. It is intended to aid in the rapid differential diagnosis of influenza A and B viral infections. It is recommended that negative test results be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other management decisions.
Prescription Use × (Part 21 CFR 801 Subpart D)
AND/OR Over-The-Counter Use (Part 21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - (CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
| 510(k) | K092349 |
|---|---|
| -------- | --------- |
§ 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.