(57 days)
Not Found
No
The description focuses on isothermal nucleic acid amplification technology and fluorescence detection, with no mention of AI or ML.
No.
The device is an in vitro diagnostic test for the qualitative detection and discrimination of influenza A and B viral RNA, used as an aid in diagnosis, not for treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is a "rapid molecular in vitro diagnostic test" intended "for the qualitative detection and discrimination of influenza A and B viral RNA" and "for use as an aid in the differential diagnosis of influenza A and B viral infections."
No
The device description clearly outlines multiple hardware components including a Sample Receiver, Test Base, Transfer Cartridge, and the Alere™ i Instrument repeat use reader, which are integral to the device's function.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Alere™ i Influenza A & B assay is a "rapid molecular in vitro diagnostic test".
- Method: It utilizes "isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA". This is a laboratory-based test performed on biological samples (nasal/nasopharyngeal swabs).
- Purpose: It is intended for use "as an aid in the differential diagnosis of influenza A and B viral infections in humans". This clearly indicates its use in a diagnostic context.
- Sample Type: It analyzes "direct nasal swabs or nasopharyngeal swabs eluted in viral transport media from patients". These are biological specimens.
All of these points align with the definition of an In Vitro Diagnostic device, which is a medical device used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
N/A
Intended Use / Indications for Use
The Alere™ i Influenza A & B assay performed on the Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA in direct nasal swabs or nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the differential diagnosis of influenza A and B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay is not intended to detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2014-2015 influenza seasons when influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Product codes (comma separated list FDA assigned to the subject device)
OCC, OZE, OOI
Device Description
Alere™ i Influenza A & B is a rapid, instrument-based isothermal test for the qualitative detection and differentiation of influenza A and influenza B from nasal or nasopharyngeal swabs eluted in viral transport media from patients presenting with signs and symptoms of respiratory infection. The Alere™ i Influenza A & B System utilizes isothermal nucleic acid amplification technology and is comprised of:
- Sample Receiver - single use, disposable containing the elution buffer
- . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
- Transfer Cartridge – single use, disposable for transfer of the eluted sample to the Test Base, and
- Alere™ i Instrument repeat use reader ●
The reaction tubes in the Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i Influenza A & B utilizes a pair of templates (similar to primers) for the specific amplification of RNA from influenza A and B and a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets. Alere™ i Influenza A & B is performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This minimizes the risk of instrument contamination and sample carry-over between measurements.
To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, resuspending the lyophilized pellet contained within the Test Base and initiating target amplification. Heating mixing and detection by fluorescence is provided by the instrument, with results automatically reported.
Results are displayed by the Alere™ i Instrument separately for influenza B. Results are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasal swabs, nasopharyngeal swabs
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Professional use, in a medical laboratory or point-of-care.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A total of 1,273 nasal or nasopharyngeal swab specimens were collected from patients presenting with flu-like symptoms in a multi-site prospective study during the 2014-2015 flu season in the U.S. Specimens were placed in viral transport media. An FDA-cleared influenza real-time Polymerase Chain Reaction (RT-PCR) test was utilized as the comparator method for this study. All discrepant samples were tested on a different FDA-cleared influenza real-time RT-PCR assay at Alere Scarborough Inc. to confirm influenza status. External control testing, using Alere™ i Influenza A & B Positive and Negative Controls, was performed prior to sample testing each day and on each Alere™ i instrument for the clinical study. 1,270 viral transport media specimens were tested with the Alere™ i Influenza A & B assay. Of these, 27 specimens generated invalid results after repeat testing, resulting in 1,243 specimens for performance analysis.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Sensitivity (Limit of Detection - LOD):
The LOD for various influenza A and B strains was determined in natural nasal swab matrix. For direct swab testing, LOD ranged from 5.55 x 10^0 TCID50/Swab to 1.88 x 10^3 TCID50/Swab. For swab eluted in VTM testing, LOD ranged from 9.82 x 10^1 TCID50/Swab to 5.20 x 10^3 TCID50/Swab.
Analytical Reactivity (Inclusivity):
The Alere™ i Influenza A & B assay detected all tested influenza A and B strains that represent temporal and geographic diversity at specified concentrations. This was tested using contrived swab samples with virus dilutions. An additional analytical reactivity study also demonstrated equivalent analytical reactivity performance for testing nasopharyngeal swab samples eluted in Viral Transport Media compared to direct swab samples.
Analytical Specificity (Cross Reactivity):
53 commensal and pathogenic microorganisms (37 bacteria, 15 viruses, and 1 yeast) were tested at varying concentrations. All were negative, indicating no cross-reactivity.
Interfering Substances:
21 substances commonly found in respiratory specimens or artificially introduced were evaluated and found not to affect test performance.
Inhibition by other Microorganisms:
The test demonstrated no inhibition in the presence of other non-influenza respiratory pathogens (Adenovirus Type 1, Rhinovirus Type 1A, Respiratory Syncytial Virus, Type B, Strain 18537) at the concentrations evaluated, for both direct swab and VTM eluted samples.
Inhibition by High Levels of Influenza A and B (Co-infection):
No impact on test performance was observed when high levels of influenza A and B were present in contrived co-infection swab specimens, for both direct swab and VTM eluted samples.
Carry-Over Contamination:
No false positive results were obtained in the direct swab study (15 rounds of alternating positive/negative swabs). In the VTM study (30 rounds), one false positive for Flu B was observed. The overall conclusion states that there is little risk of false positive results caused by carryover or cross-contamination when recommended laboratory practices are followed.
Clinical Study (Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media):
A multi-site prospective study was conducted during the 2014-2015 flu season.
Sample size: 1,243 evaluable specimens.
Comparator method: FDA-cleared influenza real-time RT-PCR test.
Discrepant samples were re-tested with an alternative FDA-cleared RT-PCR assay.
Results for Influenza A:
Sensitivity: 97.8% (221/226) (95%CI: 94.9%-99.1%)
Specificity: 96.6% (982/1017) (95%CI: 95.3%-97.5%)
Note: Flu A nucleic acid was detected in 31/35 False Positive specimens using an alternative FDA-cleared molecular test.
Results for Influenza B:
Sensitivity: 92.9% (92/99) (95%CI: 86.1%-96.5%)
Specificity: 98.3% (1125/1141) (95%CI: 97.4%-98.9%)
Note: Flu B nucleic acid was detected in 3/19 False Positive specimens using an alternative FDA-cleared molecular test.
Performance Stratified by Patient Age:
- ≤ 5 Years of Age (n = 706):
- Flu A Sensitivity: 99.1% (105/106) (94.8%, 99.8%)
- Flu A Specificity: 98.2% (589/600) (96.7%, 99.0%)
- Flu B Sensitivity: 100% (39/39) (91.0%, 100%)
- Flu B Specificity: 98.2% (655/667) (96.9%, 99.0%)
- 6 - ≤ 21 Years of Age (n = 388):
- Flu A Sensitivity: 97.0% (98/101) (91.6%, 99.0%)
- Flu A Specificity: 95.8% (275/287) (92.8%, 97.6%)
- Flu B Sensitivity: 94.2% (49/52) (84.4%, 98.0%)
- Flu B Specificity: 98.5% (331/336) (96.6%, 99.4%)
- ≥ 22 Years of Age (n = 149):
- Flu A Sensitivity: 94.7% (18/19) (75.4%, 99.1%)
- Flu A Specificity: 90.8% (118/130) (84.6%, 94.6%)
- Flu B Sensitivity: 50% (4/8) (21.5%, 78.5%)
- Flu B Specificity: 98.6% (139/141) (95.0%, 99.6%)
Invalid Rate:
Initial invalid rate: 4.3% (54/1270) (95% CI: 3.3% to 5.5%).
After repeat testing: 2.1% (27/1270) (95% CI: 1.5%, 3.1%).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Influenza A (Clinical Study):
Sensitivity: 97.8% (221/226) (95%CI: 94.9%-99.1%)
Specificity: 96.6% (982/1017) (95%CI: 95.3%-97.5%)
Influenza B (Clinical Study):
Sensitivity: 92.9% (92/99) (95%CI: 86.1%-96.5%)
Specificity: 98.3% (1125/1141) (95%CI: 97.4%-98.9%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Alere™ i Influenza A & B Assay, K141520
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.
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Image /page/0/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, with three figures in profile facing right. The symbol is black and the background is white.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
July 28, 2015
Alere Scarborough, Inc. Angela Drysdale Vice President, Regulatory and Clinical Affairs - Infectious Disease 10 Southgate Road Scarborough, ME 04074
Re: K151464
Trade/Device Name: Alere™ i Influenza A&B Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: II Product Code: OCC, OZE, OOI Dated: June 02, 2015 Received: June 03, 2015
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA 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 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
1
medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Tamara V. Feldblyum -S for
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K151464
Device Name Alere™ i Influenza A & B
Indications for Use (Describe)
The Alere™ i Influenza A & B assay performed on the Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA in direct nasal swabs or nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the differential diagnosis of influenza A and B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay is not intended to detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2014-2015 influenza seasons when influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
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: K151464
SUBMITTER
Alere Scarborough, Inc. 10 Southgate Road Scarborough, ME 04074 Establishment Registration Number: 1221359
CONTACT PERSON
Angela Drysdale (207) 730-5737 (Office) (207) 730-5767 (FAX) Angela.drysdale@alere.com (email)
DATE PREPARED
7/8/2015
TRADE NAME Alere™ i Influenza A & B
COMMON NAME Alere™ i flu, Alere™ i, Alere™ Influenza A & B
CLASSIFICATION NAME
Respiratory Viral Panel Multiplex Nucleic Acid Assay (per 21 CFR 866.3980) Instrumentation for Clinical Multiplex Test Systems (per 21 CFR 862.2570)
CLASSIFICATION Class II
PRODUCT CODE OCC, OZE, OOI
PANEL Microbiology (83)
PREDICATE DEVICE Alere™ i Influenza A & B Assay, K141520
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DEVICE DESCRIPTION
Alere™ i Influenza A & B is a rapid, instrument-based isothermal test for the qualitative detection and differentiation of influenza A and influenza B from nasal or nasopharyngeal swabs eluted in viral transport media from patients presenting with signs and symptoms of respiratory infection. The Alere™ i Influenza A & B System utilizes isothermal nucleic acid amplification technology and is comprised of:
- Sample Receiver - single use, disposable containing the elution buffer
- . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
- Transfer Cartridge – single use, disposable for transfer of the eluted sample to the Test Base, and
- Alere™ i Instrument repeat use reader ●
The reaction tubes in the Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i Influenza A & B utilizes a pair of templates (similar to primers) for the specific amplification of RNA from influenza A and B and a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets. Alere™ i Influenza A & B is performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This minimizes the risk of instrument contamination and sample carry-over between measurements.
To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, resuspending the lyophilized pellet contained within the Test Base and initiating target amplification. Heating mixing and detection by fluorescence is provided by the instrument, with results automatically reported.
Results are displayed by the Alere™ i Instrument separately for influenza B. Results are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.
INTENDED USE
The Alere™ i Influenza A & B assay performed on the Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA in direct nasal or nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the differential diagnosis of influenza A and B viral infections in conjunction with clinical and epidemiological risk factors. The assay is not intended to detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2012-2013 and the 2014-2015 influenza seasons when influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
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TECHNOLOGICAL CHARACTERISTICS
The purpose of this submission is to expand the Alere™ i Influenza A & B test Intended Use (hereby referred to as Expanded Claim Alere™ i Influenza A & B test) to include testing of swab samples that have been eluted in viral transport media. There have been no changes to the Alere™ i Influenza A & B test or principles of operation.
DEVICE COMPARISON
The expanded claim Alere™ i Influenza A & B test was compared to the legally marketed predicate device, the 510(k) cleared Alere™ i Influenza A & B test.
| Parameter | Expanded Claim
Alere™ i Influenza A & B | Alere™ i Influenza A & B (K141520) |
|---------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| FDA Product Code | OCC,OZE, OOI | Same |
| Assay Target | Influenza A, Influenza B | Same |
| Intended Use | The Alere™ i Influenza A & B assay
performed on the Alere™ i Instrument is
a rapid molecular in vitro diagnostic test
utilizing an isothermal nucleic acid
amplification technology for the
qualitative detection and discrimination
of influenza A and B viral RNA in nasal
swabs and nasal or nasopharyngeal
swabs eluted in viral transport media
from patients with signs and symptoms
of respiratory infection. It is intended for
use as an aid in the differential diagnosis
of influenza A and B viral infections in
humans in conjunction with clinical and
epidemiological risk factors. The assay is
not intended to detect the presence of
influenza C virus.
Negative results do not preclude
influenza virus infection and should not
be used as the sole basis for diagnosis,
treatment or other patient management
decisions.
Performance characteristics for influenza
A were established during the 2012-
2013 influenza season when influenza
A/H3 and A/H1N1 pandemic were the
predominant influenza A viruses in
circulation. When other influenza A
viruses are emerging, performance
characteristics may vary.
If infection with a novel influenza A virus
is suspected based on current clinical
and epidemiological screening criteria
recommended by public health
authorities, specimens should be
collected with appropriate infection
control precautions for novel virulent
Influenza viruses and sent to state or
legal health de | The Alere™ i Influenza A & B assay performed
on the Alere™ i Instrument is a rapid
molecular in vitro diagnostic test utilizing an
isothermal nucleic acid amplification
technology for the qualitative detection and
discrimination of influenza A and B viral RNA
in nasal swab samples from patients with
signs and symptoms of respiratory infection.
It is intended for use as an aid in the
differential diagnosis of influenza A and B
viral infections in humans in conjunction with
clinical and epidemiological risk factors. The
assay is not intended to detect the presence of
influenza C virus.
Negative results do not preclude influenza
virus infection and should not be used as the
sole basis for diagnosis, treatment or other
patient management decisions.
Performance characteristics for influenza A
were established during the 2012-2013
influenza season when influenza A/H3 and
A/H1N1 pandemic were the predominant
influenza A viruses in circulation. When other
influenza A viruses are emerging,
performance characteristics may vary.
If infection with a novel influenza A virus is
suspected based on current clinical and
epidemiological screening criteria
recommended by public health authorities,
specimens should be collected with
appropriate infection control precautions for
novel virulent Influenza viruses and sent to
state or local health department for testing.
Viral culture should not be attempted in these
cases unless a BSL 3+ facility is available to
receive and culture specimens. |
| Parameter | Expanded Claim
Alere™ i Influenza A & B | Alere™ i Influenza A & B (K141520) |
| | culture should not be attempted in these
cases unless a BSL 3+ facility is available
to receive and culture specimens. | |
| Intended Environment
for Use | CLIA waived for testing direct nasal swab
samples only. Professional use, in a
medical laboratory or point-of-care. | CLIA Waived.
Professional use, in a medical laboratory or
point-of-care. |
| Instrumentation | Alere™ i Instrument | Same |
| Self-Contained System | Integrated PC, Software, and Touch
Screen Display | Same |
| Automated Assay | Yes. Sample preparation, amplification,
detection, and result interpretation. | Same |
| Assay Information | | |
| Sample Type | Nasal Swab and Nasal or Nasopharyngeal
Swabs Eluted in Viral Transport Media | Nasal Swab |
| Influenza A Viral Target | PB2 segment | Same |
| Influenza B Viral Target | PA segment | Same |
| Technology | Isothermal nucleic acid amplification for
detecting the presence/absence of viral
RNA in clinical specimens | Same |
| Detection Method | Assay uses different reporter dyes for
each target | Same |
| Internal Control | Yes | Same |
| Result Interpretation | Automated | Same |
| Assay Result | Qualitative | Same |
| Time to Result | *Note: 10 ul of each virus dilution was coated onto a swab
Limit of Detection (LOD) Study Results - Natural Nasal Swab Matrix (Swab Eluted in VTM Testing)
| Influenza Strain | Influenza A
Subtype or
Influenza B
Genetic Lineage | LOD
(TCID50/mL) | LOD
(TCID50/Swab)* | LOD (Genome
Equivalents/mL) | LOD (Genome
Equivalents/Swab)* |
|------------------------|-------------------------------------------------------------|--------------------|-----------------------|--------------------------------|-----------------------------------|
| A/Puerto Rico/8/34 | A/H1N1 | $4.20 \times 10^5$ | $4.20 \times 10^3$ | $4.59 \times 10^6$ | $4.59 \times 10^4$ |
| A/Perth/16/2009 | A/H3N2 | $9.82 \times 10^3$ | $9.82 \times 10^1$ | $1.25 \times 10^6$ | $1.25 \times 10^4$ |
| A/California/7/2009 | A/2009 H1N1 pdm | $5.20 \times 10^5$ | $5.20 \times 10^3$ | $7.77 \times 10^6$ | $7.77 \times 10^4$ |
| B/Malaysia/2506/2004 | B Victoria lineage | $1.05 \times 10^5$ | $1.05 \times 10^3$ | $2.29 \times 10^6$ | $2.29 \times 10^4$ |
| B/Bangladesh/3333/2007 | B Yamagata lineage | $1.34 \times 10^4$ | $1.34 \times 10^2$ | $1.98 \times 10^6$ | $1.98 \times 10^4$ |
- Note: 10 ul of each virus dilution was coated onto a swab; each contrived swab was further diluted into 3 mL of UTM
REACTIVITY TESTING
An analytical reactivity (inclusivity) study was performed to determine whether the Alere™ i Influenza A & B assay is able to detect a variety of influenza A and B strains that represent temporal and geographic diversity.
Vender provided stocks of influenza A and B strains were diluted in UTM to generate virus dilutions for testing. The concentration (in TCIDso/mL, or EID50/mL) for each strain was determined by standard virologic method. The concentration for each dilution (in genome equivalents/mL) was also assessed using laboratory developed and validated influenza A and influenza B quantitative real-time PCR assays.
Contrived swab samples were prepared by coating 10 microliters of virus dilution onto each swab. The contrived swab samples were tested without further elution in viral transport media according to the test procedure for Direct Nasal Swab.
The starting dilution concentration selected for testing in this study was higher than the established LODs in the Limit of Detection study. Each starting dilution per virus strain was tested in triplicates initially. If the initial testing concentration tested positive for all three replicates, the strain was further diluted 10-fold and tested in triplicates until at least one out three replicates generated a negative result. When a negative result was obtained, additional 2-fold dilutions were tested, starting from the highest dilution that produced 100% (3/3) positive results. A concentration level was considered "reactive/positive" in this study for all but one strain tested (i.e., B/Texas/06/2011 – see footnote "c" under the table below) if all three replicates generated a positive result for the expected influenza virus.
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The Alere™ i Influenza A & B assay detected all strains tested at the concentrations indicated in the table below:
Analytical Reactivity Study Results
| Influenza Strain | Influenza A
Subtype or
Influenza B
Genetic Lineage | Test Concentration (in TCID50 or Genome Equivalents,
unless indicated otherwise) | | | | Flu A
Result
(n=3,
unless
indicate
otherwise) | Flu B
Result
(n=3,
unless
indicate
otherwise) |
|----------------------------------|-------------------------------------------------------------|-------------------------------------------------------------------------------------|---------------------------------|------------------------------|---------------------------------|--------------------------------------------------------------|--------------------------------------------------------------|
| | | TCID50/mL | TCID50/Swab* | Genome
Equivalents/
mL | Genome
Equivalent
s/Swab* | | |
| A/New Caledonia/20/1999 a | A/H1N1 | $9.19 x 10^5$ | $9.19 x 10^3$ | $4.09 x 10^6$ | $4.09 x 10^4$ | + | - |
| A/New Jersey/8/76 a | A/H1N1 | $3.41 x 10^1$ | $3.41 x 10^{-1}$ | $1.52 x 10^5$ | $1.52 x 10^3$ | + | - |
| A/Brisbane/59/2007 a | A/H1N1 | $2.11 x 10^4$ | $2.11 x 10^2$ | $3.39 x 10^5$ | $3.39 x 10^3$ | + | - |
| A/WSN/33 a | A/H1N1 | $2.11 x 10^2$ | $2.11 x 10^0$ | $2.43 x 10^5$ | $2.43 x 10^3$ | + | - |
| A/Port Chalmers/1/73 | A/H3N2 | $4.22 x 10^4$ | $4.22 x 10^2$ | $1.31 x 10^6$ | $1.31 x 10^4$ | + | - |
| A/Hong Kong/8/68 | A/H3N2 | $7.03 x 10^0$ | $7.03 x 10^{-2}$ | $2.70 x 10^5$ | $2.70 x 10^3$ | + | - |
| A/Aichi/2/68 | A/H3N2 | $2.08 x 10^5$ | $2.08 x 10^3$ | $7.47 x 10^6$ | $7.47 x 10^4$ | + | - |
| A/Victoria/3/75 | A/H3N2 | $3.68 x 10^5$ | $3.68 x 10^3$ | $3.39 x 10^6$ | $3.39 x 10^4$ | + | - |
| A/Wisconsin/67/2005 | A/H3N2 | $6.81 x 10^4$ | $6.81 x 10^2$ | $2.57 x 10^6$ | $2.57 x 10^4$ | + | - |
| A/Brisbane/10/2007 | A/H3N2 | $3.16 x 10^2$ | $3.16 x 10^0$ | $3.37 x 10^5$ | $3.37 x 10^3$ | + | - |
| A/Texas/50/2012 | A/H3N2 | $2.5 x 10^0$ | $2.50 x 10^{-2}$ | $6.35 x 10^3$ | $6.35 x 10^1$ | + | - |
| A/Victoria/361/2011 | A/H3N2 | $1.56 x 10^1$ | $1.56 x 10^{-1}$ | $3.53 x 10^5$ | $3.53 x 10^3$ | + | - |
| A/California/4/2009 | A/H1N1 (pdm) | $1.47 x 10^4$ | $1.47 x 10^2$ | $1.07 x 10^6$ | $1.07 x 10^4$ | + | - |
| A/Maryland/04/2011 | A/H1N1 (pdm) | $7.88 x 10^4$ | $7.88 x 10^2$ | $3.81 x 10^6$ | $3.81 x 10^4$ | + | - |
| A/New York/18/2009 | A/H1N1 (pdm) | $1.25 x 10^2$ | $1.25 x 10^0$ | $9.16 x 10^5$ | $9.16 x 10^3$ | + | - |
| A/Anhui/1/2013
(Inactivated)a | A/H7N9
(Detected in China
in 2013) | $4.00 x 10^6$
EID50/mL | $4.00 x 10^4$
EID50/Swab | $1.72 x 10^6$ | $1.72 x 10^4$ | + | - |
| A/Indiana/10/2011ª | A/H3N2v | $2.00 x 10^8$
EID50/mL | $2.00 x 10^6$
EID50/Swab | $5.94 x 10^4$ | $5.94 x 10^2$ | + | - |
| B/Lee/40 | Victoria Lineage | $5.00 x 10^1$
CEID50/mL | $5.00 x 10^{-1}$
CEID50/Swab | $5.40 x 10^4$ | $5.40 x 10^2$ | - | + |
| B/Victoria/504/2000 | Victoria Lineage | $1.19 x 10^3$ | $1.19 x 10^1$ | $6.24 x 10^4$ | $6.24 x 10^2$ | - | + |
| B/Nevada/03/2011 | Victoria Lineage | $1.75 x 10^3$ | $1.75 x 10^1$ | $8.29 x 10^4$ | $8.29 x 10^2$ | - | + |
| B/Montana/05/2012 | Victoria Lineage | $9.00 x 10^1$ | $9.00 x 10^{-1}$ | $2.55 x 10^4$ | $2.55 x 10^2$ | - | + |
| B/Maryland/1/59 | Yamagata Lineage | $8.51 x 10^2$ | $8.51 x 10^0$ | $1.13 x 10^5$ | $1.13 x 10^3$ | - | + |
| B/Russia/69b | Yamagata Lineage | $4.44 x 10^1$ | $4.44 x 10^{-1}$ | $2.96 x 10^6$ | $2.96 x 10^4$ | - | + |
| B/Wisconsin/01/2010c | Yamagata Lineage | $3.68 x 10^4$ | $3.68 x 10^2$ | $1.16 x 10^6$ | $1.16 x 10^4$ | - | + |
| B/Massachusetts/2/2012 | Yamagata Lineage | $6.25 x 10^1$ | $6.25 x 10^{-1}$ | $2.28 x 10^5$ | $2.28 x 10^3$ | - | + |
| B/Texas/06/2011c | Yamagata Lineage | $2.89 x 10^5$ | $6.25 x 10^3$ | $2.00 x 10^6$ | $2.00 x 10^4$ | - | + |
*Note: 10 ul of each virus dilution was coated onto a swab
4 Although this test has been shown to detect A/H1N9 (detected in China in 2013) and A/H3N2v viruses cultured from positive human respiratory specimens, the performance characteristics of this device with clinical speciment that are positive for the A/H1N1 (pre-2009 pandemic), A/H7N9 (detected in China in 2013) and A/H3N2v viruses have not been established.
4 Influenza B/Russia/69 lowest level in which 3/3 replicates were positive is approximately 40 to 150 x the LOD (as comparing to the Genome Equivalents/Swab values generated in the LOD with simulated clinical matrix study testing B/Malaysia/2008, respectively). A polymorphism within segment PA of the Influenza B genome was identified at a position which is 4 nucleotides from the 3 -end of template 2. This G to A polymorphism results in a G/C (product/template) match to an A/C (product/template) mismatch is determined to be moderately destabilizing, and coupled to its position only 4 nucleotides from the 2 recognition region, its impact on annealing is potentially great. The frequency of this is determined to be very low. In analyzing the strains present in the NCBI Influenza Virus Resource database from 2/2005 to 3/2014 (N=986), no strains contained this polymorphism, suggesting that it has not been circulating for an extended period of time.
c Influenza B/Wisconsin/01/2010 lowest level in which 3/3 replicates were positive is approximately 15 to 60 x the LOD, and Influenza B/Texas/06/2011 lowest level in which at least 1/3 replicates were positive is approximately 25 to 100 x the LOD (as comparing to the Genome Equivalents/Swab values generated in the LOD with simulated clinical matrix study testing B/Malaysia / 60/2008, respectively). A single G to A polymorphism within segment PA of the Influenza B genome was identified at a position which is 5 not the 3end of the molecular beacon annealing region in both strains. The G to A polymorphism results in a C/A mismatch between the molecular beacon and product 1. The C./A mismatch is determined to be moderately destabilizing that can significantly reduce assay sensitivity. An assessment of what impact this polymorphism would have on the melting temperature (Tm) of the molecular beacon/product 1 annealing was performed and the results showed a Tm drop from 62.3°C to 55.6°C, just below the assay running temperature. This suggests that annealing would occur, but at a greatly reduced level, with a concomitant loss of assay sensitivity. The frequency of this G to A polymorphism is approximately 5% within the NCBI Influenza Virus Resource database covering the time from 2/2005 through 3/2014.
An additional analytical reactivity study was also performed testing the same set of influenza A and B strains as described in the table above following the test procedure for Nasopharyngeal Swab Eluted in Viral Page 6 of 11
9
Transport Media, and demonstrated equivalent analytical reactivity performance to that of testing direct swab samples.
Analytical Specificity (Cross Reactivity)
To determine the analytical specificity of Alere™ i Influenza A & B, 53 commensal and pathogenic microorganisms (37 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), 104 to 10° TCIDs0/mL (viruses), and 10° cells/mL (yeast).
| Bacteria | Viruses | Yeast |
|---|---|---|
| Acinetobacter calcoaceticus | Adenovirus type 1 | Candida albicans |
| Bacteroides fragilis | Adenovirus type 7 | |
| Bordetella pertussis | Human Coronavirus OC43 | |
| Chlamydia pneumoniae | Human Coronavirus 229E | |
| Corynebacterium diphtheriae | Enterovirus/Coxsackievirus B4 | |
| Enterococcus faecalis | Human Cytomegalovirus (CMV) (Herpes V) | |
| Escherichia coli | Epstein Barr Virus | |
| Gardnerella vaginalis | Human metapneumovirus | |
| Haemophilus influenzae | Measles (Edmonston) | |
| Klebsiella pneumoniae | Mumps (Enders) | |
| Lactobacillus casei | Parainfluenza 1 | |
| Lactobacillus plantarum | Parainfluenza 2 | |
| Legionella pneumophila | Parainfluenza 3 | |
| Listeria monocytogenes | Respiratory Syncytial Virus type B | |
| Moraxella/Branhamella catarrhalis | Rhinovirus type 1A | |
| Mycobacterium avium | ||
| Mycobacterium intracellulare | ||
| Mycobacterium tuberculosis | ||
| Mycoplasma pneumoniae | ||
| Neisseria gonorrhoeae | ||
| Neisseria meningitidis | ||
| Neisseria sicca | ||
| Neisseria subflava | ||
| Proteus vulgaris | ||
| Pseudomonas aeruginosa | ||
| Serratia marcescens | ||
| Staphylococcus aureus | ||
| Staphylococcus epidermidis | ||
| Streptococcus, Group A | ||
| Streptococcus, Group B | ||
| Streptococcus, Group C | ||
| Streptococcus, Group F | ||
| Streptococcus, Group G | ||
| Streptococcus mutans | ||
| Streptococcus pneumoniae | ||
| Streptococcus salivarius |
Streptococcus sanguinis
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Interfering Substances
The following substances, naturally present in respiratory specimens or that may be artificially introduced into the nasal cavity or nasopharynx, were evaluated with Alere™ i Influenza A & B at the concentrations listed below and were found not to affect test performance.
| Substance | Concentration |
|---|---|
| Mucin | 20 µg/mL |
| Whole Blood | 50 µl/mL |
| Sinus Buster Nasal Spray | 200 µl/mL |
| NeoSynephrine Cold & Sinus Extra Strength Spray | 200 µl/mL |
| Zicam Extreme Congestion Relief | 200 µl/mL |
| Afrin PumpMist Original | 200 µl/mL |
| 4-acetamidophenol | 200 µg/mL |
| Acetylsalicylic acid | 650 µg/mL |
| Albuterol | 400 ng/mL |
| Chlopheniramine | 145 ng/mL |
| Dexamethasone | 0.80 mg/mL |
| Dextromethorphan | 1 µl/mL |
| Diphenhydramine | 5 µg/mL |
| Doxylamine Succinate | 236 ng/mL |
| Ephedrine | 237 ng/mL |
| Flunisolide | 6.8 ng/mL |
| Guaiacol glycerol ether | 3.5 ng/mL |
| Mupirocin | 12 mg/mL |
| Oxymetazoline | 0.6 mg/mL |
| Phenylephrine | 12 mg/mL |
| Rebetol | 4.5 µg/mL |
| Relenza | 282 ng/mL |
| Rimatadine | 282 ng/mL |
| Tamiflu | 1.1 µg/mL |
| Tobryamycin | 2.43 mg/mL |
| Triamcinolone | 40 µg/mL |
Inhibition by other Microorganisms
Alere™ i Influenza A & B test performance in the presence of non-influenza respiratory pathogens was evaluated. Vendor provided stocks of influenza A and B strains were diluted in UTM to approximately 2 to 3 times the limit of detection. Contrived influenza A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. The following panel of non-influenza viruses were tested at the concentration provided in the table below and was found not to affect test performance.
| Virus Panel | Concentration
(TCID50/ml) |
|------------------------------------------------------|------------------------------|
| Adenovirus Type 1 | 1.58 x 107 |
| Rhinovirus Type 1A | 1.58 x 107 |
| Respiratory Syncytial Virus, Type B, Strain
18537 | 8.89 x 105 |
In an additional study, contrived influenza A and B positive swab specimens were also eluted into UTM and tested according the test procedure for Nasal or Nasopharyngeal Swab Eluted in Viral Transport Media using
11
the same panel of non-influenza respiratory viruses as described in the table above. None of the non-influenza respiratory viruses tested was found to affect test performance at the concentrations evaluated.
Inhibition by High Levels of Influenza A and B
Alere™ i Influenza A & B test performance in the presence of influenza A and B was evaluated. Vendor provided stocks of influenza A and B strains were diluted in UTM to approximately 2 to 3 times the limit of detection. Contrived influenza A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. To create the co-infection swabs, diluted influenza A (at a concentration approximately 5 times the LOD) was added to the near LOD Flu B swab. Likewise, diluted influenza B (at a concentration approximately 40 times the LOD) was added to the near LOD Flu A swab. No impact on test performance was observed.
Alere™ i Influenza A & B test performance in the presence of influenza A and B was also evaluated in an additional study following the test procedure for Nasopharyngeal Swab Eluted in Viral Transport Media. No impact on test performance was observed at the concentrations tested.
Carry-Over Contamination
An analytical carry-over study was performed to demonstrate that when recommended laboratory practices are followed, there is little risk of false positive results caused by carryover or cross-contamination in the Alere™ i Influenza A & B test. Vendor provided stocks of influenza A and B strains were diluted in UTM to a minimum of 106 TCID50/ml. Contrived influenza A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. Testing of the contrived positive swabs was alternated with testing of a negative swab sample for a total of 15 rounds. There were no false positive results obtained.
An additional analytical carry-over study was performed testing contrived positive VTM samples alternated with negative VTM samples following the test procedure for Nasopharyngeal Swab Eluted in Viral Transport Media for a total of 30 rounds. No false positive results were observed in this study except for one Flu B false positive result.
An additional analytical reactivity study was also performed testing the same set of influenza A and B strains as described in the table above following the test procedure for Nasopharyngeal Swab Eluted in Viral Transport Media, and demonstrated equivalent analytical reactivity performance to that of testing direct swab samples.
CLINICAL STUDY
Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media
Clinical performance characteristics of Alere™ i Influenza A & B were evaluated in a multi-site prospective study during the 2014-2015 flu season in the U.S. A total of three investigational sites across the U.S. participated in the study. To be enrolled in the study, patients had to be presenting at the participating study centers with flu-like symptoms. Nasal or nasopharyngeal swab specimens were collected from patients with flu-like symptoms and were placed in viral transport media. The samples were processed and tested using the Alere™ i Influenza A & B assay according to the test procedure for Nasal or Nasopharyngeal Swab Eluted in Viral Transport Media. An FDA-cleared influenza real-time Polymerase Chain Reaction (RT-PCR) test was utilized as the comparator method for this study. All discrepant samples were tested on a different FDAcleared influenza real-time RT-PCR assay at Alere Scarborough Inc. to confirm influenza status. External control testing, using Alere™ i Influenza A & B Positive and Negative Controls, was performed prior to sample testing each day and on each Alere™ i instrument for the dinical study. A total of 1,273 nasal or nasopharyngeal swabs eluted in viral transport media were enrolled in this study. Of those, 3 specimens did not meet eligibility criteria. A total of 1,270 viral transport media specimens were tested with the Alere™ i Influenza A & B assay. Patient age and gender distribution for all included specimens in this study is presented in the table below.
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| Age Group | Female | Male |
|---|---|---|
| 21 to 60 years | 52 | 37 |
| >60 years | 42 | 24 |
| Total | 636 | 634 |
Age and Gender Distribution - Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media Study
Of the 1,270 specimens, Alere™ i Influenza A & B generated invalid results for 27 specimens after repeat testing per the product instructions, resulting in a total of 1,243 specimens for performance analysis.
Compared to the comparator method, the performance of Alere™ i Influenza A & B for influenza B are presented in the two tables below.
Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media - Performance Obtained for Influenza A with Alere™ i Influenza A & B against the Comparator Method
| Alere™ i
Influenza A & B
- Flu A | | Comparator Method | | |
|----------------------------------------|----------|----------------------|-------|--|
| | Positive | Negative | Total | |
| Positive | 221 | 35a | 256 | |
| Negative | 5 | 982 | 987 | |
| Total | 226 | 1017 | 1243 | |
| Sensitivity: 221/226 | 97.8% | (95%CI: 94.9%-99.1%) | | |
| Specificity: 982/1017 | 96.6% | (95%CI: 95.3%-97.5%) | | |
a Flu A nucleic acid was detected in 31/35 False Positive specimens using an alternative FDA-cleared molecular test
Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media - Performance Obtained for Influenza B with Alere™ i Influenza A & B against the Comparator Method
| Alere™ i
Influenza A & B
- Flu B | Comparator Method | | |
|----------------------------------------|-------------------|----------------------|-------|
| | Positive | Negative | Total |
| Positive | 92 | 19a | 111 |
| Negative | 7 | 1125 | 1132 |
| Total | 99 | 1144 | 1243 |
| Sensitivity: 92/99 | 92.9% | (95%CI: 86.1%-96.5%) | |
| Specificity: 1125/1141 | 98.3% | (95%CI: 97.4%-98.9%) | |
ª Flu B nucleic acid was detected in 3/19 False Positive specimens using an alternative FDA-cleared molecular test
Performance of Alere™ i Influenza A & B for the detection of influenza A and influenza B versus the comparator method in this study is presented in the table below stratified by patient age.
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Nasal or Nasopharyngeal Swabs Eluted in Viral Transport Media - Performance Obtained for Influenza A and Influenza B with Alere™ i Influenza A & B in Comparison to the Comparator Method – Stratified by Patient Age
| | ≤ 5 Years of Age
(n = 706) | | 6 - ≤ 21 Years of Age
(n = 388) | | ≥ 22 Years of Age
(n = 149) | |
|-------------------|------------------------------------|------------------------------------|------------------------------------|------------------------------------|----------------------------------|------------------------------------|
| Influenza
Type | Sensitivity
95% CI | Specificity
95% CI | Sensitivity
95% CI | Specificity
95% CI | Sensitivity
95% CI | Specificity
95% CI |
| Flu A | 99.1%
(105/106)
94.8%, 99.8% | 98.2%
(589/600)
96.7%, 99.0% | 97.0%
(98/101)
91.6%, 99.0% | 95.8%
(275/287)
92.8%, 97.6% | 94.7%
(18/19)
75.4%, 99.1% | 90.8%
(118/130)
84.6%, 94.6% |
| Flu B | 100%
(39/39)
91.0%, 100% | 98.2%
(655/667)
96.9%, 99.0% | 94.2%
(49/52)
84.4%, 98.0% | 98.5%
(331/336)
96.6%, 99.4% | 50%
(4/8)
21.5%, 78.5% | 98.6%
(139/141)
95.0%, 99.6% |
During this prospective clinical study, the initial invalid rate (before repeat testing per the product instructions) was 4.3% (54/1270) (95% Cl: 3.3% to 5.5%). After repeat testing per the product instructions, the invalid rate was 2.1% (27/1270) (95% CI: 1.5%, 3.1%).