(249 days)
Not Found
No
The description focuses on PCR and lateral flow technologies, automated fluid handling, and embedded firmware for controlling the process and providing status. There is no mention of AI or ML being used for analysis, interpretation, or decision-making.
No
The device is an in vitro diagnostic test intended to aid in the diagnosis of influenza infection, not to treat or provide therapy.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states, "The Accula Flu A/Flu B assay is intended as an aid in the diagnosis of influenza infection in conjunction with clinical and epidemiological risk factors."
No
The device description clearly states the system consists of a reusable "Dock" which is an electronic module containing electrical systems, controls, and logic, and a single-use disposable test cassette. This indicates the device includes significant hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Accula Flu A/Flu B Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection and differentiation of influenza A and influenza B viral RNA."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The Accula Flu A/Flu B Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection and differentiation of influenza A and influenza B viral RNA. The Accula Flu A/Flu B Test uses a nasal swab specimen collected from patients with signs and symptoms of respiratory infection. The Accula Flu A/Flu B assay is intended as an aid in the diagnosis of influenza infection 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 treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2016-2017 influenza season. 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 public 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
Device Description
The Accula Flu A/Flu B Test is a semi-automated, colorimetric, multiplex reverse-transcription polymerase chain reaction (RT-PCR) nucleic acid amplification test to qualitatively detect influenza A and B viral RNA from unprocessed nasal swabs that have not undergone prior nucleic acid extraction. The system integrates nucleic acid extraction, reverse transcription, a novel Mesa Biotech PCR nucleic acid amplification technology named OscARTM, and hybridization-based visual detection into a completely self-contained and automated system. The Accula Flu A/Flu B system consists of a small reusable Dock to drive the automated testing process, and a single-use disposable test cassette that contains all the enzymes and reagents.
The Accula Flu A/Flu B Test Kit contains all the materials needed to run a test, except for the Accula Dock, which is provided separately. The Accula Flu A/Flu B Test Kit contains the following components: Puritan Rayon Swabs for nasal swab collection (25), Accula Nasal Swab Buffer (25), Accula Transfer Pipettes (25), Accula Flu A/Flu B Test Cassettes (25), Control Swab (1): Flu A+; Flu B-, Control Swab (1): Flu B+; Flu A-, Package Insert, Quick Reference Instructions.
The Accula Dock is an electronic module which executes in vitro diagnostic tests on compatible Mesa Biotech Test Cassettes. It consists of an electro-mechanical interface to a single Test Cassette. The Dock contains all electrical systems, controls and logic necessary to orchestrate in vitro diagnostic tests within the inserted Test Cassette.
Upon insertion of a Test Cassette, the Dock will detect and identify the Cassette type. After the user transfers a clinical test sample into the Cassette and closes the Dock lid, embedded firmware in the Dock will control fluid flow of the sample into the various chambers of the Cassette, apply controlled voltage signals to the various Cassette heaters (monitored by sensors within the Dock), and provide visual status to the user with critical information such as estimated time to read, and various error states, should they be encountered.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasal
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Clinical lab and 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
Prospective Clinical Study:
- Sample Size: 1258 evaluable specimens from a total of 1331 subjects.
- Data Source: Multisite prospective study during the 2016-2017 flu season in the U.S. Sixteen investigational sites participated.
- Annotation Protocol: Patients presenting at study centers with flu-like symptoms. Two nasal swabs collected from one nostril from each subject. One nasal swab tested with Accula Flu A/Flu B Test. The other nasal swab transported to one of two central laboratories for testing using a comparator method (FDA-cleared molecular influenza assay). All discrepant results analyzed using an alternative FDA-cleared molecular assay at the reference laboratory.
Reproducibility Studies:
- Sample Size: Each sample type (Flu A Low Positive, Flu A Moderate Positive, Flu B Low Positive, Flu B Moderate Positive, Flu A and B Negative) was tested at three CLIA-waived sites and one moderately complex site. Each sample was tested in triplicate (from separate swabs) by two operators across 5 non-consecutive days, resulting in 30 observations for each site per sample type. Overall, 119/119 for Flu A Low/Mod Positive, 120/120 for Flu B Low/Mod Positive, and 120/120 for True Negative.
- Data Source: Contrived nasal swabs.
- Annotation Protocol: Test panel consisted of five samples at virus concentration near the respective LoD: Flu A and B Negative, Flu A Low Positive, Flu A Moderate Positive, Flu B Low Positive, and Flu B Moderate Positive. Samples prepared using Flu A and B strains (Flu A/California/07/2009 and Flu B/Massachusetts/2/2012) spiked into clinical matrix. Samples were blinded and randomized. Each operator tested one panel per day, maximum of five samples at a time. Results reported as percent agreement: actual result/expected result x 100.
CLIA Waiver Studies - Clinical Performance by Intended Users:
- Sample Size: 1258 evaluable specimens from patients with flu-like symptoms.
- Data Source: Sixteen intended use sites (CLIA-waived clinical setting) by non-laboratory personnel in a prospective clinical study during the 2016-2017 flu season in the U.S.
- Annotation Protocol: Nasal swabs were collected from patients with flu-like symptoms and were tested with the Accula Flu A/Flu B Test and the comparator method (FDA-cleared molecular influenza assay). All specimens generating discrepant results were investigated by testing using an alternative FDA-cleared molecular assay.
CLIA Waiver Studies - Performance Near the Cut-Off:
- Sample Size: Panel of 60 samples for each site (20 replicates of each of three sample types) tested across three CLIA-waived sites.
- Data Source: Contrived samples.
- Annotation Protocol: Three CLIA-waived sites. Three untrained intended operators at each site. Test panel consisted of three contrived samples: Flu A Low Positive, Flu B Low Positive, and a True Negative. Samples prepared using Flu A and B strains (Flu A/California/07/2009 and Flu B/Massachusetts/2/2012) spiked into clinical matrix. Targeted concentrations for Low Positive samples were approximately 1X the respective LoD (C95 concentration). Flu A and B Negative samples contained no Flu virus. Test samples were coded and blinded to the operators. Swab specimens presented to operators throughout the course of a normal testing day and masked as subject samples. Testing performed over two weeks on non-consecutive days, while the clinical study was in progress. Each operator tested 5 samples each testing day. Testing performed with one lot of Accula Flu A/Flu B Test cassettes.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Prospective Clinical Study:
- Study Type: Multisite prospective clinical study
- Sample Size: 1258 evaluable specimens
- Key Results:
- Flu A Performance:
- Sensitivity: 97% (95% CI: 94.1% - 98.5%)
- Specificity: 94% (95% CI: 92.0% - 95.2%)
- 47/60 False Positive Flu A specimens detected using an alternative FDA-cleared molecular Influenza A+B Assay.
- 3/9 False Negative Flu A specimens not detected using an alternative FDA-cleared molecular Influenza A+B Assay.
- Flu B Performance:
- Sensitivity: 94% (95% CI: 88.2% - 97.2%)
- Specificity: 99% (95% CI: 97.9% - 99.3%)
- 9/14 False Positive Flu B specimens detected using an alternative FDA-cleared molecular Influenza A+B Assay.
- 5/8 False Negative Flu B specimens not detected using an alternative FDA-cleared molecular Influenza A+B Assay.
- Flu A Performance:
Reproducibility Studies:
- Study Type: Reproducibility study
- Sample Size: Over 100 observations per sample category across 4 sites, by 2 operators on 5 non-consecutive days.
- Key Results: Agreement was 100% across all sites, operators and days for all sample categories (Low Pos Flu A, Mod Pos Flu A, Low Pos Flu B, Mod Pos Flu B, True Neg). Overall % agreement and 95% CI:
- Low Pos Flu A: 100% (119/119) (96.9%, 100%)
- Mod Pos Flu A: 100% (119/119) (96.9%, 100%)
- Low Pos Flu B: 100% (120/120) (96.9%, 100%)
- Mod Pos Flu B: 100% (120/120) (96.9%, 100%)
- True Neg: 100% (120/120) (96.9%, 100%)
- No significant differences observed within run, between run, between sites, or between operators.
Limit of Detection (LoD):
- Study Type: Analytical study
- Key Results: LoD was determined at >= 95% detection for:
- A/California/07/2009 (H1N1): 300 TCID50/mL
- A/Texas/50/2012 (H3N2): 1200 TCID50/mL
- B/Nevada/3/2011 (Victoria): 1350 CEID50/mL
- B/Massachusetts/2/2012 (Yamagata): 400 TCID50/mL
Analytical Reactivity (Inclusivity):
- Study Type: Analytical study
- Key Results: All twenty-three (23) strains of Influenza were detected at concentration of about 2x LoD.
Analytical Specificity (Cross-Reactivity):
- Study Type: Analytical study
- Key Results: All 33 exclusivity organisms were negative at the concentrations tested. Exclusivity is verified for the strains tested.
Interfering Substances:
- Study Type: Analytical study
- Key Results: The Accula Flu A/Flu B test performance is not negatively affected by the potentially interfering substances (Mucin, Blood, Neo-Synephrine, Afrin, Nasacort, Zicam, Cepacol, Zanamivir, Mupirocin, Tobramycin) under "worst case" concentration conditions. Agreement with expected results was 100% for all targets (Negative, FluA/Cali, FluA/Texas, FluB/Nevada, FluB/Mass) across all interferents.
CLIA Waiver Studies - Clinical Performance by Intended Users:
- Study Type: Prospective clinical study by non-laboratory personnel in a CLIA-waived setting.
- Sample Size: 1258 evaluable specimens.
- Key Results:
- Flu A Performance:
- Sensitivity: 97% (95% CI: 94.4% - 98.4%)
- Specificity: 94% (95% CI: 92.0% - 95.1%)
- 47/60 False Positive Flu A specimens detected using an alternative FDA-cleared molecular Influenza Assay.
- 3/9 False Negative Flu A specimens not detected using an alternative FDA-cleared molecular Influenza Assay.
- Flu B Performance:
- Sensitivity: 94% (95% CI: 88.7% - 97.0%)
- Specificity: 99% (95% CI: 97.9% - 99.3%)
- 9/14 False Positive Flu B specimens detected using an alternative FDA-cleared molecular Influenza Assay.
- 5/8 False Negative Flu B specimens not detected using an alternative FDA-cleared molecular Influenza Assay.
- Flu A Performance:
- The study demonstrates the performance of the Accula Flu A /Flu B test in a CLIA Waived clinical setting.
CLIA Waiver Studies - Performance Near the Cut-Off:
- Study Type: Study to demonstrate performance by untrained intended operators.
- Sample Size: Panel of 60 samples for each site, across 3 sites.
- Key Results: Untrained use operators are able to accurately perform and interpret the Mesa Biotech Flu A/Flu B test at the level of the LoD for both Influenza A and Influenza B.
- Low A Positive: 58/60 = 97% agreement
- Low B Positive: 58/60 = 97% agreement
- Negative: 59/59 = 100% agreement (1 negative result resulted in an unresolved Invalid)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Prospective Clinical Study (Overall):
- Flu A:
- Sensitivity: 97% (95% CI: 94.1% - 98.5%)
- Specificity: 94% (95% CI: 92.0% - 95.2%)
- Flu B:
- Sensitivity: 94% (95% CI: 88.2% - 97.2%)
- Specificity: 99% (95% CI: 97.9% - 99.3%)
Reproducibility Studies (Percent Agreement with Expected):
- Low Pos Flu A: 100%
- Mod Pos Flu A: 100%
- Low Pos Flu B: 100%
- Mod Pos Flu B: 100%
- True Neg: 100%
CLIA Waiver Studies - Clinical Performance by Intended Users:
- Flu A:
- Sensitivity: 97% (95% CI: 94.4% - 98.4%)
- Specificity: 94% (95% CI: 92.0% - 95.1%)
- Flu B:
- Sensitivity: 94% (95% CI: 88.7% - 97.0%)
- Specificity: 99% (95% CI: 97.9% - 99.3%)
CLIA Waiver Studies - Performance Near the Cut-Off (Agreement of Observed/Expected):
- Low A Positive: 97% (58/60)
- Low B Positive: 97% (58/60)
- Negative: 100% (59/59)
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.
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.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
February 6, 2018
Mesa Biotech, Inc. Barbara Stevens Regulatory Affairs Consultant 6190 Cornerstone Court, Suite 220 San Diego, California 92121
Re: K171641
Trade/Device Name: Accula Flu A/Flu B Test Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC. OZE Dated: June 1, 2017 Received: June 2, 2017
Dear Barbara Stevens:
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Steven R. Gitterman -S
for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K171641
Device Name Accula Flu A/Flu B Test
Indications for Use (Describe)
The Accula Flu A/Flu B Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection and differentiation of influenza A and influenza B viral RNA. The Accula Flu B Test uses a nasal swab specimen collected from patients with signs and symptoms of respiratory infection. The Accula Flu A/Flu B assay is intended as an aid in the diagnosis of influenza infection 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 treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2016-2017 influenza season. 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 public 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
Section 5. 510(k) Summary of Safety and Effectiveness
This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: _____K171641
Sponsor/Applicant Name and Address 1. Company Name: Mesa Biotech, Inc. Address: 6190 Cornerstone Court, Suite 220 San Diego, CA 92121 Telephone: 858-800-4929 Contact Person: Barbara Stevens Regulatory Consultant Date Summary Prepared: 06/01/2017 2. Device Name and Classification Trade Name: Accula Flu A/Flu B Test Classification of Device: 21 CFR 866.3980, Respiratory viral panel multiplex nucleic acid assay OZE, OCC Product Code
Predicate Device 3.
K141520, Alere i Influenza A&B Assay
Device Description 4.
Operating Principle
The Accula Flu A/Flu B Test is a semi-automated, colorimetric, multiplex reverse-transcription polymerase chain reaction (RT-PCR) nucleic acid amplification test to qualitatively detect influenza A and B viral RNA from unprocessed nasal swabs that have not undergone prior nucleic acid extraction. The system integrates nucleic acid extraction, reverse transcription, a novel Mesa Biotech PCR nucleic acid amplification technology named OscARTM, and hybridization-based visual detection into a completely self-contained and automated system. The Accula Flu A/Flu B system consists of a small reusable Dock to drive the automated testing process, and a single-use disposable test cassette that contains all the enzymes and reagents.
Flu A/Flu B Kit Contents
The Accula Flu A/Flu B Test Kit contains all the materials needed to run a test, except for the Accula Dock, which is provided separately. The Accula Flu A/Flu B Test Kit contains the following components.
4
- Puritan Rayon Swabs for nasal swab collection (25) ●
- Accula Nasal Swab Buffer (25) ●
- Accula Transfer Pipettes (25)
- Accula Flu A/Flu B Test Cassettes (25)
- Control Swab (1): Flu A+; Flu B-
- Control Swab (1): Flu B+; Flu A-
- Package Insert
- Quick Reference Instructions ●
Accula Dock
The Accula Dock is an electronic module which executes in vitro diagnostic tests on compatible Mesa Biotech Test Cassettes. It consists of an electro-mechanical interface to a single Test Cassette. The Dock contains all electrical systems, controls and logic necessary to orchestrate in vitro diagnostic tests within the inserted Test Cassette.
Upon insertion of a Test Cassette, the Dock will detect and identify the Cassette type. After the user transfers a clinical test sample into the Cassette and closes the Dock lid, embedded firmware in the Dock will control fluid flow of the sample into the various chambers of the Cassette, apply controlled voltage signals to the various Cassette heaters (monitored by sensors within the Dock), and provide visual status to the user with critical information such as estimated time to read, and various error states, should they be encountered.
5. Indications for Use
The Accula Flu A/Flu B Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection and differentiation of influenza B viral RNA. The Accula Flu A/Flu B Test uses a nasal swab specimen collected from patients with signs and symptoms of respiratory infection. The Accula Flu A/Flu B assay is intended as an aid in the diagnosis of influenza infection 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 treatment or other patient management decisions.
Performance characteristics for influenza A were established during the 2016-2017 influenza season. 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.
6. Comparison to Predicate Device
The following table provides a comparison of the characteristics of the Accula Flu A Test to the predicate device, the Alere i Influenza A&B Test.
5
| Item | 510(k) Device:
Mesa Biotech
Accula Flu A/Flu B Test | Predicate Device:
Alere i Influenza A&B
(K141520) |
|-------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | The Accula Flu A/Flu B Test
performed on the Accula Dock
is a molecular in vitro
diagnostic test utilizing
polymerase chain reaction
(PCR) and lateral flow
technologies for the
qualitative, visual detection
and differentiation of influenza
A and influenza B viral RNA.
The Accula Flu A/Flu B Test
uses a nasal swab specimen
collected from patients with
signs and symptoms of
respiratory infection. The
Accula Flu A/Flu B assay is
intended as an aid in the
diagnosis of influenza infection
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
treatment or other patient
management decisions.
Performance characteristics for
influenza A were established
during the 2016-2017 influenza
season. When other influenza
A viruses are emerging,
performance characteristics
may vary. | 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 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 |
| | 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. | 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
cultures should not be
attempted in these cases unless
a BSL 3+ facility is available
to receive and culture
specimens. |
| Assay Targets | Influenza A virus, influenza B
virus | Influenza A virus, influenza B
virus; |
| Sample Type | Nasal swab | Nasal swab |
| Assay Results | Qualitative | Qualitative |
| Intended Users and
Use Locations | Clinical lab and point of care | Clinical lab and point of care |
| Nucleic Acid
Purification | No | No |
| Influenza A Target | PB2 subunit gene | PB2 gene segment |
| Influenza B Target | Matrix Gene | PA gene segment |
| Internal Control | Yes | Yes |
| Positive and
Negative Control
Swabs | Yes | Yes |
| Assay Technology | PCR amplification and visual
identification of amplification
products by hybridization to a
test strip. | Isothermal nucleic acid
amplification and detection of
specific amplification products
using molecular beacon probes |
| Detection | Multiplex assay using dyed
microparticle conjugates to
specifically detect and identify
amplification reaction
products.
Visual interpretation of the
presence or the absence of
colored lines on a test strip. | Multiplex assay using
fluorescently-labeled
molecular beacons to
specifically identify each of the
amplified RNA targets.
Optical detection of
fluorescence |
| Instrument | Amplification controlled by
the Accula Dock.
No detection by the
instrument. | Amplification and detection
performed on the Alere i
instrument |
6
7
Performance Summary 7.
Expected Values
The prevalence of influenza varies from year to year, with outbreaks occurring during the fall and winter months. The influenza positivity rate is dependent upon many factors, including specimen collection, test method, and geographic location. Prevalence varies throughout the flu season and from location to location.
The Mesa Biotech clinical study was conducted during the 2016-2017 influenza season. The following tables show the prevalence of influenza A and influenza B observed in three subject age categories in that clinical study.
| | Prospective Clinical Study during
the 2016/2017 Influenza Season | | |
|----------------------|---------------------------------------------------------------------|---------------------------------------------|--------------------------------------|
| Age Group | Number of
Nasal
Swab
Specimens | Number
of
Influenza
A
Positives | Influenza
A
Positivity
Rate |
| ≤ 5 Years of Age | 488 | 97 | 19.9% |
| 6 to 21 Years of Age | 601 | 172 | 28.6% |
| ≥ 22 Years of Age | 169 | 20 | 11.8% |
| Total | 1258 | 289 | 23.0% |
8
| | Prospective Clinical Study during
the 2016/2017 Influenza Season | | |
|----------------------|---------------------------------------------------------------------|---------------------------------------------|--------------------------------------|
| Age Group | Number of
Nasal
Swab
Specimens | Number
of
Influenza
B
Positives | Influenza
B
Positivity
Rate |
| ≤ 5 Years of Age | 488 | 27 | 5.5% |
| 6 to 21 Years of Age | 601 | 91 | 15.1% |
| ≥ 22 Years of Age | 169 | 8 | 4.7% |
| Total | 1258 | 126 | 10.0% |
AcculaTM Flu A/Flu B Test vs. a FDA-Cleared Molecular Influenza Assay: Prospective Clinical Study
Clinical performance characteristics of the Accula Flu A/Flu B Test were evaluated in a multisite prospective study during the 2016-2017 flu season in the U.S. A total of sixteen investigational sites participated in the study. To be enrolled in the study, patients had to be presenting at the participating study centers with flu-like symptoms. Two nasal swabs were collected from one nostril from each subject using standard collection methods. One nasal swab was eluted in 5-mL of Accula Nasal Swab Buffer and tested with the Accula Flu A/Flu B Test according to product instructions. The other nasal swab was eluted in a 3-mL of viral transport media (VTM) and transported to one of two central laboratories for testing using the comparator method. All discrepant results were analyzed using an alternative FDA-cleared molecular assay at the reference laboratory.
A total of 1331 subjects were enrolled in this study. Of those, 73 specimens are unevaluable (i.e., failed to meet inclusion criteria, were not transported to a Reference Laboratory per the conditions required by the clinical protocol, had invalid result for the comparator assay or had two invalid results on the Accula Flu A/Flu B Test. A total of 1258 specimens were considered evaluable. The performance of the Accula Flu A/Flu B test for influenza A and influenza B as compared to a FDA-cleared molecular comparator are presented in the tables below.
| Accula
Flu A/Flu B -
| Flu A | Comparator | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| Positive | 289 | 60a | 349 | |
| Negative | 9b | 900 | 909 | |
| Total | 298 | 960 | 1258 | |
| Sensitivity: | 97% (95% CI: 94.1% - 98.5%) | |||
| Specificity: | 94% (95% CI: 92.0% - 95.2%) |
Accula Flu A/Flu B Test Flu A Performance against the Comparator Method
9
ª FLU A was detected in 47/60 False Positives specimens using an alternative FDA-cleared molecular Influenza A+B Assay
b FLU A was not detected in 3/9 False Negative specimens using an alternative FDA-cleared molecular Influenza A+B Assay
| Accula
Flu A/Flu B -
| Flu B | Alere™ i Influenza A & B Assay | ||
|---|---|---|---|
| Positive | Negative | Total | |
| Positive | 126 | 14a | 140 |
| Negative | 8b | 1110 | 1118 |
| Total | 134 | 1124 | 1258 |
| Sensitivity: | 94% (95% CI: 88.2% - 97.2%) | ||
| Specificity: | 99% (95% CI: 97.9% - 99.3%) |
Accula Flu A/Flu B Test Flu B Performance against the Comparator Method
a FLU B was detected in 9/14 False Positives specimens using an alternative FDA-cleared molecular Influenza A+B Assav
b FLU B was not detected in 5/8 False Negative specimens using an alternative FDA-cleared molecular Influenza A+B Assay
Reproducibility Studies
The Reproducibility study was performed to demonstrate the reproducibility of the Accula Flu A/Flu B Test with contrived nasal swabs at three CLIA-waived sites and one moderately complex site based in the United States. The objective of this study was to test panels of contrived nasal swab samples with the Accula Flu A/Flu B Test to demonstrate reproducibility of the assay in the hands of multiple users at multiple sites over multiple non-consecutive days.
The test panel consisted of five samples at virus concentration near the respective LoD (i.e., Flu A and B Negative, Flu A Low Positive, Flu A Moderate Positive, Flu B Low Positive and Flu B Moderate Positive). Each sample was prepared using the Flu A and B strains spiked into clinical matrix. The Flu A strain used in this study was Flu A/California/07/2009 and the Flu B strain used in this study was Flu B/Massachusetts/2/2012. The targeted concentrations for the Moderate Positive samples were approximately 3 X the respective LoD, the targeted concentrations for the Low Positive samples were approximately 1 X the respective LoD (C95 concentration), and the Flu A and B Negative samples contained no Flu virus.
Samples were provided to testing operators in panels of 5 samples (Flu A Low Positive and Moderate Positive, Flu B Low Positive and Moderate Positive, and Negative). Samples were blinded and randomized. Each operator tested one panel per day, testing a maximum of five samples at a time. Each sample was tested in triplicate (from separate swabs) (2 operators x 1 run x 3 swabs x 5 non-consecutive days = 30 observations for each site per sample type). Results are reported as percent agreement: actual result/expected result x 100. Results were evaluated by site, by operator and by day. Agreement was 100% across all sites, operators and days. Two
10
samples did not produce results because re-tests of invalid results were invalid on re-test. Results are shown below by site.
| Sample
Category | Site 1 | | Site 2 | | Site 3 | | Site 4 | | Overall % and
95% CI |
|-----------------------------------------------|--------|--------|--------|-------|--------|--------|--------|-------|------------------------------------|
| | % | Count | % | Count | % | Count | % | Count | |
| Low Pos
Flu A | 100% | 30/30 | 100% | 30/30 | 100% | 29/29* | 100% | 30/30 | 100%
(119/119)
(96.9%, 100%) |
| Mod Pos
Flu A | 100% | 29/29* | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100%
(119/119)
(96.9%, 100%) |
| Low Pos
Flu B | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100%
(120/120)
96.9%, 100%) |
| Mod Pos
Flu B | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100%
(120/120)
(96.9%, 100%) |
| True Neg | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100%
(120/120)
(96.9%, 100%) |
| *re-run of second test resulted in an invalid | | | | | | | | | |
Site to Site Reproducibility: Percent Agreement
Agreement of actual results with expected results was 100%. There were no significant differences observed within run (replicates tested by one operator), between run (five different days), between sites (four sites), or between operators (eight operators).
Limit of Detection
Multiple analyte levels were tested in 20 replicates until the LoD was determined (the level at which at least 19/20 results are positive). Four (4) influenza strains were run in replicates of twenty (20) for each concentration. The influenza strains selected for testing included a 2009like seasonal H1N1 influenza A strain, an H3N2 influenza A strain, and two influenza B strains representing Victoria and Yamagata lineages. Virus was serially diluted into Pooled Negative Clinical Matrix and spiked onto a swab to create the contrived sample for each technical replicate in LoD determination.
| Volume Spiked | Final Concentration (TCID50/mL) | Observed/ Expected |
|---|---|---|
| Swab | Positives | |
| 10 µL | A/CA 300 TCID50/mL | 20/20 |
| 10 µL | A/CA 300 TCID50/mL | 20/20 |
| 10 µL | A Texas 2400 TCID50/mL | 20/20 |
| 10 µL | A Texas 1200 TCID50/mL | 20/20 |
Limit of Detection: Observed/Expected
11
| 10 μL | B Nevada 675 CEID50/mL | 18/20 |
|---|---|---|
| 10 μL | B Nevada 1350 CEID50/mL | 20/20 |
| 10 μL | B/MA 300 TCID50/mL | 17/18 |
| 10 μL | B/MA 400 TCID50/mL | 20/20 |
The limit of detection (LoD) for the Accula Flu A/Flu B Test for both Flu A and Flu B were determined with ≥ 95% detection at:
A/California/07/2009 (H1N1): 300 TCID50/mL
A/Texas/50/2012 (H3N2): 1200 TCID50/mL
B/Nevada/3/2011 (Victoria): 1350 CEID50/mL
B/Massachusetts/2/2012 (Yamagata): 400 TCID50/mL
Analytical Reactivity
Inclusivity verification was evaluated for the Accula Flu B test at Mesa Biotech. The panel consisted of 23 influenza strains. The chosen strains represented subtypes in the population, including A: H1N1, A: H3N2, A: H1N1 (2009), B Victoria lineage strains, and B Yamagata lineage strains. At least ten (10) Influenza A strains and five (5) Influenza B strains were included, and emphasis was placed on contemporary strains. Virus was diluted into a Pooled clinical matrix and spiked onto a swab to create contrived swab samples. Each strain was tested in triplicate, at final concentration of about 2x LoD of each Influenza subtype. The following test results were obtained.
| Inclusivity Verification: Influenza A and Influenza B Strains, Target Concentrations and | ||||
|---|---|---|---|---|
| Test Results | ||||
| Influenza Strain | Subtype/ | |||
| Lineage | Viral Titer | |||
| TCID50/mLa | Flu A Test Result | |||
| (# of FluA | ||||
| Positive /3) | Flu B Test Result | |||
| (# of FluB | ||||
| Positive /3) | ||||
| A/Beijing/262/1995 | H1N1 | 6.00E+02 | 3/3 | 0/3 |
| A/Brisbane/59/2007 | H1N1 | 6.00E+02 | 3/3 | 0/3 |
| A/Brisbane/10/2007 | H3N2 | 2.40E+03 | 3/3 | 0/3 |
| A/England/42/1972 | H3N2 | 2.40E+03 | 3/3 | 0/3 |
| A/Fort Monmouth/1/1947 | H1N1 | 6.00E+02 | 3/3 | 0/3 |
| A/New Caledonia/20/1999 | H1N1 | 6.00E+02 | 3/3 | 0/3 |
| A/Perth/16/2009 | H3N2-like | 2.40E+03 | 3/3 | 0/3 |
| A/Port Chalmers/1/1973 | H3N2 | 2.40E+03 | 3/3 | 0/3 |
| A/Puerto Rico/8/1934 | H1N1 | 6.00E+02 | 3/3 | 0/3 |
| A/Solomon | ||||
| Islands/3/2006 | H1N1 | 6.00E+02 | 3/3 | 0/3 |
| A/Switzerland/9715293/2 | ||||
| 013 | H3N2-like | 2.40E+03 | 3/3 | 0/3 |
| A/Sydney/5/1997 | H3N2 | 2.40E+03 | 3/3 | 0/3 |
| A/Victoria/3/1975 | H3N2 | 2.40E+03 | 3/3 | 0/3 |
| A/Victoria/361/2011 | H3N2 | 2.40E+03 | 3/3 | 0/3 |
12
| Influenza Strain | Subtype/
Lineage | Viral Titer
TCID50/mLa | Flu A Test Result
(# of FluA
Positive /3) | Flu B Test Result
(# of FluB
Positive /3) |
|--------------------------------------------------------------------------------------------------------------------------------------------|---------------------|---------------------------|-------------------------------------------------|-------------------------------------------------|
| A/Wisconsin/67/2005 | H3N2-like | 2.40E+03 | 3/3 | 0/3 |
| B/Brisbane/60/2008 | Victoria | 2.70E+03 | 0/3 | 3/3 |
| B/Florida/4/2006 | Yamagata | 8.00E+02 | 0/3 | 3/3 |
| B/Lee/1940 | Victoria | 2.70E+03 | 0/3 | 3/3 |
| B/Malaysia/2506/2004 | Victoria | 2.70E+03 | 0/3 | 3/3 |
| B/Maryland/1/1959 | Yamagata | 8.00E+02 | 0/3 | 3/3 |
| B/Phuket/3073/2013 | Yamagata | 8.00E+02 | 0/3 | 3/3 |
| B/Russia/1969 | Yamagata | 8.00E+02 | 0/3 | 3/3 |
| B/Wisconsin/1/2010 | Yamagata | 8.00E+02 | 0/3 | 3/3 |
| a Concentration of contrived sample after 10uL of virus dilution Spiked onto Swab and Swirled in 5mL assuming 100% viral elution recovery. | | | | |
All twenty-three (23) strains of Influenza were detected with the Mesa Biotech FluA/FluB Test at concentration of about 2x LoD.
The Analytical Specificity (Cross- Reactivity)
The analytical specificity was evaluated with a panel of common organisms when tested on the Accula Flu A/Flu B assay internally at Mesa Biotech. Thirty-three (33) organisms were obtained from Zeptometrix Corporation excepted for Chlamydia pneumonia and Corynebacterium glycinophilum (were obtained from ATCC). These potentially cross-reacting non-influenza organisms were tested in replicates of three (3) in this study. The organisms were diluted into a Pooled Negative Nasal Sample (PNNS) matrix to create samples at the concentration in the table below for testing.
| Organism
Key # | Organism Name | Stock Concentration | Test Level | FluA Result
(# Positive /
3) | FluB Result
(# Positive /
3) |
|-------------------|------------------------------------------|---------------------|-----------------------|------------------------------------|------------------------------------|
| 1 | Adenovirus Type 1 | 1.02E+08 TCID50/mL | 5.10E+05
TCID50/mL | 0/3 | 0/3 |
| 2 | Adenovirus Type 7 | 6.61E+06 TCID50/mL | 3.31E+04
TCID50/mL | 0/3 | 0/3 |
| 3 | Human herpesvirus 5
(Cytomegalovirus) | 2.19E+06 TCID50/mL | 1.10E+04
TCID50/mL | 0/3 | 0/3 |
| 4 | Human coronavirus 229E | 2.19E+06 TCID50/mL | 1.10E+04
TCID50/mL | 0/3 | 0/3 |
| 5 | Human coronavirus
OC43 | 5.89E+07 TCID50/mL | 2.95E+05
TCID50/mL | 0/3 | 0/3 |
| 6 | Human Enterovirus 71
(HEV-71) | 4.17E+05 TCID50/mL | 1.04E+04
TCID50/mL | 0/3 | 0/3 |
| 7 | Epstein-Barr virus | 7.95E+09 cp/mL | 3.98E+07 cp/mL | 0/3 | 0/3 |
| 8 | Human parainfluenza
virus 1 | 1.26E+06 TCID50/mL | 1.26E+04
TCID50/mL | 0/3 | 0/3 |
| 9 | Human parainfluenza
virus 2 | 2.19E+06 TCID50/mL | 1.10E+04
TCID50/mL | 0/3 | 0/3 |
| 10 | Human parainfluenza
virus 3 | 5.89E+05 TCID50/mL | 1.18E+04
TCID50/mL | 0/3 | 0/3 |
| 11 | Measles virus | 5.89E+07 TCID50/mL | 2.95E+05
TCID50/mL | 0/3 | 0/3 |
| 12 | Human metapneumovirus | 3.55E+05 TCID50/mL | 1.01E+04
TCID50/mL | 0/3 | 0/3 |
| 13 | Mumps virus | 1.95E+07 TCID50/mL | 9.75E+04
TCID50/mL | 0/3 | 0/3 |
| 14 | Respiratory syncytial
virus | 3.16E+06 TCID50/mL | 1.58E+04
TCID50/mL | 0/3 | 0/3 |
| 15 | Human rhinovirus 17 | 6.61E+06 TCID50/mL | 3.31E+04
TCID50/mL | 0/3 | 0/3 |
| 16 | Bordetella pertussis | 8.43E+08 cfu/mL | 4.22E+06 cfu/mL | 0/3 | 0/3 |
| 17 | Chlamydia pneumoniae | ≥ 5E+03 IFU/mL* | ≥ 1.67E+04
IFU/mL | 0/3 | 0/3 |
| 18 | Corynebacterium
glycinophilum | ≥ 5.56E+07 IFU/mL** | ≥ 1.59E+06
IFU/mL | 0/3 | 0/3 |
| 19 | Escherichia coli | 3.83E+09 cfu/mL | 1.92E+07 cfu/mL | 0/3 | 0/3 |
| 20 | Haemophilus influenzae | 2.40E+08 cfu/mL | 1.20E+06 cfu/mL | 0/3 | 0/3 |
| 21 | Lactobacillus sp. | 6.00E+08 cfu/mL | 3.00E+06 cfu/mL | 0/3 | 0/3 |
| 22 | Legionella longbeachae | 1.93E+09 cfu/mL | 9.65E+06 cfu/mL | 0/3 | 0/3 |
| 23 | Moraxella catarrhalis | 3.97E+07 cfu/mL | 1.99E+05 cfu/mL | 0/3 | 0/3 |
| 24 | Mycobacterium
tuberculosis | 7.23E+08 cfu/mL | 3.62E+06 cfu/mL | 0/3 | 0/3 |
| 25 | Mycoplasma pneumoniae | 5.62E+07 CCU/mL | 2.81E+05
CCU/mL | 0/3 | 0/3 |
| 26 | Neisseria meningitidis | 2.55E+08 cfu/mL | 1.28E+06 cfu/mL | 0/3 | 0/3 |
| 27 | Neisseria subflava | 1.46E+09 cfu/mL | 7.30E+06 cfu/mL | 0/3 | 0/3 |
| 28 | Pseudomonas aeruginosa | 1.21E+08 cfu/mL | 6.05E+05 cfu/mL | 0/3 | 0/3 |
| 29 | Staphylococcus aureus | 1.39E+10 cfu/mL | 6.95E+07 cfu/mL | 0/3 | 0/3 |
| 30 | Staphylococcus
epidermidis | 6.47E+09 cfu/mL | 3.24E+07 cfu/mL | 0/3 | 0/3 |
| 31 | Streptococcus pneumonia | 4.17E+08 cfu/mL | 2.09E+06 cfu/mL | 0/3 | 0/3 |
| 32 | Streptococcus pyogenes | 5.43E+09 cfu/mL | 2.72E+07 cfu/mL | 0/3 | 0/3 |
| 33 | Streptococcus salivarius | 4.63E+08 cfu/mL | 2.32E+06 cfu/mL | 0/3 | 0/3 |
Analytical Exclusivity - Organisms Tested, Concentrations and Test Results
13
All 33 exclusivity organisms were negative at the concentrations tested. Exclusivity is verified for the strains tested.
14
Interfering Substances
To assess substances with the potential to interfere with the performance of the Accula Flu A/ Flu B test, four (4) influenza strains were tested in replicates of three (3) with each interfering substance at the "worst case" concentration. The influenza strains selected for testing include a 2009 pandemic swine-like H1N1 influenza A strain, an H3N2 influenza A strain, and two influenza B strains representing Victoria and Yamagata lineages. Virus was serially diluted into a pooled clinical matrix to achieve a 1.5X LoD concentration. Each influenza strain was tested with the "worst case" interferent concentration, representing the highest concentration likely to be found in a respiratory sample. Additionally, each strain was tested without the interfering substance as a control.
The results are shown in the table. The Accula Flu A/Flu B test performance is not negatively affected by the potentially interfering substances under "worst case" concentration conditions.
| Interferent Description,
Concentration | Target | % Agreement with Expected
Results |
|---------------------------------------------------|-------------|--------------------------------------|
| Mucin,
20 µg Mucin/mL | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| Blood (Human)
1% (v/v) | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| Neo-Synephrine (phenylephrine
nasal spray) | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| Afrin (Oxymetazoline nasal spray) | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| Nasacort (Triamcinolone, nasal
corticosteroid) | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| No Interferent | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
Interfering Substances: Agreement of Observed/Expected
15
| Interferent Description,
Concentration | Target | % Agreement with Expected
Results |
|-----------------------------------------------------------|-------------|--------------------------------------|
| Zicam (Nasal gel, homeopathic
allergy relief medicine) | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| Cepacol
(throat lozenge) | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| Zanamivir
(anti-viral drug)
10mg/mL | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| Mupirocin (antibiotic)
12 mg/mL | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
| Tobramycin (antibacterial)
2.43 mg /mL | FluB/Nevada | 100% (3/3) |
| | FluB/Mass | 100% (3/3) |
| | Negative | 100% (3/3) |
| | FluA/Cali | 100% (3/3) |
| | FluA/Texas | 100% (3/3) |
CLIA Waiver Studies
Clinical Performance by Intended Users
The performance of the Accula Flu A/Flu B Test was evaluated at sixteen intended use sites by non-laboratory personnel in a prospective clinical study during the 2016-2017 flu season in the U.S. Nasal swabs were collected from patients with flu-like symptoms and were tested with the Accula Flu A/Flu B Test and the comparator method, a FDA-cleared molcular influenza assay. All specimens generating discrepant results were investigated by testing using an alternative FDA-cleared molcular assay. The performance of the Accula Flu A/Flu B test for influenza A and influenza B compared with the comparator method are presented in the tables below.
16
| Accula
Flu A/Flu B -
| Flu A | Comparator | ||
|---|---|---|---|
| Positive | Negative | Total | |
| Positive | 289 | 60a | 349 |
| Negative | 9b | 900 | 909 |
| Total | 298 | 960 | 1258 |
| Sensitivity: | 97% (95% CI: 94.4% - 98.4%) | ||
| Specificity: | 94% (95% CI: 92.0% - 95.1%) |
Accula Flu A/Flu B Test Flu A performance against the Comparator Method
ª FLU A was detected in 47/60 False Positives specimens using an alternative FDA-cleared molecular Influenza Assay
b FLU A was not detected in 3/9 False Negative specimens using an alternative FDA-cleared molecular Influenza Assay
| Accula Flu A/Flu B Test Flu B performance against the Comparator Method | ||
|---|---|---|
| Accula
Flu A/Flu B -
| Flu B | Comparator | ||
|---|---|---|---|
| Positive | Negative | Total | |
| Positive | 126 | 14a | 140 |
| Negative | 8b | 1110 | 1118 |
| Total | 134 | 1124 | 1258 |
| Sensitivity: | 94% (95% CI: 88.7% - 97.0%) | ||
| Specificity: | 99% (95% CI: 97.9% - 99.3%) |
ª FLU B was detected in 9/14 False Positives specimens using an alternative FDA-cleared molecular Influenza Assay
b FLU B was not detected in 5/8 False Negative specimens using an alternative FDA-cleared molecular Influenza Assay
The study demonstrates the performance of the Accula Flu A /Flu B test in a CLIA Waived clinical setting.
Performance Near the Cut-Off
Three CLIA-waived sites that participated in the prospective clinical study participated in the Near Cut-off study. The testing was performed by three (3) untrained intended operators at each of the sites. This study was conducted to demonstrate that untrained intended users could perform the Accula Flu A/Flu B Test and consistently detect Low Positive samples at the Limit of Detection.
The test panel consisted of three contrived samples: Flu A Low Positive, Flu B Low Positive, and a True Negative. Each sample was prepared using Flu A and B strains spiked into clinical
17
matrix. The Flu A strain used in this study was Flu A/California/07/2009 and the Flu B strain used in this study was Flu B/Massachusetts/2/2012. The targeted concentrations for the Low Positive samples were approximately 1 X the respective LoD (C95 concentration), and the Flu A and B Negative samples contained no Flu virus. Test samples of Influenza A or Influenza B were coded and blinded to the operators. Swab specimens were presented to the intended use operators throughout the course of a normal testing day and were masked as subject samples. Testing took place over the course of two weeks on non-consecutive days, while the clinical study was in progress. Each operator tested 5 samples each testing day. Each site ultimately tested a panel of 60 samples: 20 replicates of each sample. Testing was performed with one lot of Accula Flu A/Flu B Test cassettes.
Test results are shown in the table below. This study demonstrates untrained use operators are able to accurately perform and interpret the Mesa Biotech Flu A/Flu B test at the level of the LoD for both Influenza A and Influenza B.
| Site | Swab Type | ||
|---|---|---|---|
| Low A | |||
| Positive/Total | Low B | ||
| Positive/Total | Negative/Total | ||
| ADP | 19/20 | 19/20 | 19/19* |
| DCO | 20/20 | 20/20 | 20/20 |
| GVP | 19/20 | 19/20 | 20/20 |
| Total Agreement | 58/60 = 97% | 58/60 = 97% | 59/59 = 100% |
| *1 negative result resulted in an unresolved Invalid (2 invalid results on the same sample) |
Near Cut-off Study Test Results: Agreement of Observed/Expected
Conclusion 8.
The information presented in this Premarket Notification demonstrates that the performance of the Accula Flu A/Flu B Test is substantially equivalent in intended use, technological characteristics, and performance to the predicate device, thereby supporting 510(k) clearance.