(152 days)
Not Found
No
The device description and performance studies indicate a rapid immunoassay with visual interpretation, not involving computational analysis or pattern recognition typically associated with AI/ML.
No.
This device is an in vitro diagnostic device intended for the qualitative detection of influenza A/H5N1 virus. It is used for diagnosis, not for treatment or therapy.
Yes
The "Intended Use / Indications for Use" section states: "The AVantage™ A/H5N1 Flu Test is intended for the in vitro qualitative detection of influenza A/H5N1 virus directly from symptomatic patient nasal or throat swab specimens or in viral cultures for the presumptive laboratory identification of influenza A/H5N1 virus." This clearly indicates its purpose is to identify a medical condition (influenza A/H5N1 virus) in patients, which is the definition of a diagnostic device. The "Device Description" also refers to it as a "rapid diagnostic device".
No
The device description clearly outlines a physical immunoassay kit with reagents, a cassette, and visual interpretation of results, indicating it is a hardware-based diagnostic test, not software only.
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 device is "intended for the in vitro qualitative detection of influenza A/H5N1 virus directly from symptomatic patient nasal or throat swab specimens or in viral cultures". The phrase "in vitro" is a key indicator of an IVD, meaning it is used to test samples outside of the body.
- Device Description: The description details how the device works by analyzing a patient sample (nasal or throat swab) to detect the presence of a specific viral antigen (H5N1 NS1). This process of analyzing a biological sample to diagnose or detect a condition is the core function of an IVD.
- Sample Type: The device uses "symptomatic patient nasal or throat swab specimens or in viral cultures", which are biological samples commonly used in in vitro diagnostic testing.
- Purpose: The purpose is to provide "presumptive laboratory identification of influenza A/H5N1 virus", which is a diagnostic purpose.
- Regulatory Language: The mention of "Prescription Use device" and the requirement for testing to be performed in "high complexity laboratories" are consistent with the regulatory requirements for certain IVDs.
Therefore, based on the provided information, the AVantage™ A/H5N1 Flu Test clearly fits the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The AVantage™ A/H5N1 Flu Test is intended for the in vitro qualitative detection of influenza A/H5N1 virus directly from symptomatic patient nasal or throat swab specimens or in viral cultures for the presumptive laboratory identification of influenza A/H5N1 virus.
Results from testing with the AVantage™ A/H5N1 Flu Test should be used in conjunction with other laboratory testing and clinical and epidemiological risk factors for the presumptive identification of patients infected with Influenza H5N1 virus. AVantage™ A/H5N1 Flu Test is intended as a Prescription Use device.
Testing should not be performed unless the patient meets the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 either directly from patient specimens or from viral cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Product codes
OMS
Device Description
The AVantage™ A/H5N1 Flu Test is a rapid diagnostic device that detects the presence of the H5N1 subtype from throat swabs or nose swabs collected from patients with flu symptoms, or in viral cultures for the presumptive laboratory identification of influenza H5N1 virus. It is an immunoassay, using a combination of monoclonal antibodies and recombinant proteins containing PDZ domains to capture and detect NS1.
The AVantage™ A/H5N1 Flu Test begins with the extraction of the influenza A H5N1 NS1 viral antigen. The patient sample is prepared by delivering the swab to the transport medium. Sample is then transferred to the lyophilized Lysis Buffer vial (Reagent A) which contains a lysing agent where cells are lysed, releasing intracellular proteins. Next, the Loading Buffer (Reagent B) is added to condition the sample. The sample is then added to the Detector (Reagent C), which contains lyophilized colloidal gold-conjugated monoclonal anti-influenza A antibodies that recognize a broad range of influenza A subtypes and strains. After re-suspension of the antibodies, the solution is added to the sample well of the AVantage™ A/H5N1 Flu Test cassette, where NS1 in the specimen will react with reagents on the membrane of the cassette. The results are read visually by observing the presence or absence of lines on the membrane at the indicated locations.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasal, Throat
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use device, For use only in high complexity laboratories.
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
Precision/Repeatability Study:
- Sample Size: Recombinant H5N1 NS1 protein at a range of concentrations. Specific sample sizes for each concentration (high negative, low positive, moderate positive) are not explicitly stated, but 24 tests per day for five days were performed.
- Data Source: Recombinant H5N1 NS1 protein.
- Annotation Protocol: Not explicitly stated, but based on the results, it involved determining positive/negative results.
Reproducibility Study:
- Sample Size: Negative control, high negative, moderate positive, and high positive recombinant protein H5N1 NS1 samples.
- Data Source: Recombinant protein H5N1 NS1 samples.
- Annotation Protocol: Not explicitly stated, but performance consistency was measured.
Sensitivity Study (H5N1 isolates from infected individuals):
- Sample Size: 24 human-derived H5N1 viral culture specimens (11 from first passage, 13 from second passage) and 3 H5N1 negative samples.
- Data Source: H5N1 isolates from infected individuals collected in the course of WHO/NAMRU-3 pandemic surveillance and response activities (Clade 2.2, part of CDC global H5N1 repository).
- Annotation Protocol: H5N1-positive status verified by HAI (Haemagglutination-inhibition test). Study personnel were blinded to the true H5N1 status.
Cross-Reactivity Study:
- Sample Size: 49 bacterial and viral isolates.
- Data Source: Bacterial isolates (concentrations of approx. 1.5x10^8 cfu/mL), Viral isolates (concentrations of 10^4 - 10 TCID50 mL, or 10^2 -10^4 CEID50/mL).
- Annotation Protocol: Not explicitly stated but involved testing if pathogens showed cross-reactivity with the assay.
Interference Study:
- Sample Size: Various substances (Whole blood (2%), Mucin (500 ug/ml), Mouthwash (Scope®) (25%), Dextromethoraphan (Robitussin®) (5 mg/ml), Acetaminophen (Tyelenol®) (10 mg/ml), Throat losange (Cepacol®) (25%), Oxymetazoline (Afrin®) (10%), Erythromcyin (20 µg/ml), Nasal corticosteroids (triamcinolone) (25 mg/ml), Zanamivir (Relenza®) (1 mg/ml), Phenyephrine (Neosynephrine®) (100 mg/ml), Diphenhydramine (Benadryl®) (1 mg/ml), Luffa operculata, Galphimia glauca, Histaminum hydrochloricum and sulfur (Zicam®) (1%), Rimantadine (250 ng/ml)).
- Data Source: Commonly encountered substances in nasal and throat specimens.
- Annotation Protocol: Not explicitly stated but involved testing for inhibitory effects on assay performance.
Summary of Performance Studies
Precision/Repeatability:
- Study Type: Within-laboratory test.
- Sample Size: Recombinant H5N1 NS1 protein at various concentrations.
- Standalone Performance: High negative sample yielded 8% positive results, low positive yielded 96% positive results, and moderate positive yielded 100% positive results.
Reproducibility:
- Study Type: Multi-site study.
- Sample Size: Negative control, high negative, moderate positive, and high positive recombinant protein H5N1 NS1 samples. Five days, three sites, two operators per site.
- Key Results: Reproducible performance across days, sites, and operators.
Sensitivity Study (H5N1 viral culture samples):
- Study Type: Comparison with Gold Standard (HAI).
- Sample Size: 24 H5N1-positive viral culture specimens (confirmed by HAI), 3 H5N1-negative samples.
- Key Results: 100% Positive Agreement with viral culture for H5N1 (+) samples. 100% Negative Agreement for H5N1 (-) samples.
Clinical Specificity (Prospective Clinical Study):
- Study Type: Prospective clinical study during the 2007-2008 flu season.
- Sample Size: 464 symptomatic subjects from four clinics at three sites.
- Sample Status Confirmation: Sample status confirmed by IFA and haemagglutination-inhibition test (HAI).
- Key Results: 100% Specificity (95% CI: (99.57%; 100%)) against Influenza A (+) H5N1 (-), Influenza B (+) H5N1 (-), and Influenza A&B (-) H5N1 (-). No false positive results. No true positive samples were identified by Gold Standard methods in this specific clinical sample set for H5N1.
Cross-Reactivity:
- Study Type: Evaluation against bacterial and viral isolates.
- Sample Size: 21 bacterial isolates and 28 viral isolates.
- Key Results: No cross-reactivity observed with any of the tested bacterial or viral isolates.
Interference:
- Study Type: Evaluation against commonly encountered substances.
- Sample Size: Various substances at specified concentrations.
- Key Results: None of the tested substances had an inhibitory effect on assay performance.
Key Metrics
- Positive Agreement (Sensitivity): 100% (95% CI = (86.2%, 100%)) for H5N1 viral culture samples.
- Negative Agreement: 100% (95% CI = (43.8%, 100%)) for H5N1 viral culture samples.
- Specificity (Clinical): 100% (95%CI = (99.57%; 100%)) for prospective clinical samples.
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3332 Reagents for detection of specific novel influenza A viruses.
(a)
Identification. Reagents for detection of specific novel influenza A viruses are devices that are intended for use in a nucleic acid amplification test to directly detect specific virus RNA in human respiratory specimens or viral cultures. Detection of specific virus RNA aids in the diagnosis of influenza caused by specific novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids in the presumptive laboratory identification of specific novel influenza A viruses to provide epidemiological information on influenza. These reagents include primers, probes, and specific influenza A virus controls.(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses.” See § 866.1(e) for information on obtaining this document.
(2) The distribution of these devices is limited to laboratories with experienced personnel who have training in standardized molecular testing procedures and expertise in viral diagnosis, and appropriate biosafety equipment and containment.
0
.
Arbor Vita Corporation AVantage™ A/H5N1 Flu Test Pre-market Notification
Ko83278
APR - 8 2009
SECTION 7
510(k) SUMMARY
Section 7: 510(k) Summary
Arbor Vita Corporation, Confidential
.
:
1
Arbor Vita Corporation AVantage™ A/H5N1 Flu Test Pre-market Notification
SECTION 7 510(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 K083278.
AVantage™ A/H5N1 Flu Test 807.92 (a)(1): Name:
772 Lucerne Drive Address: Sunnyvale, CA 94085
Phone: 408-585-3909 FAX: 408-585-3901 Dr. Linda McAllister Contact:
807,92 (a)(2): Device name- trade name and common name, and classification
| Trade name: | AVantage™A/H5N1 Flu Test |
|---|---|
| Common Name: | Reagents for the qualitative detection of influenza virus subtype H5N1 |
CFR §21.866.3332 Classification:
807.92 (a)(3); Identification of the legally marketed predicate device
The AVantage™ A/H5N1 Flu Test is substantially equivalent to two previously cleared products, namely the CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel (Centers for Disease Control and Prevention, Atlanta, GA) based on intended use and cleared under K080570, and the QuickVue Influenza A+B Test (Quidel Corporation, San Diego, CA), based on technological characteristics and cleared under K053146.
.............................................................................................................
Section 7: 510(k) Summary
Arbor Vita Corporation, Confidential
2
807.92 (a)(4): Device Description
The AVantage™ A/H5N1 Flu Test is a rapid diagnostic device that detects the presence of the H5N1 subtype from throat swabs or nose swabs collected from patients with flu symptoms, or in viral cultures for the presumptive laboratory identification of influenza H5N1 virus. It is an immunoassay, using a combination of monoclonal antibodies and recombinant proteins containing PDZ domains to capture and detect NS1.
The AVantage™ A/H5N1 Flu Test begins with the extraction of the influenza A H5N1 NS1 viral antigen. The patient sample is prepared by delivering the swab to the transport medium. Sample is then transferred to the lyophilized Lysis Buffer vial (Reagent A) which contains a lysing agent where cells are lysed, releasing intracellular proteins. Next, the Loading Buffer (Reagent B) is added to condition the sample. The sample is then added to the Detector (Reagent C), which contains lyophilized colloidal gold-conjugated monoclonal anti-influenza A antibodies that recognize a broad range of influenza A subtypes and strains. After re-suspension of the antibodies, the solution is added to the sample well of the AVantage™ A/H5N1 Flu Test cassette, where NS1 in the specimen will react with reagents on the membrane of the cassette. The results are read visually by observing the presence or absence of lines on the membrane at the indicated locations.
807.92 (a)(5): Intended Use
The AVantage™ A/H5N1 Flu Test is intended for the in vitro qualitative detection of influenza A/H5N1 virus directly from symptomatic patient nasal or throat swab specimens or in viral cultures for the presumptive laboratory identification of influenza A/H5N1 virus.
Results from testing with the AVantage™ A/H5N1 Flu Test should be used in conjunction with other laboratory testing and clinical and epidemiological risk factors for the presumptive identification of patients infected with Influenza H5N1 virus. AVantage™ A/H5N1 Flu Test is intended as a Prescription Use device.
Testing should not be performed unless the patient meets the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 either directly from patient specimens or from viral cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
3
April ',
1
Arbor Vita Corporation
AVantage™ A/HSN1 Flu Test
Pre-market Notification
807.92 (a)(6): Technological Similarities and Differences to the Predicat
| CHARACTERISTIC | | Arbor Vita AVantageTM A/H5N1
Flu Test | CDC Human Influenza Virus Real-time
RT-PCR Detection and
Characterization Pannel
(rRT-PCR Flu Panel) K080570 | Quidel QuickVue Influenza A+B Test)
K053146 |
|----------------|--|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | | The AVantageTM A/H5N1 Flu Test is
intended for the in vitro qualitative
detection of Influenza H5N1 virus
directly from symptomatic patient nasal
or throat swab specimens or in viral
culture for the presumptive laboratory
identification of Influenza H5N1 virus.
Results from testing with the
AVantageTM A/H5N1 Flu Test should
be used in conjunction with other
laboratory testing and clinical and
epidemiological risk factors for the
presumptive identification of patients
infected with Influenza H5N1 virus.
AVantageTM A/H5N1 Flu Test is
intended as a Prescription Use device.
Testing should not be performed unless
the patient meets the most current U.S.
Department of Health and Human
Services (DHHS) clinical and
epidemiologic criteria for testing
suspect A/H5 specimens. The
definitive identification of influenza
A/H5 (Asian lineage) either directly
from patient specimens or from viral
cultures requires additional laboratory
testing, along with clinical and
epidemiological assessment in
consultation with national influenza
surveillance experts.
Negative results do not preclude | The test is intended for use in real-time RT-
PCR assays on an ABI 7500 Fast Dx Real-
Time PCR instrument in conjunction with
clinical and epidemiological information:
- for qualitative detection of influenza
virus type A or B in symptomatic
patients from viral RNA in
nasopharyngeal and/or nasal swab
specimens, - for determination of the subtype of
seasonal human influenza A virus, as
seasonal A/H1 or A/H3, if present, from
viral RNA in nasopharyngeal and/or
nasal swab specimens, - for presumptive identification of virus in
patients who may be infected with
influenza A/H5 (Asian lineage) from
viral RNA in human respiratory
specimens and viral culture in
conjunction with clinical and
epidemiological risk factors - to provide epidemiologic information for
surveillance for influenza viruses.
The definitive identification of influenza A/H5
(Asian lineage) either directly from patient
specimens or from virus cultures requires
additional laboratory testing, along with
clinical and epidemiological assessment in
consultation with national influenza
surveillance experts. Negative results do not
preclude influenza virus infection and should
not be used as the sole basis for treatment or
other management decisions.
All users, analysts and any person reporting | Rapid qualitative detection of influenza type A
and type B antigens directly from nasal swab,
nasal wash and/or nasal aspirate specimens.
Intended for uses as an aid in the rapid diagnosis
of acute influenza virus infections. Negative
results should be confirmed by culture. |
Section 7: 510(k) Summary
Arbor Vita Corporation, Confidentia
4
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| ಳ |
Arbor Vita Corporation
AVantage™ AVHSNI Flu Test
| CHARACTERISTIC | Pre-market Notification | ||
|---|---|---|---|
| Arbor Vita AVantage™ A/H5N1 | |||
| Flu Test | CDC Human Influenza Virus Real-time | ||
| RT-PCR Detection and | |||
| Characterization Pannel | |||
| (rRT-PCR Flu Panel) K080570 | Quidel QuickVue Influenza A+B Test) | ||
| K053146 | |||
| Indications for | |||
| Use/Limitations | influenza virus infection and should not | ||
| be used as the sole basis for treatment | |||
| or other patient management decisions. | trained to perform and interpret the results | ||
| from this procedure by a CDC instructor or | |||
| designee prior to use. | For In Vitro diagnostic use | ||
| For prescription use only | |||
| The AVantage™ A/H5N1 Flu Test is | |||
| indicated for use only in high | |||
| complexity laboratories. | (Same as Intended Use) | ||
| Special instrument required is the ABI 7500 | |||
| Fast Dx Real-Time PCR instrument. The | |||
| special condition for use is for prescription use | |||
| only. | |||
| Sample | Throat or nasal swab, or virus culture. | Nasopharyngeal or nasal swab respiratory | |
| specimens, or virus culture | Nasal swab, nasal wash and/or nasal aspirate | ||
| Sample Preparation | M4 viral transport media and swabs | ||
| supplied by REMEL should be used for | |||
| sample collection. Swabs are applied to | |||
| the throat or nose, and rotation and | |||
| slight pressure are applied to collect | |||
| specimen. The specimen in the swab is | |||
| then placed in 3 mL M4 Viral Transport | |||
| Media (REMEL). | Using reagents and specific lots recommended | ||
| by CDC, RNA is extracted and purified from | |||
| the cellular specimen matrix. cDNA is | |||
| produced from RNA with RT-PCR reaction. | |||
| Fluorescently labeled probes anneal to | |||
| amplified DNA fragments and the fluorescent | |||
| signal is monitored by the ABI 7500 Fast Dx | |||
| instrument during each PCR cycle. | |||
| Amplification of target is recorded as increase | |||
| of fluorescence over time in comparison of a | |||
| background signal. | Nasal swabs are applied to nostril with most | ||
| secretion, and pressed against the nasal wall with | |||
| rotation. The material from the swab is then | |||
| extracted with reagents supplied in the kit. | |||
| Nasal aspirates/wash are collected by instilling | |||
| with a syringe 2.5 ml sterile normal saline into | |||
| one nostril of the patient. Collect fluid into a dry | |||
| specimen container. Swabs are supplied in the | |||
| kit. | |||
| Methodology | Two step test (gold-mAb detector dried | ||
| in a tube). Test is based on | |||
| immunochromatographic principles. | RNA is extracted and purified from the | ||
| cellular specimen matrix. Using reverse | |||
| transcription, cDNA is made from the RNA. | |||
| The cDNA is amplified, and an increasing | |||
| fluorescent signal is produced through each | |||
| PCR cycle by fluorescently labeled probes that | |||
| anneal to amplified DNA fragments. The | |||
| fluorescence intensity is monitored by the ABI | |||
| 7500 Fast Dx instrument during each cycle. | One step test (latex-mAb detector dried in a pad | ||
| within a dipstick). Test is based on | |||
| immunochromatographic principles. | |||
| Quality Control | Each kit contains a positive control | ||
| (external quality control) that must be | |||
| successfully run before using the kit. | |||
| Testing with the negative control (M4 | |||
| Viral Transport Media (not included in | |||
| the kit) must also be performed before | |||
| using the kit. When running the test, the | |||
| appearance of a red Control Line in | |||
| each test indicates proper function of | The kit contains several controls: |
The Internal positive control, the human
RNASE P (RP) primer and probe set detects
human RP and ensures that adequate isolation
of nucleic acid resulted from extraction from
the specimen as well as overall instrument
performance.
The Human Specimen Control (HSC) is a | Each kit contains external positive and negative
control swabs supplied in the kit. Controls
should be tested with each new lot or shipment
of materials. The test also contains built-in
procedural control features. The appearance of a
blue procedural Control Line provides three
forms of positive internal control by
demonstrating:, 2) capillary flow occurred, 3)
functional integrity of the Test Strip was |
| | Arbor Vita Corporation
AVantage™ A/H5N1 Flu Test
Pre-market Notification | | |
| | Arbor Vita AVantage™ A/H5N1 CDC Human Influenza Virus Real-time
Flu Test | Quidel QuickVue Influenza A+B Test)
K053146 | |
| | the buffer reagents, capillary flow, and
functional integrity. If the control line
does not appear, the test is considered
Invalid. | maintained. If the Control Line does not show
up, the test is considered invalid. | |
| | | | |
| | (rRT-PCR Flu Panel) K080570
noninfectious cultured human cell material
that demonstrates successful recovery of RNA
as well as extraction reagent integrity.
The Seasonal Influenza Virus Control (SIVC)
consists of three different influenza viruses
representing A/H1, A/H3 and Influenza B
viruses and cultured human cells. The SIVC
control demonstrates that the master mix and
primer probe sets are functioning properly.
The influenza Virus A/H5N1 Positive Control
(H5VC) is a genetically modified reassortant
human influenza virus (BSL2 category) and
cultured human cells. This control
demonstrates that the master mix and primer
and probe sets for Influenza A, Influenza
A/H5 (H5a, H5b), and RP are functioning
properly. | | |
| | | | |
| Visual | Real Time Fluorescence which is monitored
by fluorimeter | Visual | |
| Professional use | CDC Influenza Division will limit the
distribution of this device to only those users
who have successfully completed training
provided by CDC instructors or designees. | Professional use | |
| Detection levels were: | Limit of Detection levels were reported for
influenza A/H1N1, A/H3N2, A/H5N1 and B.
The following are the LoD's reported for
A/H5N1: | Detection levels range from 6.6x106 pfu/ml to
1.6x107 pfu/ml for influenza A viruses | |
| 36 TCID50/ml for H5N1 isolate
2006914724 (Influenza A virus)
(A/Egypt/14724-
NAMRU3/2006(H5N1) (CDC Genbank
#200512) | LoD of 1010 EID50/ml for
A/Vietnam/1203/2004xA/Puerto Rico/8/34
reassortant. | | |
| 134 TCID50/ml for H5N1 isolate
2008903158 (Influenza A virus)
(A/Egypt/3158-NAMRU3/2008(H5N1)
(CDC Genbank # FJ226060) | LoD of 1010 EID50/ml for
A/Anhui/01/2005xA/Puerto Rico/8/34
reassortant | | |
| CHARACTERISTIC | Arbor Vita AVantage™ A/H5N1 Flu Test | CDC Human Influenza Virus Real-time RT-PCR Detection and Characterization Pannel
(rRT-PCR Flu Panel) K080570 | Quidel QuickVue Influenza A+B Test)
K053146 |
| | cultured specimens (total of 24) were tested, with 100 % positive agreement with viral culture. All samples were of Clade 2.2 | Positive Agreement with viral culture (56.6%-100%) 95% CI. A total of 19 H5N1-positive cultured specimens were also tested, with 100 % positive agreement (83.2-100%) 95% CI with viral culture. Samples tested were from Clades 2.2.1, 2.2, and 2.3. | The QuickVue Influenza Test was evaluated with a total of 62 bacterial and viral isolates. Bacterial isolates were evaluated at a concentration between $10^7$ and $10^9$ org/ml. Viral isolates were evaluated at a concentration of at least $10^4$ - $10^8$ TCID50/ml. None of the organisms tested gave a positive result in the QuickVue Influenza Test. |
| Cross-Reactivity | The AVantage™ A/H5N1 Flu Test did not cross-react with 21 bacterial isolates and 28 viral isolates (including seasonal influenza A and B). Bacterial isolates were evaluated at a concentration of:
$1.5x10^8$ cfu/ml. Viral isolates were evaluated at a concentration of at least $8.89x10^3$ TCID50/ml | The H5N1 component of the rRT-PCR Flu Panel test did not cross-react with ten (10) influenza virus strains of A/H1N1, A/H3N2 and Influenza B at low virus concentrations at $10^2$ TCID50/ml.
The rRT-PCR Flu Panel test did not cross-react with nucleic acids extracted from 27 organisms (9 non-influenza A/B viruses, 17 bacteria, and 1 yeast) representing common respiratory pathogens or flora commonly present in specimens from the nasopharynx region. Bacteria and yeast were tested at concentrations greater than or equal to $10^6$ cfu/ml. Non-influenza respiratory viruses were tested at concentrations greater than $10^6$ TCID50/ml with the exception of human parainfluenza type 2 which was tested at $10^{3.1}$ TCID50/ml and Human Corona viruses OC43 (50.4 ng/ul of total RNA from culture) and 299E (31.6 ng/ul total RNA from culture). | |
| Clinical Specificity | | A total of 415 prospective seasonal specimens collected for routine influenza testing from nasal and nasopharyngeal swabs were used in this study. The H5N1 component of the rRT-PCR Flu Panel test had 100% Percent Negative Agreement with viral culture (99.1%-100%) 95% CI. | Nasal Swabs: 96 % [95% C.I. 91%-98%]
160/167
Nasal Wash or Aspirates: 99% [95% C.I. 91%-100%] 68/69 |
| Interference | | | Whole blood, Mucin and 19 over-the-counter (OTC) products were tested in excess of |
| | 100% negative agreement with 440 throat and 447 nasal swab samples (95% CI::99.1% - 100%) | | |
| CHARACTERISTIC | Arbor Vita AVantage™ A/H5N1 Flu Test | CDC Human Influenza Virus Real-time
RT-PCR Detection and
Characterization Pannel
(rRT-PCR Flu Panel) K080570 | Quidel QuickVue Influenza A+B Test)
K053146 |
| | did not interfere with the AVC Avian
Flu Test. | | physiological levels and did not interfere with
the QuickVue Influenza Test. |
| | Testing of AVantage™ A/H5N1 Flu
Test was conducted at three sites using
a panel of coded specimens containing
recombinant H5N1 NS1 protein. Two
operators at each site performed three
replicates/sample, for a total of 24 tests
per day for five days. Panel contained
negative, high negative, moderate
positive and high positive specimens.
The fifth day contained an extra
challenge sample for an additional 6
measurements. No significant
differences were observed between runs
(5 days), between operators (2
operators) or between sites (3 sites). | Reproducibility and precision studies were
done at 3 sites, using a panel of 9 simulated
samples (two viral concentrations: low viral
RNA titer range concentration and 1:10
dilution of the previous sample) for influenza
A/H1N1, A/H3N2, A/H5N1 (reassortant) and
B. The panels and assay controls were tested
at each site by two operators on five (5)
different days within a 10-day period. The
"low viral RNA titer" concentration was
generally one log above the assay cutoff for all
analytes, whereas the 1:10 dilution of the same
sample approximated a sample at the assay
cutoff. Each participating clinical site tested
one of four RNA purification methods to
evaluate reproducibility of the CDC rRT-PCR
Flu Panel on the validated ABI 7500 Fast Dx
Real-Time PCR instruments. | Evaluation of QuickVue Influenza Test was
conducted at three Physicians Offices using a
panel of coded specimens. Personnel with
diverse backgrounds performed the test. Panel
contained neg., low positive and moderate
positive specimens. Each specimen level was
tested in each site in replicates of at least six
over a period of three days. The results at each
site agreed 99% with the expected results. No
significant differences were observed within run
(6 replicates), between runs (3 different days), or
between the three sites. |
| Reproducibility | | | |
| | | For H5N1 studies, the total agreement with
expected results was as follows:
H5a (low viral titer): 40/40 (95% CI: 91.2-
100 %
H5b (low viral titer): 39/40 (95% CI: 86.8-
99.9 %)
H5a (1/10 of low viral titer): 31/40 (95% CI:
61.6-89.2)
H5b (1/10 of low viral titer): 27/40 (95% CI:
50.9-81.4 %) | |
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ייר
ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺴﺘ
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ection 7: 510(k) Summary
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Section 7: 510(k) Summary
April
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April 1
Arbor Vita Corporation
AVantage™ A/H5NI Flu Test
Pre-market Notification
Section 7: 510(k) Summary
7
April ↑
Arbor Vita Corporation
AVantage™ A/H5N1 Flu Test
Pre-market Notification
-: 2
. .
. . ..
Section 7: 510(k) Summary
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. . . . . . .
807.92 (b)(1) and 807.92 (b)(2):
Brief Description of Nonclinical and Clinical Data
The precision/repeatability of the AVantage™ A/H5N1 Flu Test was demonstrated by conducting within-laboratory tests at a range of recombinant H5N1 NS1 protein analyte concentrations over twelve consecutive days. Performance of the assay was consistent, with the high negative sample vielding 8% positive results while the low positive and moderate positive samples vielding respectively 96% and 100% positive results.
The reproducibility of the AVantage™ A/H5N1 Flu Test was determined by measuring the consistency of assay performance using negative control, and high negative, moderate positive, and high positive recombinant protein H5N1 NS1 samples over five days at three sites with two operators at each site. The results showed reproducible performance across days, sites and operators.
Due to the rare occurrence of H5N1 infection and the absence of infection in the United States, sensitivity studies of the AVantage™ A/H5N1 Flu Test were performed using H5N1 isolates from infected individuals, collected in the course of WHO/NAMRU-3 pandemic surveillance and response activities. All isolates studied herein were classified as Clade 2.2 and are part of the CDC global H5N1 repository.
The 24 human-derived H5N1 viral culture specimens were grown in MDCK cells or eggs. Included in the study were three HSNI negative samples. Study personnel were blinded to the true H5N1 status. The reference method used to verify H5N1-positive status of the viral culture samples was HAI. Eleven of these specimens were from first passage cultures, and 13 of the specimens were from second passage cultures. The study was conducted in BSL-3 labs at NAMRU-3 by NAMRU-3 personnel. The AVantage™ A/H5N1 Flu Test used in this study was performed according to the AVC Test Instructions for Use.
A Vantage™ A/H5N1 Flu Test results showed 100% positive agreement for all 24 H5N1-postive in the AVantage™ A/H5N1 Flu Test.
| NAMRU-3
Comparison
| Results | Virus Culture (Gold Standard) Results | Performance | |
|---|---|---|---|
| H5N1 (+) | H5N1 (-) | ||
| AVantage™ A/H5N1 | |||
| Flu Test Positive | 24 | 0 | 100% Positive Agreement* |
| 95% CI = (86.2%, 100% ) | |||
| AVantage™ A/H5N1 | |||
| Flu Test Negative | 0 | 3 | 100% Negative Agreement |
| 95% CI = ( 43.8%, 100% ) | |||
| Total | 24 | 3 |
Performance Summary - AVantage™ A/H5N1 testing with viral culture samples
Twenty four H5N1+ viral culture specimens; eleven were from first passage cultures, and thirteen were from second passage cultures. Sample status was confirmed by HAI.
Section 7: 510(k) Summary
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Arbor Vita Corporation, Confidential
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The specificity of the AVantage™ A/H5N1Flu Test was assessed in a prospective clinical study during the 2007-2008 flu season. Symptomatic subjects were recruited from four clinics at three sites into a broader surveillance study conducted by the Naval Health Research Center (NHC). A portion of subjects (464) was recruited into the AVC study. Of these 464 symptomatic subjects, 110 had influenza infection (73, Influenza A and 37 Influenza B). AVC testing was performed in two laboratories and yielded no false positive results.
| NHRC
Comparison
| Results | Virus Culture (Gold Standard) Results | Performance | |||
|---|---|---|---|---|---|
| H5N1 (+) | Influenza A (+) | ||||
| H5N1 (-) | Influenza B (+) | ||||
| H5N1 (-) | Influenza A&B (-) | ||||
| H5N1 (-) | |||||
| AVantage™ | |||||
| A/H5N1 | |||||
| Flu Test Positive | 0 | 0 | 0 | 0 | N/A* |
| AVantage™ | |||||
| A/H5N1 | |||||
| Flu Test Negative | 0 | 113 | 55 | 727 | 100% |
| Specificity | |||||
| 95%CI = | |||||
| (99.57%; | |||||
| 100%) | |||||
| Total | 0 | 113 | 55 | 727 |
Performance Summary - AVantage™ A/H5N1 testing prospective clinical samples
Sample status was confirmed by IFA and haemagglutination-inhibition test (HAI).
- No true positive samples were identified by Gold Standard methods.
** 8 samples were not subtyped by IFA or HAI, but were determined to be H3 by Lightcycler RT-PCR using primers developed by the Air Force Institute of Operational Health.
The AVantage™ A/H5N1 Flu Test was evaluated for potential cross-reactivity with a total of 49 bacterial and viral isolates. The bacterial isolates were tested at concentrations of approximately 1.5x108 cfu/mL. The viral isolates were used at concentrations of 104 - 10 TCID50 mL, or 102 -104 CEID50/mL.
None of the pathogens tested showed cross-reactivity with the assay.
Bacterial Panel: Bacteroides fragilis Bordetella pertussis Corynebacterium xerosis Escherichia coli Haemophilus influenzae Lactobacillus casei Legionella pneumonphila Moraxella catarrhalis Mvcoplasma pneumoniae Neisseria meningitidis... ...... ... ... ... ... .... .... ................................................................................................................... Neisseria mucosa Peptostreptococcus anaerobius Porphyromonas asaccharolyticus Section 7: 510(k) Summary
Arbor Vita Corporation, Confidential
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Pseudomonas aeruginosa Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus pyogenes Group.A Streptococcus salivarius Streptococcus sp. Group B Streptococcus sp. Group C
Viral Panel
Adenovirus, Type 2 Adenovirus Type 3 Adenovirus Type 7 Adenovirus Type 14 Coronavirus OC 43 Coronavirus 299E Coxsackievirus Type A9 Coxsackievirus Type B5 Cytomegalovirus Echovirus Type 2 Echovirus Type 3 Echovirus Type 6 Enterovirus Herpes simplex virus Type 1 Measles virus Mumps virus Parainfluenza virus Type 1 Parainfluenza virus Type 2 Parainfluenza virus Type 3 Rhinovirus Type 1A Respiratory Syncytial virus Type A Respiratory Syncytial virus Type B A2/Wisconsin/67/2005 (H3N2-like) A/Hiroshima/52/2005 (H3N2-like) A/Port Chalmers/1/73 (H3N2) A/PR8/34 (H1N1) A1/Denver/1/57 B/Hong Kong/5/72
Substances commonly encountered in nasal and throat specimens were tested for their potential inhibitory effect on the performance of the AVantage™ A/H5N1 Flu Test. Listed below are the substances and concentrations at which they were tested. None of the substances tested had an inhibitory effect on assay performance.
Whole blood (2%) Mucin (500 ug/ml) Section 7: 510(k) Summary
11
Mouthwash (Scope®) (25%) Dextromethoraphan (Robitussin®) (5 mg/ml) Acetaminophen (Tyelenol®) (10 mg/ml) Throat losange (Cepacol® - cetypyridium chloride, benzocaine and menthol) (25%) Oxymetazoline (Afrin®) (10%) Erythromcyin (20 µg/ml) Nasal corticosteroids (triamcinolone) (25 mg/ml) Zanamivir (Relenza®) (1 mg/ml) Phenyephrine (Neosynephrine®) (100 mg/ml) Diphenhydramine (Benadryl®) (1 mg/ml) Luffa operculata, Galphimia glauca, Histaminum hydrochloricum and sulfur (Zicam®) (1%) Rimantadine (250 ng/ml)
807.92 (b)(3): Conclusions from Nonclinical and Clinical Testing
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Nonclinical and clinical testing was performed for the AVantage™ A/H5N1 Flu Test. The test system was shown to be safe and effective for its intended use.
Section 7: 510(k) Summary
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" are arranged in a circular pattern around the bird symbol.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Linda McAllister, MD, PhD Executive Vice President of Diagnostics Chief Medical Officer Regulatory Affairs Arbor Vita Corporation 772 Lucerne Drive Sunnyvale, CA 94087
APR - 8 2009
Re: K083278
Trade/Device Name: AVantage™A/H5N1 Flu Test Regulation Number: 21 CFR 866.3332 Regulation Name: Reagent for detection of specific novel influenza A viruses Regulatory Class: Class II Product Code: OMS Dated: April 7, 2009 Received: April 7, 2009
Dear Dr. McAllister:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
13
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Your device is classified (see above) into class II (Special Controls) and is subject to additional controls as outlined in the Class II Special Controls Guidance Document: Reagents for Detection of Specific Novel Influenza A Viruses including the post market measures described in Section 8 "Postmarket Measures".
Sincerely vours.
Sallastm
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
14
Indication for Use
510(k) Number (if known): K083278
Device Name: AVantage™ A/H5N1 Flu Test
Indication For Use:
The AVantage™ A/H5N1 Flu Test is intended for the in vitro qualitative detection of influenza A/H5N1 virus directly from symptomatic patient nasal or throat swab specimens or in viral cultures for the presumptive laboratory identification of influenza A/H5N1 virus.
Results from testing with the AVantage™ A/H5N1 Flu Test should be used in conjunction with other laboratory testing and clinical and epidemiological risk factors for the presumptive identification of patients infected with Influenza H5N1 virus. A Vantage™ A/H5N1 Flu Test is intended as a Prescription Use device.
Testing should not be performed unless the patient meets the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A/H5 specimens. The definitive identification of influenza A/H5 either directly from patient specimens or from viral cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.
Prescription Use X X (21 CFR Part 801 Subpart D) . . ..............................................................................................................................................
And/Or
Over the Counter Use
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
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Office of In Vitto Diagnostic Device increase of the more of the more of the security of the Evaluation and Safety
510(k)