(92 days)
The Alere™ i RSV 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 of respiratory syncytial virus (RSV) viral RNA in direct nasopharyngeal swabs and nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the diagnosis of RSV in children <18 years and adults ≥60 years in conjunction with clinical and epidemiological risk factors.
The Alere™ i RSV is a rapid, instrument-based test for the qualitative detection and differentiation of respiratory syncytial virus (RSV) viral RNA from direct nasopharyngeal swab (NPS) and NPS eluted in viral transport media from patients with signs and symptoms of respiratory infection. The Alere™ i RSV System utilizes isothermal nucleic acid amplification technology and is comprised of:
- Sample Receiver – single use, disposable containing the elution buffer
- . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
- . Transfer Cartridge – Single use, disposable for transfer of the eluted sample to the Test Base, and
- Alere™ i Instrument repeat use reader ●
The reaction tubes in the Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i RSV utilizes a pair of templates (similar to primers) for the specific amplification of RNA from RSV A and B, which occur in two separate reaction tubes. Each reaction tube contains a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets. Alere™ i RSV is performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This minimizes the risk of instrument contamination and sample carry-over between measurements.
To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, re-suspending the lyophilized pellets contained within the Test Base and initiating target amplification. Heating, mixing and detection by fluorescence are provided by the instrument, with results automatically reported.
Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.
Here's a summary of the acceptance criteria and study details for the Alere™ i RSV device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance results needed for substantial equivalence, specifically the sensitivity and specificity values. The document presents the results directly after the methods.
| Acceptance Criteria | Alere™ i RSV Performance (Nasopharyngeal Swab Direct) | Alere™ i RSV Performance (Nasopharyngeal Swab Eluted in VTM) |
|---|---|---|
| Sensitivity | 98.6% (95% CI: 94.9%, 99.6%) | 98.6% (95% CI: 94.9%, 99.6%) |
| Specificity | 98.0% (95% CI: 96.0%, 99.1%) | 97.8% (95% CI: 95.7%, 98.9%) |
| Initial Invalid Rate | 4.1% (95% CI: 2.7% to 6.3%) | 2.2% (95% CI: 1.2% to 3.9%) |
| Invalid Rate (after repeat testing) | 0.8% (95% CI: 0.3% to 2.0%) | 0% (95% CI: 0.0% to 0.8%) |
Note: The document doesn't explicitly state "acceptance criteria" but presents these performance metrics as the outcome of the clinical study, implying they met the bar for substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Nasopharyngeal Swab Direct: 497 evaluable specimens
- Nasopharyngeal Swab Eluted in Viral Transport Media (VTM): 501 evaluable specimens
- Data Provenance: Multi-center, prospective clinical study conducted at nine US trial sites during the 2015-2016 respiratory season. This indicates that the data is prospective and collected in the USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document states that the Alere™ i RSV performance was compared to "FDA-cleared PCR test" which served as the ground truth. It does not mention the use of human experts (e.g., radiologists, pathologists) to establish the ground truth for this clinical performance study. The ground truth was established by an objective laboratory test (PCR).
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by an FDA-cleared PCR test, not by human expert adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is not an imaging device or one that involves human "readers" or AI assistance in interpretation in the way a typical MRMC study would assess. It's an in vitro diagnostic test with an automated result interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the clinical performance study reported is for the standalone algorithm (device) performance. The Alere™ i Instrument automatically reports results: "Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive..." There is no mention of a human-in-the-loop component for result interpretation for the performance assessment.
7. The type of ground truth used
The ground truth used for the clinical performance study was an FDA-cleared PCR test. This is an objective laboratory reference method.
8. The sample size for the training set
The document does not specify a separate training set or its sample size. The description provided is for the clinical performance study (test set) and analytical studies. For in vitro diagnostic devices, the development and training (if applicable for machine learning components) are typically internal, and the regulated submission focuses on the validation of the final locked algorithm using a distinct clinical test set.
9. How the ground truth for the training set was established
As no specific training set is detailed, information on how its ground truth was established is not provided.
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Image /page/0/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines connecting them.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 18, 2016
Alere Scarborough, Inc. Angela Drysdale Vice President Regulatory Affairs 10 Southgate Road Scarborough, ME 04074
Re: K161375 Trade/Device Name: Alere i RSV Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid System Regulatory Class: II Product Code: OCC. OOI Dated: May 19, 2016 Received: May 20, 2016
Dear Ms. Drysdale:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Tamara V. Feldblyum -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K161375
Device Name Alere™ i RSV
Indications for Use (Describe)
The Alere™ i RSV 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 of respiratory syncytial virus (RSV) viral RNA in direct nasopharyngeal swabs and nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the diagnosis of RSV in children <18 years and adults ≥60 years in conjunction with clinical and epidemiological risk factors.
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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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: K161375
SUBMITTER
Alere Scarborough, Inc. 10 Southgate Road Scarborough, Maine 04074 Establishment Registration Number: 1221359
PRIMARY CONTACT PERSON
Angela Drysdale (207) 730-5737 (office) (207) 730-5767 (FAX) angela.drysdale@alere.com (email)
DATE PREPARED
August 15, 2016
TRADE NAME Alere™ i RSV
COMMON NAME Alere™ i RSV, Alere™ i
CLASSIFICATION NAME
Respiratory Viral Panel Multiplex Nucleic Acid System (per 21 CFR 866.3980) Instrumentation for Clinical Multiplex Test Systems (per 21 CFR 862.2570)
CLASSIFICATION Class II
PRODUCT CODE OCC, OOI
PANEL Microbiology (83)
PREDICATE DEVICE
Quidel Molecular RSV + hMPV Assay (Lyra) K131813
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DEVICE DESCRIPTION
The Alere™ i RSV is a rapid, instrument-based test for the qualitative detection and differentiation of respiratory syncytial virus (RSV) viral RNA from direct nasopharyngeal swab (NPS) and NPS eluted in viral transport media from patients with signs and symptoms of respiratory infection. The Alere™ i RSV System utilizes isothermal nucleic acid amplification technology and is comprised of:
- Sample Receiver – single use, disposable containing the elution buffer
- . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
- . Transfer Cartridge – Single use, disposable for transfer of the eluted sample to the Test Base, and
- Alere™ i Instrument repeat use reader ●
The reaction tubes in the Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i RSV utilizes a pair of templates (similar to primers) for the specific amplification of RNA from RSV A and B, which occur in two separate reaction tubes. Each reaction tube contains a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets. Alere™ i RSV is performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This minimizes the risk of instrument contamination and sample carry-over between measurements.
To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, re-suspending the lyophilized pellets contained within the Test Base and initiating target amplification. Heating, mixing and detection by fluorescence are provided by the instrument, with results automatically reported.
Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.
INTENDED USE
The Alere™ i RSV 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 of respiratory syncytial virus (RSV) viral RNA in direct nasopharyngeal swabs and nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the diagnosis of RSV in children <18 years and adults ≥60 years in conjunction with clinical and epidemiological risk factors.
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TECHNICAL CHARACTERISTICS
Alere™ i RSV and the predicate device, Quidel Molecular RSV + hMPV Assay, have the same intended use, indications for use, and utilize similar basic principles of operation. They are both molecular tests for the qualitative detection of RSV viral RNA.
DEVICE COMPARISON
Alere™ i RSV was compared to the legally marketed predicate device, the Quidel Molecular RSV + hMPV Assay.
| Parameter | Alere™ i RSV | Quidel Molecular RSV + hMPV Assay(Lyra) (K122189, K131813) |
|---|---|---|
| FDA Product Code | OCC, OOI | OEM, OCC |
| Assay Target | RSV | RSV + hMPV |
| Intended Use | The Alere™ i RSV assay performed onthe Alere™ i Instrument is a rapidmolecular in vitro diagnostic testutilizing an isothermal nucleic acidamplification technology for thequalitative detection of respiratorysyncytial virus (RSV) viral RNA indirect nasopharyngeal swabs andnasopharyngeal swabs eluted in viraltransport media from patients withsigns and symptoms of respiratoryinfection. It is intended for use as anaid in the diagnosis of RSV in children<18 years and adults ≥60 years inconjunction with clinical andepidemiological risk factors. | The Quidel Molecular RSV + hMPV Assay isa multiplex Real-Time PCR (RT-PCR) assayfor the qualitative detection andidentification of respiratory syncytial virus(RSV) and human metapneumovirus(hMPV) ribonucleic acid (RNA) extractedfrom nasal and nasopharyngeal swabspecimens from patients with signs andsymptoms of respiratory infection. This invitro diagnostic test is intended to aid inthe differential diagnosis of RSV and hMPVinfection in humans in conjunction withclinical and epidemiological risk factors.This test is not intended to differentiatethe two subtypes of RSV or the four geneticsub-lineages of hMPV.Negative results do not preclude RSVinfection and/or hMPV infection andshould not be used as the sole basis fordiagnosis, treatment or other patientmanagement decisions.Conversely, positive results do not rule-outbacterial infection or co-infection withother viruses. The agent detected may notbe the definite cause of disease. The use ofadditional laboratory testing and clinicalpresentation must be considered in orderto obtain the final diagnosis of respiratoryviral infection.The Quidel Molecular RSV + hMPV Assaycan be performed using the LifeTechnologies QuantStudio™ Dx RT-PCRInstrument, the Applied Biosystems®7500 Fast Dx RT-PCR Instrument, or theCepheid SmartCycler® II System. |
| Parameter | Alere™ i RSV | Quidel Molecular RSV + hMPV Assay(Lyra) (K122189, K131813) |
| IntendedEnvironment for Use | Professional use, in a medicallaboratory or point-of-care | Professional use, in a medical laboratory |
| Instrumentation | Alere™ i Instrument | Cepheid SmartCycler® II System, theApplied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Life TechnologiesQuantStudio™ Dx RT-PCR Instrument |
| Assay Information | ||
| Sample Type | Nasopharyngeal Swab,Nasopharyngeal Swab eluted in ViralTransport Media | Nasopharyngeal swab and nasal swab |
| RSV Target | NS2 gene and nucleocapsid gene N | NS2 genes, L viral polymerase |
| Technology | Isothermal nucleic acid amplificationfor detecting the presence/absence ofviral RNA in clinical specimens. | RT-PCR-based system for detecting thepresence or absence of viral RNA in clinicalspecimens |
| Internal Control | Yes | Yes |
| Results Interpretation | Automated | Same |
| Assay Result | Qualitative | Same |
| Time to Result | <15 minutes | <70 minutes |
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PERFORMANCE SUMMARY
CLINICAL STUDY
The clinical performance of Alere™ i RSV was established in a multi-center, prospective clinical study conducted at nine US trial sites during the 2015-2016 respiratory season.
A total of 497 evaluable nasopharyngeal swab and 501 evaluable nasopharyngeal swab specimens eluted in Viral Transport Media (VTM) collected from children <18 years and adults ≥60 years presenting with symptoms of respiratory infection, were evaluated with Alere™ i RSV, and compared to PCR. 46.6% of the population tested was female and 53.4% was male.
In this study, two nasopharyngeal swabs were collected from each Subject. One swab was tested directly with Alere™ i RSV, according to product instructions for testing swabs. The other swab was eluted in VTM, and a sample of the VTM eluate was tested with Alere™ i RSV.
Alere™ i RSV performance, including 95% confidence intervals, versus FDA-cleared PCR test, is provided below for nasopharyngeal swab direct specimens and nasopharyngeal swab eluted in VTM specimens.
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| PCR + | PCR - | ||
|---|---|---|---|
| Alere™ i + | 137 | 7 | 144 |
| Alere™ i - | 2 | 351 | 353 |
| 139 | 358 | 497 |
Nasopharyngeal Swab Direct
Nasopharyngeal Swab Eluted in VTM
| PCR + | PCR - | ||
|---|---|---|---|
| Alere™ i + | 138 | 8 | 146 |
| Alere™ i - | 2 | 353 | 355 |
| 140 | 361 | 501 |
| Sensitivity: 137/139 = 98.6%(95% CI: 94.9%, 99.6%) | Sensitivity: 138/140 = 98.6(95% CI: 94.9%, 99.6%) |
|---|---|
| Specificity: 351/358 = 98.0%(95% CI: 96.0%, 99.1%) | Sensitivity: 353/361 = 97.8%(95% CI: 95.7%, 98.9%) |
During the prospective clinical study, the initial invalid rate for direct nasopharyngeal swab samples (before repeat testing per the product instructions) was 4.1% (21/506) (95% Cl: 2.7% to 6.3%). After repeat testing per the product instructions, the invalid rate was 0.8% (4/506) (95% CI: 0.3% to 2.0%).
The initial invalid rate for nasopharyngeal swabs eluted in viral transport media was 2.2% (11/506) (95% CI: 1.2% to 3.9%). After repeat testing per the product instructions, the invalid rate was 0% (0/506) (95% CI: 0.0% to 0.8%).
ANALYTICAL STUDIES
ANALYTICAL SENSITIVITY
Alere™ i RSV limit of detection (LOD or C95), defined as the concentration of RSV that produces positive Alere™ i RSV results approximately 95% of the time, was identified by evaluating one RSV A strain and one RSV B strain for both direct swab and swab eluted in VTM testing in Alere™ i RSV. The concentrations identified as the LOD (or C95) levels for each strain and testing method are listed below.
| TestingMethod | Strain | ConcentrationTCID50/mL | ConcentrationGenomeEquivalents/mL |
|---|---|---|---|
| SwabDirect | RSV A/2 | 5.82 x $10^2$ | 7.78 x $10^4$ |
| RSV B/9320 | 6.0 x $10^1$ | 5.43 x $10^3$ | |
| VTM | RSV A/2 | 9.15 x $10^3$ | 1.06 x $10^6$ |
| RSV B/9320 | 9.64 x $10^2$ | 1.48 x $10^5$ |
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ANALYTICAL REACTIVITY (INCLUSIVITY)
The following RSV strains were tested and produced positive reactions at or near the stated assay limit of detection of the Alere™ i RSV test: RSV A Long, RSV B1 and RSV B 18537.
ANALYTICAL SPECIFICITY (CROSS-REACTIVITY)
To determine the analytical specificity of Alere™ i RSV, 40 commensal and pathogenic microorganisms (21 bacteria, 18 viruses and 1 yeast) that may be present in the nasal cavity or nasopharynx were tested. All of the following microorganisms were negative when tested at concentrations ranging from 103 to 1010 cells/mL or CFU/mL (bacteria), 104 to 108 TCIDso/mL, and 108 cells/mL (yeast).
| Bacteria | Viruses | Yeast |
|---|---|---|
| Bordetella pertussis | Adenovirus Type 1 | Candida albicans |
| Corynebacterium diptheriae | Adenovirus type 7 | |
| Escherichia coli* | Coxsackievirus B4 | |
| Haemophilus influenzae | Enterovirus Type 70 | |
| Klebsiella pneumoniae | Epstein Barr virus | |
| Lactobacillus plantarum | Human Coronavirus OC43 | |
| Legionella pneumophila | Human Coronavirus 229E | |
| Moraxella/Branhamella catarrhalis* | Human Cytomegalovirus (CMV) (Herpes V) | |
| Mycobacterium tuberculosis | Human Echovirus 7, Strain Wallace | |
| Mycoplasma pneumoniae | Human metapneumovirus | |
| Neisseria gonorrhoeae | Influenza A | |
| Neisseria meningitidis | Influenza B | |
| Neisseria sicca | Measles virus, strain Edmonston | |
| Neisseria subflava | Mumps virus, strain Enders | |
| Proteus vulgaris* | Parainfluenza virus 1 | |
| Pseudomonas aeruginosa | Parainfluenza virus 2 | |
| Staphylococcus aureus | Parainfluenza virus 3 | |
| Staphylococcus epidermidis | Rhinovirus Type 1A | |
| Streptococcus Group A | ||
| Streptococcus pneumoniae | ||
| Streptococcus salivarius |
- Some cross-reactivity was observed for E. coli at concentrations greater than 2.75 x10°, Moraxella catarrhalis at concentrations greater than 1.50 x109, and Proteus vulgaris at concentrations greater than 4.69 x 108.
In addition, in silico analysis was performed to determine whether there is any significant overlap between Alere™ i RSV target nucleic acid sequence and the genomes of the following upper respiratory tract microorganism. None of the organisms maintained genomic sequence that was significantly similar to the Alere™ i RSV target sequences.
| Bacteria | Viruses |
|---|---|
| Bordetella bronchiseptica | Adenovirus 2 |
| Chlamydia pneumonia | Adenovirus 3 |
| Chlamydia trachomatis | Adenovirus 4 |
| Neisseria mucosa | Adenovirus 5 |
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Proteus mirabilis
Adenovirus 11 Adenovirus 14 Adenovirus 31 Coronavirus NL63 Coxsackievirus B35 Echovirus 6 Echovirus 9 Echovirus 11 Enterovirus 71
INTERFERING SUBSTANCES
The following substances, naturally present or artificially introduced into the nasal cavity/nasopharynx were evaluated with Alere™ i RSV at the concentrations listed below and were found not to affect test performance.
| Substance | Concentration |
|---|---|
| Mucin | 0.0625% |
| Whole Blood | 1% |
| NeoSynephrine Cold & Sinus Extra Strength Spray | 20% |
| Afrin Pump Mist Original | 20% |
| Ocean Saline | 20% |
| Chloroseptic Max | 20% |
| Zicam Allergy Relief | 20% |
| Beclomethasone | 0.068 mg/mL |
| Dexamethasone | 0.48 mg/mL |
| Flunisolide | 0.04 mg/mL |
| Triamcinolone | 0.04 mg/mL |
| Budesonide | 0.051 mg/mL |
| Mometasone furoate | 0.04 mg/mL |
| Fluticasone propionate | 0.04 mg/mL |
| Zanamivir (Relenza) | 0.284 mg/mL |
| Mupirocin | 4.3 mg/mL |
| Tobramycin | 1.44 mg/mL |
INHIBITION BY OTHER MICROORGANISMS
Alere™ i RSV test performance in the presence of non-RSV respiratory pathogens was evaluated. Vendor provided stocks of RSV A and B strains were diluted in UTM to approximately 3 times the limit of detection. Contrived RSV A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. The following panel of non-RSV viruses was tested at the concentration provided in the table below and was found not to affect test performance.
| Virus Panel | Concentration(TCID50/ml) |
|---|---|
| Adenovirus Type 1 | 1.58 x 107 |
| Rhinovirus Type 1A | 1.58 x 107 |
| Influenza A | 5.00 x 107 |
| Influenza B | 1.00 x 108 |
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CARRY-OVER CONTAMINATION
An analytical carry-over study was performed to demonstrate that when recommended laboratory practices are followed, there is little risk of false positive results caused by carryover or crosscontamination in the Alere™ i RSV test. Vendor provided stocks of RSV A and B strains were diluted in UTM to approximately 30 times the limit of detection. Contrived RSV A and B positive swab specimens were prepared by coating 10 microliters of virus dilution onto each swab. Testing of the contrived positive swabs was alternated with testing of a negative swab sample for a total of 15 rounds. In addition, testing of contrived positive VTM samples was alternated with negative VTM samples following the test procedure for Nasopharyngeal Swab Eluted in Viral Transport Media for a total of 15 rounds. No false positive results were observed in this study.
REPRODUCIBILITY
A reproducibility study of Alere™ i RSV was conducted by operators from 3 sites using panels of blind coded specimens containing negative, low positive (at the limit of detection), and moderate positive (above the limit of detection) RSV A and B samples. Participants tested each sample multiple times on 5 different days. The percent agreement with expected results for the RSV A moderate positive and low positive samples were 100% (89/89) and 98.9% (89/90), respectively. The percent agreement with expected results for the RSV B moderate positive and low positive samples were 98.9% (89/90) and 100% (90/90), respectively. All of the negative samples (90) generated negative test results. There were no significant differences within run (replicates tested by one operator), between run (5 different days), between sites (3 sites), or between operators (9 operators).
The results of the analytical and clinical studies performed with Alere™ i RSV support the determination of substantial equivalence in accordance with the stated intended use and device labeling.
§ 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.