(389 days)
Not Found
No
The description focuses on the biochemical and mechanical processes of the test and instrument, with software interpreting results based on predefined melt curve analysis, not AI/ML.
No.
The device is a diagnostic test intended for qualitative detection and identification of respiratory viral and bacterial nucleic acids. It does not provide treatment or therapy.
No
The device aids in the diagnosis of respiratory infections but the manufacturer states that "The results of this test should not be used as for diagnosis, treatment, or other management decisions."
No
The device is a multiplexed nucleic acid test that requires a specific instrument (FilmArray 2.0 EZ Configuration instrument) and physical components (pouch with reagents, bladders, seal points, pneumatic pistons, Peltier devices, digital camera) to perform the testing and analysis. While software is used for interpretation, it is integral to a larger hardware system.
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 a "multiplexed nucleic acid test intended for use with the FilmArray 2.0 EZ Configuration instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections." This clearly describes a test performed in vitro (outside the body) on a biological specimen (nasopharyngeal swab) to aid in the diagnosis of a disease (respiratory tract infections).
- Device Description: The "Device Description" details the process of performing the test on a patient specimen within the FilmArray RP pouch, including nucleic acid purification, reverse transcription, and PCR. This further confirms that the test is conducted in vitro.
- Specimen Type: The test uses "nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections," which is a common type of biological specimen used in in vitro diagnostic testing.
- Purpose: The purpose is to "aid in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information." This aligns with the definition of an IVD, which provides information to assist in diagnosis.
Therefore, based on the provided information, the FilmArray Respiratory Panel EZ meets the criteria of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
FilmArray Respiratory Panel EZ (RP EZ) is a multiplexed nucleic acid test intended for use with the FilmArray 2.0 EZ Configuration instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types and subtypes are identified using the FilmArray RP EZ: Adenovirus, Coronavirus, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3. Influenza A subtype H1-2009. Influenza B, Parainfluenza Virus, Human Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test or, lower respiratory tract infection that is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the FilmArray RP EZ may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Product codes (comma separated list FDA assigned to the subject device)
OCC, OEM, OOU, OEP, OTG, OOI, OZX, OZY, OOW, OZZ
Device Description
The FilmArray Respiratory Panel EZ (RP EZ) is a multiplex nucleic acid test designed to be used with the FilmArray 2.0 EZ Configuration instrument. The FilmArray RP pouch (a component of the FilmArray RP EZ test system) contains freeze-dried reagents to perform nucleic acid purification, reverse transcription, and nested, multiplex PCR with DNA melt analysis. FilmArray RP EZ simultaneously conducts 14 tests for the identification of respiratory pathogens from nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections (Table 1). Results from the FilmArray RP EZ test are available within about one hour.
A test is initiated by loading Hydration Solution and an unprocessed patient nasopharyngeal swab (NPS) specimen (i.e. specimen mixed with Sample Buffer) into the FilmArray RP pouch. The pouch contains all of the reagents required for specimen testing and analysis in a freezedried format; the addition of Hydration Solution and specimen/Sample Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.
The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.
Nucleic acid extraction occurs within the FilmArray RP pouch using mechanical and chemical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the filmArray performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LCGreen® Plus, BioFire Defense, LLC). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 200 stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the array captures fluorescent images of the PCR reactions and software interprets the data.
The FilmArray software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal swabs (NPS)
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D), CLIA-waived setting
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Verification and Validation (V&V) of Software Modifications: The FilmArray EZ software was modified from the FilmArray 2.0 software by removing the multi-instrument dashboard and ability to run multiple instruments, removing PCR evaluator, and simplifying the user interface. In addition, the FilmArray RP EZ pouch module was modified from the FilmArray RP pouch module in order to simplify the results report format and also to combine all four Parainfluenza Virus subtypes into a single Parainfluenza Virus result and all four Coronavirus subtypes into a single Coronavirus result. Verification and Validation activities comprising automated and manual test cases confirmed that the FilmArray EZ software and the FilmArray RP EZ pouch module function as intended when used together in the FilmArray RP EZ test system.
External Control Material Study: A study was performed to assess the ability of the intended user to perform external control testing using the recommended control material and testing procedure for the FilmArray Respiratory Panel (RP) EZ in a CLIA-waived setting. The primary metric evaluated by this study was the ability of these users to acquire and accurately interpret FilmArray RP EZ results when testing the provided external control material. The RP EZ test was performed according to the manufacturer's instructions by users with training and educational backgrounds consistent with those in the CLIA-waived testing environment (i.e. the intended users). User training on use of the FilmArray RP EZ was limited to the training video and quick guide provided with the EZ system. Testing consisted of three positive and three negative controls run per day, and spanned a period of 10 days (total of 60 control runs per site). Multiple operators participated in testing at each of the three locations. Three lots each of external control material and three lots of RP EZ pouches were tested across all sites. A total of 182 external controls were tested (91 positive and 91 negative) by RP EZ users. Two tests were excluded from final data analysis due to invalid results caused by internal pouch control failures. Data for the remaining 180 control tests are shown below in Table 1.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
External control study results:
Site 1: Positive 100% (30/30), Negative 93.3% (28/30), Total 96.7% (58/60)
Site 2: Positive 100% (30/30), Negative 100% (30/30), Total 100% (60/60)
Site 3: Positive 100% (30/30), Negative 100% (30/30), Total 100% (60/60)
Total: Positive 100% (90/90), Negative 97.8% (88/90), Total 98.9% (178/180)
Overall, the users acquired correct control test results in 98.9% of the controls tested.
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/1 description: The image shows the logo for the United States Department of Health and Human Services. The logo consists of a stylized eagle with three stripes representing the three branches of government. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
October 3, 2016
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
BioFire Diagnostics, LLC Kristen J. Kanack, Ph.D. Vice President of Regulated Products and Clinical Affairs 390 Wakara Way Salt Lake City, UT 84108
Re: K152579
Trade/Device Name: FilmArray® Respiratory Panel EZ (RP EZ) Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: II Product Code: OCC. OEM. OOU. OEP. OTG. OOW. OOI. OZZ. OZY, OZX Dated: June 2, 2016 Received: June 3, 2016
Dear Dr. Kanack:
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
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of 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,
Uwe Scherf -S
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
2
Indications for Use
510(k) Number (if known) K152579
Device Name FilmArray® Respiratory Panel EZ (RP EZ)
Indications for Use (Describe)
FilmArray Respiratory Panel EZ (RP EZ) is a multiplexed nucleic acid test intended for use with the FilmArray 2.0 EZ Configuration instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types are identified using the FilmArray RP EZ: Adenovirus, Coronavirus, Human Metapneumovirus, Influenza A subtype H1, Influenza A subtype H3, Influenza A subtype H1-2009, Influenza Virus, Human Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as for diagnosis, treatment, or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test or, lower respiratory tract is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the FilmArray RP EZ may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Bordetella pertussis, Coronavirus, Influenza A H1, Influenza A H3, Influenza A H1-2009, Influenza B. Mycoplasma pneumoniae, and Parainfluenza Virus were established primarily with retrospective clinical specimens. Performance characteristics for Chlamydophila pneumoniae were established primarily using contrived clinical specimens.
Due to the genetic similarity between Human Rhinovirus and Enterovirus, the FilmArray RP EZ cannot reliably differentiate them. A positive FilmArray RP EZ Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.
Performance characteristics for Influenza A were established when Influenza A H1-2009, A H1, and A H3 were the predominant Influenza A viruses in circulation. Performance of detecting Influenza A may vary if other Influenza A strains are circulating or a novel Influenza A virus emerges. 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 departments 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)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
3
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
4
510(k) Summary BioFire Diagnostics, LLC
FilmArrav Respiratory Panel EZ (RP EZ)
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitted by:
BioFire Diagnostics, LLC 390 Wakara Way Salt Lake City, UT 84108
Telephone: 801-736-6354 Facsimile: 801-588-0507
Contact: Kristen Kanack, ext. 330
Date Submitted: September 04, 2015
Device Name and Classification:
Trade Name: FilmArray Respiratory Panel EZ (RP EZ)
Regulation Number: 21 CFR 866.3980
Classification Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay
Product Codes: OCC, OEM, OOU, OEP, OTG, OOI, OZX, OZY, OOW and OZZ
Predicate Device:
K143080 - FilmArray Respiratory Panel for use with FilmArray 2.0 System and FilmArray Injection Vials
Intended Use:
FilmArray Respiratory Panel EZ (RP EZ) is a multiplexed nucleic acid test intended for use with the FilmArray 2.0 EZ Configuration instrument for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections. The following organism types and subtypes are identified using the FilmArray RP EZ: Adenovirus, Coronavirus, Human Metapneumovirus, Influenza A, Influenza A subtype H1, Influenza A subtype H3. Influenza A subtype H1-2009. Influenza B, Parainfluenza Virus, Human Rhinovirus/Enterovirus, Respiratory Syncytial Virus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of a respiratory infection
5
aids in the diagnosis of respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other management decisions. Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test or, lower respiratory tract infection that is not detected by a nasopharyngeal swab specimen. Positive results do not rule out co-infection with other organisms: the agent(s) detected by the FilmArray RP EZ may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.
Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Bordetella pertussis, Coronavirus, Influenza A H1, Influenza A H3, Influenza A H1-2009, Influenza B, Mycoplasma pneumoniae, and Parainfluenza Virus were established primarily with retrospective clinical specimens. Performance characteristics for Chlamydophila pneumoniae were established primarily using contrived clinical specimens.
Due to the genetic similarity between Human Rhinovirus and Enterovirus, the FilmArray RP EZ cannot reliably differentiate them. A positive FilmArray RP EZ Rhinovirus/Enterovirus result should be followed-up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.
Performance characteristics for Influenza A were established when Influenza A H1-2009, A H1, and A H3 were the predominant Influenza A viruses in circulation. Performance of detecting Influenza A may vary if other Influenza A strains are circulating or a novel Influenza A virus emerges. 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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Device Description:
The FilmArray Respiratory Panel EZ (RP EZ) is a multiplex nucleic acid test designed to be used with the FilmArray 2.0 EZ Configuration instrument. The FilmArray RP pouch (a component of the FilmArray RP EZ test system) contains freeze-dried reagents to perform nucleic acid purification, reverse transcription, and nested, multiplex PCR with DNA melt analysis. FilmArray RP EZ simultaneously conducts 14 tests for the identification of respiratory pathogens from nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections (Table 1). Results from the FilmArray RP EZ test are available within about one hour.
| Viral Targets Detected | Bacterial Targets Detected |
|---|---|
| Adenovirus | Bordetella pertussis |
| Coronavirus | Chlamydophila pneumoniae |
Table 1. Pathogens Detected by the FilmArray RP EZ
6
| Human Metapneumovirus | Mycoplasma pneumoniae |
|---|---|
| Human Rhinovirus/Enterovirus | |
| Influenza A, including subtypes | |
| H1, H3 and H1-2009 | |
| Influenza B | |
| Parainfluenza Virus | |
| Respiratory Syncytial Virus |
A test is initiated by loading Hydration Solution and an unprocessed patient nasopharyngeal swab (NPS) specimen (i.e. specimen mixed with Sample Buffer) into the FilmArray RP pouch. The pouch contains all of the reagents required for specimen testing and analysis in a freezedried format; the addition of Hydration Solution and specimen/Sample Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.
The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.
Nucleic acid extraction occurs within the FilmArray RPpouch using mechanical and chemical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the filmArray performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LCGreen® Plus, BioFire Defense, LLC). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 200 stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the array captures fluorescent images of the PCR reactions and software interprets the data.
The FilmArray software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.
Substantial Equivalence:
7
The FilmArray Respiratory Panel EZ is substantially equivalent to the FilmArray Respiratory Panel for use with FilmArray 2.0 and FilmArray Injection Vials (K143080), which was cleared on February 17, 2015 and determined to be a Class II device.
The following table compares the FilmArray Respiratory Panel EZ to the previously cleared FilmArray Respiratory Panel for use with FilmArray System 2.0 and FilmArray Injection Vials (K143080). The table outlines the similarities and differences between the two systems.
| Element | New Device:
FilmArray Respiratory Panel EZ (for use
with FilmArray 2.0 EZ Configuration) | Predicate:
FilmArray Respiratory Panel for use
with FilmArray System 2.0 and
FilmArray Injection Vials
(K143080) |
|--------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Organisms
Detected | Influenza A, Influenza A subtype H1,
Influenza A subtype H3, Influenza A
subtype 2009 H1, Influenza B, Respiratory
Syncytial Virus, Human Metapneumovirus,
Adenovirus, Parainfluenza, Human
Rhinovirus/Enterovirus, Coronavirus,
Mycoplasma pneumoniae, Chlamydophila
pneumoniae, and Bordetella pertussis. | Influenza A, Influenza A subtype H1,
Influenza A subtype H3, Influenza A
subtype 2009 H1, Influenza B, Respiratory
Syncytial Virus, Human Metapneumovirus,
Adenovirus, Parainfluenza 1, Parainfluenza
2, Parainfluenza virus 3, Parainfluenza 4,
Human Rhinovirus/Enterovirus,
Coronavirus HKU1, Coronavirus NL63,
Coronavirus 229E, Coronavirus OC43,
Mycoplasma pneumoniae, Chlamydophila
pneumoniae, and Bordetella pertussis. |
| Analyte | RNA/DNA | Same |
| Specimen Types | Nasopharyngeal swabs | Same |
| Technological
Principles | Nested multiplex RT-PCR followed by high
resolution melting analysis to confirm
identity of amplified product. | Same |
| Instrumentation | FilmArray 2.0 EZ Configuration | FilmArray or FilmArray 2.0 |
| Time to result | About 1 hour | Same |
| Test
Interpretation | Automated test interpretation and report
generation. | Same |
| Reagent
Hydration and
Sample Loading | FilmArray Injection Vial-based loading
procedure. | Same |
| Sample
Preparation
Method | Sample Processing is automated in the
FilmArray RP pouch. | Same |
| Reagent Storage | Reagents are stored at room temperature. | Same |
| Controls | Two controls are included in each reagent
pouch to control for sample processing and
both stages of PCR and melt analysis. | Same |
| Element | New Device:
FilmArray Respiratory Panel EZ (for use
with FilmArray 2.0 EZ Configuration) | Predicate:
FilmArray Respiratory Panel for use
with FilmArray System 2.0 and
FilmArray Injection Vials
(K143080) |
| User
Complexity | Low | Moderate |
Table 2. Comparison of the FilmArray Respiratory Panel EZ to the FilmArray Respiratory Panel for use with FilmArray System 2.0 and FilmArray Injection Vials.
8
Summary of Supporting Data:
Previous Clinical and Analytical Studies
The FilmArray RP reagent pouch and the FilmArray 2.0 instrument (both of which are components of the FilmArray RP EZ system) remain unchanged. Clinical and Analytical performance data have been provided in previous 510(k) submissions (K103175, K110764, K120267, K123620, K143080).
Verification and Validation (V&V) of Software Modifications:
The FilmArray EZ software was modified from the FilmArray 2.0 software by removing the multi-instrument dashboard and ability to run multiple instruments, removing PCR evaluator, and simplifying the user interface. In addition, the FilmArray RP EZ pouch module was modified from the FilmArray RP pouch module in order to simplify the results report format and also to combine all four Parainfluenza Virus subtypes into a single Parainfluenza Virus result and all four Coronavirus subtypes into a single Coronavirus result. Verification and Validation activities comprising automated and manual test cases confirmed that the FilmArray EZ software and the FilmArray RP EZ pouch module function as intended when used together in the FilmArray RP EZ test system.
External Control Material:
BioFire recommends the use of an external control panel manufactured by Maine Molecular Quality Controls, Inc., Scarborough, ME (online at www.mmqci.com) to be used with the FilmArray RP EZ:
FilmArray RP EZ Control Panel M265, Part number M265 (Also available as BioFire Diagnostics Part Number CHEM-CTL-0001)
- 6 vials of RP EZ Positive M266, Part number M266 .
- 6 vials of RP EZ Negative M267, Part number M267 .
The panel is comprised of six individual ready-to-use vials of a positive control material (containing all FilmArray RP EZ analytes) and six individual ready-to-use vials of a negative control material (containing no analytes). This external control panel should be tested when receiving a new shipment of test pouches and when training a new user.
9
A study was performed to assess the ability of the intended user to perform external control testing using the recommended control material and testing procedure for the FilmArray Respiratory Panel (RP) EZ in a CLIA-waived setting. The primary metric evaluated by this study was the ability of these users to acquire and accurately interpret FilmArray RP EZ results when testing the provided external control material. The RP EZ test was performed according to the manufacturer's instructions by users with training and educational backgrounds consistent with those in the CLIA-waived testing environment (i.e. the intended users). User training on use of the FilmArray RP EZ was limited to the training video and quick guide provided with the EZ system.
Testing consisted of three positive and three negative controls run per day, and spanned a period of 10 days (total of 60 control runs per site). Multiple operators participated in testing at each of the three locations. Three lots each of external control material and three lots of RP EZ pouches were tested across all sites.
A total of 182 external controls were tested (91 positive and 91 negative) by RP EZ users. Two tests were excluded from final data analysis due to invalid results caused by internal pouch control failures. Data for the remaining 180 control tests are shown below in Table 1.
| Site | Positive | Negative | Total |
|---|---|---|---|
| Site 1 | 30/30 | ||
| (100%) | 28/30 | ||
| (93.3%) | 58/60 | ||
| (96.7%) | |||
| Site 2 | 30/30 | ||
| (100%) | 30/30 | ||
| (100%) | 60/60 | ||
| (100%) | |||
| Site 3 | 30/30 | ||
| (100%) | 30/30 | ||
| (100%) | 60/60 | ||
| (100%) | |||
| Total | 90/90 | ||
| (100%) | 88/90 | ||
| (97.8%) | 178/180 | ||
| (98.9%) |
Table 1. Summary of RP EZ external control test results
Overall, the users acquired correct control test results in 98.9% of the controls tested, indicating that intended users can accurately perform external control testing in the intended use setting.
Conclusion:
The fundamental scientific technology of the FilmArray RP reagent pouch and FilmArray 2.0 instrument remain unchanged components of the new FilmArray RP EZ system. Data presented demonstrate that the FilmArray RP EZ for use with the FilmArray 2.0 EZ Configuration, which contain modifications to increase simplicity of test use, is substantially equivalent to the FilmArray RP for use with the FilmArray 2.0 system.