(59 days)
No
The description details a multiplexed nucleic acid test using PCR and melt curve analysis. The software interprets the results based on these analyses and internal controls. There is no mention of AI or ML being used for data interpretation, pattern recognition, or any other function.
No.
The device is a diagnostic test that detects and identifies nucleic acids from pathogens and resistance genes, providing diagnostic information rather than treatment.
Yes
The device is described as "a multiplexed nucleic acid test intended for use with BioFire® FilmArray® 2.0 (...) systems for the simultaneous detection and identification of nucleic acids from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (...) or bronchoalveolar lavage (BAL)-like specimens." It directly aids in the "differential diagnosis of MERS-CoV infection" and identifies specific pathogens, clearly indicating its role in diagnosis.
No
The device description clearly outlines a system that includes hardware components (BioFire FilmArray 2.0 or Torch systems, pouches with reagents, bladders, seals, pistons, Peltier devices, digital camera) in addition to the software. The software controls the hardware and interprets the data generated by the hardware.
Based on the provided text, the device is indeed an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The text explicitly states the device is a "multiplexed nucleic acid test intended for use with BioFire® FilmArray® 2.0 (BioFire® FilmArray® Torch (BioFire Torch) systems for the simultaneous detection and identification of nucleic acids from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens... or bronchoalveolar lavage (BAL)-like specimens... obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria." This describes a test performed on biological specimens in vitro (outside the body) to provide information for diagnosis.
- Device Description: The description details the process of extracting and analyzing nucleic acids from the specimen using a laboratory instrument and reagents contained within a pouch. This is characteristic of an in vitro diagnostic test.
- Regulatory Information: The mention of predicate device K181324 - FilmArray Pneumonia Panel plus, which is a K number associated with FDA submissions for medical devices, further supports its classification as an IVD.
Therefore, the BioFire® FilmArray® Pneumonia Panel plus is clearly described as an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The BioFire® FilmArray® Pneumonia Panel plus (BioFire Pneumonia Panel plus) is a multiplexed nucleic acid test intended for use with BioFire® FilmArray® 2.0 (BioFire® FilmArray® Torch (BioFire Torch) systems for the simultaneous detection and identification of nucleic acids from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobi-al resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like speci-mens (BAL or mini-BAL) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria.
Testing with BioFire Pneumonia Panel plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected MERS-CoV specimens. This includes: clinical signs and symptoms associated with MERS-CoV infection, contact with a probable or confirmed MERS-CoV case, history of travel to geographic locations where MERS-CoV cases were detected, or other epidemiological links for which MERS-CoV testing may be indicated.
The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5, or ge10^7 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:
Bacteria reported with bins of 10^4, 10^5, 10^6, or ge10^7 copies/mL
- Acinetobacter calcoaceticus-baumannii complex
- Enterobacter cloacae complex
- Escherichia coli
- Haemophilus influenza
- Klebsiella aerogenes
- Klebsiella oxytoca
- Klebsiella pneumoniae group
- Moraxella catarrhalis
- Proteus spp.
- Pseudomonas aeruginosa
- Serratia marcescens
- Staphylococcus aureus
- Streptococcus agalactiae
- Streptococcus pneumoniae
- Streptococcus pyogenes
The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively:
Atypical Bacteria
- Chlamydia pneumoniae
- Legionella pneumophila
- Mycoplasma pneumoniae
Viruses
- Middle East respiratory syndrome coronavirus (MERS-CoV)
- Adenovirus
- Coronavirus
- Human metapneumovirus
- Human rhinovirus/enterovirus
- Influenza A virus
- Influenza B virus
- Parainfluenza virus
- Respiratory syncytial virus
Antimicrobial Resistance Genes
- CTX-M
- IMP
- KPC
- NDM
- OXA-48-like
- VIM
- mecA/C and MREJ (MRSA)
The detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals meeting MERS-CoV clinical and/or epidemiological criteria aids in the differential diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the guidelines provided by the appropriate public health authorities.
BioFire Pneumonia Panel plus MERS-CoV positive results are for the identification of MERS-CoV. The definitive identification of MERS-CoV requires additional testing and confirmation procedures in consultation with the appropriate public health authorities (e.g., local or state public health departments, etc.) for whom reporting is necessary. The diagnosis of MERS-CoV infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of MERS-CoV.
BioFire Pneumonia Panel plus MERS-CoV negative results, even in the con-text of a BioFire Pneumonia Panel plus positive result for one or more of the common respiratory pathogens, do not preclude MERS-CoV infection and should not be used as the sole basis for patient management decisions. The levels of MERS-CoV that would be present in sputum-like or BAL-like speci-mens from individuals with early infection and from asymptomatic MERS-CoV cariers are not well understood. A negative BioFire Pneumonia Panel plus MERS-CoV result in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infec-tious.
Viral culture should not be attempted on specimens with positive BioFire Pneumonia Panel plus results for MERS-CoV unless a BSL 3 facility is available to receive and culture specimens.
Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the BioFire Pneumonia Panel plus 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 lower respiratory tract infection.
Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semiquantitative Bin (copies/mL) results generated by the BioFire Pneumonia Panel plus are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFU/ mL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine signifi-cance of semi-quantitative Bin (copies/mL) for clinical management.
The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease. Negative results for these antimicrobi-al resistance gene assays do not indicate susceptibility to corresponding classes of antimicrobials, as multiple mechanisms of antimicrobial resistance exist.
Antimicrobial resistance can occur via multiple mechanisms. A "Not Detected" result for a genetic marker of antimicrobial resistance does not indicate sus-ceptibility to associated antimicrobial drugs or drug classes. A "Detected" result for a genetic marker of antimicrobial resistance cannot be definitively linked to the microorganism(s) detected. Culture is required to obtain isolates for antimicrobial susceptibility testing, and BioFire Pneumonia Panel plus results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance.
Due to the genetic similarity between human rhinovirus and enterovirus, the test cannot reliably differentiate them. A positive Rhinovirus/Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.
Culture is required to identify pathogens not detected by the BioFire Pneumonia Panel plus, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10^4 copies/mL bin if desired, and for antimicrobial susceptibility testing.
Product codes
QDS
Device Description
The FilmArray Pneumonia Panel plus is designed to simultaneously identify MERS-CoV and 26 potential pathogens of lower respiratory tract infection (LRTI) and associated antimicrobial resistance (AMR) genes from a sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) or bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria in a time (~1 hour). The FilmArray Pneumonia Panel plus is compatible with BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic BioFire FilmArray 2.0 (K143178) and BioFire FilmArray Torch (K160068) systems for infectious disease testing. A specific software module (i.e., FilmArray Pneumonia Panel plus pouch module) is used to perform FilmArray Pneumonia Panel plus testing on these systems.
A test is initiated by loading Hydration Solution into one port of the FilmArrav pouch and a soutumlike or BAL-like sample mixed with the provided Sample Buffer into the port of the FilmArray Pneumonia Panel plus pouch and placing it in a FilmArray instrument. The pouch contains all the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray Software quides 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 pouch using mechanical and chemical lvsis 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 first stage, 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 (LC Green Plus, BioFire Diagnostics). 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 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the end 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 2nd stage PCR 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
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL)
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
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)
Not Found
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
N/A
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".
October 27, 2022
BioFire Diagnostics, LLC Kevin Bourzac Vice President, Regulatory & Clinical Affairs 515 Colorow Drive Salt Lake City, Utah 84108
Re: K222601
Trade/Device Name: FilmArray Pneumonia Panel plus Regulation Number: 21 CFR 866.4001 Regulation Name: A Multiplex Respiratory Panel To Detect And Identify Emerging Respiratory Pathogen(S) And Common Respiratory Pathogens In Human Clinical Specimens Regulatory Class: Class II Product Code: QDS Dated: August 25, 2022 Received: August 29, 2022
Dear Kevin Bourzac:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
for
Noel Gerald Branch Chief DMD: Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K181324
Device Name BioFire FilmArray Pneumonia Panel plus
Indications for Use (Describe)
The BioFire® FilmArray® Pneumonia Panel plus (BioFire Pneumonia Panel plus) is a multiplexed nucleic acid test intended for use with BioFire® FilmArray® 2.0 (BioFire® FilmArray® Torch (BioFire Torch) systems for the simultaneous detection and identification of nucleic acids from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria.
Testing with BioFire Pneumonia Panel plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected MERS-CoV specimens. This includes: clinical signs and symptoms associated with MERS-CoV infection, contact with a probable or confirmed MERS-CoV case, history of travel to geographic locations where MERS-CoV cases were detected, or other epidemiological links for which MERS-CoV testing may be indicated.
The following bacteria are reported semi-quantitatively with bins representing approximately 10°4, 10°5, or ≥10°7 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:
Bacteria reported with bins of 10^4, 10^5, 10^6, or ≥10^7 copies/mL
- · Acinetobacter calcoaceticus-baumannii complex
- · Enterobacter cloacae complex
- · Escherichia coli
- · Haemophilus influenza
- · Klebsiella aerogenes
- · Klebsiella oxytoca
- · Klebsiella pneumoniae group
- · Moraxella catarrhalis
- · Proteus spp.
- · Pseudomonas aeruginosa
- · Serratia marcescens
- · Staphylococcus aureus
- · Streptococcus agalactiae
- · Streptococcus pneumoniae
- · Streptococcus pyogenes
The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively:
Atypical Bacteria
- · Chlamydia pneumoniae
- · Legionella pneumophila
- · Mycoplasma pneumoniae
Viruses
· Middle East respiratory syndrome coronavirus (MERS-CoV)
3
- · Adenovirus
- · Coronavirus
- · Human metapneumovirus
- · Human rhinovirus/enterovirus
- · Influenza A virus
- · Influenza B virus
- · Parainfluenza virus
- · Respiratory syncytial virus
Antimicrobial Resistance Genes
- · CTX-M
- · IMP
- · КРС
- · NDM
- · OXA-48-like
- · VIM
- · mecA/C and MREJ (MRSA)
The detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals meeting MERS-CoV clinical and/or epidemiological criteria aids in the differential diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the guidelines provided by the appropriate public health authorities.
BioFire Pneumonia Panel plus MERS-CoV positive results are for the identification of MERS-CoV. The definitive identification of MERS-CoV requires additional testing and confirmation procedures in consultation with the appropriate public health authorities (e.g., local or state public health departments, etc.) for whom reporting is necessary. The diagnosis of MERS-CoV infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of MERS-CoV.
BioFire Pneumonia Panel plus MERS-CoV negative results, even in the context of a BioFire Pneumonia Panel plus positive result for one or more of the common respiratory pathogens, do not preclude MERS-CoV infection and should not be used as the sole basis for patient management decisions. The levels of MERS-CoV that would be present in sputum-like or BAL-like specimens from individuals with early infection and from asymptomatic MERS-CoV cariers are not well understood. A negative BioFire Pneumonia Panel plus MERS-CoV result in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infectious.
Viral culture should not be attempted on specimens with positive BioFire Pneumonia Panel plus results for MERS-CoV unless a BSL 3 facility is available to receive and culture specimens.
Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the BioFire Pneumonia Panel plus 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 lower respiratory tract infection.
Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semi-quantitative Bin (copies/mL) results generated by the BioFire Pneumonia Panel plus are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFU/ mL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.
4
The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease. Negative results for these antimicrobial resistance gene assays do not indicate susceptibility to corresponding classes of antimicrobials, as multiple mechanisms of antimicrobial resistance exist.
Antimicrobial resistance can occur via multiple mechanisms. A "Not Detected" result for a genetic marker of antimicrobial resistance does not indicate susceptibility to associated antimicrobial drugs or drug classes. A "Detected" result for a genetic marker of antimicrobial resistance cannot be definitively linked to the microorganism(s) detected. Culture is required to obtain isolates for antimicrobial susceptibility testing, and BioFire Pneumonia Panel plus results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance.
Due to the genetic similarity between human rhinovirus and enterovirus, the test cannot reliably differentiate them. A positive Rhinovirus/Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.
Culture is required to identify pathogens not detected by the BioFire Pneumonia Panel plus, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10°4 copies/mL bin if desired, and for antimicrobial susceptibility testing.
| 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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5
Special 510(k) Summary BioFire Diagnostics, LLC
FilmArrav Pneumonia Panel plus
Introduction:
Purpose
The content of this Special 510(k) submission is limited to obtaining FDA clearance for the FilmArray Pneumonia Panel plus (K181324) with modified labeling to address stability results of the adenovirus2 assay used for the detection of adenovirus C species.
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.
Background
Stability study results showed that the Adenovirus2 assay on Pneumonia Panels (Pneumonia Panel and Pneumonia Panel plus) exhibited an increased rate of unexpected Negative results in pouches that were more than 6 months from the date of manufacture (i.e. within 6 months of expiration). As a result of the stability testing, BioFire conducted a voluntary recall of the FilmArray Pneumonia Panels (Part No. RFIT-ASY-0142, RFIT-ASY-0143, RFIT-ASY-0144, and RFIT-ASY-0145) in June 2021 (refer to Recall Event 88117/ Z-2039-2021, Z-2040-2021).
In addition, and as a corrective action, the FilmArray Pneumonia Panel 'Limitations' section in the instructions for use was modified to include new limitations as well as an additional footnote on the analytical Limit of Detection (LoD) table that addresses the detection of adenovirus in the FilmArray Pneumonia Panel within 6 months of expiration. This corrective action was accepted and cleared under special 510(k) K212727.
BioFire would now like to clear the same limitations for the FilmArray Pneumonia Panel plus instructions for use (this submission).
Submitted by:
BioFire Diagnostics, LLC (BioFire) 515 Colorow Drive Salt Lake City, UT 84108
Contact:
Kevin Bourzac, Ph.D. Telephone: 801-736-6354, ext. 1358 Fax: 801-588-0507 Email: kevin.bourzac@biomerieux.com
Date Submitted:
August 25, 2022
BioFire Diagnostics, LLC Special 510(k) FilmArray Pneumonia Panel plus - Label Modification Page 1
6
Trade Name: FilmArray Pneumonia Panel plus
Classification Name:
21 CFR 866.4001 - MERS-CoV and common respiratory pathogens multiplex nucleic acid detection system
Predicate Device:
K181324 - FilmArray Pneumonia Panel plus
Intended Use:
The BIOFIRE® FILMARRAY® Pneumonia Panel plus (BIOFIRE Pneumonia Panel plus) is a multiplexed nucleic acid test intended for use with BIOFIRE® FILMARRAY® 2.0 (BIOFIRE 2.0) or BIOFIRE® FILMARRAY® TORCH (BIOFIRE TORCH) systems for the simultaneous detection and identification of nucleic acids from Middle East respiratory syndrome coronavirus (MERS-CoV) and multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria.
Testing with BIOFIRE Pneumonia Panel plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected MERS-CoV specimens. This includes: clinical signs and symptoms associated with MERS-CoV infection, contact with a probable or confirmed MERS-CoV case, history of travel to geographic locations where MERS-CoV cases were detected, or other epidemiological links for which MERS-CoV testing may be indicated.
The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5, 10^6, or ≥10^7 genomic copies of bacterial nucleic acid per millliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:
| Bacteria reported with bins of $10^4$ , $10^5$ , $10^6$ , or $\geq 10^7$ copies/mL | ||
|---|---|---|
| Acinetobacter calcoaceticus-baumannii | ||
| complex | Klebsiella oxytoca | Serratia marcescens |
| Enterobacter cloacae complex | Klebsiella pneumoniae | |
| group | Staphylococcus aureus | |
| Escherichia coli | Moraxella catarrhalis | Streptococcus agalactiae |
| Haemophilus influenzae | Proteus spp. | Streptococcus pneumoniae |
| Klebsiella aerogenes | Pseudomonas aeruginosa | Streptococcus pyogenes |
The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively:
7
| Atypical Bacteria | ||
|---|---|---|
| Chlamydia pneumoniae | Legionella pneumophila | Mycoplasma pneumoniae |
| Viruses | ||
| Middle East respiratory syndrome coronavirus (MERS-CoV) | ||
| Adenovirus | Human rhinovirus/enterovirus | Parainfluenza virus |
| Coronavirus | Influenza A virus | Respiratory syncytial virus |
| Human metapneumovirus | Influenza B virus | |
| Antimicrobial Resistance Genes | ||
| CTX-M | NDM | mecA/C and MREJ (MRSA) |
| IMP | OXA-48-like | |
| KPC | VIM |
The detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals meeting MERS-CoV clinical and/or epidemiological criteria aids in the differential diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the guidelines provided by the appropriate public health authorities.
BIOFIRE Pneumonia Panel plus MERS-CoV positive results are for the presumptive identification of MERS-CoV. The definitive identification of MERS-CoV requires additional testing and confirmation procedures in consultation with the appropriate public health authorities (e.g., local or state public health departments, etc.) for whom reporting is necessary. The diagnosis of MERS-CoV infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of MERS-CoV.
BIOFIRE Pneumonia Panel plus MERS-CoV negative results, even in the context of a BIOFIRE Pneumonia Panel plus positive result for one or more of the common respiratory pathogens, do not preclude MERS-CoV infection and should not be used as the sole basis for patient management decisions. The levels of MERS-CoV that would be present in sputum-like or BALlike specimens from individuals with early infection and from asymptomatic MERS-CoV cariers are not well understood. A negative BIOFIRE Pneumonia Panel plus MERS-CoV result in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infectious.
Viral culture should not be attempted on specimens with positive BIOFIRE Pneumonia Panel plus results for MERS-CoV unless a BSL 3 facility is available to receive and culture specimens.
Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the BIOFIRE Pneumonia Panel plus may not be the definite cause of disease. Additional laboratory testing (e.q. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible lower respiratory tract infection.
BioFire Diagnostics, LLC Special 510(k) FilmArray Pneumonia Panel plus - Label Modification
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Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semi-quantitative Bin (copies/mL) results generated by the BIOFIRE Pneumonia Panel plus are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFU/mL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.
The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease. Negative results for these antimicrobial resistance gene assays do not indicate susceptibility to corresponding classes of antimicrobials, as multiple mechanisms of antimicrobial resistance exist.
Antimicrobial resistance can occur via multiple mechanisms. A "Not Detected" result for a genetic marker of antimicrobial resistance does not indicate susceptibility to associated antimicrobial drugs or drug classes. A "Detected" result for a genetic marker of antimicrobial resistance cannot be definitively linked to the microorganism(s) detected. Culture is required to obtain isolates for antimicrobial susceptibility testing, and BIOFIRE Pneumonia Panel plus results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance.
Due to the genetic similarity between human rhinovirus and enterovirus, the test cannot reliably differentiate them. A positive Rhinovirus/Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.
Culture is required to identify pathogens not detected by the BIOFIRE Pneumonia Panel plus, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10^4 copies/mL bin if desired, and for antimicrobial susceptibility testing.
Device Description:
The FilmArray Pneumonia Panel plus is designed to simultaneously identify MERS-CoV and 26 potential pathogens of lower respiratory tract infection (LRTI) and associated antimicrobial resistance (AMR) genes from a sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) or bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria in a time (~1 hour). The FilmArray Pneumonia Panel plus is compatible with BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic BioFire FilmArray 2.0 (K143178) and BioFire FilmArray Torch (K160068) systems for infectious disease testing. A specific software module (i.e., FilmArray Pneumonia Panel plus pouch module) is used to perform FilmArray Pneumonia Panel plus testing on these systems.
A test is initiated by loading Hydration Solution into one port of the FilmArrav pouch and a soutumlike or BAL-like sample mixed with the provided Sample Buffer into the port of the FilmArray Pneumonia Panel plus pouch and placing it in a FilmArray instrument. The pouch contains all the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared,
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the FilmArray Software quides 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 pouch using mechanical and chemical lvsis 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 first stage, 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 (LC Green Plus, BioFire Diagnostics). 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 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the end 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 2nd stage PCR 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.
Device Comparison:
Table 1 outlines the similarities and differences between the two panels.
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Table 1 Comparison of the FilmArray Pneumonia Panel plus with modified labeling to the current FilmArray Pneumonia Panel plus.
| Element | Modified Device:
FilmArray Pneumonia Panel plus (with
modified labeling) | Predicate:
FilmArray Pneumonia Panel
plus
(K181324) |
|---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------|
| Organisms
Detected | Bacteria: Acinetobacter calcoaceticus-baumannii
complex, Enterobacter aerogenes, Enterobacter
cloacae complex, Escherichia coli, Haemophilus
influenzae, Klebsiella oxytoca, Klebsiella
pneumoniae group, Moraxella catarrhalis,
Proteus spp., Pseudomonas aeruginosa, Serratia
marcescens, Staphylococcus aureus,
Streptococcus agalactiae, Streptococcus
pneumoniae, Streptococcus pyogenes
Atypical Bacteria: Chlamydia pneumoniae,
Legionella pneumophila, Mycoplasma
pneumoniae | Same |
| | Antimicrobial Resistance Genes: CTX-M, IMP,
KPC, mecA/C + MREJ, NDM, Oxa48-like, VIM | |
| | Viruses: Middle East Respiratory Syndrome
Coronavirus, Adenovirus, Coronavirus, Human
Metapneumovirus, Human
Rhinovirus/Enterovirus, Influenza A, Influenza B,
Parainfluenza virus,
Respiratory Syncytial virus | |
| Analyte | DNA/RNA | Same |
| Specimen
Types | Positive blood culture samples containing gram-
positive or gram-negative bacteria and/or yeast. | Same |
| Technological
Principles | Nested multiplex PCR followed by high resolution
melting analysis to confirm the identity of
amplified product. | Same |
| Instrumentation | Single instrument FilmArray 2.0 System, or
FilmArray Torch System | Same |
| Time to result | About 1 hour | Same |
| Test
Interpretation | Automated test interpretation and report
generation. User cannot access raw data. | Same |
| Sample
Preparation
Method | Sample Processing is automated in the BioFire
FilmArray PN pouch. | Same |
| Reagent
Storage | Reagents are stored at room temperature. | Same |
| Shelf-Life | 12 months from Date of Manufacture (DOM)* | Same |
| Element | Modified Device:
FilmArray Pneumonia Panel plus (with
modified labeling) | Predicate:
FilmArray Pneumonia Panel
plus
(K181324) |
| Controls | Two controls are included in each reagent pouch
to control for sample processing and both stages
of PCR and melt analysis. | Same |
| User
Complexity | Moderate/High | Same |
BioFire Diagnostics, LLC Special 510(k)
FilmArray Pneumonia Panel plus - Label Modification
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- LoD for adenovirus species C is 10 - 100 x impaired when pouches are within 6 months of expiration
The purpose of this submission is to modify the labeling of the FilmArray Pneumonia Panel plus to include the following limitations in the instructions for use:
- There is an increased risk of false negative Adenovirus results for adenovirus species C when using a pouch that is within 6 months of the expiration date due to a 10-100 x loss in sensitivity (i.e. impairment leading to an increase in the LoD). The test performance is not impacted if kits are more than 6 months from expiration date. Performance for other adenovirus species is not impacted.
- If using a pouch that is within 6 months of expiration when a patient is suspected of adenovirus C infection, confirm all negative Adenovirus results using another method prior to reporting the result, or alternatively, do not report a negative Adenovirus result.
An additional footnote in the Analytical LoD section (Table 63) of the Pneumonia Panel plus instructions for use will also be included.
Conclusion:
The fundamental scientific technology, performance, and risk of the FilmArray Pneumonia Panel plus is unchanged from the legally marketed FilmArray Pneumonia Panel plus. There is no change to the product itself, only to the labeling (instructions for use). Therefore, the modified FilmArray Pneumonia Panel plus performs as well as the predicate device.