(30 days)
The text states "Reference Device(s) / Not Found".
No
The document describes a multiplexed nucleic acid test using PCR and melting curve analysis. There is no mention of AI or ML in the intended use, device description, or performance studies. The semi-quantitative reporting is based on bins of genomic copies, not on AI/ML interpretation.
No.
Explanation: The device is a diagnostic test kit that detects nucleic acids from various bacteria, viruses, and antimicrobial resistance genes to aid in the diagnosis of lower respiratory tract infections. It does not provide any form of therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device "aids in the diagnosis of lower respiratory infection" and "aids in the differential diagnosis of MERS-CoV infection." Although it also states that results "should not be used as for diagnosis, treatment, or other patient management decisions" alone, the primary function is to provide information for diagnostic purposes.
No
The device is a multiplexed nucleic acid test that requires specific hardware systems (BIOFIRE FILMARRAY 2.0 or TORCH) to function. While software is used for reporting and controlling aspects of the test, it is not a standalone software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device 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 of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like speciorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL) obtained from individuals suspected of lower respiratory tract infection." This clearly describes a test performed on biological specimens in vitro (outside the body) to provide information for diagnosis.
- Purpose: The device is used to detect and identify specific viral and bacterial nucleic acids and estimate the relative abundance of bacterial nucleic acids. This information "aids in the diagnosis of lower respiratory infection" and "aids in the differential diagnosis of MERS-CoV infection." This aligns with the definition of an IVD, which is used to examine specimens from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
- Specimen Type: The device uses biological specimens (sputum-like and BAL-like specimens) obtained from individuals.
- Technology: It utilizes molecular techniques (nested, multiplex reverse transcription polymerase chain reaction (PCR), followed by melting curve analysis) to analyze these specimens.
The device description and performance studies further support its classification as an IVD by detailing the technology used to analyze biological samples and providing performance metrics relevant to diagnostic testing (sensitivity, specificity, etc.).
N/A
Intended Use / Indications for Use
BIOFIRE FILMARRAY Pneumonia Panel:
The BIOFIRE FILMARRAY Pneumonia Panel (BIOFIRE Pneumonia Panel) 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 of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like speciorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL) obtained from individuals suspected of lower respiratory tract infection.
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
- · 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:
Atypical Bacteria
- Chlamydia pneumoniae
- · Legionella pneumophila
- Mycoplasma pneumoniae
Viruses
- · Adenovirus
- Human rhinovirus/enterovirus
- · Parainfluenza virus
- · Coronavirus
- · Influenza A virus
- Respiratory syncytial virus
• Human metapneumovirus
-
Influenza B 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, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals exhibiting signs and/or symptoms of a respiratory infection, aids in the diagnosis of lower respiratory infection with other clinical and epidemiological information. The results of this test should not be used as for diagnosis, treatment, or other patient 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, 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 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 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 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, 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.
BIOFIRE FILMARRAY Pneumonia Panel plus:
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. Thical signs and symptoms assocated 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 influenzae
- 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 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 BAL-like specimens from individuals with early infection and from asymptomatic MERS-CoV carriers 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.
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.
Product codes
ODS, ODP
Device Description
The BIOFIRE FILMARRAY Pneumonia Panel and BIOFIRE FILMARRAY Pneumonia Panel plus use nested, multiplex reverse transcription polymerase chain reaction (PCR), followed by melting curve analysis for the detection of select organisms and antimicrobial resistance (AMR) genes in sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) and bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens. The panels allow for the identification of specific bacteria, atypical bacteria, viruses, and AMR genes as indicated in Table 1. The BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus pouches are identical, but the BIOFIRE Pneumonia Panel plus includes reporting of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is not included in the BIOFIRE Pneumonia Panel. Reporting of MERS-CoV is controlled through software masking of the MERS-CoV result for the BIOFIRE Pneumonia Panel.
The BIOFIRE Pneumonia Panels are compatible with bioMérieux's PCR-based in vitro diagnostic BIOFIRE FILMARRAY 2.0 and BIOFIRE FILMARRAY TORCH Systems for infectious disease testing. Specific software module (i.e. BIOFIRE Pneumonia Panel Pouch Module Software) are used to perform BIOFIRE Pneumonia Panels testing on these systems.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
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)
Reanalysis of the performance data with the modified pouch module software did not result in an overall change of the study conclusions or performance claims for non-clinical/analytical studies. While mitigated by the software modification, a description of the cross-reactivity with human genomic DNA has been added to the Analytical Specificity (exclusivity) study. For the clinical performance evaluations, there was a slight increase in the clinical specificity/NPA of the Coronavirus assay from 98.4% to 98.7% in BAL specimens and from 99.3% in 99.5% in sputum specimens from the prospective evaluation. Additionally, the change in interpretation of four Coronavirus results in the Clinical Prospective Study from Detected, resulted in an update to the Expected Values data.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
clinical specificity/NPA of the Coronavirus assay from 98.4% to 98.7% in BAL specimens and from 99.3% in 99.5% in sputum specimens
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 contains the logo of the U.S. Food and Drug Administration (FDA) along with the Department of Health & Human Services. The FDA logo features a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG" in blue, and "ADMINISTRATION" in a smaller font size below. To the left of the FDA logo is the symbol of the Department of Health & Human Services, which consists of a stylized human figure.
November 6, 2024
BioFire Diagnostics, LLC (bioMerieux) Karli Plenert Director, Regulatory Affairs 515 Colorow Drive Salt Lake City, Utah 84108
Re: K243222
Trade/Device Name: BIOFIRE FILMARRAY Pneumonia Panel (BIOFIRE Pneumonia Panel); BIOFIRE FILMARRAY Pneumonia Panel plus (BIOFIRE 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: ODS. ODP Dated: October 3, 2024 Received: October 7, 2024
Dear Karli Plenert:
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 (the 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 available 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.
1
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-regulatory
2
assistance/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,
Digitally signed by Bryan M. Bryan M. Grabias -S Grabias -> 14:35:01 -05'00' Bryan Grabias, Ph. D. Acting Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
Indications for Use
510(k) Number (if known) K243222
Device Name
BIOFIRE FILMARAY Pneumonia Panel (BIOFIRE Pneumonia Panel); BIOFIRE FILMARRAY Pneumonia Panel plus (BIOFIRE Pneumonia Panel plus)
Indications for Use (Describe)
BIOFIRE FILMARRAY Pneumonia Panel:
The BIOFIRE FILMARRAY Pneumonia Panel (BIOFIRE Pneumonia Panel) 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 of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like speciorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL) obtained from individuals suspected of lower respiratory tract infection.
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
- · 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:
Atypical Bacteria
- Chlamydia pneumoniae
- · Legionella pneumophila
- Mycoplasma pneumoniae
Viruses
- · Adenovirus
- Human rhinovirus/enterovirus
- · Parainfluenza virus
- · Coronavirus
- · Influenza A virus
- Respiratory syncytial virus
4
• Human metapneumovirus
-
Influenza B 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, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals exhibiting signs and/or symptoms of a respiratory infection, aids in the diagnosis of lower respiratory infection with other clinical and epidemiological information. The results of this test should not be used as for diagnosis, treatment, or other patient 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, 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 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 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 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, 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.
BIOFIRE FILMARRAY Pneumonia Panel plus:
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
5
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. Thical signs and symptoms assocated 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 influenzae
- 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
6
- · 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 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 BAL-like specimens from individuals with early infection and from asymptomatic MERS-CoV carriers 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.
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.
7
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)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/8/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo consists of a blue circle at the top, with the company name "BIOMÉRIEUX" in white letters inside. The bottom half of the circle is split into two colors, yellow and green, with a white horizontal line separating the top and bottom halves of the circle.
BIOFIRE® FILMARRAY® Pneumonia Panel BIOFIRE® FILMARRAY® Pneumonia Panel plus
Special 510(k) Summary BioFire Diagnostics, LLC
Introduction:
The content of this Special 510(k) submission is limited to obtaining FDA clearance for the BIOFIRE® FILMARRAY® Pneumonia Panel (BIOFIRE Pneumonia Panel) (K212727) and the BIOFIRE® FILMARRAY® Pneumonia Panel plus (BIOFIRE Pneumonia Panel plus) (K222601) with software updates to mitigate the risk of false positive Coronavirus and CTX-M results.
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 (bioMérieux) 515 Colorow Drive Salt Lake City, UT 84108
Contact: Karli Plenert, MBA Telephone: +1 385-414-4985 Email: Karli.Plenert@biomerieux.com
Date Submitted: November 5, 2024
Device Name and Classification:
Trade Name: BIOFIRE FILMARRAY Pneumonia Panel (BIOFIRE Pneumonia Panel)
- Regulation Number: 21 CFR 866.3985 ●
- Classification Name: Device to detect and identify microorganisms and associated resistance ● marker nucleic acids directly in respiratory specimens
Trade Name: BIOFIRE FILMARRAY Pneumonia Panel plus (BIOFIRE Pneumonia Panel plus)
- Requlation Number: 21 CFR 866.4001 ●
- . Classification Name: MERS-CoV and common respiratory pathogens semi-quantitative and quantitative multiplex nucleic acid detection system
Predicate Devices:
- K212727 BIOFIRE FILMARRAY Pneumonia Panel (BIOFIRE Pneumonia Panel) ●
- K222601 BIOFIRE FILMARRAY Pneumonia Panel plus (BIOFIRE Pneumonia Panel plus) ●
9
Background:
Routine post-market monitoring and complaint investigations combined with concurrent findings from an internal product development study identified a previously unrecognized risk and/or rate of false positive Coronavirus (CoV) results on the BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus.
A corrective and preventative action (CAPA) investigation was initiated and a field safety notice indicating a risk of false positive Coronavirus results was issued for the BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus (FDA Recall Event # 93592 (Z-0993-2024).
The internal study also identified several runs with a unique amplicon melt profile for the CTX-M assay. This profile corresponded to a higher than anticipated rate of positive CTX-M assay results (suspected false positive) for the panel under development. A higher rate of positive CTX-M assay results associated with this melt profile has not been observed in the field with the BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus, but the risk for these panels was investigated as a precaution.
Investigations concluded that there is a risk for false positive CoV results as a consequence of non-specific interactions (cross-reactivity) between panel primers and high levels of human genomic DNA (hgDNA) present in some lower respiratory samples tested by the BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus. It was concluded that the CTX-M assay can also cross-react with high levels of hgDNA, but the non-specific amplicon melt is routinely excluded (called negative) by the existing analysis.
The BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus pouch modules (software) have been updated to mitigate the risk of false positive CoV results from cross-reactivity with hgDNA, and to further protect against a risk of false CTX-M results from hgDNA cross-reactivity. The software change does not impact the performance and analysis of the other analytes detected by the panels.
Software Update:
| Previous Version | Updated Version | |
|---|---|---|
| BIOFIRE Pneumonia Panel Pouch Module Software | v2.0 – v2.1.3 | v2.0 – v2.1.4 |
| BIOFIRE Pneumonia Panel plus Pouch Module | v2.0 – v2.1.0 | v2.0 – v2.1.1 |
The software update includes modifications to the software analysis parameters of the BIOFIRE Pneumonia Panel Pouch Module and BIOFIRE Pneumonia Panel plus Pouch Module.
Reanalysis of the performance data with the modified pouch module software did not result in an overall change of the study conclusions or performance claims for non-clinical/analytical studies. While mitigated by the software modification, a description of the cross-reactivity with human genomic DNA has been added to the Analytical Specificity (exclusivity) study. For the clinical performance evaluations, there was a slight increase in the clinical specificity/NPA of the Coronavirus assay from 98.4% to 98.7% in BAL specimens and from 99.3% in 99.5% in sputum specimens from the prospective evaluation. Additionally, the change in interpretation of four Coronavirus results in the Clinical Prospective Study from Detected, resulted in an update to the Expected Values data.
The additional cross-reactivity and the clinical performance changes are documented in the updated BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus IFUs.
Instructions for Use Update:
The instructions for use for both BIOFIRE Pneumonia Panels have been updated to reflect the increase in the clinical specificity/NPA of the coronavirus assay changes due to the software modification, along with additional updates to performance tables (unrelated to the software change).
The software change does not affect the intended use, design, manufacture, or labeling of the BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus reagent pouches or reagent kits.
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Intended Use: BIOFIRE FILMARRAY Pneumonia Panel
The BIOFIRE® FILMARRAY® Pneumonia Panel (BIOFIRE Pneumonia Panel) 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 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 suspected of lower respiratory tract infection.
The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^6, 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 | 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:
| Atypical Bacteria | ||
|---|---|---|
| Chlamydia pneumoniae | Legionella pneumophila | Mycoplasma pneumoniae |
| Viruses | ||
| 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, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals exhibiting signs and/or symptoms of a respiratory infection, aids in the diagnosis of lower 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 patient 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, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 104 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the BIOFIRE Pneumonia Panel 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 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
11
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 in conjunction with culture results for determination of bacterial susceptibility or resistance.
Due to the genetic similarity between human rhinovirus, the test cannot reliably differentiate them. A positive Rhinovirus 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, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10% copies/mL bin if desired, and for antimicrobial susceptibility testing.
Intended Use: BIOFIRE FILMARRAY Pneumonia Panel plus
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 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 | 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:
| 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 |
12
КРС
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 criterial l diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the quidelines 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 sputumlike or BAL-like specimens from individuals with early infection and from asymptomatic MERS-CoV carriers 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 104 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.
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, the test cannot reliably differentiate them. A positive Rhinovirus 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 1044 copies/mL bin if desired, and for antimicrobial susceptibility testing.
13
Device Description:
The BIOFIRE® FILMARRAY® Pneumonia Panel and BIOFIRE® FILMARRAY® Pneumonia Panel plus use nested, multiplex reverse transcription polymerase chain reaction (PCR), followed by melting curve analysis for the detection of select organisms and antimicrobial resistance (AMR) genes in sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) and bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens. The panels allow for the identification of specific bacteria, atypical bacteria, viruses, and AMR genes as indicated in Table 1. The BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus pouches are identical, but the BIOFIRE Pneumonia Panel plus includes reporting of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is not included in the BIOFIRE Pneumonia Panel. Reporting of MERS-CoV is controlled through software masking of the MERS-CoV result for the BIOFIRE Pneumonia Panel.
The BIOFIRE Pneumonia Panels are compatible with bioMérieux's PCR-based in vitro diagnostic BIOFIRE® FILMARRAY® 2.0 and BIOFIRE® FILMARRAY® TORCH Systems for infectious disease testing. Specific software module (i.e. BIOFIRE Pneumonia Panel Pouch Module Software) are used to perform BIOFIRE Pneumonia Panels testing on these systems.
Device Comparison:
Table 1 outlines the similarities and differences between the modified panels and the predicate panels.
| Element | Modified Device:
BIOFIRE Pneumonia Panel / BIOFIRE Pneumonia Panel
plus
(with software update) | Predicate:
BIOFIRE Pneumonia Panel (K212727) /
BIOFIRE Pneumonia Panel plus
(K222601) |
|------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------|
| | See Intended Use: BIOFIRE FILMARRAY Pneumonia Panel
The BIOFIRE® FILMARRAY® Pneumonia Panel (BIOFIRE
Pneumonia Panel) 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 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 suspected of lower respiratory tract
infection. | Same |
| Intended Use | See Intended Use: BIOFIRE FILMARRAY Pneumonia Panel
plus
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. | Same |
| Element | Modified Device:
BIOFIRE Pneumonia Panel / BIOFIRE Pneumonia Panel
plus
(with software update) | Predicate:
BIOFIRE Pneumonia Panel (K212727) /
BIOFIRE Pneumonia Panel plus
(K222601) |
| Organisms
Detected | Bacteria: Acinetobacter calcoaceticus-baumannii complex,
Enterobacter cloacae complex, Escherichia coli , Haemophilus
influenzae, Klebsiella aerogenes, 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
Antimicrobial Resistance Genes: CTX-M, IMP, KPC, mecA/C +
MREJ, NDM, OXA48-like, VIM
Viruses: Adenovirus, Coronavirus, Human Metapneumovirus,
Human Rhinovirus/Enterovirus, Influenza A,
Only available on the BIOFIRE Pneumonia Panel plus:
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Same |
| Analyte | DNA/RNA | Same |
| Specimen Types | BAL-like specimens and Sputum-like specimens | Same |
| Technological
Principles | Nested multiplex PCR followed by high resolution melting
analysis to confirm the identity of amplified product. | Same |
| Instrumentation | BIOFIRE 2.0 System or BIOFIRE 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 System. | Same |
| Reagent Storage | Reagents are stored at room temperature. | Same |
| Shelf-Life | 12 months from Date of Manufacture,
with the exception that pouches aged greater than 6 months
post manufacture have an elevated risk of erroneous reporting
of Adenovirus Not Detected results when testing low titer
samples containing adenovirus species C isolates. | Same |
| 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 | High | Same |
Table 1. Comparison of the BIOFIRE Pneumonia Panels with current BIOFIRE Pneumonia Panels.
14
Conclusion:
The software update and update to the labeling (instructions for use) do not affect the fundamental scientific technology, performance claims, or risk of the BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus. Therefore, the modified BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus are substantially equivalent to their predicate devices.