(26 days)
No
The description details a multiplexed nucleic acid test using PCR and melt curve analysis with software interpretation of fluorescent images. There is no mention of AI or ML algorithms being used for data analysis, interpretation, or reporting. The semi-quantitative reporting is based on comparison to a quantified standard material, not an AI/ML model.
No
The device is a multiplexed nucleic acid test intended for the simultaneous detection of multiple respiratory viral and bacterial nucleic acids, and select antimicrobial resistance genes, in clinical specimens to aid in the diagnosis of lower respiratory infection. It provides diagnostic information and explicitly states that results should not be used for diagnosis, treatment, or patient management decisions. Therefore, it is not a therapeutic device.
Yes
The device "aids in the diagnosis of lower respiratory infection" by detecting specific viral and bacterial nucleic acids and estimating the relative abundance of nucleic acid from common bacterial analytes. This information is used for diagnostic purposes when combined with other clinical and epidemiological information.
No
The device is a multiplexed nucleic acid test that requires specific hardware systems (FilmArray 2.0 or FilmArray Torch) and a physical pouch containing reagents to perform the testing. While software is used for interpretation and control, it is an integral part of a larger hardware-based diagnostic system.
Based on the provided text, the FilmArray® Pneumonia Panel is indeed an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is a "multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® Torch systems for the simultaneous detection of 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 suspected of lower respiratory tract infection." This clearly describes a test performed in vitro (outside the body) on biological specimens to aid in diagnosis.
- Device Description: The "Device Description" further reinforces this by detailing how the test is performed on biological samples (sputum-like or BAL-like specimens) using a specific instrument and reagents within a pouch. It describes the process of nucleic acid extraction, PCR amplification, and detection, all of which are characteristic of in vitro diagnostic procedures.
- Regulatory Context: The mention of "BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic FilmArray 2.0 (K143178) and FilmArray Torch (K160068) systems for infectious disease testing" and the predicate device K180966 (FilmArray Pneumonia (PN) Panel) strongly indicate that this device is regulated as an IVD. The K numbers are associated with FDA clearances for medical devices, including IVDs.
Therefore, the FilmArray® Pneumonia Panel fits the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The FilmArray® Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® Torch systems for the simultaneous detection 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, 10^5, 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
- -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 -Adenovirus - -Coronavirus
- -Human Metapneumovirus
- -Human Rhinovirus/Enterovirus
- -Influenza A
- -Influenza B
- -Parainfluenza Virus
- -Respiratory Syncytial Virus
Antimicrobial Resistance Genes -CTX-M -IMP -KPC -NDM -OXA-48-like -VIM -mecA/C and MREJ
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 FilmArray 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 FilmArray Pneumonia Panel are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFUmL. 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 FilmArray 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 FilmArray 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.
Product codes (comma separated list FDA assigned to the subject device)
QDP
Device Description
The FilmArray Pneumonia (PN) Panel is designed to simultaneously identify 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 with signs and/or symptoms of lower respiratory tract infection in a time (~1 hour) that allows the test results to be used in determining appropriate patient treatment and management. FilmArray PN Panel is compatible with BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic FilmArray 2.0 (K143178) and FilmArray Torch (K160068) systems for infectious disease testing. A specific software module (i.e. FilmArray PN Panel pouch module) is used to perform FilmArray PN Panel testing on these systems.
A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a sputum-like or BAL-like sample mixed with the provided Sample Buffer into the other port of the FilmArray PN Panel pouch and placing it in a FilmArray instrument. The pouch contains all of 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 guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.
The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.
Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the 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 single plex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 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.
A feature of the FilmArray PN Panel is the reporting of organism abundance for common bacteria in discrete bins representing 10^4, 10^5, 10^6, and >10^7 genomic copies/mL. The panel accomplishes this by comparing the amplification of the bacterial assays with that of a Quantified Standard Material (QSM) present in the pouch.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
lower respiratory tract
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): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3985 Device to detect and identify microorganisms and associated resistance marker nucleic acids directly in respiratory specimens.
(a)
Identification. A device to detect and identify microorganisms and associated resistance marker nucleic acids directly from respiratory specimens is an in vitro diagnostic device intended for the detection and identification of microorganisms and associated resistance markers in respiratory specimens collected from patients with signs or symptoms of respiratory infection. The device is intended to aid in the diagnosis of respiratory infection in conjunction with clinical signs and symptoms and other laboratory findings. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist other than those detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) The 21 CFR 809.10(b) labeling must include:
(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.
(ii) Performance characteristics from analytical studies, including, but not limited to, limit of detection, inclusivity, reproducibility, cross reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, and linearity, as applicable.
(iii) A limiting statement that the device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing.
(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.
(v) A limiting statement that negative results for microorganisms do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
(vi) If applicable, a limiting statement that detected microorganisms may not be the cause of lower respiratory tract infection and may be indicative of colonizing or normal respiratory flora.
(vii) If applicable, a limiting statement that detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora.
(viii) If applicable, a limiting statement that detection of antibiotic resistance markers may not correlate with phenotypic gene expression.
(3) The 21 CFR 809.10(b) labeling and any test report generated by the device must include a limiting statement that negative results for resistance markers do not indicate susceptibility of detected microorganisms.
(4) Design verification and validation must include:
(i) Performance characteristics from clinical studies that include prospective (sequential) samples and, if appropriate, additional characterized samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from an FDA accepted reference method and/or FDA accepted comparator method, as appropriate. Results from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.
(ii) A detailed device description including the following:
(A) Thorough description of the assay methodology including, but not limited to, primer/probe sequences, primer/probe design, and rationale for target sequence selection, as applicable.
(B) Algorithm used to generate a final result from raw data (e.g., how raw signals are converted into a reported result).
(iii) A detailed description of device software, including, but not limited to, validation activities and outcomes.
(iv) As part of the risk management activities, an appropriate end user device training program must be offered as an effort to mitigate the risk of failure from user error.
0
September 22, 2021
Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
BioFire Diagnostics, LLC Kevin Bourzac Vice President, Regulatory & Clinical Affairs 515 Colorow Drive Salt Lake City, Utah 84108
Re: K212727
Trade/Device Name: FilmArray Pneumonia Panel Regulation Number: 21 CFR 866.3985 Regulation Name: Device To Detect And Identify Microorganisms And Associated Resistance Marker Nucleic Acids Directly In Respiratory Specimens Regulatory Class: Class II Product Code: QDP Dated: August 26, 2021 Received: August 27, 2021
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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
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 (OS) 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 mediation-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,
Maria I. Garcia -S
Maria Ines Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K180966
Device Name FilmArray Pneumonia (PN) Panel
Indications for Use (Describe)
The FilmArray® Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® Torch systems for the simultaneous detection 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°5 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 -Adenovirus -
-Coronavirus
-
-Human Metapneumovirus
-
-Human Rhinovirus/Enterovirus
-
-Influenza A
-
-Influenza B
-
-Parainfluenza Virus
-
-Respiratory Syncytial Virus
3
Antimicrobial Resistance Genes -CTX-M -IMP -KPC -NDM -OXA-48-like -VIM -mecA/C and MREJ
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 FilmArray 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 FilmArray Pneumonia Panel are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFUmL. 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 FilmArray 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 FilmArray 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.
| 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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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5
Special 510(k) Summary BioFire Diagnostics, LLC
FilmArray Pneumonia Panel
Introduction:
Purpose
The content of this Special 510(k) submission is limited to obtaining FDA clearance for the FilmArray PN Panel (K180966) with modified labeling to address recent 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 the PN Panel exhibited an increased rate of unexpected Negative results in pouches that are 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 PN Panel (Part No. RFIT-ASY-0144 and RFIT-ASY-0145) in June 2021 (refer to Recall Event 88117/ Z-2039-2021).
In addition, and as a corrective action, the FilmArray PN Panel 'Limitations' section in the Instructions for Use has been modified to include new limitations as well as an additional footnote on the analytical Limit of Detection (LoD) table (Table 62 in the Instructions for Use) that addresses the detection of adenovirus in the FilmArray PN Panel within 6 months of expiration.
Submitted by:
BioFire Diagnostics, LLC 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@biofiredx.com
Date Submitted:
August 26, 2021
Trade Name: FilmArrav Pneumonia Panel
BioFire Diagnostics, LLC Special 510(k) FilmArray PN Panel Label Modification
6
Classification Name:
Device to detect and identify microorganisms and associated resistance marker nucleic acids directly in respiratory specimens (21 CFR 866.3985)
Predicate Device:
K180966 – FilmArray Pneumonia (PN) Panel
Intended Use:
The FilmArray® Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® 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, 10^5, 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 | Respiratory Syncytial Virus |
| Human Metapneumovirus | Influenza B | |
| Antimicrobial Resistance Genes | ||
| CTX-M | NDM | mecA/C and MREJ |
| IMP | OXA-48-like | |
| KPC | VIM |
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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 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the FilmArray 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 FilmArray 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 FilmArray 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 FilmArray 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.
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Device Description:
The FilmArray Pneumonia (PN) Panel is designed to simultaneously identify 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 with signs and/or symptoms of lower respiratory tract infection in a time (~1 hour) that allows the test results to be used in determining appropriate patient treatment and management. FilmArray PN Panel is compatible with BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic FilmArray 2.0 (K143178) and FilmArray Torch (K160068) systems for infectious disease testing. A specific software module (i.e. FilmArray PN Panel pouch module) is used to perform FilmArray PN Panel testing on these systems.
| Bacteria - Quantitative Results | Antimicrobial Resistance Genes |
|---|---|
| Acinetobacter calcoaceticus-baumannii complex | blaCTX-M (Extended spectrum beta-lactamase (ESBL)) |
| Enterobacter cloacae complex | blaIMP (Carbapenem resistance) |
| Escherichia coli | blaKPC (Carbapenem resistance) |
| Haemophilus influenzae | mecA/mecC and MREJ (Methicillin resistance) |
| Klebsiella aerogenes | blaNDM (Carbapenem resistance) |
| Klebsiella oxytoca | blaOXA48-like (Carbapenem resistance) |
| Klebsiella pneumoniae group | blaVIM (Carbapenem resistance) |
| Moraxella catarrhalis | Viruses |
| Proteus spp. | Adenovirus |
| Pseudomonas aeruginosa | Coronavirus |
| Serratia marcescens | Human Metapneumovirus |
| Staphylococcus aureus | Human Rhinovirus/Enterovirus |
| Streptococcus agalactiae | Influenza A |
| Streptococcus pneumoniae | Influenza B |
| Streptococcus pyogenes | Parainfluenza Virus |
| Bacteria (Atypical) - Qualitative Results | Respiratory Syncytial Virus |
| Chlamydia pneumoniae | |
| Legionella pneumophila | |
| Mycoplasma pneumoniae |
A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a sputum-like or BAL-like sample mixed with the provided Sample Buffer into the other port of the FilmArray PN Panel pouch and placing it in a FilmArray instrument. The pouch contains all of 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 guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.
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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 lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the 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 single plex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 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.
A feature of the FilmArray PN Panel is the reporting of organism abundance for common bacteria in discrete bins representing 10^4, 10^5, 10^6, and >10^7 genomic copies/mL. The panel accomplishes this by comparing the amplification of the bacterial assays with that of a Quantified Standard Material (QSM) present in the pouch.
Device Comparison:
Table 1 outlines the similarities and differences between the two panels.
| Element | Modified Device:
FilmArray PN Panel (with modified labeling) | Predicate:
FilmArray PN Panel
(K180966) |
|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------|
| Organisms
Detected | Bacteria: Acinetobacter calcoaceticus-baumannii
complex, Enterobacter aerogenes, Enterobacter
cloacae complex, Escherichia coli, Haemophilus
influenzae, Klebsiella oxytoca, Klebsiella | Same |
| Table 1 Comparison of the FilmArray PN with modified labeling to the current FilmArray PN Panel. | ||||
|---|---|---|---|---|
BioFire Diagnostics, LLC Special 510(k) FilmArray PN Panel Label Modification
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| Element | Modified Device:
FilmArray PN Panel (with modified labeling) | Predicate:
FilmArray PN Panel
(K180966) |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------|
| | 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, 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 FilmArray PN
pouch. | Same |
| Reagent Storage | Reagents are stored at room temperature. | Same |
| Shelf-Life | 12 months from Date of Manufacture (DOM)* | 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 | Moderate/Low | Same |
- 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 PN Panel to include the following limitations in the Instructions for Use:
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- 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 (Table 62) of the Instructions for Use will also be included.
Conclusion:
The fundamental scientific technology, performance, and risk of the FilmArray PN Panel is unchanged from the legally marketed FilmArray PN Panel. There is no change to the product itself. only to the labeling (Instructions for Use). Therefore, the modified FilmArray PN Panel performs as well as the predicate device.