(29 days)
Not Found
No
The description focuses on the biochemical and hardware aspects of the device (nucleic acid extraction, PCR, melt curve analysis, image capture) and standard software interpretation of melt curve data. There is no mention of AI or ML algorithms being used for data analysis or interpretation.
No.
This device is an in vitro diagnostic test used to identify microorganisms and detect antimicrobial resistance genes in positive blood cultures, aiding in diagnosis rather than providing direct therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The FilmArray Blood Culture Identification (BCID) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test..." and "FilmArray BCID Panel is indicated as an aid in the diagnosis of specific agents of bacteremia and fungemia and results should be used in conjunction with other clinical and laboratory findings."
No
The device description clearly outlines hardware components like the FilmArray instrument with bladders, seal points, pneumatic pistons, Peltier devices, and a digital camera, in addition to the software.
Yes, this device is an IVD (In Vitro Diagnostic).
The intended use explicitly states: "The FilmArray Blood Culture Identification (BCID) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems."
N/A
Intended Use / Indications for Use
The FilmArray Blood Culture Identification (BCID) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems. The FilmArray BCID Panel is capable of simultaneous detection and identification of multiple bacterial and yeast nucleic acids and select genetic determinants of antimicrobial resistance. The FilmArray BCID Panel assay is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results.
The following gram-positive bacteria, gram-negative bacteria, and yeast are identified using the FilmArray BCID Panel: Enterococci, Listeria monocytogenes, Staphylococci (including specific differentiation of Staphylococcus aureus), Streptococci (with specific differentiation of Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes), Acinetobacter baumannii, Enterobacteriaceae (including specific differentiation of the Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus, and Serratia marcescens), Haemophilus influenzae, Neisseria meningitidis (encapsulated), Pseudomonas aeruginosa, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis.
The FilmArray BCID Panel also contains assays for the detection of genetic determinants of resistance to methicillin (mecA), vancomycin (vanA and vanB), and carbapenems (blaxe) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene assays do not indicate susceptibility, as multiple mechanisms of resistance to methicillin, vancomycin, and carbapenems exist.
FilmArray BCID Panel is indicated as an aid in the diagnosis of specific agents of bacteremia and fungemia and results should be used in conjunction with other clinical and laboratory findings. Positive FilmArray results do not rule out co-infection with organisms not included in the FilmArray BCID Panel. FilmArray BCID Panel is not intended to monitor treatment for bacteremia or fungemia.
Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not detected by the FilmArray BCID Panel, and for species determination of some Staphylococci, Enterococci, Streptococci, and Enterobacteriaceae that are not specifically identified by the FilmArray BCID Panel assays.
Product codes
PEN, PAM
Device Description
The FilmArray Blood Culture Identification (BCID) Panel is a multiplex nucleic acid test designed to be used with a FilmArray system. The FilmArray BCID pouch contains freeze-dried reagents to perform nucleic acid purification and nested, multiplex PCR with DNA melt analysis. The FilmArray Blood Culture Identification (BCID) Panel simultaneously tests a single positive blood culture sample to provide results for 24 different organisms and organism groups that cause bloodstream infections and three genetic markers that are known to confer antimicrobial resistance (see Table 1).
A test is initiated by loading Hydration Solution and a positive blood culture sample mixed with the provided Sample Buffer into the FilmArray BCID pouch. 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 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 lysis and standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, a nested multiplex PCR is executed in two stages. During the first stage, a single, large volume, highly multiplexed PCR reaction which includes all primers of the outer primer sets, is performed. 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 Defense, LLC). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the array captures fluorescent images of the PCR reactions and software interprets the data.
The FilmArray software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.
Mentions image processing
A digital camera placed in front of the array captures fluorescent images of the PCR reactions and software interprets the data.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Blood culture samples
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)
BioFire performed additional interference testing of two bioMerieux blood culture media bottle types (BacT/ALERT FA Plus and BacT/ALERT FN Plus) in order to add them as acceptable bottle types for use with the FilmArray BCID Panel.
Seven contrived blood culture samples (six positive and one negative) were prepared in each of three media or bottle types and subsequently tested with the FilmArray BCID Panel. The aim was to compare results obtained from samples prepared with a control or reference media (BD BACTEC Plus Aerobic/F) to those from samples prepared with aerobic and anaerobic media/bottle types which contain resin for antibiotic adsorption (BacT/ALERT FA Plus and BacT/ALERT FN Plus). Samples prepared in the BD BACTEC Plus Aerobic/F and BacT/ALERT FA Plus media had been evaluated in the original study, though the BacT/ALERT FA Plus bottles used in the study were obtained from the manufacturer (Biomerieux) prior to IVD labeling and use of the bottles in the United States. Testing of samples in BacT/ALERT FN Plus media was not performed in the original study.
All 21 runs were valid with passed controls and no errors or unexpected results.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3365 Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures.
(a)
Identification. A multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures is a qualitative in vitro device intended to simultaneously detect and identify microorganism nucleic acids from blood cultures that test positive by Gram stain or other microbiological stains. The device detects specific nucleic acid sequences for microorganism identification as well as for antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device does not replace traditional methods for culture and susceptibility testing.(b)
Classification. Class II (special controls). The special control for this device is FDA's guideline document entitled “Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures.” For availability of the guideline document, see § 866.1(e).
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left and the FDA logo on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue.
July 5, 2018
BioFire Diagnostics, LLC Kristen Kanack Senior Vice President, Regulatory & Clinical Affairs 515 Colorow Drive Salt Lake City, Utah 84108
Re: K181493
Trade/Device Name: FilmArray Blood Culture Identification (BCID) Panel Regulation Number: 21 CFR 866.3365 Regulation Name: Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures. Regulatory Class: Class II Product Code: PEN, PAM Dated: June 5, 2018 Received: June 6, 2018
Dear Kristen Kanack:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
Indications for Use (Describe)
Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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3
Special 510(k) Summary BioFire Diagnostics, LLC
FilmArray Blood Culture Identification (BCID) Panel
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitted by:
BioFire Diagnostics, LLC 515 Colorow Drive Salt Lake City, UT 84108
Contact:
Kristen J. Kanack, Ph.D. Telephone: 801-736-6354. ext. 1330 Fax: 801-588-0507 Email: Kristen.kanack@biofiredx.com
Date Submitted:
June 5, 2018
Trade Name: FilmArray Blood Culture Identification (BCID) Panel
Classification Name:
Multiplex devices that use DNA hybridization to detect bacteria and their resistance markers. (21 CFR 866.3365)
Predicate Device:
K160457 - FilmArray Blood Culture Identification (BCID) Panel
Intended Use:
The FilmArray Blood Culture Identification (BCID) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems. The FilmArray BCID Panel is capable of simultaneous detection and identification of multiple bacterial and yeast nucleic acids and select genetic determinants of antimicrobial resistance. The FilmArray BCID Panel assay is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results.
The following gram-positive bacteria, gram-negative bacteria, and yeast are identified using the FilmArray BCID Panel: Enterococci, Listeria monocytogenes, Staphylococci (including specific differentiation of Staphylococcus aureus), Streptococci (with specific differentiation of Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes), Acinetobacter baumannii, Enterobacteriaceae (including specific differentiation of the Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae,
BioFire Diagnostics, LLC Special 510(k) FilmArray BCID Panel Modification
4
Proteus, and Serratia marcescens), Haemophilus influenzae, Neisseria meningitidis (encapsulated), Pseudomonas aeruginosa, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis.
The FilmArray BCID Panel also contains assays for the detection of genetic determinants of resistance to methicillin (mecA), vancomycin (vanA and vanB), and carbapenems (blaxe) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene assays do not indicate susceptibility, as multiple mechanisms of resistance to methicillin, vancomycin, and carbapenems exist.
FilmArray BCID Panel is indicated as an aid in the diagnosis of specific agents of bacteremia and fungemia and results should be used in conjunction with other clinical and laboratory findings. Positive FilmArray results do not rule out co-infection with organisms not included in the FilmArray BCID Panel. FilmArray BCID Panel is not intended to monitor treatment for bacteremia or fungemia.
Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not detected by the FilmArray BCID Panel, and for species determination of some Staphylococci, Enterococci, Streptococci, and Enterobacteriaceae that are not specifically identified by the FilmArray BCID Panel assays.
Device Description:
The FilmArray Blood Culture Identification (BCID) Panel is a multiplex nucleic acid test designed to be used with a FilmArray system. The FilmArray BCID pouch contains freeze-dried reagents to perform nucleic acid purification and nested, multiplex PCR with DNA melt analysis. The FilmArray Blood Culture Identification (BCID) Panel simultaneously tests a single positive blood culture sample to provide results for 24 different organisms and organism groups that cause bloodstream infections and three genetic markers that are known to confer antimicrobial resistance (see Table 1).
| Gram-Positive Bacteria | Gram-Negative Bacteria | Yeast |
|---|---|---|
| Enterococcus | Acinetobacter baumannii | Candida albicans |
| Listeria monocytogenes | Enterobacteriaceae | Candida glabrata |
| Staphylococcus | Enterobacter cloacae complex | Candida krusei |
| Staphylococcus aureus | Escherichia coli | Candida parapsilosis |
| Streptococcus | Klebsiella oxytoca | Candida tropicalis |
| Streptococcus agalactiae | Klebsiella pneumoniae | Antimicrobial resistance genes |
| Streptococcus pneumoniae | Proteus | mecA – methicillin resistance |
| Streptococcus pyogenes | Serratia marcescens | vanA/B - vancomycin resistance |
| Haemophilus influenzae | blaKPC - carbapenem resistance | |
| Neisseria meningitidis (encapsulated) | ||
| Pseudomonas aeruginosa |
Table 1. FilmArray BCID Panel Test Results.
5
A test is initiated by loading Hydration Solution and a positive blood culture sample mixed with the provided Sample Buffer into the FilmArray BCID pouch. 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 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 lysis and standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, a nested multiplex PCR is executed in two stages. During the first stage, a single, large volume, highly multiplexed PCR reaction which includes all primers of the outer primer sets, is performed. 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 Defense, LLC). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the array captures fluorescent images of the PCR reactions and software interprets the data.
The FilmArray software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.
Device Comparison:
The purpose of this submission is to modify the intended use and labeling of the FilmArray Blood Culture Identification (BCID) Panel. The previously cleared FilmArray BCID Panel test was intended to be performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system that demonstrate the presence of organisms as determined by Gram stain. The intended use is being modified so that results can instead be used in conjunction with Gram stain results.
Additional labeling modifications are also being incorporated, including:
- . Removal of false positive warnings for manufacturer-specific (bioMérieux BacT/ALERT SN) blood culture bottles.
- Additional interference testing to include bioMérieux BacT/ALERT FA plus and FN plus ● blood culture bottles
BioFire Diagnostics, LLC Special 510(k) FilmArray BCID Panel Modification
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- Addition of newly identified organism cross-reactivity ●
The following table compares the modified FilmArray BCID Panel to the previously cleared FilmArray BCID Panel (K160457). The table outlines the similarities and differences between the two panels.
Table 2. Comparison of the FilmArray Blood Culture Identification (BCID) Panel with modified intended use and labeling to the current FilmArray Blood Culture Identification (BCID) Panel.
| Element | Modified Device:
FilmArray BCID Panel (with modified intended
use and labeling) | Predicate:
FilmArray BCID Panel
(K160457) |
|--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------|
| Organisms
Detected | Enterococci, Listeria monocytogenes, Staphylococci
(including specific differentiation of Staphylococcus
aureus), Streptococci (with specific differentiation of
Streptococcus agalactiae, Streptococcus pneumoniae,
and Streptococcus pyogenes), Acinetobacter
baumannii, Enterobacteriaceae (including specific
differentiation of the Enterobacter cloacae complex,
Escherichia coli, Klebsiella oxytoca, Klebsiella
pneumoniae, Proteus, and Serratia marcescens),
Haemophilus influenzae, Neisseria meningitidis
(encapsulated), Pseudomonas aeruginosa, Candida
albicans, Candida glabrata, Candida krusei,
Candida parapsilosis, Candida tropicalis, and
resistance markers mecA, vanA, vanB, and blakpc
(KPC) | Same |
| Analyte | DNA | Same |
| Specimen Types | Positive blood culture samples. | Same |
| Technological
Principles | Nested multiplex PCR followed by high resolution
melting analysis to confirm identity of amplified
product. | Same |
| Instrumentation | Single instrument FilmArray System, 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 |
| Reagent
Hydration and
Sample Loading | FilmArray Injection Vial-based loading procedure | Same |
| Sample
Preparation
Method | Sample Processing is automated in the FilmArray
BCID pouch. | Same |
| Reagent Storage | Reagents are stored at room temperature. | Same |
| Controls | Two controls are included in each reagent pouch to
control for sample processing and both stages of PCR
and melt analysis. | Same |
| User
Complexity | Moderate/Low | Same |
7
Updates to the FilmArray BCID Panel Instruction Booklet
Removal of False Positive Warnings for Manufacturer-Specific Blood Culture Bottles
In 2014, BioFire reported an increased risk of false positive results (specifically for Enterococcus and Pseudomonas aeruginosa) when the FilmArray BCID Panel is used with bioMérieux BacT/ALERT Standard Anaerobic (SN) blood culture bottles (Recall Event ID 68352). The source of these false positive results has been identified, corrected, and removed. Therefore, the following limitation, along with similar warnings throughout the Instruction Booklet is being removed, as it is no longer accurate:
- -There is an increased risk of false positive test results for Pseudomonas aeruginosa and Enterococcus when the FilmArray BCID Panel is used to test bioMérieux BacT/ALERT SN standard anaerobic blood culture bottles. If the FilmArray BCID Panel is used with these bottles, then positive results for Pseudomonas aeruginosa and Enterococcus should be confirmed by another method prior to reporting the test results.
Additional Interference Testing
BioFire performed additional interference testing of two bioMerieux blood culture media bottle types (BacT/ALERT FA Plus and BacT/ALERT FN Plus) in order to add them as acceptable bottle types for use with the FilmArray BCID Panel.
Seven contrived blood culture samples (six positive and one negative) were prepared in each of three media or bottle types and subsequently tested with the FilmArray BCID Panel. The aim was to compare results obtained from samples prepared with a control or reference media (BD BACTEC Plus Aerobic/F) to those from samples prepared with aerobic and anaerobic media/bottle types which contain resin for antibiotic adsorption (BacT/ALERT FA Plus and BacT/ALERT FN Plus). Samples prepared in the BD BACTEC Plus Aerobic/F and BacT/ALERT FA Plus media had been evaluated in the original study, though the BacT/ALERT FA Plus bottles used in the study were obtained from the manufacturer (Biomerieux) prior to IVD labeling and use of the bottles in the United States. Testing of samples in BacT/ALERT FN Plus media was not performed in the original study.
All 21 runs were valid with passed controls and no errors or unexpected results. The FilmArray BCID Panel Instruction Booklet will be updated to include these bottle types as shown in Table 3 below in red (refer to Table 77 in the Instruction Booklet).
| Endogenous
Substances | Exogenous Substances | | Technique-
Specific
Substances |
|-----------------------------------|----------------------|------------------------------------|--------------------------------------|
| Hemoglobin | Fluconazole | Ceftriaxone | Bleach |
| Triglycerides | Vancomycin | Tetracycline | Ethanol |
| Bilirubin | Ciprofloxacin | Amoxicillin/Clavulanate | |
| γ-globulin | Gentamicin sulfate | Heparin | |
| Human Genomic DNA | Imipenem | Sodium Polyanetholesulfonate (SPS) | |
| On-Panel Competing Microorganisms | | Off-Panel Competing Microorganisms | |
| Staphylococcus epidermidis | | Corynebacterium jeikeium | |
| Escherichia coli | | Bacillus cereus | |
| Streptococcus mitis | | Micrococcus luteus | |
| | | Clostridium perfringens | |
| | | Propionibacterium acnes | |
| Table 3. Potentially Interfering Substances Tested (No Interference Observed) |
|---|
8
| Blood Culture Media/Bottle Types | ||
|---|---|---|
| BACTEC Plus Aerobic/F | BacT/ ALERT SA Standard Aerobic | VersaTREK REDOX 1 |
| BACTEC Standard Aerobic | BacT/ ALERT SN Standard Anaerobic | VersaTREK REDOX 2 |
| BACTEC Standard Anaerobic | BacT/ ALERT FA Aerobic FAN | |
| BACTEC Plus Anaerobic/F | BacT/ ALERT FN Anaerobic FAN | |
| BACTEC Pediatric Plus | BacT/ ALERT PF Pediatric FAN | |
| BACTEC Lytic/10 Anaerobic/F | BacT/ALERT FA Plus Aerobic | |
| BacT/ALERT FN Anaerobic |
Note: While not shown to interfere in this evaluation, blood culture bottles that contain charcoal have the potential to generate false positive results presumably due to the presence of nucleic acids from non-viable organisms and are listed as contraindicated for use with the FilmArray BCID Panel system.
Newly Identified Organism Cross-Reactivities
BioFire has identified new organism cross-reactivity not previously found during premarket analytical and clinical studies. These findings will be added to the FilmArray BCID Panel Instruction Booklet where appropriate, including Table 4 listed below - updates show in red (see Table 72 in Instruction Booklet).
| FilmArray BCID Panel Result | Cross-Reactive Organism(s)/Isolate(s)/Gene |
|---|---|
| Gram-positive Bacteria | |
| Enterococcus | Some coagulase-negative Staphylococcia |
| Gram-negative Bacteria | |
| Acinetobacter baumannii | Acinetobacter calcoaceticus-baumannii (ACB) complex species: |
| Acinetobacter calcoaceticus (ssp. anitratus) b | |
| Acinetobacter pittii (formerly genomospecies 3)b | |
| Acinetobacter seifertii b,c | |
| Escherichia coli/ | |
| Enterobacteriaceae | Escherichia fergusonnii |
| Shigella species (S. boydii, S. dysenteriae, S. flexneri, S. sonnei) | |
| Enterobacter cloacae complex/ | |
| Enterobacteriaceae | Pantoea (Enterobacter) agglomerans c |
| Klebsiella oxytoca/ | |
| Enterobacteriaceae | Klebsiella michiganensis d |
| Klebsiella pneumoniae/ | |
| Enterobacteriaceae | Klebsiella quasipneumoniae e |
| Klebsiella variicola (aka Klebsiella pneumoniae variant 342) | |
| Enterobacter aerogenes (reclassified as Klebsiella aerogenes) | |
| Raoultella ornithinolytica | |
| Serratia marcescens/ | |
| Enterobacteriaceae | Serratia species (S. entomophilaa, S. ficaria, S. odoriferaa, and S. rubidaeaa) |
| Raoultella ornithinolytica | |
| Pseudomonas aeruginosa (ATCC 25619) h | |
| Some Pseudomonas species (e.g. P. putida, P. poae, and P. veronii) i | |
| Some Pantoea species (e.g. P. calida, P. gavinia, and P. septica)i | |
| Haemophilus influenzae | Some Haemophilus species (H. haemolyticus, H. sputorum, and H. influenzae biotype |
| IV (H. quentini)) j | |
| Listeria monocytogenes | Listeria innocua c |
| Yeast | |
| Candida parapsilosis | Candida orthopsilosis (Group III Candida parapsilosis) l |
| Candida multigemmis c | |
| Candida krusei | Some Streptococcus species (S. mitis, S. pneumoniae, S. dysgalactiae, S. equi, S. |
| oralis, S. parauberis, S. pyogenes, S. salivarious, and S. thermophilus) l | |
| Antimicrobial Resistance Genes | |
| vanA/B | vanMm |
Table 4. Predicted and Observed Cross-Reactivity with On-Panel or Off-Panel Organisms
BioFire Diagnostics, LLC Special 510(k) FilmArray BCID Panel Modification
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3 Cross-reactivity was not observed in analytical sesting, but is predicted by in silico analysis to occur only with some species (i.e. S. epidermis, S. capitis and S. haemolyticus) when present in a sample at very high levels. The predicted cross-reactivity was observed infrequently in pre-analytical studies and the clinical evaluation (estimated occurrence of -0.25% of all Staphylococus positive patient samples).
- Acinetobacter calcoaceticus-baumannii (ACB) complex species are often mis-identified as A. baumannii by automated and manual microbial identification methods.
· Detection was not observed in analytical specificity testing and/or sequence analysis predicts that detection due to cross-
- reactivity may be possible at higher concentrations. d Identified as a new species that is closely related to K. oxytoca [82].
e Identified as a new species (with subspecies) that is closely related to K. pneumoniae [83].
l Cross-reactivity was not observed when ATCC 31898 was tested at a concentration ~1x10 CFU/mL, but cross-reactivity was observed in clinical positive blood cultures containing R. ornithinolytica.
9 Cross-reactivity was observed only at high organism concentration (≥10° CFU/mL); rare human pathogens.
1 No cross-reactivity was observed with five other Pseudomonas aeruginosa isolates tested at ≥10° CFU/mL
I Primarily environmental microorganisms, may cause rare opportunistic infections in humans. The potential for cross-reactivity was identified in contrived samples and/or clinical blood culture specimens.
l Haemophilus spp. that are infrequently isolated from human blood culture and are difficult to distinguish from H. influenzae by automated and manual microbial identification methods. The potential for cross-reactivity with H. sputorum and H. quentini was identified in clinical blood culture specimens.
- Candida orthopsilosis is mis-identified as C. parapsilosis by automated and manual microbial identification methods.
l Cross-reactivity was not observed in analytical specificity testing, but inefficient cross-reactivity with high levels of select streptococi (S.
mitis and S. pneumoniae) has been identified via investigation of false results in silico analysis also predicts potential
cross-reactivity with S. dysgalactiae, S. equi, S. oralis, S. parauberis, S. salivarius, and S. thermophilus.
m Identified from a vancomycin-resistant Enterococcus faecium isolated in Asia, 2011; vanBresistance phenotype.
Conclusion:
The fundamental scientific technology, performance, and risk of the FilmArray BCID Panel is unchanged from the legally marketed FilmArray BCID Panel. There is no change to the product itself, only to the intended use and the labeling (Instruction Booklet). Therefore, the modified FilmArray BCID Panel performs as well as the predicate device.