The FilmArray Blood Culture Identification (BCID) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with 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 BCID assay is 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 following gram-positive bacteria, gram-negative bacteria, and yeast are identified using the FilmArray BCD 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 Enterchacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus, and Serratia marcescens), Haemophilus influenzae, Neisseria meningitidis (encapsulated), Pseudomonas aeruginosa, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis.

The FilmArray BCID Panel also contains assays for the determinants of resistance to methicillin (mecA), vancomycin (vanA and vanB), and carbapenems (blaKPC) 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 carbapenens exist. FilmArray BCID is indicated as an aid in the diagnosis 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 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, Streptococci, 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).

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the FilmArray Blood Culture Identification (BCID) Panel for use with FilmArray Torch, based on the provided document:

Acceptance Criteria and Device Performance

The document doesn't explicitly state numerical acceptance criteria in a dedicated section with thresholds. However, it describes the performance goal and the reported device performance as follows:

Acceptance Criteria / Performance Goal	Reported Device Performance
Reproducible detection of each FilmArray BCID analyte (including antibiotic resistance markers) at concentrations consistent with levels in positive blood culture bottles at initial positivity.	Reproducible detection was confirmed for each FilmArray BCID analyte. 100% of samples tested on FilmArray Torch systems yielded the expected "Detected" results.
Agreement with expected negative results ("Not Detected") for each analyte.	Agreement with the expected negative results (Not Detected) was >98% for each analyte.
Substantial equivalence in performance characteristics (including reproducibility) to the predicate device (FilmArray BCID Panel on FilmArray and FilmArray 2.0 systems).	"Non-clinical validation studies have established that the performance characteristics of FilmArray BCID, including reproducibility, are substantially equivalent on FilmArray, FilmArray 2.0, and FilmArray Torch." (This is a qualitative statement of equivalence based on the quantitative results above).

Study Information

2. Sample size used for the test set and the data provenance:

Sample Size: 30 replicates per analyte per system for 90 total replicates per analyte. (The document doesn't specify how many analytes are on the panel, but Table 1 lists 24 organism targets and 4 resistance markers, implying a total of 28 analytes. So, for each of these 28 analytes, 90 samples were tested).
Data Provenance: The study used "contrived samples" containing analytes at specific concentrations. This indicates a prospective, laboratory-controlled study, rather than retrospective clinical data. No country of origin is explicitly stated, but the submission is to the FDA (USA).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This study evaluates an in vitro diagnostic (IVD) device that directly detects nucleic acids. The ground truth for the contrived samples would be established by the known composition and concentration of the analytes spiked into the samples during their preparation, not by human expert interpretation. Therefore, no external human experts were involved in establishing the ground truth for this specific test set.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not applicable. As this is an IVD device testing contrived samples against known concentrations, there is no need for expert adjudication. The result is either "Detected" or "Not Detected" compared to the known content of the contrived sample.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated IVD and does not involve human readers interpreting results in the same way an AI for image analysis would. Its output is an automated interpretation of molecular detection.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:

Yes, this was effectively a standalone performance evaluation of the FilmArray Torch system running the BCID Panel. The "algorithm" (the automated processes and software interpretation within the FilmArray system) directly processed the samples and generated results without human interpretation of raw data; the user only sees automated test interpretation and report generation.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the test set, the ground truth was known composition and/or spiking of analytes (nucleic acids) at specific concentrations in the contrived samples.

8. The sample size for the training set:

The document describes a submission for a modified device (FilmArray Torch) to be used with an existing reagent panel (FilmArray BCID Panel). It states "There have been no changes to the previously cleared FilmArray BCID Panel reagent kit itself." Therefore, the training of the assay (the BCID Panel's detection algorithms) would have occurred during the development and clearance of the original K143171 predicate device. This document does not provide details on the training set for that original assay, as the focus here is on the new instrument's equivalence. The study described (using 90 replicates per analyte) is a validation/test set, not a training set.

9. How the ground truth for the training set was established:

As noted above, details about the training set for the original BCID Panel assay are not provided in this document. For molecular diagnostic assays like this, training data would typically involve:
- Known positive samples: Samples containing confirmed target organisms/genes (e.g., pure cultures, reference materials).
- Known negative samples: Samples confirmed to lack the target organisms/genes.
- Specificity panels: Samples containing closely related organisms or common co-infecting agents to ensure accurate differentiation and minimize cross-reactivity.
- The ground truth would be established through gold standard microbiology methods (e.g., culture, sequencing, validated reference PCRs) for organisms, and often sequencing or known genetic constructs for resistance genes.

Summary

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Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal features the department's name in a circular arrangement around a stylized eagle symbol. The eagle is depicted with three overlapping profiles, creating a sense of depth and unity.

March 15, 2016

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

BIOFIRE DIAGNOSTICS, LLC KRISTEN KANACK, PHD VICE PRESIDENT, REGULATED PRODUCTS & CLINICAL AFFAIRS 390 WAKARA WAY SALT LAKE CITY UT 84108

Re: K160457

Trade/Device Name: FilmArray Blood Culture Identification (BCID) Panel for use with FilmArray Torch Regulation Number: 21 CFR 866.3365 Regulation Name: Blood Culture Identification Panel (BCID) multiplex nucleic acid assay Regulatory Class: II Product Code: PEN, PAM, OOI Dated: February 18, 2016 Received: February 19, 2016

Dear Dr. Kanack:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

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You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Steven R. Gitterman -S

For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K160457

Device Name

FilmArray Blood Culture Identification (BCID) Panel

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

✖ Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
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Special 510(k) Summary BioFire Diagnostics, LLC

FilmArray Blood Culture Identification (BCID) Panel for use with FilmArray Torch

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Submitted by:

BioFire Diagnostics, LLC 390 Wakara Way Salt Lake City, UT 84108

Contact:

Kristen J. Kanack, Ph.D. Telephone: 801-736-6354, ext. 330 Fax: 801-588-0507 Email: Kristen.kanack@biofiredx.com

Date Submitted:

February 18, 2016

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:

K143171 - 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 veast nucleic acids and select genetic determinants of antimicrobial resistance. The BCID assay is 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 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,

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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 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 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:

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.

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Device Comparison:

The purpose of this submission is to add FilmArray Torch as an additional instrument system for use with the FilmArray Blood Culture Identification (BCID) Panel. There have been no changes to the previously cleared FilmArray BCID Panel reagent kit itself. In order to increase throughput capacity, the FilmArray 2.0 was modified to develop the FilmArray Torch by organizing densely packaged instruments (now called FilmArray Torch Modules) into a "tower" configuration having the computer with touchscreen interface incorporated into the system base. Pouches are now inserted horizontally rather than from the top. This configuration allows the FilmArray Torch Modules to be stacked directly on top of each other to minimize system footprint.

The following table compares the FilmArray BCID Panel for use with the FilmArray Torch to the previously cleared FilmArray BCID Panel for Use with the FilmArray 2.0 (K143171). The table outlines the similarities and differences between the two systems.

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Table 2. Comparison of the FilmArray Blood Culture Identification (BCID) Panel for use with the FilmArray Torch to the current FilmArray Blood Culture Identification (BCID) Panel.

Element	Modified Device:FilmArray Blood Culture Identification(BCID) Panel for use with FilmArrayTorch	Predicate:FilmArray Blood Culture Identification(BCID) Panel for use with FilmArray 2.0(K143171)
OrganismsDetected	Enterococci, Listeria monocytogenes,Staphylococci (including specificdifferentiation of Staphylococcus aureus),Streptococci (with specific differentiationof Streptococcus agalactiae, Streptococcuspneumoniae, and Streptococcus pyogenes),Acinetobacter baumannii,Enterobacteriaceae (including specificdifferentiation of the Enterobacter cloacaecomplex, Escherichia coli, Klebsiellaoxytoca, Klebsiella pneumoniae, Proteus,and Serratia marcescens), Haemophilusinfluenzae, Neisseria meningitidis(encapsulated), Pseudomonas aeruginosa,Candida albicans, Candida glabrata,Candida krusei, Candida parapsilosis,Candida tropicalis, and resistance markersmecA, vanA, vanB, and blaKPC (KPC)	Same
Analyte	DNA	Same
Specimen Types	Positive blood culture samples containinggram-positive or gram-negative bacteriaand/or yeast.	Same
TechnologicalPrinciples	Nested multiplex PCR followed by highresolution melting analysis to confirmidentity of amplified product.	Same
Instrumentation	Single instrument FilmArray System,FilmArray 2.0 System, orFilmArray Torch System	Single instrument FilmArray System orFilmArray 2.0 System
Instrument-SoftwareCommunication	Communication for multiple FilmArrayTorch Modules travels via Ethernetcable/port.	Same (multiple instruments)
Time to result	About 1 hour	Same
TestInterpretation	Automated test interpretation and reportgeneration. User cannot access raw data.	Same
ReagentHydration andSample Loading	FilmArray Injection Vial-based loadingprocedure	Same
SamplePreparationMethod	Sample Processing is automated in theFilmArray BCID pouch.	Same
Element	Modified Device:FilmArray Blood Culture Identification(BCID) Panel for use with FilmArrayTorch	Predicate:FilmArray Blood Culture Identification(BCID) Panel for use with FilmArray 2.0(K143171)
Controls	Two controls are included in each reagentpouch to control for sample processing andboth stages of PCR and melt analysis.	Same
UserComplexity	Moderate/Low	Same

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Performance Characteristics of FilmArray BCID Panel on FilmArray Torch

Contrived samples containing each FilmArray BCID analyte (including antibiotic resistance markers) at concentrations consistent with the levels measured in positive blood culture bottles at the time of the initial indication of positivity were tested on three complete FilmArray Torch systems (12 FilmArray Torch Modules per system) over five days (30 replicates per analyte per system) for 90 total replicates per analyte. Reproducible detection was confirmed for each FilmArray BCID analyte with the expected Detected results for 100% of samples tested on FilmArray Torch systems. Agreement with the expected negative results (Not Detected) was >98% for each analyte.

Conclusion:

The intended use and fundamental scientific technology of the FilmArray BCID Panel used with the modified device. FilmArray Torch, is unchanged from use of the legally marketed FilmArray BCID Panel on FilmArray and FilmArray 2.0 systems. Non-clinical validation studies have established that the performance characteristics of FilmArray BCID, including reproducibility, are substantially equivalent on FilmArray, FilmArray 2.0, and FilmArray Torch. These data demonstrate that the device performs as well as the predicate device.

Regulation Number and Section

§ 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).