The BIOFIRE FILMARRA Y Tropical Fever (TF) Panel is an automated qualitative, multiplexed, polymerase chain reaction (PCR) test intended for use with BIOFIRE FILMARRAY 2.0 and BIOFIRE FILMARRAY TORCH Systems. The BIOFIRE FILMARRAY TF Panel detects and identifies selected bacterial, viral, and parasitic nucleic acids directly from EDTA whole blood collected from individuals with signs and/or symptoms of acute febrile illness or recent acute febrile illness and known or suspected exposure to the following target pathogens: chikungunya virus, dengue virus (serotypes 1, 2, 3 and 4), Leptospira spp., and Plasmodium species differentiation of Plasmodium falciparum and Plasmodium vivax/ovale).

Evaluation for more common causes of acute febrile illness (e.g., infections of the upper and lower respiratory tract or gastroenteritis, as well as non-infectious causes) should be considered prior to evaluation with this panel. Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the relevant public health authorities.

The BIOFIRE FILMARRA Y TF Panel is not intended to be used as the sole basis for diagnosis, treatment, or other management decisions. Positive results do not rule out co-infection with other organisms not included on the BIOFIRE FILMARRA Y TF Panel, nor do negative results rule out infection. Negative results from the BIOFIRE FILMARRA Y TF Panel may require additional testing if clinically indicated. Not all pathogens that cause acute febrile illness are detected by this test, and negative results do not rule out the presence of other infections.

In the United States, patient travel history, exposure risk, and consultation of the CDC Yellow Book should be considered prior to use of the BIOFIRE FILMARRAY TF Panel as some pathogens are more common in certain geographical locations.

Device Description

The BIOFIRE FILMARRAY TF Panel is a rebranded version of the BioFire Global Fever Panel. It is designed to simultaneously identify 6 pathogens from whole blood specimens collected in EDTA tubes. The BIOFIRE FILMARRAY TF Panel is compatible with BioFire's PCR-based in vitro diaqnostic BIOFIRE® FILMARRAY® 2.0 and BIOFIRE® FILMARRAY® TORCH Systems for infectious disease testing. A panel-specific software module (i.e., BIOFIRE FILMARRAY TF Panel pouch module software) is used to perform BIOFIRE FILMARRAY TF Panel testing on these systems. Results from the BIOFIRE FILMARRAY TF Panel test are available within about one hour.

A test is initiated by loading Hydration into one port of the pouch and a whole blood or positive blood culture specimen mixed with the provided Sample Buffer into the port of the BIOFIRE FILMARRAY TF Panel pouch and placing it in a BIOFIRE System. The pouch contains all the reacents required for speciment testing and analysis in a freezedried format; the addition of Hydration and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the BIOFIRE Software quides the user though the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The BIOFIRE System 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 BIOFIRE 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 BIOFIRE system performs a nested multiplex PCR that is executed in two stages. During the first stage, the BIOFIRE System performs a single, large volume, highly multiplexed reverse transcription 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. The solution is then distributed to each 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 end of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data.

The BIOFIRE 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

This document describes the BIOFIRE FILMARRAY Tropical Fever (TF) Panel, a rebranded version of the BioFire Global Fever Panel (K220870). The submission is a Special 510(k), indicating that the modifications are minor and do not affect the fundamental scientific technology, performance claims, or risk of the device. Therefore, the acceptance criteria and study proving its performance are based on the predicate device, the BioFire Global Fever Panel (K220870), as the performance claims of the rebranded panel remain identical.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a re-branding with identical performance claims, the "acceptance criteria" for the BIOFIRE FILMARRAY TF Panel are implicitly met by demonstrating substantial equivalence to the predicate device, which has already met its own acceptance criteria. The document states: "The performance claims of the BIOFIRE FILMARRAY TF Panel remain identical to the predicate BioFire Global Fever Panel."

Therefore, the performance data provided would be from the studies conducted for the predicate device, K220870 (BioFire Global Fever Panel). While the specific performance table demonstrating these results is not directly included in the provided text, the implication is that the predicate met the necessary performance metrics (e.g., sensitivity, specificity, accuracy for each target pathogen).

For illustrative purposes, if this were a new device submission, a table would look like this (conceptual, based on the device type):

Pathogen/Performance Metric	Acceptance Criteria (e.g., % Sensitivity, % Specificity)	Reported Device Performance (from K220870 studies)
Chikungunya virus Sensitivity	≥ X%	Y%
Chikungunya virus Specificity	≥ X%	Y%
Dengue virus (all serotypes) Sensitivity	≥ X%	Y%
Dengue virus (all serotypes) Specificity	≥ X%	Y%
Leptospira spp. Sensitivity	≥ X%	Y%
Leptospira spp. Specificity	≥ X%	Y%
Plasmodium falciparum Sensitivity	≥ X%	Y%
Plasmodium falciparum Specificity	≥ X%	Y%
Plasmodium vivax/ovale Sensitivity	≥ X%	Y%
Plasmodium vivax/ovale Specificity	≥ X%	Y%
Overall Agreement/Accuracy	≥ X%	Y%

The document explicitly states that the performance claims are identical to the predicate, meaning the predicate's performance metrics serve as the "acceptance criteria" implicitly met by this re-branding.

2. Sample Size Used for the Test Set and Data Provenance

The provided text does not contain the specific sample sizes used for the clinical/test set for the predicate device (K220870). It also does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Such details would typically be found in the original 510(k) submission for K220870 or its associated clinical study reports.

However, given it's a panel for tropical fevers, it's highly probable that the data would be from regions where these pathogens are endemic, and likely include both prospective and/or retrospective samples to
cover various disease states and prevalence.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

For an in vitro diagnostic (IVD) device like the BIOFIRE FILMARRAY TF Panel, especially one that detects nucleic acids, the "ground truth" for the test set is typically established through a combination of:

Clinical Diagnosis: Based on patient symptoms, travel history, other laboratory findings, and epidemiological data.
Confirmatory Laboratory Testing: Often using highly sensitive and specific reference methods (e.g., CDC-validated PCR assays, sequencing, culture where applicable) for the target pathogens.

This process generally does not involve a "number of experts" in the same way an imaging AI ground truth would. Instead, it relies on validated laboratory methods and comprehensive clinical assessment. The qualifications would be laboratory professionals using validated reference methods and clinicians making diagnoses based on standard medical practice. The text does not provide specific details on the number or qualifications of experts involved in establishing ground truth for the predicate device.

4. Adjudication Method for the Test Set

As the ground truth for an IVD device like this is primarily established by laboratory reference methods and clinical outcomes, an "adjudication method" in the sense of multiple human readers resolving disagreements (common in imaging AI) is not directly applicable. The resolution of discrepancies would involve retesting by reference methods, review of patient charts, or further clinical investigation, rather than expert consensus reading of images.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, an MRMC comparative effectiveness study was not done, and is not applicable for this type of IVD device. MRMC studies are primarily used for medical imaging AI devices to assess the impact of AI assistance on human reader performance. This device is a qualitative, multiplexed PCR test that provides automated results, not an imaging diagnostic that assists human readers.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the performance study for this device (or its predicate) is inherently a standalone performance assessment. The BIOFIRE FILMARRAY TF Panel is an automated test. The "algorithm" (the instrument's software interpreting PCR data) provides the final qualitative result (positive/negative for each pathogen) without a human interpreting raw data or images. The results are automatically interpreted and reported. The human "in the loop" is the lab technician who performs the test and interprets the results in a clinical context, but not one who influences the primary diagnostic output of the device itself.

The description explicitly states: "The BIOFIRE 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." This confirms its standalone nature.

7. The Type of Ground Truth Used

The ground truth for an IVD diagnostic like this is typically established by:

Reference Laboratory Methods: Gold standard molecular assays (e.g., highly sensitive and specific PCR assays, sometimes developed or validated by national reference labs like the CDC), possibly combined with sequencing.
Clinical Data and Outcomes: Patient symptoms, travel history, other clinical laboratory findings, and sometimes follow-up data to confirm true positive or true negative status.

The document states: "The BIOFIRE FILMARRAY TF Panel is not intended to be used as the sole basis for diagnosis, treatment, or other management decisions. Positive results do not rule out co-infection with other organisms... nor do negative results rule out infection. Negative results... may require additional testing if clinically indicated." This implies that while the device offers a direct result, the final clinical diagnosis relies on a broader set of information, and the device's performance is validated against established methods or confirmed clinical diagnoses.

8. The Sample Size for the Training Set

The document does not provide details on the training set for the algorithm (software). For PCR-based IVD devices, the "training" analogous to machine learning often involves significant laboratory work to:

Design and optimize primers/probes: Extensive testing with known positive and negative samples, various concentrations of targets, and interfering substances.
Establish cutoff values: For determining positive vs. negative results based on fluorescence thresholds and melt curve characteristics.
Verify analytical performance: Limit of detection (LoD), inclusivity, exclusivity, cross-reactivity, precision, etc.

This "training" or development process heavily relies on characterized biological samples (clinically relevant strains, spiked samples, negative controls). The specific number of samples for each stage of this development is not given in this document, as it focuses on the equivalence to a predicate.

9. How the Ground Truth for the Training Set Was Established

For IVD development, the ground truth for training/development samples is established through:

Well-characterized Isolates/Strains: Using verified pathogen cultures or nucleic acid extracts with confirmed identity and quantification.
Spiking Studies: Adding known amounts of target nucleic acids into clinical matrix (e.g., whole blood) from healthy donors.
Known Clinical Samples: Samples previously characterized by highly accurate reference methods or confirmed clinical diagnosis.

This process ensures that the assay design (e.g., primer selection, PCR conditions, interpretation algorithms) effectively detects and differentiates the target pathogens from non-targets and in the presence of various confounding factors. The specific methodology for ground truth establishment for the training set of the predicate is not detailed in the provided text.

Summary

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December 5, 2024

BioFire Diagnostics, LLC (bioMerieux) Karli Plenert Sr Director, Regulatory Affairs 515 Colorow Drive Salt Lake City, Utah 84108

Re: K243463

Trade/Device Name: BIOFIRE FILMARRAY Tropical Fever Panel Regulation Number: 21 CFR 866.3966 Regulation Name: Device To Detect And Identify Selected Microbial Agents That Cause Acute Febrile Illness Regulatory Class: Class II Product Code: OMV Dated: November 7, 2024 Received: November 8, 2024

Dear Karli Plenert:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about 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).

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Sincerely,

Bryan M. Digitally signed by Bryan M. Grabias -S Grabias -S Date: 2024.12.05 14:24:06 -05'00'

Bryan Grabias Acting Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K243463

Device Name BIOFIRE FILMARRAY Tropical Fever 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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BIOFIRE® FILMARRAY® Tropical Fever Panel

Special 510(k) Summary BioFire Diagnostics, LLC

Introduction:

The content of this Special 510(k) submission is limited to obtaining FDA clearance for the BIOFIRE® Tropical Fever (TF) Panel, a rebranded version of the BioFire Global Fever Panel (K220870). According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Submitted by:

BioFire Diagnostics, LLC (bioMérieux) 515 Colorow Drive Salt Lake City, UT 84108

Contact:

Karli Plenert, MBA Telephone: +1 385-414-4985 Email: Karli.Plenert@biomerieux.com

Date Submitted: November 07, 2024

Device Name and Classification:

Trade Name: BIOFIRE FILMARRAY Tropical Fever (TF) Panel

Requlation Number: 21 CFR 866.3966

Classification Name: Device To Detect And Identify Selected Microbial Agents That Cause Acute Febrile Illness

Predicate Devices:

K220870 - BioFire Global Fever Panel

Background:

The BioFire Global Fever Panel (K220870) is designed, and currently manufactured by BioFire Defense, LLC (a wholly owned subsidiary of bioMérieux, Inc.). The BIOFIRE FILMARRAY Tropical Fever (TF) Panel is a rebranded version of the BioFire Global Fever panel that includes updated pouch module software, product labeling, instructions for use, and a new panel name. The performance claims of the BIOFIRE FILMARRAY TF Panel remain identical to the predicate BioFire Global Fever Panel.

BioFire Defense will remain the legal manufacturer of the BioFire Global Fever Panel. BioFire Diagnostics, LLC (also a wholly owned subsidiary of bioMérieux, lnc.) will be the legal manufacturer of the BIOFIRE FILMARRAY TF Panel and BioFire Defense will be the contract manufacturer for the device.

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Modifications:

Software Update

The BIOFIRE FILMARRAY TF Panel Pouch Module software has been developed to support the rebranded panel and includes the following changes:

. Change to the panel name,
Update to report to align the report appearance and layout with other BIOFIRE FILMARRAY IVD panels sold by bioMérieux, and
Add cross-compatibility with the latest BIOFIRE FILMARRAY Systems Software. ●

Labeling and Branding Update:

A new BIQFIRE FILMARRAY TF Panel instructions for use has been created to align with bioMérieux branding quidelines for the BIOFIRE product line and reflects the updated panel name. In addition, physical product labeling has been created to include the new product branding and panel name.

Intended Use:

The BIOFIRE® FILMARRAY® Tropical Fever (TF) Panel is an automated, qualitative, multiplexed polymerase chain reaction (PCR) test intended for use with BIOFIRE® FILMARRAY® 2.0 and BIOFIRE® FILMARRAY® TORCH Systems. The BIOFIRE FILMARRAY TF Panel detects and identifies selected bacterial, viral, and parasitic nucleic acids directly from EDTA whole blood collected from individuals with signs and/or symptoms of acute febrile illness and known or suspected exposure to the following target pathogens: chikungunya virus (serotypes 1, 2, 3 and 4), Leptospira spp., and Plasmodium species differentiation of Plasmodium falciparum and Plasmodium vivax/ovale).

The BIOFIRE FILMARRAY TF Panel is not intended to be used as the sole basis for diagnosis, treatment, or other management decisions. Positive results do not rule out co-infection with other organisms not included on the BIOFIRE FILMARRAY TF Panel, nor do negative results rule out infection. Negative results from the BIOFIRE FILMARRAY TF Panel may require additional testing if clinically indicated. Not all pathogens that cause acute febrile illness are detected by this test, and negative results do not rule out the presence of other infections.

Intended User and Use Environment

The BIOFIRE FILMARRAY TF Panel is intended for use by trained medical and laboratory professionals in a laboratory setting or under the supervision of a trained laboratory professional.

Device Description:

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Device Comparison:

Table 1 outlines the similarities and differences between the BIOFIRE FILMARRAY TF Panel with the BioFire Global Fever Panel.

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Table 1. Comparison of the BIOFIRE FILMARRAY TF Panel with the BioFire Global Fever Panel.

Element	Modified Device:BIOFIRE FILMARRAY TF Panel	Predicate:BioFire Global Fever Panel (K220870)
Intended Use	The BIOFIRE® FILMARRAY® Tropical Fever (TF) Panel is anautomated, qualitative, multiplexed polymerase chain reaction(PCR) test intended for use with BIOFIRE® FILMARRAY® 2.0and BIOFIRE® FILMARRAY® TORCH Systems. The BIOFIREFILMARRAY TF Panel detects and identifies selectedbacterial, viral, and parasitic nucleic acids directly from EDTAwhole blood collected from individuals with signs and/orsymptoms of acute febrile illness or recent acute febrile illnessand known or suspected exposure to the following targetpathogens: chikungunya virus, dengue virus (serotypes 1, 2, 3and 4), Leptospira spp., and Plasmodium spp. (includingspecies differentiation of Plasmodium falciparum andPlasmodium vivax/ovale).Evaluation for more common causes of acute febrile illness(e.g., infections of the upper and lower respiratory tract orgastroenteritis, as well as non-infectious causes) should beconsidered prior to evaluation with this panel. Results aremeant to be used in conjunction with other clinical,epidemiologic, and laboratory data, in accordance with theguidelines provided by the relevant public health authorities.The BIOFIRE FILMARRAY TF Panel is not intended to beused as the sole basis for diagnosis, treatment, or othermanagement decisions. Positive results do not rule out co-infection with other organisms not included on the BIOFIREFILMARRAY TF Panel, nor do negative results rule outinfection. Negative results from the BIOFIRE FILMARRAY TFPanel may require additional testing if clinically indicated. Notall pathogens that cause acute febrile illness are detected bythis test, and negative results do not rule out the presence ofother infections.In the United States, patient travel history, exposure risk, andconsultation of the CDC Yellow Book should be consideredprior to use of the BIOFIRE FILMARRAY TF Panel as somepathogens are more common in certain geographicallocations.	The BioFire® Global Fever Panel is a qualitative,multiplexed, nucleic acid-based in vitrodiagnostic test intended for use with BioFire®FilmArray® 2.0 and BioFire® FilmArray® TorchSystems. The BioFire Global Fever Paneldetects and identifies selected bacterial, viral,and protozoan nucleic acids directly from EDTAwhole blood collected from individuals with signsand/or symptoms of acute febrile illness or recentacute febrile illness and known or suspectedexposure to the following target pathogens:chikungunya virus, dengue virus (serotypes 1, 2,3 and 4), Leptospira spp., and Plasmodium spp.(including species differentiation of Plasmodiumfalciparum and Plasmodium vivax/ovale).Evaluation for more common causes of acutefebrile illness (e.g., infections of the upper andlower respiratory tract or gastroenteritis, as wellas non-infectious causes) should be consideredprior to evaluation with this panel. Results aremeant to be used in conjunction with otherclinical, epidemiologic, and laboratory data, inaccordance with the guidelines provided by therelevant public health authorities.Positive results do not rule out co-infections withpathogens not included on the BioFire GlobalFever Panel. Not all pathogens that cause acutefebrile illness are detected by this test, andnegative results do not rule out the presence ofother infections. In the United States, patienttravel history and consultation of the CDC YellowBook should be considered prior to use of theBioFire Global Fever Panel as some pathogensare more common in certain geographicallocations.
Organisms Detected	Leptospira spp.Chikungunya virusDengue virus (serotypes 1, 2, 3 and 4)Plasmodium spp.Plasmodium falciparumPlasmodium vivax/ovale	Same
Analyte	DNA/RNA	Same
Specimen Types	Whole blood (collected in EDTA tube)	Same
TechnologicalPrinciples	Nested multiplex PCR followed by high resolution meltinganalysis to confirm the identity of amplified product.	Same
Instrumentation	BIOFIRE 2.0 System or BIOFIRE TORCH System	Same
Time to result	~ 50 minutes	Same
Test Interpretation	Automated test interpretation and report generation. Usercannot access raw data.	Same
Sample PreparationMethod	Sample Processing is automated in the BIOFIRE System.	Same
Reagent Storage	Reagents are stored at room temperature.	Same
Shelf Life	12 months from Date of Manufacture.	Same
Element	Modified Device:BIOFIRE FILMARRAY TF Panel	Predicate:BioFire Global Fever Panel (K220870)
Controls	Two controls are included in each reagent pouch to control forsample processing and both stages of PCR and melt analysis.	Same
User Complexity	Moderate	Same
Legal Manufacturer	*BioFire Diagnostics, LLC.	*BioFire Defense, LLC.

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*Note: BioFire Diagnostics, LLC and BioFire Defense, LLC are both wholly owned subsidiaries of bioMérieux, Inc.

Conclusion:

The fundamental scientific technology, performance claims, or risk of the BIOFIRE FILMARRAY TF Panel are unchanged from the legally marketed BioFire Global Fever Panel. There is no change to the product itself, except for updated software that has been verfied and validated to show no change in safety and effectiveness, instructions for use, product labeling, and branding. Therefore, the BIOFIRE FILMARRAY TF Panel is substantially equivalent to its predicate device.

Regulation Number and Section

§ 866.3966 Device to detect and identify selected microbial agents that cause acute febrile illness.

(a)
Identification. A device to detect and identify selected microbial agents that cause acute febrile illness is identified as an in vitro device intended for the detection and identification of microbial agents in human clinical specimens from patients with signs and symptoms of acute febrile illness who are at risk for exposure or who may have been exposed to these agents. It is intended to aid in the diagnosis of acute febrile illness in conjunction with other clinical, epidemiologic, and laboratory data, including patient travel, pathogen endemicity, or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) An intended use that includes a detailed description of targets the device detects and measures, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(ii) Limiting statements indicating:
(A) Not all pathogens that cause febrile illness are detected by this test and negative results do not rule out the presence of other infections;
(B) Evaluation of more common causes of acute febrile illness should be considered prior to evaluation with this test;
(C) Test results are to be interpreted in conjunction with other clinical, epidemiologic, and laboratory data available to the clinician; and
(D) When using this test, consider patient travel history and exposure risk, as some pathogens are more common in certain geographical locations.
(iii) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.
(iv) Detailed discussion of the performance characteristics of the device for all claimed specimen types as shown by the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section, except specimen stability performance characteristics.
(v) A statement that nationally notifiable results are to be reported to public health authorities in accordance with local, state, and federal law.
(3) Design verification and validation must include:
(i) A detailed device description (
e.g., all device parts, control elements incorporated into the test procedure, reagents required but not provided, the principle of device operation and test methodology), and the computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including those demonstrating Limit of Detection (LoD), inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate.
(iii) Detailed documentation and performance results from a clinical study that includes prospective (sequentially collected) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical 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 FDA-accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.