The BioFire® Global Fever Panel is a qualitative, multiplexed, nucleic acid-based in vitro diagnostic test intended for use with BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BioFire Global Fever Panel detects and identifies selected bacterial, viral, and protozoan nucleic acids directly from EDTA whole blood collected from individuals with signs and/or symptoms of acute illness or recent 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 spp. (including 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.

Positive results do not rule out co-infections with pathogens not included on the BioFire Global Fever Panel. 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 and consultation of the CDC Yellow Book should be considered prior to use of the BioFire Global Fever Panel as some pathogens are more common in certain geographical locations.

For In Vitro Diagnostic Use.

Device Description

The BioFire Global Fever Panel is a multiplexed nucleic acid-based test for the detection and identification of six pathogens which cause acute febrile illness (AFI) from whole blood specimens on BioFire FilmArray systems. The BioFire Global Fever Panel detects and identifies the following pathogens: chikungunya virus, dengue virus, Leptospira spp., and Plasmodium spp., including species differentiation between P. falciparum and P. vivax/ovale. The BioFire Global Fever Panel was originally described and was granted De Novo classification in DEN200043.

The BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel is an assayed quality control intended for monitoring the diagnostic performance of the BioFire Global Fever Panel. The Control Kit consists of Positive and Negative External Controls in a FilmArray Control Injection Vial format. The Positive External Control contains external assayed quality control material consisting of a set of non-infectious DNA segments dried on the filter of a FilmArray Control Injection Vial and detected by the Global Fever Panel. The Negative External Control contains no DNA and is also provided in the Control Injection Vial format. Analysis of the controls is carried out by specific pouch modules that are included in the BioFire Global Fever Panel Pouch Module Package. The BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel was fully described and cleared in K202382.

The purpose of this submission is to add BioFire FilmArray Torch as an additional instrument system for use with the BioFire Global Fever Panel and BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel, which were previously marketed for use with BioFire FilmArray 2.0 Systems. The FilmArray Torch is a modular configuration of the FilmArray 2.0 that minimizes instrument footprint by stacking up to twelve individual FilmArray Torch Modules on top of a single FilmArray Torch System Base. This 510(k) request describes modifications to the BioFire Global Fever Panel Pouch Module Package software and validation efforts to support adding FilmArray Torch Systems to the intended use of both the BioFire Global Fever Panel and associated BIOFIRE SHIELD Control Kit.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state formal "acceptance criteria" in a separate section. Instead, the performance data is presented as a comparison to the predicate device (BioFire FilmArray 2.0 system), implying that non-inferiority or comparable performance to the established predicate is the implicit acceptance criterion.

Metric	Acceptance Criteria (Implied: Comparable to FilmArray 2.0)	Reported Device Performance (FilmArray Torch)
Overall Agreement with Expected Result (BioFire Global Fever Panel for all analytes, all concentrations combined)	99.4% [98.7-99.7%] (FilmArray 2.0)	98.9% [98.1-99.4%] (FilmArray Torch)
Detection Rate: Leptospira interrogans (Moderate Positive, 3xLoD)	100% [95.9-100%]	100% [95.9-100%]
Detection Rate: Leptospira interrogans (Low Positive, 1xLoD)	95.6% [89.1-98.3%]	94.4% [87.6-97.6%]
Detection Rate: Leptospira interrogans (Negative)	100% [95.9-100%]	100% [95.9-100%]
Detection Rate: Dengue virus DENV-2 (Moderate Positive, 3xLoD)	100% [95.9-100%]	100% [95.9-100%]
Detection Rate: Dengue virus DENV-2 (Low Positive, 1xLoD)	100% [95.9-100%]	98.9% [94.0-99.8%]
Detection Rate: Dengue virus DENV-2 (Negative)	100% [95.9-100%]	98.9% [94.0-99.8%]
Detection Rate: Plasmodium falciparum (Moderate Positive, 3xLoD)	100% [95.9-100%]	100% [95.9-100%]
Detection Rate: Plasmodium falciparum (Low Positive, 1xLoD)	100% [95.9-100%]	100% [95.9-100%]
Detection Rate: Plasmodium falciparum (Negative)	100% [95.9-100%]	100% [95.9-100%]
Detection Rate: Plasmodium spp. (BEI / MRA-1238) (Moderate Positive, 3xLoD)	100% [95.9-100%]	98.9% [94.0-99.8%]
Detection Rate: Plasmodium spp. (BEI / MRA-1238) (Low Positive, 1xLoD)	96.7% [90.7-98.9%]	95.6% [89.1-98.3%]
Detection Rate: Plasmodium spp. (BEI / MRA-1238) (Negative)	100% [95.9-100%]	100% [95.9-100%]
Overall Agreement with Expected Result (BIOFIRE SHIELD Control Kit, Positive Control)	Not explicitly stated (implied: high agreement)	100% [97.2-100%]
Overall Agreement with Expected Result (BIOFIRE SHIELD Control Kit, Negative Control)	Not explicitly stated (implied: high agreement)	99.3% [95.9-99.9%]
Overall Agreement with Expected Result (BIOFIRE SHIELD Control Kit, all controls combined)	Not explicitly stated (implied: high agreement)	99.6% [97.9-99.9%]

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

Test Set for BioFire Global Fever Panel (Table 3):
- Sample Size: For each analyte (e.g., Leptospira interrogans), there were 3 concentrations tested (Moderate Positive, Low Positive, Negative). Each concentration was tested with 3 FilmArray 2.0 systems and 3 FilmArray Torch systems. On each system, 30 replicates were run.
  - For a single analyte and concentration, 30 replicates/system * 3 systems = 90 replicates for each platform.
  - Total replicates per analyte (3 concentrations): 90 replicates/platform * 3 concentrations = 270 replicates for each platform.
  - Total replicates across all analytes and concentrations for comparison: 1080 replicates on FilmArray 2.0 and 1080 replicates on FilmArray Torch.
  - The exact number of unique "samples" (batches of contrived material) is not specified, but the number of test runs is clear.
- Data Provenance: The replicates are "contrived samples containing representative pathogens... at concentrations near the limit of detection (LoD)" and "negative samples containing no analyte." The exact country of origin is not stated, but the study was conducted by BioFire Defense, LLC (Salt Lake City, UT, USA). It is a prospective study as new testing was performed to evaluate the FilmArray Torch system.
Test Set for BIOFIRE SHIELD Control Kit (Table 4):
- Sample Size:
  - Positive External Controls: 135 replicates (45 replicates/system * 3 FilmArray Torch systems).
  - Negative External Controls: 135 replicates (45 replicates/system * 3 FilmArray Torch systems).
  - Total: 270 replicates.
- Data Provenance: Details are for the BioFire FilmArray Torch platform only. The data is prospective, generated specifically for this evaluation.

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

For both studies (BioFire Global Fever Panel and BIOFIRE SHIELD Control Kit), the ground truth was established by the known concentration/presence of the analyte in the contrived samples or controls. While operators performed the tests, there is no mention of "experts" establishing the ground truth of the test material, as it's an analytical performance study using characterized samples.

4. Adjudication Method for the Test Set

There is no mention of an adjudication method in the context of expert review. The "expected result" for each test run (Detected/Not Detected) was based on the known composition of the contrived samples or control materials.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, What was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance?

This type of study was not performed, nor is it applicable. The device is an in vitro diagnostic test that provides automated interpretation and report generation. There is no "human reader" component in the interpretation of the results to be improved by AI assistance. The document explicitly states: "Automated test interpretation and report generation; user cannot access raw data."

6. If a Standalone (i.e. Algorithm only without human-in-the-loop performance) was Done

Yes, a standalone study was done. The BioFire Global Fever Panel runs on the FilmArray system, which is an automated device. The performance data presented in Table 3 and Table 4 reflects the algorithm's performance (i.e., the device's ability to detect and identify targets) directly on the FilmArray Torch system, without human intervention in the result interpretation. The objective of this submission was to evaluate the performance of the existing panel on a new instrument system (FilmArray Torch), which itself is automated.

7. The Type of Ground Truth Used

The ground truth used was known composition of contrived samples/controls. This means:

For positive samples, the specific analytes and their concentrations (e.g., 3xLoD, 1xLoD) were pre-determined.
For negative samples and controls, the absence of the target analyte was pre-determined.

8. The Sample Size for the Training Set

The document does not provide information on a training set. This submission is for adding a new instrument system (BioFire FilmArray Torch) for an already existing and cleared device (BioFire Global Fever Panel). The "BioFire Global Fever Panel was originally described and was granted De Novo classification in DEN200043." Therefore, any initial development and potential "training" (if applicable for the underlying algorithm) would have occurred during the development phase for DEN200043, and those details are not part of this 510(k) summary. The current study is a verification/validation for expanded instrument compatibility.

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

As no training set information is provided in this document, the method for establishing its ground truth is also not available here.

Summary

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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue box, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

BioFire Defense, LLC David Rabiger Associate Director of Regulatory, Quality, and Clinical Affairs 79 W 4500 S. Suite 14 Salt Lake City, Utah 84107

Re: K220870

Trade/Device Name: BioFire Global Fever Panel, BIOFIRE SHIELD Control Kit for the BioFire Global 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: QMV, PMN Dated: March 24, 2022 Received: March 25, 2022

Dear David Rabiger:

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

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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mdr-how-report-medical-device-problems.

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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-

542 of the Act); 21 CFR 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reporting-

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for

Noel Gerald Branch Chief 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) K220870

Device Name BioFire® Global Fever Panel

Indications for Use (Describe)

For In Vitro Diagnostic Use.

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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510(k) Summary

I. Submitter

BioFire Defense, LLC 79 West 4500 South, Suite 14 Salt Lake City, UT 84107 Phone: (801) 262-3592 Fax: (801) 447-6907

Contact Person: David Rabiger, Ph.D. Date Prepared: 2022-03-24

II. Device

Name of Device: BioFire® Global Fever Panel Common or Usual Name: Same Regulation: 21 CFR 866.3966 Classification Name: Device to detect and identify selected microbial agents that cause acute febrile illness Product Code: QMV Regulatory Class: Class II (Special Controls) Panel: Microbiology - 83

Name of Device: BioFire® SHIELD™ Control Kit for the BioFire® Global Fever Panel Common or Usual Name: Same Regulation: 21 CFR 866.3920 Classification Name: Assayed quality control material for clinical microbiology assays Product Code: PMN Regulatory Class: Class II (Special Controls) Panel: Microbiology - 83

III. Predicate Devices

BioFire® Global Fever Panel (BioFire Defense, LLC) [DEN200043] This predicate has not been subject to a design-related recall.

BioFire® SHIELD™ Control Kit for the BioFire® Global Fever Panel (BioFire Defense, LLC) [K202382]

This predicate has not been subject to a design-related recall.

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IV. Device Description

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Intended Use V.

BioFire Global Fever Panel Intended Use:

The BioFire® Global Fever Panel is a qualitative, multiplexed, nucleic acid-based in vitro diagnostic test intended for use with BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BioFire Global Fever Panel detects and identifies selected bacterial, viral, and protozoan 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 spp. (including 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.

For In Vitro Diagnostic Use.

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BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel Intended Use:

The BIOFIRE® SHIELD™ Control Kit for the BioFire® Global Fever Panel contains Positive and Negative External Controls intended for use as assayed quality controls to monitor the performance of in vitro diagnostic laboratory nucleic acid testing procedures for the qualitative detection of chikungunya virus, dengue virus (serotypes 1, 2, 3, and 4), Leptospira spp., and Plasmodium spp. (including species differentiation of Plasmodium falciparum and Plasmodium vivax/ovale) when using the BioFire® Global Fever Panel on BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel is designed for and intended to be used solely with the BioFire Global Fever Panel. This product does not replace manufacturer internal controls provided as part of the BioFire Global Fever Panel device.

Both the Positive and Negative External Controls are provided in a FilmArray Control Injection Vial format. The Positive Control Injection Vial contains dried synthetic DNA segments in buffer and stabilizer to assess the presence of each individual assay on the BioFire Global Fever Panel. The Negative Control Injection Vial contains no DNA and is non-reactive with the BioFire Global Fever Panel assays.

Substantial Equivalence VI.

The purpose of this 510(k) submission is to add BioFire FilmArray Torch systems to the intended use of both the BioFire Global Fever Panel and the BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel. No changes have been made to the BioFire Global Fever Panel or BIOFIRE SHIELD Control Kit themselves. Only minor modifications to the BioFire Global Fever Panel Pouch Module Package have been made to add compatibility with BioFire FilmArray Torch systems.

The BioFire Global Fever Panel for use with BioFire FilmArray Torch (BioFire Global Fever Panel v2.1) is substantially equivalent to the BioFire Global Fever Panel v2.0. Table 1 compares the BioFire Global Fever Panel v2.1 to the previously granted BioFire Global Fever Panel v2.0.

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		Table 1. BioFire Global Fever Panel Predicate Comparison

Element	Subject Device:BioFire Global Fever Panel	Predicate:BioFire Global Fever Panel[DEN200043]
Specimen Type	Whole blood (collected in EDTA tube)	Same as subject device
Intended Use	Individuals with signs and/or symptoms ofacute febrile illness and known orsuspected exposure to pathogens on thepanel	Same as subject device
Pathogens Detected	Chikungunya virus, dengue virus (serotypes1, 2, 3, and 4), Leptospira spp., Plasmodiumspp. (including species differentiation of P.falciparum and P. vivax/ovale.	Same as subject device
Analyte	RNA/DNA	Same as subject device
Technological Principles	Highly multiplexed, nested, nucleic acidamplification test with melt analysis	Same as subject device
Instrumentation	BioFire FilmArray 2.0 or BioFire FilmArrayTorch systems	BioFire FilmArray 2.0 systems
Time to Result	~1 hour	Same as subject device
Reagent Storage	Room temperature	Same as subject device
Test Interpretation	Automated test interpretation and reportgeneration; user cannot access raw data	Same as subject device
Controls	Two controls are included in each reagentpouch to control for sample processing andboth stages of PCR and melt analysis	Same as subject device
Assayed External Controls	BIOFIRE SHIELD Control Kit for the BioFireGlobal Fever Panel (Part No. DFA2-ASY-0006)	Same as subject device
User Complexity	Moderate	Same as subject device

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The BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel for use with BioFire FilmArray Torch is substantially equivalent to the previously cleared BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel. Table 2 outlines the similarities and differences between the two control kits.

Element	Subject Device:BIOFIRE SHIELD Control Kit for theBioFire Global Fever Panel	Predicate:BIOFIRE SHIELD Control Kit for theBioFire Global Fever Panel[K202382]
Intended Use	Positive and negative external assayedquality controls to monitor assayperformance in the BioFire GlobalFever Panel	Same as subject device
Physical Format	External control material dried onControl Injection Vial filter	Same as subject device
Composition	Tm-shifted synthetic DNA (positivecontrol only)	Same as subject device
Targets Monitored	Chikungunya virus, dengue virus(serotypes 1, 2, 3, and 4), Leptospiraspp., and Plasmodium spp. (includingspecies differentiation of P. falciparumand P. vivax/ovale.	Same as subject device
Instrumentation	BioFire Global Fever Panel run onBioFire FilmArray 2.0 or BioFireFilmArray Torch systems	BioFire Global Fever Panel run on BioFireFilmArray 2.0 systems
Test Interpretation	Automated test interpretation andreport generation; user cannot accessraw data	Same as subject device
Reagent Storage	Room temperature	Same as subject device

Table 2. BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel Predicate Comparison

Summarv of Performance Data VII.

Performance of the BioFire Global Fever Panel on BioFire FilmArray Torch Systems

Negative samples containing no analyte and contrived samples containing representative pathogens on the BioFire Global Fever Panel at concentrations near the limit of detection (LoD) were tested in parallel on three BioFire FilmArray 2.0 systems and three BioFire FilmArray Torch systems. Testing was performed over five days by two operators per system for a total of 90 replicates per sample per platform. The performance of the BioFire Global Fever Panel on the BioFire FilmArray Torch platform was similar to performance on the BioFire FilmArray 2.0 platform. Overall agreement with expected results for the BioFire Global Fever Panel on the BioFire FilmArray Torch platform was 98.9% as compared to 99.4% on the BioFire FilmArrav 2.0 platform. Detection rates and percent agreement between observed and expected test results are shown in Table 3.

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Analyte(Source / ID)	ConcentrationTested(copies/mL)	ExpectedResult	FilmArray 2.0 PlatformDetection Rate (n/N)% Agreement with Expected Result			All FA 2.0Systems[95% CI]	FilmArray Torch PlatformDetection Rate (n/N)% Agreement with Expected Result			All FA TorchSystems[95% CI]
			System 1	System 2	System 3		System 1	System 2	System 3
Leptospira interrogansserovaricterohaemorrhagiae(ATTC / 23581)	Moderate Positive3xLoD(1.0E+03)	Detected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
	Low Positive1xLoD(3.4E+02)	Detected	29/3096.7%	29/3096.7%	28/3093.3%	86/9095.6%[89.1-98.3%]	29/3096.7%	28/3093.3%	28/3093.3%	85/9094.4%[87.6-97.6%]
	Negative(No Analyte)	NotDetected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
Dengue virusDENV-2New Guinea C(Zeptometrix /0810089CF)	Moderate Positive3xLoD(1.0E+03)	Detected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
	Low Positive1xLoD(3.4E+02)	Detected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	29/3096.7%	30/30100%	89/9098.9%[94.0-99.8%]
	Negative(No Analyte)	NotDetected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	29/3096.7%	89/9098.9%[94.0-99.8%]
Plasmodiumspp.PlasmodiumfalciparumIPC 4884	Moderate Positive3xLoD(5.4E+02)	Detected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
	Low Positive1xLoD(1.8E+02)	Detected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
	Negative(No Analyte)	NotDetected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
(BEI / MRA-1238)	Moderate Positive3xLoD(5.4E+02)	Detected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	29/3096.7%	30/30100%	89/9098.9%[94.0-99.8%]
	Low Positive1xLoD(1.8E+02)	Detected	30/30100%	28/3093.3%	29/3096.7%	87/9096.7%[90.7-98.9%]	30/30100%	28/3093.3%	28/3093.3%	86/9095.6%[89.1-98.3%]
	Negative(No Analyte)	NotDetected	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]	30/30100%	30/30100%	30/30100%	90/90100%[95.9-100%]
Overall Agreement withExpected Result		All Concentrations	All Results			1073/108099.4%[98.7-99.7%]				1068/108098.9%[98.1-99.4%]

Table 3. Reproducibility of the BioFire Global Fever Panel on BioFire FilmArray Platforms

Abbreviations: FA – FilmArray; 95% CI – 95% Confidence Interval

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Performance of the BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel on BioFire FilmArray Torch Systems

Reproducibility of the BIOFIRE SHIELD Control Kit on the BioFire FilmArray Torch platform was evaluated by testing Positive External Controls and Negative External Controls on three BioFire FilmArray Torch systems over five days by two users per system for a total of 135 replicates for each control type. Overall agreement with the expected results was 99.6%. Results are summarized in Table 4.

SHIELD Control Type	Expected Result	Observed/Expected(Percent Agreement)
		Torch System 1	Torch System 2	Torch System 3	Overall[95% Confidence Interval]
Positive	Passed	45/45(100%)	45/45(100%)	45/45(100%)	135/135(100%)[97.2-100%]
Negative	Passed	44/45(97.8%)	45/45(100%)	45/45(100%)	134/135(99.3%)[95.9-99.9%]
Overall Agreement with Expected Result				269/270(99.6%)[97.9-99.9%]

Table 4. Reproducibility of the BIOFIRE SHIELD Control Kit on the BioFire FilmArray Torch Platform

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.