BioFire Global Fever Panel, BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel

K220870 · Biofire Defense, LLC · QMV · Oct 20, 2022 · Microbiology

Device Facts

• Record ID: K220870
• Device Name: BioFire Global Fever Panel, BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel
• Applicant: Biofire Defense, LLC
• Product Code: QMV · Microbiology
• Decision Date: Oct 20, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3966
• Device Class: Class 2

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. 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 Story

The BioFire Global Fever Panel is a multiplexed, nucleic acid-based diagnostic test for detecting six pathogens causing acute febrile illness from EDTA whole blood. The device uses the FilmArray Torch or FilmArray 2.0 instrument systems. The process involves automated sample preparation, nested nucleic acid amplification, and melt analysis within a closed pouch system. The device provides qualitative results for specific bacterial, viral, and protozoan targets within approximately one hour. It is intended for use by laboratory professionals to assist in clinical decision-making alongside other clinical and epidemiologic data. The BIOFIRE SHIELD Control Kit provides positive and negative external controls to monitor assay performance. The system is designed to minimize manual steps and prevent user access to raw data, ensuring standardized interpretation. By identifying specific pathogens, the device aids in the rapid diagnosis of febrile illnesses, potentially guiding appropriate clinical management and public health interventions.

Clinical Evidence

Bench testing only. Reproducibility study compared performance on FilmArray 2.0 vs. Torch systems using 90 replicates per sample per platform. Overall agreement with expected results was 98.9% for Torch and 99.4% for 2.0. Control kit reproducibility on Torch showed 99.6% agreement.

Technological Characteristics

Multiplexed, nested nucleic acid amplification test with melt analysis. Uses FilmArray pouch technology for automated sample processing and detection. Compatible with FilmArray 2.0 and FilmArray Torch systems. Controls consist of dried synthetic DNA segments in a vial format. Software performs automated test interpretation and report generation. No changes to assay cut-offs or technological principles from the predicate.

Indications for Use

Indicated for individuals with signs/symptoms of acute febrile illness or recent acute febrile illness and known or suspected exposure to chikungunya virus, dengue virus, Leptospira spp., or Plasmodium spp. (P. falciparum, P. vivax/ovale).

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• FilmArray Global Fever Panel (DEN200043)
• FilmArray Global Fever Panel External Control Kit (K202382)

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K220870

B Applicant

BioFire Defense, LLC

C Proprietary and Established Names

BioFire Global Fever Panel, BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel

## D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QMV | Class II | 21 CFR 866.3966 - Device To Detect And Identify Selected Microbial Agents That Cause Acute Febrile Illness | MI - Microbiology |
| PMN | Class II | 21 CFR 866.3920 - Assayed quality control material for clinical microbiology assays | MI - Microbiology |

## II Submission/Device Overview:

### A Purpose for Submission:

To obtain a substantial equivalence determination for both the BioFire Global Fever Panel and the BIOFIRE SHIELD Control Kit for the Global Fever Panel on the FilmArray Torch instrument system.

### B Measurand:

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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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.

## C Type of Test:

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.

## III Intended Use/Indications for Use:

### A Intended Use(s):

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.

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.

### 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.

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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.

**B Indication(s) for Use:**
Same as intended use.

**C Special Conditions for Use Statement(s):**
Rx - For Prescription Use Only
For in vitro diagnostic use only.

**D Special Instrument Requirements:**
The FilmArray Global Fever Panel and the BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel are for use with the FilmArray 2.0 or FilmArray Torch instrument systems.

**IV Device/System Characteristics:**

**A 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 FilmArray Global Fever Panel simultaneously conducts six tests for the identification of bacterial, viral, and protozoan organisms from whole blood specimens collected in EDTA tubes. Results from the FilmArray Global Fever Panel are available within about one hour.

The BioFire Global Fever Panel was previously cleared under DEN200043 for use with BioFire FilmArray 2.0 systems. Please refer to DEN200043 for additional information regarding the BioFire Global Fever Panel. In this 510(k) submission, the FilmArray Torch system is being added as an additional instrument system for use with the BioFire Global Fever Panel. 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.

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. Analysis of the controls is carried out by specific pouch modules that are included in the BioFire Global Fever Panel Pouch Module Package. The Positive External Control has been optimized to be detected by all pathogen assays contained in the Global Fever Panel (Table 1). The Negative External Control

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contains no nucleic acid, and a successful run will be negative for all assays on the panel. These controls are not intended to replace the internal FilmArray Global Fever Panel pouch controls (RNA process control and second stage PCR array control). The Global Fever Panel External Control Kit contains no biological hazards and is 100% non-infectious.

Table 1: Pathogens Detected by the FilmArray Global Fever Panel

| Disease | Pathogen Assay Result | Type |
| --- | --- | --- |
| Leptospirosis | Leptospira spp. | Bacterial |
| Malaria | Plasmodium spp.
Plasmodium falciparum
Plasmodium vivax/ovale | Protozoan |
| Chikungunya fever | Chikungunya virus | Viral |
| Dengue fever | Dengue virus | |

The BioFire SHIELD Control Kit for the Global Fever Panel was previously cleared for use with FilmArray 2.0 instrument system under K202382 as the FilmArray Global Fever Panel External Control Kit. The information contained in this 510(k) submission is provided to support equivalent performance of the external control material on the FilmArray Torch instrument system.

V Substantial Equivalence Information:

A Predicate Device Name(s):

FilmArray Global Fever Panel and FilmArray Global Fever Panel External Control Kit

B Predicate 510(k) Number(s):

DEN200043, K202382

C Comparison with BioFire Global Fever Panel

| Device & Predicate Device(s): | K220870 | DEN200043 |
| --- | --- | --- |
| Device Trade Name | BioFire Global Fever Panel | BioFire Global Fever Panel |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For 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 | Same |

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| | 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. 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, |
| --- | --- |

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| | 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. | |
| --- | --- | --- |
| Specimen Type | Whole blood (collected in EDTA tube) | Same |
| Pathogens Detected | Chikungunya virus, dengue virus (serotypes 1, 2, 3, and 4), *Leptospira* spp., *Plasmodium* spp. (including species differentiation of *P. falciparum* and *P. vivax*/ovale. | Same |
| Analyte | RNA/DNA | Same |
| Technological Principles | Highly multiplexed, nested, nucleic acid amplification test with melt analysis | Same |
| Time to Result | ~1 hour | Same |
| Test Interpretation | Automated test interpretation and report generation; user cannot access raw data | Same |
| Controls | Two controls are included in each reagent pouch to control for sample processing and both stages of PCR and melt analysis | Same |
| Assayed External Controls | BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel | Same |
| User Complexity | Moderate | Moderate |

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Comparison with FilmArray Global Fever Panel External Control Kit

| Device & Predicate Device(s): | K220870 | K202382 |
| --- | --- | --- |
| Device Trade Name | BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel | FilmArray Global Fever Panel External Control Kit |
| General Device Characteristic Similarities | | |
| 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) on the | The FilmArray Global Fever Panel External Control Kit 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 FilmArray Global Fever Panel targets on FilmArray 2.0 systems. The Global Fever Panel External Control Kit is designed for and intended to be used solely with the FilmArray Global Fever Panel. This product |

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| | BioFire Global Fever Panel performed 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. | does not replace manufacturer internal controls provided as part of the 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 FilmArray Global Fever Panel. The Negative Control Injection Vial contains no DNA, and is non-reactive with the Global Fever Panel assays. |
| --- | --- | --- |
| Physical Format | External control material dried on Control Injection Vial filter | Same |
| Composition | Tm-shifted synthetic DNA (positive control only) | Same |
| Targets Monitored | Chikungunya virus, dengue virus (serotypes 1, 2, 3, and 4), Leptospira spp., and | Same |

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| | Plasmodium spp.
(including species
differentiation of P.
falciparum and P.
vivax/ovale. | |
| --- | --- | --- |
| Test Interpretation | Automated test
interpretation and report
generation; user cannot
access raw data | Same |
| Reagent Storage | Room temperature | Same |
| General Device
Characteristic Differences | | |
| Instrumentation | BioFire Global Fever
Panel run on FilmArray
2.0 or FilmArray Torch
systems | BioFire Global Fever
Panel run on FilmArray
2.0 systems |

VI Standards/Guidance Documents Referenced:

- IEC 62304:2006/A1:2016, ‘Medical device software – Software life-cycle processes’
- ISO 14971:2007/(R)2010, ‘Medical devices – Application of risk management to medical devices’
- ISO 15223-1:2016 ‘Medical Devices – Symbols to be used with medical device labels, labeling and information to be supplied – Part 1: General requirements’
- Assay Migration Studies for In Vitro Diagnostic Devices, Guidance for Industry and FDA Staff (April 2013)
- Bundling Multiple Devices or Multiple Indications in a Single Submission, Guidance for Industry and Food and Drug Administration Staff (June 22, 2007)
- Deciding When to Submit a 510(k) for a Change to an Existing Device, Guidance for Industry and FDA Staff (October 2017)
- General Principle of Software Validation, Final Guidance for Industry and FDA Staff (January 11, 2002)
- Guidance for Industry and Food and Drug Administration Staff – Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices (August 27, 2014)
- Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, Guidance for Industry and FDA Staff (May 11, 2005)
- Off-The-Shelf Software Use in Medical Devices, Guidance for Industry and FDA Staff (September 27, 2019)
- Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests, FDA Guidance Document (March 13, 2007)
- Molecular Diagnostic Methods for Infectious Diseases, Clinical and Laboratory Standards Institute (CLSI) Guideline, MM03-Ed3 (February 2015)

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- User Protocol for Evaluation of Qualitative Test Performance, Clinical and Laboratory Standards Institute (CLSI) Approved Guideline – Second Edition, EP12-A2 (January 2008)
- User Verification of Performance for Precision and Trueness, Clinical and Laboratory Standards Institute (CLSI) Approved Guideline – Second Edition EP15-A2 (April 2006)

## VII Performance Characteristics (if/when applicable):

### A Analytical Performance:

#### 1. Precision/Reproducibility:

**Performance of the BioFire Global Fever Panel on BioFire FilmArray Torch System**

A reproducibility study was performed to establish equivalent analyte detection of the BioFire Global Fever Panel on the BioFire FilmArray 2.0 and FilmArray Torch systems. Reproducibility of BioFire Global Fever Panel test results between the two instrument systems was directly compared. The study incorporated potential variation introduced by different instruments (three), days (five), replicates (six), systems/modules, and reagent kit lots. The site variable was simulated using three different FilmArray Torch and three different FilmArray 2.0 systems.

Briefly, three contrived whole blood samples were prepared with different mixtures of panel analytes: *Leptospira interrogans*, dengue virus, and *Plasmodium falciparum*. For each analyte, one sample was spiked at a Moderate Positive (3×LoD) level, another sample at a Low Positive (1×LoD) level, and the third sample was not spiked (negative). Six aliquots (replicates) of each sample were tested on each system on five different days, providing a total of 90 replicate test results per sample per FilmArray platform. On each test day, two operators per system used three FilmArray 2.0 instruments and three FilmArray Torch modules; three BioFire Global Fever Panel pouch reagent lots were rotated daily.

Reproducibility was assessed by comparing the observed test results (Detected/Not Detected) to the expected test results (Detected for spiked samples, Not Detected for unspiked samples). The overall agreement between observed and expected results for the FilmArray 2.0 platform was 99.4% and the overall agreement for the FilmArray Torch platform was 98.9%. Detection rates and percent agreement between observed and expected test results are shown in Table 2 below.

Table 2: Reproducibility of the BioFire Global Fever Panel on FilmArray Platforms

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| Analyte (Source / ID) | Concentration in Tested (copies/mL) | Expected Result | Detection Rate (n/N) % Agreement with Expected Result | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | FilmArray 2.0 Platform | | | | FilmArray Torch Platform | | | | |
| | | | System 1 | System 2 | System 3 | All FA 2.0 Systems [95% CI] | System 1 | System 2 | System 3 | All FA Torch Systems [95% CI] | |
| Leptospira interrogans serovar icterohaemorrhagiae (ATTC / 23581) | 3×LoD (1.0E+03) | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | |
| | | 1×LoD (3.4E+02) | Detected | 29/30 96.7% | 29/30 96.7% | 28/30 93.3% | 86/90 95.6% [89.1-98.3%] | 29/30 96.7% | 28/30 93.3% | 28/30 93.3% | 85/90 94.4% [87.6-97.6%] |
| | | Negative | Not Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] |
| Dengue virus DENV-2 New Guinea C (Zeptometrix / 0810089CF) | 3×LoD (1.0E+03) | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | |
| | | 1×LoD (3.4E+02) | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 29/30 96.7% | 30/30 100% | 89/90 98.9% [94.0-99.8%] |
| | | Negative | Not Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 29/30 1 96.7% | 89/90 98.9% [94.0-99.8%] |
| Plasmodium falciparum IPC 4884 (BEI / MRA-1238) | Plasmodium spp. Detection Results | 3×LoD (5.4E+02) | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] |
| | | 1×LoD (1.8E+02) | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] |
| | | Negative | Not Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] |
| | Plasmodium falciparum Detection Results | 3×LoD (5.4E+02) | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 29/30 96.7% | 30/30 100% | 89/90 98.9% [94.0-99.8%] |
| | | 1×LoD (1.8E+02) | Detected | 30/30 100% | 28/30 93.3% | 29/30 96.7% | 87/90 96.7% [90.7-98.9%] | 30/30 100% | 28/30 93.3% | 28/30 93.3% | 86/90 95.6% [89.1-98.3%] |
| | | Negative | Not Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [95.9-100%] |
| | Overall Agreement with Expected Result | | | | 1073/1080 99.4% [98.7-99.7%] | | | | 1068/1080 98.9% [98.1-99.4%] | | |

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There was one unexpected dengue virus Detected result for the FilmArray Torch platform for an overall agreement of $98.9\%$ (89/90). The unexpected dengue virus Detected result may have been the result of contamination introduced during sample preparation, handling, and/or sample loading.

A second assessment of reproducibility was conducted based on variability in the melt temperature (Tm) of the amplification products measured as standard deviation. Variability in the melt temperatures for the assays evaluated with both FilmArray Platforms was within the expected range $(\leq 0.5^{\circ}\mathrm{C})$ for each simulated site, the Tm standard deviation varying between $0.2^{\circ}\mathrm{C}$ and $0.3^{\circ}\mathrm{C}$ . Melt temperature means, standard deviations, and coefficient of variation (CV) are shown in Table 3 below.

Table 3. Summary of Tm (°C) Analyses for BioFire Global Fever Panel Assays

| Analyte | Assay | FA Platform | Observed Tm (°C) | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Simulated Site 1 | | | Simulated Site 2 | | | Simulated Site 3 | | | Overall | | |
| | | | Mean | ±StDev | CV | Mean | ±StDev | CV | Mean | ±StDev | CV | Mean | ±StDev | CV |
| Controls | | | | | | | | | | | | | | |
| RNA Process Control | Yeast RNA | FA 2.0 | 82.0 | 0.3 | 0.4% | 82.1 | 0.3 | 0.4% | 82.1 | 0.3 | 0.4% | 82.1 | 0.3 | 0.4% |
| | | Torch | 82.4 | 0.2 | 0.2% | 82.3 | 0.2 | 0.2% | 82.3 | 0.2 | 0.2% | 82.3 | 0.2 | 0.2% |
| PCR2 Control | PCR2 | FA 2.0 | 76.0 | 0.3 | 0.4% | 76.0 | 0.2 | 0.3% | 76.1 | 0.2 | 0.3% | 76.0 | 0.2 | 0.3% |
| | | Torch | 76.3 | 0.2 | 0.3% | 76.2 | 0.2 | 0.3% | 76.2 | 0.2 | 0.3% | 76.2 | 0.2 | 0.3% |
| Bacteria | | | | | | | | | | | | | | |
| Leptospira interrogans | Lepto 1 | FA 2.0 | 81.7 | 0.3 | 0.4% | 81.7 | 0.3 | 0.4% | 81.8 | 0.2 | 0.2% | 81.8 | 0.3 | 0.4% |
| | | Torch | 82.0 | 0.2 | 0.2% | 81.9 | 0.2 | 0.2% | 81.9 | 0.2 | 0.2% | 82.0 | 0.2 | 0.2% |
| Viruses | | | | | | | | | | | | | | |
| Dengue virus Type 2 | DENV 2_1 | FA 2.0 | 80.3 | 0.3 | 0.4% | 80.3 | 0.2 | 0.2% | 80.4 | 0.2 | 0.2% | 80.3 | 0.2 | 0.2% |
| | | Torch | 80.6 | 0.2 | 0.2% | 80.5 | 0.2 | 0.2% | 80.5 | 0.2 | 0.2% | 80.5 | 0.3 | 0.4% |
| Protozoa | | | | | | | | | | | | | | |
| Plasmodium falciparum | Plas spp. | FA 2.0 | 79.1 | 0.3 | 0.4% | 79.2 | 0.3 | 0.4% | 79.3 | 0.2 | 0.3% | 79.2 | 0.2 | 0.3% |
| | | Torch | 79.5 | 0.2 | 0.3% | 79.4 | 0.2 | 0.3% | 79.4 | 0.2 | 0.3% | 79.4 | 0.2 | 0.3% |
| | Plas falciparum | FA 2.0 | 74.2 | 0.3 | 0.4% | 74.3 | 0.2 | 0.3% | 74.3 | 0.2 | 0.3% | 74.3 | 0.2 | 0.3% |
| | | Torch | 74.6 | 0.2 | 0.3% | 74.5 | 0.2 | 0.3% | 74.5 | 0.2 | 0.3% | 74.5 | 0.2 | 0.3% |

BioFire FilmArray 2.0 and Torch Systems met the reproducibility acceptance criteria showing an overall agreement between expected and observed results of $\geq 95\%$ , and Tm variability of $\leq 0.5^{\circ}\mathrm{C}$ .

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

Performance of the BIOFIRE SHIELD Control Kit on the BioFire FilmArray 2.0 system was established in K202382. 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. Testing included two operators per system for a total of 135 replicates for each control type over five days. Reproducibility was evaluated by calculating the percent agreement between observed test results (Passed or Failed) and expected test results (Passed) for

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both negative and positive SHIELD controls. The expected percent agreement for controls was 99.6%. Results are summarized in Table 4 below.

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

| External Control Type | Expected Result | Observed/Expected (Percent Agreement) | | | |
| --- | --- | --- | --- | --- | --- |
| | | System 1 | System 2 | System 3 | All Operators [95% Confidence Interval] |
| Positive | Passed^{1} | 45/45 (100%) | 45/45 (100%) | 45/45 (100%) | 135/135 (100%) [97.2-100%] |
| Negative | Passed^{2} | 44/45^{3} (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%] | | | |

1. All Global Fever Panel assays have a positive amplicon melt in the PEC melt range.
2. All Global Fever Panel assays have no melt in both the PEC melt range and in the organism/virus melt range.
3. One single unexpected dengue virus Detected result was observed for a Negative External Control on System 1. The failure was due to detection of Positive External Control amplicon and may been due to contamination with Positive External Control during control preparation and pouch loading.

2. Linearity:
Not applicable.

3. Analytical Specificity/Interference:
Not applicable.

4. Assay Reportable Range:
Not applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Not applicable.

6. Detection Limit:
Not applicable.

7. Assay Cut-Off:
Assay cut-offs remain unchanged from the previously cleared version of the Global Fever panel (see DEN200043).

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B Comparison Studies:

1. Method Comparison with Predicate Device:
Not applicable.

2. Matrix Comparison:
Not applicable.

C Clinical Studies:

1. Clinical Sensitivity:
Clinical performance of the BioFire Global Fever Panel was established in DEN200043. Please refer to the published decision summary for additional details.

2. Clinical Specificity:
Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.

D Clinical Cut-Off:
Not applicable.

E Expected Values/Reference Range:
Expected values of the BioFire Global Fever Panel were established in DEN200043. Please refer to the published decision summary for additional details.

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.