FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

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

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.