The BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid is an automated qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with BIOFIRE FILMARRAY Systems. The BIOFIRE FILMARRAY GI Panel Mid is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria, parasites, and viruses are identified using the BIOFIRE FILMARRAY GI Panel Mid:

· Campylobacter (C. jejuni/C. coli/C. upsaliensis)
· Clostridioides (Clostridium) difficile (toxin A/B)
· Salmonella
· Vibrio (V. parahaemolyticus/V. vulnificus/ V. cholerae)
· Yersinia enterocolitica
· Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2
· Shigella/ Enteroinvasive Escherichia coli (EIEC)
Cryptosporidium
· Cyclospora cayetanensis
· Giardia lamblia (also known as G. intestinalis and G. duodenalis)
Norovirus GI/GII

The BIOFIRE FILMARRAY GI Panel Mid is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the BIOFIRE FILMARRA Y GI Panel Mid. The agent detected may not be the definite cause of the disease.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Yersinia enterocolitica, were established primarily with retrospective clinical specimens.

Performance characteristics for Vibrio (V. parahaemolyticus, and Vibrio cholerae) was established primarily using contrived clinical specimens.

Negative BIOFIRE FILMARRAY GI Panel Mid results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis. irritable bowel syndrome, or Crohn's disease.

A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection of acute gastroenteritis in the context of outbreaks.

Device Description

The BIOFIRE® FILMARRAY® Gastrointestinal Panel Mid is designed to simultaneously identify 11 gastrointestinal pathogens from stool specimens collected in Cary Blair transport medium. The BIOFIRE FILMARRAY GI Panel Mid is compatible with BioFire's PCR-based in vitro diagnostic BIOFIRE® FILMARRAY® 2.0 and BIOFIRE® FILMARRAY® TORCH Systems for infectious disease testing. A panel-specific software module (i.e., BIOFIRE FILMARRAY GI Panel Mid pouch module software) is used to perform BIOFIRE FILMARRAY GI Panel Mid testing on these systems. Results from the BIOFIRE FILMARRAY GI Panel Mid test are available within about one hour.

A test is initiated by loading Hydration into one port of the BIOFIRE pouch and a stool sample (in Cary Blair transport medium) mixed with the provided Sample Buffer into the other port of the BIOFIRE FILMARRAY GI Panel Mid pouch and placing it in a BIOFIRE System. The pouch contains all the reagents required for speciment esting 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 guides 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 multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Pettier 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 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 (rt-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 (LC Green Plus®, BioFire Diagnostics). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in single plex fashion in each well of the array. At 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.

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

AI/ML Overview

The provided text is a 510(k) summary for the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid. This document primarily details the analytical and clinical performance of the device to demonstrate its substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and study data based on the provided text:

Device: BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid
Indications for Use: Automated qualitative multiplexed nucleic acid-based in vitro diagnostic test for simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection.

Specific Acceptance Criteria and Study Details:

It's important to note that this is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device. The "acceptance criteria" presented are implicitly derived from the performance shown to be equivalent to the predicate, rather than explicit pre-defined pass/fail thresholds in a typical AI/ML study. The data provided are from a clinical and analytical evaluation of the parent device (BIOFIRE FILMARRAY GI Panel), with the "Mid" version being identical in hardware and reagents, only differing in software to mask some analytes.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a diagnostic test and not an AI/ML model for image analysis, the acceptance criteria are typically framed in terms of sensitivity (or positive percent agreement - PPA) and specificity (or negative percent agreement - NPA) compared to a reference method.

BIOFIRE FILMARRAY GI Panel Mid Analyte	Acceptance Criteria (Implied) - High PPA/NPA	Reported Performance (Prospective Clinical Evaluation)
Bacteria
Campylobacter (C. jejuni/C. coli/C. upsaliensis)	High Sensitivity, High Specificity	Sensitivity/PPA: 97.1% (34/35)
		Specificity/NPA: 98.4% (1497/1521)
Clostridioides (Clostridium) difficile toxin A/B	High PPA, High NPA	PPA: 98.8% (163/165)
		NPA: 97.1% (1350/1391)
Salmonella	High Sensitivity, High Specificity	Sensitivity/PPA: 100% (31/31)
		Specificity/NPA: 99.6% (1519/1525)
Shiga-like toxin-producing E. coli (STEC) stx1/stx2	High Sensitivity, High Specificity	Sensitivity/PPA: 100% (33/33)
		Specificity/NPA: 99.7% (1518/1523)
Shigella/Enteroinvasive E. coli (EIEC)	High Sensitivity, High Specificity	Sensitivity/PPA: 95.9% (47/49)
		Specificity/NPA: 99.9% (1505/1507)
Vibrio (V. parahaemolyticus/V. vulnificus/V. cholerae)	High Sensitivity, High Specificity	Sensitivity/PPA: 0/0 (Not applicable due to no positives)
		Specificity/NPA: 99.9% (1554/1556)
Yersinia enterocolitica	High Sensitivity, High Specificity	Sensitivity/PPA: 100% (1/1)
		Specificity/NPA: 100% (1555/1555)
Parasites
Cryptosporidium	High PPA, High NPA	PPA: 100% (18/18)
		NPA: 99.6% (1532/1538)
Cyclospora cayetanensis	High PPA, High NPA	PPA: 100% (19/19)
		NPA: 100% (1537/1537)
Giardia lamblia	High PPA, High NPA	PPA: 100% (20/20)
		NPA: 99.5% (1529/1536)
Viruses
Norovirus GI/GII (2013 data)	High PPA, High NPA	PPA: 94.5% (52/55)
		NPA: 98.8% (1483/1501)
Norovirus GI/GII (2023 data)	High PPA, High NPA	PPA: 97.1% (34/35)
		NPA: 96.5% (808/837)

Note: The text explicitly states:
"C. difficile performance is reported as positive percent agreement in contrast to the table headings. The performance measures of sensibility and specificity only refer to those analytes for which the [culture method] was used as the reference method; Campylobacter, Salmonella, Vibrio, and Yersinia enterocolitica. Performance measures of positive percent agreement (NPA) refer to all other analytes, for which PCR/sequencing assays were used as comparator methods." This distinction is reflected in the table.

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

Sample Size for Test Set (Clinical Evaluation):
- The "Prospective Clinical Evaluation" mentioned in Table 2 was conducted from May through September 2013.
- The total number of specimens that contributed to the sensitivity/PPA and specificity/NPA calculations vary by analyte but are in the range of ~1500-1550 specimens per analyte (e.g., 1556 for Vibrio, 1555 for Yersinia, etc.). These numbers represent the denominator for (TP+FN) and (TN+FP) across different analytes.
- A separate, more recent "Prospective Clinical Evaluation" for Norovirus GI/GII was conducted from April through July 2023, involving 872 specimens (35 positives, 837 negatives).
- Retrospective Clinical Specimens: Used for Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) to establish performance characteristics due to small numbers of positive specimens in the prospective study. The specific number of retrospective specimens is not provided for these.
- Contrived Clinical Specimens: Used for Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) to establish performance. The specific number of contrived specimens is not provided.
Data Provenance: The document does not explicitly state the country of origin for the clinical data. It describes the studies as "prospective clinical study" and "retrospective clinical specimens." This implies they are real-world clinical samples.

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

The process for establishing ground truth is described by the reference methods used for each analyte:
- For Campylobacter, Salmonella, Vibrio, and Yersinia enterocolitica: Traditional culture methods were used as the reference.
- For all other analytes (Clostridioides difficile, STEC, Shigella/EIEC, Cryptosporidium, Cyclospora cayetanensis, Giardia lamblia, Norovirus GI/GII): PCR/sequencing assays were used as comparator methods.
The document does not mention experts being used to establish a subjective "ground truth" (e.g., expert consensus for image review). This is a molecular diagnostic test, where ground truth is typically established by established laboratory reference methods (culture, PCR/sequencing). Therefore, the concept of "number of experts" is not directly applicable in the way it would be for an AI model interpreting medical images.

4. Adjudication Method for the Test Set

This concept is not relevant for this type of in vitro diagnostic device study. Adjudication (e.g., 2+1, 3+1) is typically performed when subjective interpretations (e.g., radiologist reads) form the ground truth against which an AI model is compared. Here, the ground truth is established by objective laboratory methods (culture, PCR/sequencing). Discrepancies between the device and the reference method might undergo further investigation (e.g., "re-testing," "bi-directional sequence analysis" mentioned for "false positive" or "false negative" specimens), but this is not an "adjudication" in the MRMC sense.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC study was not done. MRMC studies are typically for medical imaging AI where the human reader performance (with and without AI assistance) is evaluated. This device is an automated molecular diagnostic test; it does not involve human "readers" interpreting results in the same way as an imaging AI. Its performance is evaluated against established laboratory reference methods, not human reader improvement.

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

Yes, the provided performance data represents standalone performance. The BIOFIRE FILMARRAY GI Panel Mid is an automated system that provides qualitative results (Detected/Not Detected). The clinical performance data (sensitivity/PPA, specificity/NPA) directly reflects the device's ability to detect the target analytes directly from the sample without human interpretation or intervention in the diagnostic call itself, beyond operational steps.

7. The Type of Ground Truth Used

Laboratory Reference Methods:
- Culture: For Campylobacter, Salmonella, Vibrio, and Yersinia enterocolitica.
- PCR/sequencing assays: For Clostridioides difficile, STEC, Shigella/EIEC, Cryptosporidium, Cyclospora cayetanensis, Giardia lamblia, Norovirus GI/GII.
The text notes that for some discrepancies, "bi-directional sequence analysis" was used to confirm findings for both false positives and false negatives, suggesting a highly definitive molecular method was used for discordant results.

8. The Sample Size for the Training Set

The document describes the BIOFIRE FILMARRAY GI Panel Mid as "an identical product to the BIOFIRE® FILMARRAY® Gastrointestinal Panel (K242367) except it uses modified labeling and modified software to mask and report only 11 of the 22 targets normally reported."
"The performance presented here was established during the original clinical and analytical evaluations for the BIOFIRE FILMARRAY GI Panel."
This implies that there wasn't a separate "training set" for the "Mid" version as per typical AI/ML development. The underlying "algorithm" (the PCR primer sets, probes, and melt curve analysis interpretation) was developed and validated on the original BIOFIRE FILMARRAY GI Panel.
The document does not provide details on the training set sizes used for the development of the original BIOFIRE FILMARRAY GI Panel. The data presented are from the test/validation phase for the original panel which is now being leveraged for this "special 510k" submission.

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

As mentioned above, specific "training set" details for an AI model are not provided because this is a molecular diagnostic hardware/reagent system, not an AI/ML software. The "ground truth" for the development and optimization of the PCR assays (which are the "algorithm" in this context) would have been established through well-characterized analytical samples (known strains, clinical isolates) and potentially early-stage clinical samples validated by comparator methods (culture, sequencing). The document focuses on the validation data (clinical and analytical performance studies) used for regulatory submission.

Summary

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January 16, 2025

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BioFire Diagnostics, LLC Karli Plenert Senior Director, Regulatory Affairs 515 Colorow Drive Salt Lake City, Utah 84108

Re: K243885

Trade/Device Name: BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid Regulation Number: 21 CFR 866.3990 Regulation Name: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assay Regulatory Class: Class II Product Code: PCH Dated: December 18, 2024 Received: December 18, 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.

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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" (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 QS 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 Rule"). 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-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-regulatory

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assistance/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,

Digitally signed by Bryan M. Bryan M. Grabias -S Date: 2025.01.16 13:45:22 Grabias -S -05'00'

Bryan Grabias, Ph. D. 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) K243885

Device Name

BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid

Indications for Use (Describe)

· Campylobacter (C. jejuni/C. coli/C. upsaliensis)
· Clostridioides (Clostridium) difficile (toxin A/B)
· Salmonella
· Vibrio (V. parahaemolyticus/V. vulnificus/ V. cholerae)
· Yersinia enterocolitica
· Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2
· Shigella/ Enteroinvasive Escherichia coli (EIEC)
Cryptosporidium
· Cyclospora cayetanensis
· Giardia lamblia (also known as G. intestinalis and G. duodenalis)
Norovirus GI/GII

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Performance characteristics for Vibrio (V. parahaemolyticus, and Vibrio cholerae) was established primarily using contrived clinical specimens.

A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection of acute gastroenteritis in the context of outbreaks.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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BIOFIRE® FILMARRAY® Gastrointestinal Panel Mid

Special 510(k) Summary BioFire Diagnostics, LLC

Introduction:

The purpose of this Special 510(k) submission is to obtain clearance for the BIOFIRE® FILMARRAY® Gastrointestinal Panel Mid (BIOFIRE FILMARRAY GI Panel Mid). The BIOFIRE FILMARRAY GI Panel Mid is compatible with the BIOFIRE® FILMARRAY® 2.0 System (K143178) and the BIOFIRE® FILMARRAY® TORCH System (K160068), a polymerase chain reaction (PCR)-based in vitro diagnostic system for infectious disease testing.

The BIOFIRE GI Panel Mid is an identical product to the BIOFIRE® FILMARRAY® Gastrointestinal Panel (K242367) except it uses modified labeling and modified software to mask and report only 11 of the 22 targets normally reported on the BIOFIRE FILMARRAY GI Panel.

Modifications to the BIOFIRE FILMARRAY GI Panel Mid labeling, which includes changes to the Instructions for Use and Quick Guide, have been made to reflect the change in panel name and reported analytes.

According to the requirements of 21 CFR 807.92, the information included with this submission 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: 385-414-4985 Email: Karli.Plenert@biomerieux.com

Date submitted: January 16, 2025

Device Name and Classification:

Trade name: BIOFIRE® FILMARRAY® Gastrointestinal (GI) Panel Mid

Primary Requlation Number for Device Classification: 21 CFR 866.3990

Regulation Number: 21 CFR 866.3990

Classification Name: Gastrointestinal microorganism multiplex nucleic acid-based assay

Predicate Device:

K242367- BIOFIRE® FILMARRAY® Gastrointestinal (GI) Panel

January 16, 2025 BioFire Diagnostics, LLC

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Intended Use:

The BIOFIRE® FILMARRAY® Gastrointestinal Panel Mid is an automated qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with BIOFIRE® FILMARRAY® Systems. The BIOFIRE FILMARRAY GI Panel Mid is capable of the simultaneous detection and identification of nultiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria, parasites, and viruses are identified using the BIOFIRE FILMARRAY GI Panel Mid:

Bacteria	Viruses	Parasites
Campylobacter (C. jejuni/C. coli/ C. upsaliensis)	Norovirus GI/GII
Clostridioides (Clostridium) difficile (toxin A/B)
Salmonella
Shiga-like toxin-producing E. coli (STEC) stx1/stx2
Shigella/Enteroinvasive E. coli (EIEC)		Cryptosporidium
Vibrio (V. parahaemolyticus/V. vulnificus/ V. cholerae)		Cyclospora cayetanensis
Yersinia enterocolitica		Giardia lamblia

The BIOFIRE FILMARRAY GI Panel Mid is indicated as an aid in the diagnosis of gastrointestinal illness and results are meant to be used in coniuncal, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the BIOFIRE FILMARRAY GI Panel Mid. The agent detected may not be the definite cause of the disease.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Yersinia enterocolitica were established primarily with retrospective clinical specimens.

Performance characteristics for Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) was established primarily using contrived clinical specimens.

Neqative BIOFIRE FILMARRAY GI Panel Mid results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative collis, irritable bowel syndrome, or Crohn's disease.

A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute qastroenteritis in the context of outbreaks.

Device Description:

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

Substantial Equivalence:

The BIOFIRE FILMARRAY GI Panel Mid is substantially equivalent to the BIOFIRE GI Panel (K242367), which was cleared on November 7, 2024, and determined to be a Class II device.

A comparison of the BIOFIRE FILMARRAY GI Panel Mid to the BIOFIRE GI Panel is provided in Table 1, differences are shown in blue text.

Element	Predicate:BIOFIRE FILMARRAY GI Panel(K242367)	New Device:BIOFIRE FILMARRAY GI Panel Mid
Intended Use	The BIOFIRE® FILMARRAY®Gastrointestinal (GI) Panel is a qualitativemultiplexed nucleic acid-based in vitrodiagnostic test intended for use withBIOFIRE® FILMARRAY® Systems. TheBIOFIRE GI Panel is capable of thesimultaneous detection and identification ofnucleic acids from multiple bacteria, viruses,and parasites directly from stool samples inCary Blair transport media obtained fromindividuals with signs and/or symptoms ofgastrointestinal infection. The followingbacteria (including several diarrheagenic E. coli/Shigella pathotypes), parasites, andviruses are identified using the BIOFIREFILMARRAY GI Panel Mid:• Campylobacter ( C. jejuni/C. coli/C. upsaliensis )• Clostridium difficile ( C. difficile ) toxin A/B• Plesiomonas shigelloides• Salmonella	The BIOFIRE® FILMARRAY®Gastrointestinal (GI) Panel Mid is anautomated qualitative multiplexed nucleicacid-based in vitro diagnostic test intendedfor use with BIOFIRE® FILMARRAY®Systems. The BIOFIRE FILMARRAY GIPanel Mid is capable of the simultaneousdetection and identification of nucleic acidsfrom multiple bacteria, viruses, andparasites directly from stool samples inCary Blair transport media obtained fromindividuals with signs and/or symptoms ofgastrointestinal infection. The followingbacteria, parasites, and viruses areidentified using the BIOFIRE FILMARRAYGI Panel Mid:• Campylobacter ( C. jejuni/C. coli/C. upsaliensis )• Clostridioides ( Clostridium ) difficile (toxinA/B)• Vibrio ( V. parahaemolyticus/V. vulnificus/ V. cholerae )

	Table 1. Similarities and differences between the BIOFIRE FILMARRAY GI Panel Mid and the BIOFIRE GI Panel

Element	Predicate:BIOFIRE FILMARRAY GI Panel(K242367)	New Device:BIOFIRE FILMARRAY GI Panel Mid
	• Vibrio ( V. parahaemolyticus/V. vulnificus/ V. cholerae ), including specific identification of Vibrio cholerae• Yersinia enterocolitica• Enteroaggregative Escherichia coli (EAEC)• Enteropathogenic Escherichia coli (EPEC)• Enterotoxigenic Escherichia coli (ETEC) lt/st• Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2 (including specific identification of the E. coli O157 serogroup within STEC)• Shigella/ Enteroinvasive Escherichia coli (EIEC)• Cryptosporidium• Cyclospora cayetanensis• Entamoeba histolytica• Giardia lamblia (also known as G. intestinalis and G. duodenalis)• Adenovirus F 40/41• Astrovirus• Norovirus GI/GII• Rotavirus A• Sapovirus (Genogroups I, II, IV, and V)	• Yersinia enterocolitica• Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2• Shigella/ Enteroinvasive Escherichia coli (EIEC)• Cryptosporidium• Cyclospora cayetanensis• Giardia lamblia (also known as G. intestinalis and G. duodenalis)• Norovirus GI/GII
	The BIOFIRE GI Panel is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the BIOFIRE GI Panel. The agent detected may not be the definite cause of the disease.	The BIOFIRE FILMARRAY GI Panel Mid is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the BIOFIRE FILMARRAY GI Panel Mid. The agent detected may not be the definite cause of the disease.
	Concomitant culture is necessary for organism recovery and further typing of bacterial agents.	Concomitant culture is necessary for organism recovery and further typing of bacterial agents.
	This device is not intended to monitor or guide treatment for C. difficile infection.	This device is not intended to monitor or guide treatment for C. difficile infection.
	Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for E. coli O157, Plesiomonas shigelloides , Yersinia enterocolitica , Astrovirus , and Rotavirus A were established primarily with retrospective clinical specimens.	Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Yersinia enterocolitica were established primarily with retrospective clinical specimens.
	Performance characteristics for Entamoeba histolytica , and Vibrio ( V. parahaemolyticus ,	Performance characteristics for Vibrio ( V. parahaemolyticus , V. vulnificus , and Vibrio cholerae ) was established primarily using contrived clinical specimens.
	V. vulnificus , and Vibrio cholerae ) were	Negative BIOFIRE FILMARRAY GI Panel Mid results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.
		A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.
Element	Predicate:BIOFIRE FILMARRAY GI Panel(K242367)	New Device:BIOFIRE FILMARRAY GI Panel Mid
	established primarily using contrived clinicalspecimens.
	Negative BIOFIRE GI Panel results in thesetting of clinical illness compatible withgastroenteritis may be due to infection bypathogens that are not detected by this testor non-infectious causes such as ulcerativecolitis, irritable bowel syndrome, or Crohn'sdisease.
	A gastrointestinal microorganism multiplexnucleic acid-based assay also aids in thedetection and identification of acutegastroenteritis in the context of outbreaks.
Analyte	DNA/RNA	Same
Specimen Types	Human stool sample collected in Cary Blairtransport media.	Same
TechnologicalPrinciples	Nested multiplex PCR followed by highresolution melting analysis to confirm theidentity of amplified product.	Same
Instrumentation	BIOFIRE FILMARRAY 2.0 System orBIOFIRE FILMARRAY TORCH System	Same
Time to result	About 1 hour	Same
Test Interpretation	Automated test interpretation and reportgeneration. User cannot access raw data.	Same
Sample PreparationMethod	Sample Processing is automated in theBIOFIRE System.	Same
Reagent Storage	Reagents are stored at room temperature.	Same
Shelf-Life	12 months from Date of Manufacture	Same
Controls	Two controls are included in each reagentpouch to control for sample processing andboth stages of PCR and melt analysis.	Same
User Complexity	Moderate	Same

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Summary of Performance Data:

The BIOFIRE FILMARRAY GI Panel Mid has an abbreviated panel menu compared to the original BIOFIRE FILMARRAY GI Panel, reporting only 11 of the original 22 analytes. The performance presented here was established during the original clinical and analytical evaluations for the BIOFIRE FILMARRAY GI Panel.

The performance data for the BIOFIRE FILMARRAY GI Panel Mid is summarized in the BIOFIRE FILMARRAY GI Panel Mid Instructions for Use. A summary of the BIOFIRE FILMARRAY GI Panel Mid performance data is also provided below.

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Clinical Performance

Table 2 provides a summary of the performance of each analyte from the Prospective Clinical Evaluation performed for the BIOFIRE FILMARRAY GI Panel Mid.

Table 2. BIOFIRE FILMARRAY GI Panel Mid Performance in the Prospective Clinical Evaluation (May through September 2013)
BIOFIRE FILMARRAY GI Panel Mid Analyte	Sensitivity/PPAa		Specificity/NPAa
	TP/(TP + FN)	%	95% CI	TN/(TN + FP)	%	95% CI
Bacteria
Campylobacter ( C. jejuni/C. coli/C. upsaliensis )	34/35b	97.1	85.1-99.9%	1497/1521b	98.4	97.7-99.0%
Clostridioides ( Clostridium ) difficile toxin A/Ba	163/165c	98.8	95.7-99.9%	1350/1391c	97.1	96.0-97.9%
Salmonella	31/31	100	88.8-100%	1519/1525d	99.6	99.1-99.9%
Shiga -like toxin-producing E. coli (STEC) stx1/stx2	33/33	100	89.4-100%	1518/1523e	99.7	99.2-99.9%
Shigella/Enteroinvasive E. coli (EIEC)	47/49	95.9	86.0-99.5%	1505/1507	99.9	99.5-100%
Vibrio ( V. parahaemolyticus/V. vulnificus/V. cholerae )	0/0	-	-	1554/1556f	99.9	99.5-100%
Yersinia enterocolitica	1/1	100	-	1555/1555	100	99.8-100%
Parasites
Cryptosporidium	18/18	100	81.5-100%	1532/1538g	99.6	99.2-99.9%
Cyclospora cayetanensis	19/19	100	82.4-100%	1537/1537	100	99.8-100%
Giardia lamblia	20/20	100	83.2-100%	1529/1536h	99.5	99.1-99.8%
Viruses
Norovirus GI/GII	52/55i	94.5	84.9-98.9%	1483/1501i	98.8	98.1-99.3%

Table 2. BIOFIRE FILMARRAY GI Panel Mid Performance in the Prospective Clinical Evaluation (May through September 2013)

C. difficile performance is reported as positive percent agrement in contrast to the table headings. The performance measures of sensibility and specificity only refer to those analytes for which the was used as the reference method; Campylobacter, Salmonella, Vibrio, and Yersinia entercoollica. Performance measures of positive percent agreement (NPA) refer to all other analytes, for which

PCR/sequencing assays were used as comparator methods.

Campylobacter jeiuni subsp. doylei was identified in the specimen using bi-drectional sequence analysis. Camp yobacter was detected in 1924 false positive specimens using bi-directional sequence analysis

^ C. difficile was detected in 1/2 false negative specimens and 41/41 false positive specimens using bi-directional sequence analysis.

d Salmonella was detected in 6/6 false positive specimens using bi-directional sequence analysis.

e STEC was detected in 5/5 false positive specimens using bi-directional sequence analysis

[ Vibrio was detected in 2/2 false positive specimens using bi-directional sequence analysis.

9 Cryptosporidium was detected in 6/6 false positive specimens using bi-directional sequence analysis.

G. lamblia was delected in 47 false positive specifice al sequence analysis. Two false positive results appear to be caused by with Bifidobacterium longum and Ruminococcus callidus.

The BIOFIRE FILMARRY G Panel Mid delected Norovines in 1/3 false negative specimens was detected in 1/2 remaining false negative specimens and 8/18 false positive specimens usings. Refer to Table 3 below for additional Norovirus G/G1 performance results

Table 3. BIOFIRE FILMARRAY GI Panel Mid Norovirus GI/Gl Performance in the Prospective Clinical Evaluation (April through July 2023)

BIOFIRE FILMARRAYGI Panel Mid Result	TP/(TP + FN)	%	95% CI	TN/(TN + FP)	%	95% CI
Norovirus GI/GII	34/35a	97.1	85.1-99.9%	808/837a	96.5	95.1-97.7%

Norovirus was detected in the single FN specimen using bi-directional sequencing analysis. Norovirus was detected in 3/29 false positive specimens using bi-directional sequencing analysis. Twenty (20) of the remaining false positive results appear to have been caused by cross-reactivity; refer to the Error! Reference source not found. section in the Instructions for Use for the cross-reactive organisms.

Analytical Performance Characteristics

Bench performance (analytical) testing for the BIOFIRE FILMARRAY GI Panel Mid was designed to validate the performance of all analytes. Table 4 provides an overall studies, their results, and conclusions.

Study	Purpose	Results & Conclusions
Limit of Detection	The purpose of the LoD studieswas to determine the limit ofdetection (LoD; lowestconcentration of analyte that canbe detected in at least 95% ofreplicates tested) for each of the	Confirmed LoD concentrations forbacteria range from 1.0E+02 CFU/mLup to 8.0E+04 cells/mL and forparasites range from 5.0E+01 to5.0E+03 units/mL. For NorovirusGI/GII, the confirmed LoD
Study	Purpose	Results & Conclusions
	organisms detected by theBIOFIRE FILMARRAY GI PanelMid. LoD was initially estimatedand confirmed on the firstgeneration BIOFIRE FILMARRAYsystem, with subsequent studies toverify that ≥95% detection could beachieved at the same LoDconcentration on the nextgeneration BIOFIRE 2.0 andBIOFIRE TORCH systems.	concentration is 1.0E+04 RNAcopies/mL.LoD testing demonstrated thatdetection at the LoD concentration isequivalent between the BIOFIREFILMARRAY (no longer inproduction), BIOFIRE 2.0, andBIOFIRE TORCH systems.The clinical data demonstrates thatthe analytically determined detectionlimit of the BIOFIRE FILMARRAY GIPanel Mid assays is appropriate forthe levels of pathogens in clinicalspecimens (including co-infections orpolymicrobial specimens).
Analytical Reactivity (Inclusivity)	The purpose of this study was toevaluate and define the analyticalreactivity of BIOFIRE FILMARRAYGI Panel Mid. The study describesthe diversity of panel analytes thatare efficiently amplified andaccurately detected, and alsoidentifies known limitations onassay reactivity with specificsubspecies, types, or variantsequences.	The reactivity of each of the panelassays was found to be consistentwith the intent of the design and theassays will accurately identify theexpected diversity of the analytes,with limitations noted in theInstructions for Use.
Reproducibility	Studies were performed to evaluatethe within-lab (intermediateprecision/repeatability) andbetween-lab (reproducibility)precision of analyte detection bythe BIOFIRE FILMARRAY GIPanel Mid on the BIOFIREFILMARRAY (no longer inproduction), BIOFIRE 2.0 and/orBIOFIRE TORCH systems. Eachstudy evaluated multiple within-laband between-lab operationalvariables including day, site,operator, instrument/system, andreagent lot.Precision for a qualitative testwithout an underlying numericalvalue is measured as percent (%)agreement between runs or %agreement with the expected result(Detected, Not Detected or N/A).The run-to-run precision wasevaluated for negative samples aswell as positive samples.The product design inputs require aminimum run-to-run agreement of85%, with a desired run-to-runagreement of 95%.	For negative samples, the expectedNot Detected (or N/A) results werereported for >95% of replicates testedon each system.For positive samples, detectionagreement between runs was >95%at the 1× and/or 3×LoDconcentrations for each analyteevaluated, with the exception ofGiardia lamblia (84.3% and 91.7% at1× LoD on the BIOFIRE FILMARRAYand TORCH Systems respectively;not tested on BIOFIRE 2.0).Subsequent investigation determinedthat the lower % agreement for G.lamblia was an artifact of instability ofthe analyte stock (experimental error)rather than imprecision of the test.Testing of G. lamblia was laterrepeated on the BIOFIREFILMARRAY, BIOFIRE 2.0 andBIOFIRE TORCH Systems withsamples prepared from a stableculture stock and run-to-runagreement for G. lamblia was 100%at the 1× LoD concentration.The combination of studiesdemonstrate that the precision ofanalyte detection by the BIOFIREFILMARRAY GI Panel Mid is high;repeatable within-day and within-laband reproducible within and betweenlabs on BIOFIRE FILMARRAY,BIOFIRE 2.0, and BIOFIRE TORCH systems.
Study	Purpose	Results & Conclusions
		systems. High reproducibility isachieved when samples are tested onmultiple reagent lots by differentoperators, on differentinstruments/modules, at differentsites, and on different days.
Exclusivity/Cross-Reactivity	The purpose of the study was toidentify on-panel or off-panelorganisms that might lead toinaccurate test results due to non-specific amplification or cross-reactivity with assay primers.On-panel organisms were tested toassess the potential for intra-panelcross-reactivity while off-panelorganisms (those not intended tobe detected by the panel) weretested to assess the potential fornon-specific amplification of normalflora or other pathogens that maybe present in stool samples.	Testing and sequence analysisidentified a subset of BIOFIREFILMARRAY GI Panel Mid assaysthat may non-specifically interact withand amplify homologous sequencesin a few closely related or near-neighbor species as well as with afew unrelated organisms that mightbe found in stool samples.In most cases, the non-specificinteraction is inefficient and very highlevels of the cross-reacting organismmust be present in the sample toobtain a false positive result.The product literature describes allknown or predicted cross-reactivities.
Interference	The purpose of this study was toevaluate the potential forsubstances that may be present ina sample to interfere with thefunction of the pouch and/or theaccuracy of test results.Testing also evaluated the potentialfor competitive inhibition ormicrobial interference on analytedetection near LoD.	Testing established that the BIOFIREFILMARRAY GI Panel Mid is a highlyrobust multi-pathogen detectiondevice that is resistant to interferencefrom a variety of substances thatcould be present in stool samples,including blood and other biologicalsubstances, oral and topicaltreatments, and high levels ofpotentially competingmicroorganisms.Warnings and recommendationsagainst the testing of stool preparedin off-label fixative-containing media isindicated in the Instructions for Use(fixative can negatively impact analytedetection) as well as risks associatedwith damage to nucleic acids that canbe caused by bleach.

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Conclusion:

The fundamental scientific technology, performance, and risk of the BIOFIRE FILMARRAY GI Panel Mid remain unchanged from the legally marketed BIOFIRE GI Panel. There is no change to the product itself, except for modified software that has been verified and validated to show no change in safety and effectiveness. Therefore, the BIOFIRE FILMARRAY GI Panel Mid performs as well as the predicate device.

Regulation Number and Section

§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.

(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).