(29 days)
Not Found
No
The description focuses on the biochemical and mechanical processes of the assay (nucleic acid extraction, PCR, melt curve analysis) and the software's role in interpreting these results based on predefined parameters (melt curve analysis and internal controls). There is no mention of the software learning from data or using complex algorithms beyond standard signal processing and interpretation of known biological reactions.
No
The device is an in vitro diagnostic test designed to detect and identify nucleic acids from various pathogens directly from stool samples to aid in the diagnosis of gastrointestinal illness. It is not intended for treatment or monitoring of treatment.
Yes.
The "Intended Use / Indications for Use" section explicitly states that "The BIOFIRE FILMARRAY GI Panel Mid is an automated qualitative multiplexed nucleic acid-based in vitro diagnostic test..." and "The BIOFIRE FILMARRAY GI Panel Mid is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness...".
No
The device is a complex in vitro diagnostic system that includes hardware components (BIOFIRE FILMARRAY Systems, pouches, bladders, seal points, pneumatic pistons, Peltier devices, digital camera) in addition to software. The software controls the hardware and interprets the results from the hardware-based assay.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicitly Stated in Intended Use: The very first sentence of the "Intended Use / Indications for Use" section clearly states: "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."
- Purpose of the Device: The device is intended to detect and identify nucleic acids from pathogens in stool samples to aid in the diagnosis of gastrointestinal infections. This is a classic function of an in vitro diagnostic device, which is used to examine specimens from the human body to provide information for the diagnosis, prevention, or treatment of disease.
- Testing of Biological Specimens: The device operates on stool samples, which are biological specimens from the human body.
- Laboratory Setting: The intended use specifies that the device is for use by trained medical and laboratory professionals in a laboratory setting. This is typical for IVD devices.
N/A
Intended Use / Indications for Use
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 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, 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.
Product codes (comma separated list FDA assigned to the subject device)
PCH
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.
Mentions image processing
A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Stool samples
Indicated Patient Age Range
Not Found
Intended User / Care Setting
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.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance:
A Prospective Clinical Evaluation for the BIOFIRE FILMARRAY GI Panel Mid was performed from May through September 2013.
- Campylobacter (C. jejuni/C. coli/C. upsaliensis): Sensitivity/PPA 97.1% (34/35), Specificity/NPA 98.4% (1497/1521). The single false negative specimen was identified as Campylobacter jejuni subsp. doylei. 24 false positive specimens had Campylobacter detected by bi-directional sequence analysis.
- Clostridioides (Clostridium) difficile toxin A/B: Sensitivity/PPA 98.8% (163/165), Specificity/NPA 97.1% (1350/1391). C. difficile was detected in 1/2 false negative specimens and 41/41 false positive specimens using bi-directional sequence analysis.
- Salmonella: Sensitivity/PPA 100% (31/31), Specificity/NPA 99.6% (1519/1525). Salmonella was detected in 6/6 false positive specimens using bi-directional sequence analysis.
- Shiga-like toxin-producing E. coli (STEC) stx1/stx2: Sensitivity/PPA 100% (33/33), Specificity/NPA 99.7% (1518/1523). STEC was detected in 5/5 false positive specimens using bi-directional sequence analysis.
- Shigella/Enteroinvasive E. coli (EIEC): Sensitivity/PPA 95.9% (47/49), Specificity/NPA 99.9% (1505/1507).
- Vibrio (V. parahaemolyticus/V. vulnificus/V. cholerae): Sensitivity/PPA - (0/0), Specificity/NPA 99.9% (1554/1556). Vibrio was detected in 2/2 false positive specimens using bi-directional sequence analysis.
- Yersinia enterocolitica: Sensitivity/PPA 100% (1/1), Specificity/NPA 100% (1555/1555).
- Cryptosporidium: Sensitivity/PPA 100% (18/18), Specificity/NPA 99.6% (1532/1538). Cryptosporidium was detected in 6/6 false positive specimens using bi-directional sequence analysis.
- Cyclospora cayetanensis: Sensitivity/PPA 100% (19/19), Specificity/NPA 100% (1537/1537).
- Giardia lamblia: Sensitivity/PPA 100% (20/20), Specificity/NPA 99.5% (1529/1536). G. lamblia was detected in 4/7 false positive specimens by sequence analysis.
- Norovirus GI/GII: Sensitivity/PPA 94.5% (52/55), Specificity/NPA 98.8% (1483/1501). Norovirus was detected in 1/3 false negative specimens. In another study (April through July 2023), Norovirus GI/GII showed 97.1% (34/35) sensitivity and 96.5% (808/837) specificity. 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.
Analytical Performance Characteristics:
- Limit of Detection (LoD): LoD concentrations for bacteria range from 1.0E+02 CFU/mL up to 8.0E+04 cells/mL. For parasites, ranges from 5.0E+01 to 5.0E+03 units/mL. For Norovirus GI/GII, the confirmed LoD concentration is 1.0E+04 RNA copies/mL. LoD testing demonstrated equivalent detection across BIOFIRE FILMARRAY, BIOFIRE 2.0, and BIOFIRE TORCH systems.
- Analytical Reactivity (Inclusivity): The reactivity of each panel assay was consistent with design intent, accurately identifying the expected diversity of analytes, with limitations noted in the Instructions for Use.
- Reproducibility: For negative samples, >95% of replicates tested on each system reported "Not Detected" (or N/A). For positive samples, detection agreement between runs was >95% at 1x and/or 3x LoD concentrations for each analyte, with the exception of Giardia lamblia (84.3% and 91.7% at 1x LoD on FILMARRAY and TORCH Systems respectively). After retesting with stable culture stock, G. lamblia showed 100% agreement at 1x LoD. High reproducibility was demonstrated across different operators, instruments, sites, and reagent lots.
- Exclusivity/Cross-Reactivity: Testing identified that some assays might non-specifically interact with and amplify homologous sequences in a few closely related or near-neighbor species as well as with a few unrelated organisms that might be found in stool samples. In most cases, very high levels of the cross-reacting organism were needed to obtain a false positive result.
- Interference: The device is resistant to interference from substances in stool samples, including blood, other biological substances, oral and topical treatments, and high levels of potentially competing microorganisms. Warnings against testing stool prepared in off-label fixative-containing media are noted.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Campylobacter (C. jejuni/C. coli/C. upsaliensis): Sensitivity/PPA 97.1%, Specificity/NPA 98.4%
- Clostridioides (Clostridium) difficile toxin A/B: Sensitivity/PPA 98.8%, Specificity/NPA 97.1%
- Salmonella: Sensitivity/PPA 100%, Specificity/NPA 99.6%
- Shiga-like toxin-producing E. coli (STEC) stx1/stx2: Sensitivity/PPA 100%, Specificity/NPA 99.7%
- Shigella/Enteroinvasive E. coli (EIEC): Sensitivity/PPA 95.9%, Specificity/NPA 99.9%
- Vibrio (V. parahaemolyticus/V. vulnificus/V. cholerae): Specificity/NPA 99.9%
- Yersinia enterocolitica: Sensitivity/PPA 100%, Specificity/NPA 100%
- Cryptosporidium: Sensitivity/PPA 100%, Specificity/NPA 99.6%
- Cyclospora cayetanensis: Sensitivity/PPA 100%, Specificity/NPA 100%
- Giardia lamblia: Sensitivity/PPA 100%, Specificity/NPA 99.5%
- Norovirus GI/GII: Sensitivity/PPA 94.5% (initial study), 97.1% (second study); Specificity/NPA 98.8% (initial study), 96.5% (second study).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K242367- BIOFIRE® FILMARRAY® Gastrointestinal (GI) Panel
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
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January 16, 2025
Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the acronym "FDA" followed by "U.S. FOOD & DRUG" and "ADMINISTRATION" stacked vertically.
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.
1
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
2
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)
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.
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:
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.
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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.
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 qualitative
multiplexed nucleic acid-based in vitro
diagnostic test intended for use with
BIOFIRE® FILMARRAY® Systems. The
BIOFIRE GI Panel 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 (including several diarrheagenic E. coli/Shigella pathotypes), parasites, and
viruses are identified using the BIOFIRE
FILMARRAY 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 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)
• 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 clinical | ||
| specimens. | ||
| Negative BIOFIRE GI Panel 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. | ||
| Analyte | DNA/RNA | Same |
| Specimen Types | Human stool sample collected in Cary Blair | |
| transport media. | Same | |
| Technological | ||
| Principles | Nested multiplex PCR followed by high | |
| resolution melting analysis to confirm the | ||
| identity of amplified product. | Same | |
| Instrumentation | BIOFIRE FILMARRAY 2.0 System or | |
| BIOFIRE FILMARRAY TORCH System | Same | |
| Time to result | About 1 hour | Same |
| Test Interpretation | Automated test interpretation and report | |
| generation. User cannot access raw data. | Same | |
| Sample Preparation | ||
| Method | Sample Processing is automated in the | |
| BIOFIRE System. | Same | |
| Reagent Storage | Reagents are stored at room temperature. | Same |
| Shelf-Life | 12 months from Date of Manufacture | Same |
| Controls | Two controls are included in each reagent | |
| pouch to control for sample processing and | ||
| both stages of PCR and melt analysis. | Same | |
| User Complexity | Moderate | Same |
8
9
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 FILMARRAY
| GI 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 studies | |
| was to determine the limit of | ||
| detection (LoD; lowest | ||
| concentration of analyte that can | ||
| be detected in at least 95% of | ||
| replicates tested) for each of the | Confirmed LoD concentrations for | |
| bacteria range from 1.0E+02 CFU/mL | ||
| up to 8.0E+04 cells/mL and for | ||
| parasites range from 5.0E+01 to | ||
| 5.0E+03 units/mL. For Norovirus | ||
| GI/GII, the confirmed LoD | ||
| Study | Purpose | Results & Conclusions |
| organisms detected by the | ||
| BIOFIRE FILMARRAY GI Panel | ||
| Mid. LoD was initially estimated | ||
| and confirmed on the first | ||
| generation BIOFIRE FILMARRAY | ||
| system, with subsequent studies to | ||
| verify that ≥95% detection could be | ||
| achieved at the same LoD | ||
| concentration on the next | ||
| generation BIOFIRE 2.0 and | ||
| BIOFIRE TORCH systems. | concentration is 1.0E+04 RNA | |
| copies/mL. | ||
| LoD testing demonstrated that | ||
| detection at the LoD concentration is | ||
| equivalent between the BIOFIRE | ||
| FILMARRAY (no longer in | ||
| production), BIOFIRE 2.0, and | ||
| BIOFIRE TORCH systems. | ||
| The clinical data demonstrates that | ||
| the analytically determined detection | ||
| limit of the BIOFIRE FILMARRAY GI | ||
| Panel Mid assays is appropriate for | ||
| the levels of pathogens in clinical | ||
| specimens (including co-infections or | ||
| polymicrobial specimens). | ||
| Analytical Reactivity (Inclusivity) | The purpose of this study was to | |
| evaluate and define the analytical | ||
| reactivity of BIOFIRE FILMARRAY | ||
| GI Panel Mid. The study describes | ||
| the diversity of panel analytes that | ||
| are efficiently amplified and | ||
| accurately detected, and also | ||
| identifies known limitations on | ||
| assay reactivity with specific | ||
| subspecies, types, or variant | ||
| sequences. | The reactivity of each of the panel | |
| assays was found to be consistent | ||
| with the intent of the design and the | ||
| assays will accurately identify the | ||
| expected diversity of the analytes, | ||
| with limitations noted in the | ||
| Instructions for Use. | ||
| Reproducibility | Studies were performed to evaluate | |
| the within-lab (intermediate | ||
| precision/repeatability) and | ||
| between-lab (reproducibility) | ||
| precision of analyte detection by | ||
| the BIOFIRE FILMARRAY GI | ||
| Panel Mid on the BIOFIRE | ||
| FILMARRAY (no longer in | ||
| production), BIOFIRE 2.0 and/or | ||
| BIOFIRE TORCH systems. Each | ||
| study evaluated multiple within-lab | ||
| and between-lab operational | ||
| variables including day, site, | ||
| operator, instrument/system, and | ||
| reagent lot. | ||
| Precision for a qualitative test | ||
| without an underlying numerical | ||
| value is measured as percent (%) | ||
| agreement between runs or % | ||
| agreement with the expected result | ||
| (Detected, Not Detected or N/A). | ||
| The run-to-run precision was | ||
| evaluated for negative samples as | ||
| well as positive samples. | ||
| The product design inputs require a | ||
| minimum run-to-run agreement of | ||
| 85%, with a desired run-to-run | ||
| agreement of 95%. | For negative samples, the expected | |
| Not Detected (or N/A) results were | ||
| reported for >95% of replicates tested | ||
| on each system. | ||
| For positive samples, detection | ||
| agreement between runs was >95% | ||
| at the 1× and/or 3×LoD | ||
| concentrations for each analyte | ||
| evaluated, with the exception of | ||
| Giardia lamblia (84.3% and 91.7% at | ||
| 1× LoD on the BIOFIRE FILMARRAY | ||
| and TORCH Systems respectively; | ||
| not tested on BIOFIRE 2.0). | ||
| Subsequent investigation determined | ||
| that the lower % agreement for G. | ||
| lamblia was an artifact of instability of | ||
| the analyte stock (experimental error) | ||
| rather than imprecision of the test. | ||
| Testing of G. lamblia was later | ||
| repeated on the BIOFIRE | ||
| FILMARRAY, BIOFIRE 2.0 and | ||
| BIOFIRE TORCH Systems with | ||
| samples prepared from a stable | ||
| culture stock and run-to-run | ||
| agreement for G. lamblia was 100% | ||
| at the 1× LoD concentration. | ||
| The combination of studies | ||
| demonstrate that the precision of | ||
| analyte detection by the BIOFIRE | ||
| FILMARRAY GI Panel Mid is high; | ||
| repeatable within-day and within-lab | ||
| and reproducible within and between | ||
| labs on BIOFIRE FILMARRAY, | ||
| BIOFIRE 2.0, and BIOFIRE TORCH systems. | ||
| Study | Purpose | Results & Conclusions |
| systems. High reproducibility is | ||
| achieved when samples are tested on | ||
| multiple reagent lots by different | ||
| operators, on different | ||
| instruments/modules, at different | ||
| sites, and on different days. | ||
| Exclusivity/Cross-Reactivity | The purpose of the study was to | |
| identify on-panel or off-panel | ||
| organisms that might lead to | ||
| inaccurate test results due to non- | ||
| specific amplification or cross- | ||
| reactivity with assay primers. | ||
| On-panel organisms were tested to | ||
| assess the potential for intra-panel | ||
| cross-reactivity while off-panel | ||
| organisms (those not intended to | ||
| be detected by the panel) were | ||
| tested to assess the potential for | ||
| non-specific amplification of normal | ||
| flora or other pathogens that may | ||
| be present in stool samples. | Testing and sequence analysis | |
| identified a subset of BIOFIRE | ||
| FILMARRAY GI Panel Mid assays | ||
| that may non-specifically interact with | ||
| and amplify homologous sequences | ||
| in a few closely related or near- | ||
| neighbor species as well as with a | ||
| few unrelated organisms that might | ||
| be found in stool samples. | ||
| In most cases, the non-specific | ||
| interaction is inefficient and very high | ||
| levels of the cross-reacting organism | ||
| must be present in the sample to | ||
| obtain a false positive result. | ||
| The product literature describes all | ||
| known or predicted cross-reactivities. | ||
| Interference | The purpose of this study was to | |
| evaluate the potential for | ||
| substances that may be present in | ||
| a sample to interfere with the | ||
| function of the pouch and/or the | ||
| accuracy of test results. | ||
| Testing also evaluated the potential | ||
| for competitive inhibition or | ||
| microbial interference on analyte | ||
| detection near LoD. | Testing established that the BIOFIRE | |
| FILMARRAY GI Panel Mid is a highly | ||
| robust multi-pathogen detection | ||
| device that is resistant to interference | ||
| from a variety of substances that | ||
| could be present in stool samples, | ||
| including blood and other biological | ||
| substances, oral and topical | ||
| treatments, and high levels of | ||
| potentially competing | ||
| microorganisms. | ||
| Warnings and recommendations | ||
| against the testing of stool prepared | ||
| in off-label fixative-containing media is | ||
| indicated in the Instructions for Use | ||
| (fixative can negatively impact analyte | ||
| detection) as well as risks associated | ||
| with damage to nucleic acids that can | ||
| be caused by bleach. |
11
12
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.