(29 days)
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 GI Panel:
- Campylobacter (C. jejuni/C. coli/C. upsaliensis)
- Clostridiodes (Clostridium) difficile (C. difficile) toxin A/B
- Plesiomonas shigelloides
- Salmonella
- 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) stx 1/stx2, including specific identification of the E. coli 0157 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)
The BIOFIRE GI Panel is indicated as an aid in the diagnosis 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.
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 E. coli 0157, Plesiomonas shigelloides, Yersinia enterocolitica, Astrovirus, and Rotavirus A were established primarily with retrospective clinical specimens.
Performance characteristics for Entamoeba histolytica, and Vibrio (V. parahaemolyticus, and Vibrio cholerae) were 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 of acute gastroenteritis in the context of outbreaks.
The BIOFIRE® FILMARRAY® Gastrointestinal (GI) Panel is designed to simultaneously identify 22 gastrointestinal pathogens from stool specimens collected in Cary Blair transport medium. The BIOFIRE GI Panel 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 GI Panel pouch module software) is used to perform BIOFIRE GI Panel testing on these systems. Results from the BIOFIRE GI Panel test are available within about one hour.
A test is initiated by loading Hydration Solution 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 GI pouch and placing it in a BIOFIRE System. The pouch contains all the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the BIOFIRE Software guides the user though the steps of placing 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 positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the PCR reactions and the melt curve analysis.
Nucleic acid extraction occurs within the BIOFIRE pouch using mechanical and chemical 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.
This FDA 510(k) summary describes a software update for the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel, not a study for a new device. Therefore, much of the requested information regarding acceptance criteria, study design, and ground truth establishment is not applicable in the typical sense of a de novo device submission demonstrating clinical performance.
The submission focuses on mitigating a known issue of false positive Cryptosporidium results due to a non-specific product generated by the Crypt 2 assay. The "acceptance criteria" here is that the software update successfully mitigates this known false positive issue without negatively impacting other performance claims.
Here's an attempt to fill out the table and answer the questions based on the provided document, noting where information is not available or not applicable for this type of submission.
1. A table of acceptance criteria and the reported device performance
Since this is a software update to address a specific false positive issue, the "acceptance criteria" isn't about overall clinical metrics but rather the successful mitigation of the identified defect. The direct "reported device performance" would pertain to how this false positive rate is reduced. This specific information is not quantitatively detailed in this summary.
| Acceptance Criteria (Implied) | Reported Device Performance (Implied by submission intent) |
|---|---|
| Mitigation of erroneous "Cryptosporidium Detected" results from non-specific Crypt 2 assay product. | Software update developed to mitigate the erroneous interpretation. (No quantitative data on the reduction of false positives is presented in this summary.) |
| No negative impact on other performance claims. | "This software change does not modify any performance claims." (No specific study data to demonstrate this is presented in this summary.) |
| Minor IFU update for Cryptosporidium canis detection limit. | IFU updated to remove one row from the "Cryptosporidium Inclusivity Results" table (Table 31) where C. canis detection was below LoD. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document mentions that an internal investigation identified the non-specific product in "a small fraction of patient samples," suggesting retrospective observation. However, it does not detail a specific "test set" with a defined sample size or provenance for evaluating the software update after its development. The submission states, "This software change does not modify any performance claims," implying that extensive re-validation of all performance characteristics was not deemed necessary for this "Special 510(k)" type of submission.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
Not applicable. The ground truth for identifying the false positive issue was based on customer reports and an internal investigation by BioFire Diagnostics. There's no mention of external experts or a formal ground truth panel for evaluating the software update's effectiveness in this summary.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. No formal adjudication method for a test set is described, as the focus is on a software modification addressing an internal issue rather than a new clinical performance study.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This device is a fully automated in vitro diagnostic test, not an AI-assisted interpretation tool for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this device operates as a standalone algorithm (pouch module software) without human-in-the-loop performance for interpretation. The software automatically interprets results. The effect of the software update is purely on the automated interpretation of the assay signals.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" for the identified problem was the observation of erroneous "Cryptosporidium Detected" results from patient samples, which were found to be due to a non-specific amplification product from the Crypt 2 assay upon internal investigation. The effectiveness of the software update is implicitly defined by its ability to correctly interpret these signals. For the original (predicate) device, performance characteristics were established using combinations of prospective clinical specimens, retrospective clinical specimens, and contrived clinical specimens for various organisms (as mentioned in the "Indications for Use" section).
8. The sample size for the training set
Not applicable in the context of this software update. This is a modification to an existing algorithm based on observed malfunction rather than a de novo algorithm development requiring a separate training set. The original development of the BIOFIRE GI Panel would have involved training data, but that is not detailed here.
9. How the ground truth for the training set was established
Not applicable for this software update. For the original predicate device, the ground truth for the various pathogens detected would have been established through a combination of standard microbiological methods (culture, reference PCR, etc.) on clinical samples, as per typical IVD validation practices, but the details are not provided in this summary.
§ 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).