(29 days)
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.
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.
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.
§ 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).